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A Review of Herbal Therapy in Multiple Sclerosis

Abstract

Multiple sclerosis is a complex autoimmune disorder which characterized by demyelination and axonal loss in the central nervous system (CNS). Several evidences indicate that some new drugs and stem cell therapy have opened a new horizon for multiple sclerosis treatment, but current therapies are partially effective or not safe in the long term. Recently, herbal therapies represent a promising therapeutic approach for multiple sclerosis disease. Here, we consider the potential benefits of some herbal compounds on different aspects of multiple sclerosis disease. The medicinal plants and their derivatives; Ginkgo biloba, Zingiber officinale, Curcuma longa, Hypericum perforatum, Valeriana officinalis, Vaccinium macrocarpon, Nigella sativa,Piper methysticum, Crocus sativus, Panax ginseng, Boswellia papyrifera, Vitis vinifera, Gastrodia elata, Camellia sinensis, Oenothera biennis, MS14 and Cannabis sativa have been informed to have several therapeutic effects in MS patients.

Keywords: Multiple sclerosis, Inflammation, Demyelination, Remyelination, Herbal therapy

Introduction

Multiple sclerosis (MS) is an autoimmune disease that mostly occurs in young adulthood.1 The etiology of MS disease is still not well understood, but both genetic and environmental factors were found to have important roles in MS disease initiation or progression.2 In MS disease, inflammatory cells demolish myelin sheath in the CNS which weakens action potential conduction.3 Two cardinal properties of MS are acute inflammation that associated with demyelination and another one is axonal loss.4 After injury, oligodendrocyte precursor cells (OPCs) which are residing at parenchyma continuously produce myelinating oligodendrocytes.3-5 In addition, regarding to the ability of neural stem cells for differentiation to OPCs, these stem cells are considered as an important source for remyelination.6-8 These endogenous stem cells proliferate, migrate and differentiate to OPCs after brain injuries. However, endogenous OPCs can produce myelin and improve some aspects of the MS disease, but endogenous repair may fail in long term.7,9 Therefore, several studies have focused on different approaches (including targeting specific signaling pathways, stem cell therapy, suppressing the inflammation process and reprogramming of glial cells to OPCs …) that improve myelination.10 Despite the potential benefits of stem cell therapy in the improvement of myelin repair,11 its clinical application has been hampered because of the possibility of teratoma formation, cell rejection and ethical problems.12,13 Therefore, there is still a need for developing new drugs which have no or less considerable side effects.

The pathophysiology of MS is not well elucidated, which makes itsʼ treatment strategy very difficult and perplexing.14 At the present time, most of the strategies in MS treatment are focused on preventing of inflammation in the CNS. 15 Interferon beta (IFN-beta) was firstly confirmed as an effective drug for treatment of MS in 1993.16 Afterward, different drugs were introduced for curing MS such as glatiramer acetate, natalizumab, alemtuzumab and fingolimod.14 All of these mentioned drugs were partially effective and their remarkable adverse effects makes them unsuitable for proloned use.17 For example, several studies indicated the adverse effects of IFN-beta consumption including, stroke, headache, migraine and depression.17 Until now, no absolute treatment has been found for MS, therefore, trying to find a completely effective and safe treatment is still ongoing.

Use of complementary and alternative medicine (CAM), in particular herbal remedies have noticeably risen in MS patients over the last decades.18,19 Herbal therapy is known as a helpful strategy for curing the different disorders from ancient to the present time.20 Previous studies reported that medicinal plants have several therapeutic effects in different disorders such as cancers, diabetes and neurodegenerative diseases. 21,22 Recently, a growing number of findings have indicated that some herbal compounds improve myelin repair and lead to suppression of inflammation.23,24 Also, there are many studies that reported the anti-inflammatory and antioxidant effects of medicinal plants, as well as other helpful properties which make them as a natural, safe and reliable remedy for treatment of neurodegenerative diseases.25,26 Perivious studies have indicated that MS patients are interested in using herbal medicines to control their disease symptoms.26 For example in China, Chinese herbal medicine (CHM) is widely used by MS patients for ameloriating the severity of disease.27 The beneficial effects of CHM in MS disease is occured by reduction of the severity of MS disease; including antioxidative properties, anti-apoptotic effects, anti-inflammatory properties and promoting the differentiation of local stem cells to myelin producing cells.28 MS patients usually use CAM, and medicinal plants as a member of this family plays a crucial role to cure MS and itsʼ associated symptoms. 29 Different herbal medicines are recommended for MS patients, but the understanding of their efficacy is not well described. In this review; we will discuss some of herbal compounds beneficial effects on MS disease ( and ). We conducted a search for all English language articles in Google Scholar, Science Direct, Scopus, PubMed and Medline for medicinal plants, that have been used for their therapeutic potentials in MS disease, studies which their publication dates from January 1960 to April 2018 were used.

Table 1

Summary of herbal medicines used in the treatment of Multiple sclerosis

Plant Author (Country) Design of study Dosage Number Duration of study Effects Ref
Ginkgo
biloba
Johnson et al (USA) Clinical trial-Double-blind, placeo-controlled 240 mg/day of ginkgo extract 22 MS patients 4 weeks Treatment with ginkgo extract relieved fatigue with no adverse effect in MS patients 34
Lovera et al (USA) Clinical trial-Double-blind, placeo-controlled 240 mg/day of ginkgo extract 38 MS patients 12 weeks Improvement of the cognitive performance were reported in treated group 37
Brochet et al (France) Clinical trial-Double-blind, placeo-controlled 240 and 360 mg/day of ginkgolide B 104 MS patients 1 week ginkgolide B was not an effective treatment for exacerbations of MS 180
Zingiber
officinale
Jafarzadeh et al (Iran) EAE model of MS in mice 200 and 300 mg/kg ginger extract 24 4 weeks Ginger extract ameliorated EAE severity and modulated the expression of IL-27, IL-33 43
Curcuma longa Xie et al (Japan) EAE model of MS in rats 100 and200 mg/kg curcumin extract 21 2 weeks Curcumin decreased the inflammation and the severity of EAE 53
Natarajan and Bright (USA) EAE model of MS in SJL/J mice 50 and 100 µg curcumin in 25 µl DMSO / day 4 weeks Curcumin decreased CNS inflammation and demyelination also,decreased the severity of EAE 54
Mohajeri et al (Iran) EAE model of MS in rats 12. 5 mg/kg of curcumin 20 17 days Treatment with polymerized nano-curcumin decreased the severity of EAE and increased the remyelination 23
Oenothera
biennis
Firouzi et al (Iran) Double blind, randomized clinical trial 18–21 g/day Evening primrose oil and C. sativa oils 100 MS patients 24 weeks Treatment with co-supplemented C. sativa and evening primrose oils decreased the clinical score in MS patients 158
Horrobin (Canada) Double blind, randomized clinical trial 14 MS patients 24 weeks Treatment with colchicine and evening primrose oil improved manual dexterity test and clinical score in MS patients 159
Hypericum
perforatum
Naziroglu et al (Turkey) In-vitro study on neutrophils of MS patients 20 μM/ml H. perforatum for 2 hours 9 MS patients Treatment with H. perforatum indicated the protective effects on oxidative stress in MS patients 69
Vaccinium
macrocarpon
Gallien et al (France) Double blind, clinical trial, placebo-controlled 36 mg/day Cranberry extract(proanthocyanidins) 171 MS patients 1 year Treatment with cranberry extract versus placebo did not prevent UTI occurrence in MS patients 81
Nigella sativa Fahmy et al (Egypt) EAE model of MS in rats 2. 8 g/kg Nigella sativa extract 22 4 weeks N. sativa ameliorated the clinical signs of EAE, suppressed inflammation and enhanced remyelination in the CNS 85
Noor et al (Egypt) EAE model of MS in rats 2.8 g/kg Nigella sativa extract 22 4 weeks N. sativa suppressed inflammation in EAE rats. Also, N sativa enhanced remyelination in the cerebellum and reduced the expression of TGF β1 87
Crocus
sativus
Ghaffari et al (Iran) EAE model of MS in rats Intrahippocampal (5and 10 μg/rat) injection of the saffron 35 3 days Local injection of saffron extract modulated the oxidative stress markers (reduced the activity of GPx and SOD enzymes), through scavenging of ROS 103
Ghazavi et al (Iran) EAE model of MS in C57bl/6 mice 100 µL saffron extract 20 3 weeks Treatment with saffron decreased inflammation in the spinal cord and decreased the severity of EAE 102
Panax
ginseng
Hwang et al (Korea) EAE model of MS in C57bl/6 mice 200 μg of an acidic polysaccharide of Panax ginseng 33 days Acidic polysaccharide of Panax ginseng decreased the infiltration of inflammatory cells in the CNS, also suppressed EAE score by inhibiting the proliferation of T cells and the production of inflammatory cytokines 113
Etemadifar et al (Iran) Randomized Double-blind, placeo-controlled 250 mg ginseng tablets 52 MS patients 12 weeks Ginseng treatment had no adverse effect on MS patients as well as reduced fatigue and had a positive effect on quality of life 114
Boswellia
papyrifera
Sedighi et al (Iran) Randomized, double-blinded, placebo-controlled study 600 mg of B. papyrifera 80 MS patients 8 weeks B. papyrifera improved the visuospatial memory of MS patients 124
Vitis
vinifera
Sato et al (USA) EAE model of MS in C57bl/6 mice 20 mg/kg per day 8 weeks Resveratrol treatment worsened the demyelination and inflammation without neuroprotective effects in the CNS 129
Kelly et al (USA) EAE model of MS in C57bl/6 mice 100 and 250 mg/kg Sigma resveratrol 4 weeks Resveratrol delayed the onset of EAE and had a significant neuroprotective effect as well as prevents neuronal loss 130
Shindler et al (USA) EAE model of MS in SJL/J mice 500 and 1000 mg/kg resveratrol 62 4 weeks Resveratrol treatment prevented neuronal loss during optic neuritis and reduced neurological dysfunction during EAE 131
Camellia
sinensis
Mahler et al (Germany) Randomized, double-blinded, placebo-controlled study 600 mg/d EGCG 18 MS patients 12 weeks Treatment with EGCG improved muscle metabolism during moderate exercise in MS patients 155
MS14 Tafreshi et al (Iran) EAE model of MS in C57bl/6 mice MS14 containing 30% of the diet 14 20 days Treatment with MS14 ameliorated the clinical signs of EAE and reduced neuropathological changes 163
Kalan et al (Iran) EAE model of MS in C57bl/6 mice MS14 containing 30% of the diet 25 35 days MS14 decreased EAE symptoms and lymphocyte infiltration into the CNS 164
Kalan et al (Iran) EAE model of MS in C57bl/6 mice MS14 containing 30% of the diet 25 35 days Treatment with MS14 reduced clinical signs of EAE, demyelination and IL-6 production 165
Cannabis sativa Zajicek et al (UK) Randomized, placebo-controlled trial Capsules containing 2. 5 mg of THC and 1.25 mg of cannabidiol 630 MS patients 15 weeks cannabinoids improved patients’ mobility and improved in spasticity 173
Zajicek et al (UK) Double blind, placebo controlled, phase III study Capsules containing cannabidiol 0.8–1.8 mg and 2.5 mg THC 279 MS patients 12 weeks Treatment with cannabinoids improved the relief from muscle stiffness in MS patients 172
Wade et al (UK) Double-blind, randomized, placebo-controlled study 120 mg cannabidiol and 120 mg THC 160 MS patients 10 weeks Treatment with cannabinoids improved patient’s spasticity, without any adverse effects 174
Greenberg et al (USA) Double-blind, randomized, placebo-controlled study Smoking one marijuana cigarette containing 1. 54% THC 10 MS patients 3 days Smoking marijuana improved eyes-open and eyes-closed tests, and noise variance values 178
Brady et al (USA) Open-label, pilot study 2.5 mg of THC and 2.5 mg
CBD per spray
10 MS patients 8 weeks Cannabinoids decreased urinary
urgency, number and volume of incontinence episodes, frequency and nocturia in MS patients.
Also, spasticity and quality of sleep improved significantly in the treated group
179

Table 2

Use of herbal medicines in Multiple sclerosis, according to the symptomatic problems

Usage Plant References
Antidepressant Hypericum perforatum

Crocus sativus
69,101
Sleeping problem Piper methysticum

Valeriana officinalis
73,93
Improvement in cognitive impairment Ginkgo biloba

Boswellia papyrifera
36,124
Urinary system dysfunction Vaccinium macrocarpon

Cannabis sativa
79,179
Fatigue Ginkgo biloba

Panax ginseng
114,34
Anti-inflammatory and neuroprotective Ginkgo biloba

Zingiber officinale
Curcuma longa

Oenothera biennis

Nigella sativa

Crocus sativus

Panax ginseng

Boswellia papyrifera

Vitis vinifera

Gastrodia elata

Camellia sinensis

Cannabis sativa

MS14
33,34,87,101,113,124,130,140,134,159,164,167

Ginkgo biloba

Ginkgo biloba L. (well-known as ginkgo), is one of the oldest living tree species from the family Ginkgoaceae. Ginkgo is native to Korea and China, but now it can be found all over the world.30 Ginkgo refers to an extract of the leaves of the G. biloba trees, which traditionally used as a remedy to improve the mental alertness and memory.31 The current reputation of G. biloba can be attributed to a pioneeering research that informed G. biloba is an effective cure for cognitive issues.32

Studies have shown that anti-inflammatory and inhibiting the platelet-activating factor (PAF) properties of ginkgo extract (EGB761) are effective on MS disease.33,34 Ginkgolides is the major component of G. biloba, its effect on the PAF activity represents the possible therapeutic role of this plant on MS.34 PAF’s role in inflammation process is obviously introduced, so ginkgo can inhibit this process.35 In addition, ginkgo reverses cognitive impairment and reduces fatigue in MS patients. 36,37G. biloba is generally safe with no side or adverse effects38 but in some few cases, dizziness, headaches and ocular bleeding associated with its usage.30 Consumption of G. biloba is almost safe and has obvious therapeutic effects for MS patients; improving functional status (fatigue) of people with MS and neuroprotective activities are the valuable medical properties of G. biloba.

Zingiber officinale

Zingiber officinale Roscoe (Ginger), is an aromatic plant in the family Zingiberaceae. Z. officinale is native to India and commonly grown in Asia, tropical Africa and Latin America.38 Ginger root is routinely used as an aromatic spice and a traditional drug.39 Recent studies acknowledged the anti-cancer,40 antioxidant41 and anti-inflammatory activities of ginger.42

Anti-inflammatory capacity of ginger is the reason of its consumption by MS patients. 43 Gingerols and its dehydrated derivatives (shogaols), are the major components of the ginger that exhibit anti-inflammatory effects.44 The anti-inflammatory effects of 6-shogaol were reported by inhibiting the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase- 2 (COX-2) in macrophages, as well as preventing dopamine reduction and reducing apoptose rate in CNS.45 10-gingerol is another important component of ginger which attribituted with anti-inflammatory effect in fresh ginger.46 10-gingerols inhibits LPS-induced NO and production of pro-inflammatory cytokines by inhibiting the NF-jB activation.46 Positive effects of ginger and itsʼ active compounds (6-shogaol and 10-gingerol) were approved in animal models of MS, by exerting anti-inflammatory and neuroprotective effects, but still clinical studies on MS patients are needed to confirm these results.

Curcuma longa

Curcuma longa L. is a tropical plant, native to southern and southeastern tropical Asia. 47C. longa is belonging to the ginger family, Zingiberaceae. A yellow coloring-matter obtained from the roots of C. longa, is named curcumin.47 Curcumin is widely used as a dietary spice and pigment. Curcumin is commonly consumed as an Asian folk remedy for treating biliary disorders, anorexia, cough, sinusitis and sore throat.48 Studies indicated that curcumin exerts a wide range of biological activities, including anti-inflammatory,49 antitumor50 and antioxidants effects.51

Anti-inflammatory effect of curcumin has been obviously examined in different studies.44,52 Curcumin does its anti-inflammatory role in two major ways: (1) inhibition of pro-inflammatory cytokines and (2) inhibition of Th27 differentiation and its related pathways.52 Curcumin ameloriated the severity of experimental autoimmune encephalomyelitis (EAE), as a animal model of MS disease, also reduced the infiltration of inflammatory cells to the CNS. 52 Curcumin modulates inflammatory process by decreasing the expression of the different pro-inflammatory and inflammatory cytokines.44,53 In one study, polymerized form of nano-curcumin was used for treating EAE model of MS, which demonstrated anti-inflammatory and antioxidative effects as well as increasing remyelination and decreasing EAE score.23 Furthermore, curcumin can decrease the secerity of MS disease by blocking IL-12 signaling pathway in T cells.54 Side effects of curcumin is associated with high dose consumption which causes nausea and diarrhea.55 Although, therapeutic effects of curcumin were demonstrated in different studies but human studies are certainly needed to confirm the recommendation of curcumin in MS patients.

Hypericum perforatum

Hypericum perforatum L. better known as St John’s Wort is a flowering plant from the family Hypericaceae. H. perforatum is a native plant in Europe and Asia but today has worldwide spread. 30 From the ancient time, H. perforatum was popular plant because it had a wide range of therapeutic effects for different diseases such as anxiety, depression and menstrual disorders.56 Currently, H. perforatum is used for treating the inflammation-related disorders,57 cancers58 and neurodegenerative diseases.59

The usage of H. perforatum in MS disease is related to its antidepressant effects.60,61 Hypericin is the main antidepressant component of H. perforatum which stimulates capillary blood flow in brain.62 Studies have showed that Hypericin strongly inhibits the MAO enzymes and has a strong affinity for Sigma receptors which regulate dopamine level.63 Recent studies have shown that hypericin acts as an antagonist for adenosine, benzodiazepine and GABA receptors.64 Many studies emphasis on another constituent, Hyperforin, for the therapeutic effects of this plant. It has been reported that Hyperforin has antidepressant effects as a result of inhibiting the uptake of dopamine, serotonin, noradrenaline, GABA, and L-glutamate.65,66 There are some clinical studies which have shown the effectiveness of H. perforatum on depression conditions.60,67,68 H. perforatum can be recommended to MS patients due to its antidepressant, antioxidative and anti-inflammatory effects.69

Valeriana officinalis

Valeriana officinalis L. (Valerian) is native to Europe, North America and parts of Asia.68 Valerian is a plant in the family of Caprifoliaceae, the root and rhizome of this herb are used for different medicinal purposes.68 In ancient Greek, valerian had various medicinal applications, for example, for digestive problems, epilepsy and urinary tract infections.70 In addition, valerian was introduced as a treatment for sleeping problems and insomnia. 71

Sleep disturbance is the most important cause of fatigue in MS patients.72 Clinical trials demonstrated that major component of V. officinalis root extract, valerenic acid, is effective in treatment of mild-to-moderate sleeping disorders.73 Like benzodiazepines which are GABA-analogs, valerenic acid has particular affinity for the GABAA receptor.30 Limited adverse effects such as stomachache and allergic reaction have been observed in patients under treatment of valerenic acids.30,74 Consumption of V. officinalis can be suggested to MS patients due to the ameliorating effects on sleeping problems and fatigue status.

Vaccinium macrocarpon

Vaccinium macrocarpon (Cranberry, Large Cranberry), is a North American species of cranberry in Ericaceae family. Cranberry juice is obtained from the V. macrocarpon fruit.75 Cranberry has been traditionally used for treatment of bladder and kidney disorders by Native Americans. 75,76

MS patients are susceptible to the urinary tract colonizations (UTC) and urinary tract infections (UTIs), as a result of the bladder dysfunction in MS disease.77 Studies have shown that cranberry juice or its produced-capsules is a beneficial remedy for treatment of UTIs.78 It has been reported that cranberry can inhibit Escherischia coli adherence to the urethra.79 Cranberry has two substantial compounds, fructose and proanthocyanidin, that stick to the fimbriae of E. coli and effectively hindering the bacteriaʼs ability to attach to the urethra.79 There are a few clinical studies that examined the preventive effects of cranberry on UTIs in MS patients.80 However, in different studies cranberry was found to be effective against urinary tract infections, but in one clinical trial of MS patients, it not showed acceptable prevention from urinary tract infections.81

Nigella sativa

Nigella sativa L. usually known as black seed is widely used as a medicinal plant belongs to the family Ranunculaceae. Black seed is native to Southern Europe, Southwest Asia and North Africa.82 Seeds and oil of N. sativa has a long historical and religious background for treatment of various illnesses such as headache, back pain and gastrointestinal problems.83,84 Several studies have shown that black seed has diverse therapeutic effects, including anticancer, analgesic, antimicrobial, anti-inflammatory, renal protective and antioxidant properties.84,85 Thymoquinone is the active compound of N. sativa seeds.86

There are several evidences that indicated the anti-inflammatory capacity of black seed oil.85,87 In vitro studies demonstrated the inhibitory effects of N. sativa oil and its active compound, thymoquinone, on the production of inflammatory mediators‏ {such as IL-1b, IL-6, TNF-a, IFN-c and PGE2}.88,89 In addition, Black seed oil inhibited COX and 5-LO pathways of arachidonate metabolism. 89,90 Thymoquinone also potently inhibiting the non-enzymatic peroxidation in brain phospholipid liposomes.84 The therapeutic effects of N. sativa in animal models of MS were reported. N. sativa enhanced remyelination in CNS, reduced inflammation processes and suppressed the expression of TGF β1 in EAE models of MS disease.87

Piper methysticum

Piper methysticum (kava kava) is a psychoactive herb in the family Piperaceace, which has been used in the Pacific Islands for hundreds of years. The root of this plant is well-known for its sedative and anesthetic properties.80 Kava traditionally used for producing a comforting and relaxing drink.80,91

Combination of kava and valerian seems to be more effective for treatment of stress-induced insomnia than either herb alone.92 The active compound of kava is cavalactones, which interacts with GABAA receptors and decreases anxiety and sleeping problems. 93,94 Kava also can potentiate the sedating effects of the drugs that usually used in MS disease such as Lioresal (Baclofen).95 Extensive use of kava may lead to hepatotoxicity, hepatic necrosis and cholestasis hepatitis.96 It can be concluded that kava alone or in combination with other herbal medicines is a promising candidate for treating anxiety disorders of MS patients.

Crocus sativus

Crocus sativus L. (Saffron) is a flowering plant in the family Iridaceae. Saffron stigma has been widely used as a medicinal plant for healing the different disorders.97 Saffron has been commonly used as an herbal drug for its sedative, stimulant and anticatarrhal properities.97,98 Several studies suggested that saffron can be effective in treatment of hypertension and memory impairments. Additionally, saffron has been demonstrated anti-inflammatory and antitussive effects.99 Crocetin and crocin are the two main active compounds of saffron stigma, which have a wide range of therapeutic activitis. 100

Antidepressant and anti-neuroinflammatory effects of saffron are evidently effective in MS disease.101-103 Crocin exerts its anti-inflammatory effects via inhibiting syncytin-1 and nitric oxide (NO)-induced astrocyte and oligodendrocyte cytotoxicity, also decreases neurological injuries in experimental autoimmune encephalomyelitis (EAE).104,105 Syncytin-1 is highly expresses in microglia, astrocytes and glial cell of MS lesions.106 Studies have shown that crocin has antidepressant effects in mild to moderate depression.99 Excessive consumption of saffron induces dizziness, nausea, vomiting and diarrhea.107 Depression is a common condition in MS disease which adversely affect health status. According to this point, antidepressant activity of saffron can be highly helpful in depressive disorders of MS patients.

Panax ginseng

Panax ginseng also known as Asian ginseng is a traditional herbal medicine in Asia for thousands of years, which belongs to the Araliaceae family. 108 Ginseng root is traditionally used in powdered form to regenerate the body and mind, increase physical strength and prevent aging.109 The main active compound of P. ginseng is ginsenosides, that exhibits anti-inflammatory, antioxidant, and anti-apoptotic properties.110,111In addition, P. ginseng is one of the most useful medicinal plants for curing different neuroinflammatory diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and Multiple sclerosis.112

Some evidences have indicated that ginseng can decrease the inflammation and fatigue, which may be useful in MS patients.113,114 Ginseng reduced the severity of EAE by inhibiting the proliferation of T cells, inhibiting the production of the inflammatory cytokines (FN-γ, IL-1β and IL-17) and depleting of CD25+ cells.113 In clinical studies ginseng led to fatigue improvement and had a positive effect on quality of life. 114 Excessive intake of ginseng can lead to several adverse effects including hypertension, insomnia, rashes and diarrhea.115 We can deduce that ginseng is an effective remedy for curing MS-related fatigue and enhancing quality of life in these patients.

Boswellia papyrifera

Boswellia papyrifera belongs to the Burseraceae family.116 Gum production through resin of B. papyrifera, has high economic value.117 The resin of B. papyrifera has been traditionally used in treatment of ulcers, chronic inflammation and for memory support.118 The main active compound of B. papyrifera resin is boswellic acids.119 Several studies have indicated the different therapeutic effects of boswellic acids such as anti-inflammatory, antitumor and antioxidant effects.120,121

Cognitive impairment is a common clinical symptom in MS patients, with incidence rates up to 70%. 122 Cognitive deficits in MS patients affect various aspects including attention, information processing efficiency, processing speed, long term memory and visual learning.123 Anti-inflammatory and neuroprotective properties of B. papyrifera, reversed the cognitive impairments in MS patients.124 In one clinical trial, patients with MS which received B. papyrifera, had a significant visuospatial memory improvement compared to the control group.124 Administration of B. papyrifera enhances cognitive impairment in MS patients, but still there is a need for large scale trials to completely clarify the therapeutic effects of B. papyrifera in MS patients.

Vitis vinifera

Vitis vinifera L. (common grape vine) is one of the most important fruit crops in the world from the family Vitaceae. V. vinifera is cultivated in the most countries of Europe, Northern Africa and Western Asia.125 The leaves and seeds of this plant have various medicinal properties. Resveratrol (trans-3, 4, 5-trihydroxystilbene) is a phenolic compound that produced in the grapes in response to injuries of fungal pathogens.126 Resveratrol has been reported to have several pharmaceutical effects such as anti-inflammatory, anticancer, antioxidant and antiviral properties.127,128

Both neuroprotective and anti-inflammatory effects of resveratrol were informed in several researches.129-131 Resveratrol exhibits neuroprotective effects by inhibiting the microglia activation and decreasing the pro-inflammatory factors production through the MAPKs, phosphoinositide3-kinase (PI3-K)/Akt, glycogen synthase kinase-3β (GSK-3β) and NADPH oxidase signaling pathway.127,132,133 Resveratrol can cross the blood–brain barrier (BBB), therefore it can be an ideal candidate for treating neuroinflammatory and neurodegenerative diseases.129,134 Excessive intake of common grape causes gastrointestinal side effects including nausea, abdominal pain, flatulence and diarrhea. 135 Neuroprotective effects of V. vinifera were demonstrated in different neurodegenerative diseases, but more specific studies on MS disease are needed to determine itʼs therapeutic role in MS.

Gastrodia elata

Gastrodia elata Blume (tianma) is a saprophytic herb from the family Orchidaceae. G. elata is a traditional Chinese plant, native to the oriental countries.136 Tianma is the dried rhizome of the G. elata which were used as a traditional herbal medicine for a variety of conditions such as headaches, vertigo and hypertension.137 In addition, tianma is commonly used for the treatment of neurodegenerative disorders and memory improvement.138,139

Due to neuroprotective and anti-neuroinflammatory effects of G. elata, it can be considered as a promising candidate for MS therapy. G. elata reduces oxygen free radicals and protects against neuronal damage.137,140,141G. elata indicated anxiolytic-like properties via the GABA-ergic nervous system.142 It has been reported that G. elata has protective effects against global ischemia, nitric oxide synthase activity and apoptosis.143 Gastrodin is the main active component of the tianma which mediates its neuroprotective effects.144 Vanillin and Benzyl alcohol are the other active compouds of G. elata that have anti-inflammatory effects by inhibiting the generation of reactive oxygen species (ROS) and inhibiting the activities of cyclooxygenase- (COX-) 1 and COX-2.145G. elata plays an important protective role in the neurorestorative processes, therefore it can be a helpful remedy for MS patients. however, future animal models and clinical studies of MS disease are needed to clarify the possible therapeutic effects of this plant on MS patients.

Camellia sinensis

Camellia sinensis L. is well known as green tea, one of the oldest beverages in the world from the Theaceae family. 146,147 Dried leaves of C. sinensis are used in green tea production.147 Green tea is used for several different purposes including weight loss, cardiovascular disorders, inflammation and neuroprotective effects.148

Green tea exhibits anti-inflammatory and neuroprotective properties.149,150 Epigallocatechin-3-gallate (EGCG) is one of the most important active compounds of green tea which is attributed to anti-inflammatory and neuroprotective properties of this plant.134 EGCG is a polyphenol compound that inhibits the production of inflammatory mediators such as TNF-α, IL-1β and IL-6 and improvs the neuroprotection in nervous system.151,152 In other studies, EGCG inhibited LPS-induced microglial activation and protected against inflammation-mediated dopaminergic neuronal injury.153 Regular and habitual consumption of green tea is safe, but, consuming high doses causes liver toxicity.154‏ Green tea has anti-inflammatory effects which can protect CNS from neurodegenerative diseases such as MS. Also, green tea regulates energy expenditure in the body which may relief MS-related fatigue.155

Oenothera biennis

Oenothera biennis L. (Evening primrose) is a species in the family of Onagraceae. Evening primrose oil is produced from the seeds of O. biennis which has numerous pharmacological effects.156 The traditional consumptions of this plant was for the treatment of swelling in the body, then were used for other problems such as skin disorders, gastro-intestinal disorders and asthma.157 Two parts of the plant; flowers and seeds, are used for extracting the oils.

The application of Evening primrose oil in treatment of MS is related to its anti-inflammatory and immune-modulating effects.158,159 These beneficial effects largely related to the evening primrose oil abundant supply of polyunsaturated fatty acids (PUFA) content.159 Gamma-linolenic acid is a precursor of prostaglandin and it is responsible for anti-inflammatory effects of evening primrose oil. 158 In clinical trials, Evening primrose oil led to significant performance improvement in the manual dexterity test.159 In another clinical study gamma-linolenic acid rich oil had an obvious effect in relapsing-remitting MS, which meaningfully decreased the relapse rate and the progression of disease.160 However, more clinical trials are needed to prove the therapeutic effects of Evening primrose oil in MS patients.

MS14 (Penaeus latisculatus, Apium graveolens and Hypericum perforatum)

MS14 is an Iranian natural herbal-marine drug, which has obvious therapeutic effects on MS patients.161,162 MS14 consists of 90% Penaeus latisculatus, 5% Apium graveolens and 5% Hypericum perforatum.163 In both animal models and human clinical trials, MS14 was effective in treatment of MS.162,164 Antioxidant and anti-inflammatory effects, are the two features of MS14 that halt the progression of MS disease. 161 MS14 showed some benefits on quality of life and improvement of patients’ mobility (lower limb).162 The neuroprotective and anti-inflammatory properties of MS14 were reported by suppressing the proliferation responses of T cells and decreasing the expression levels of IL-6, IL-5, IL-10, TNF-α and IL-1β. Furthermore, MS14 inhibited the inflammatory cell infiltration into the CNS and up-regulated LCN2 in all stages of EAE.164,165 Oral consumption of MS14 was reported properly safe without any adverse effects.162 MS14 is an herbal-marine drug that has beneficial effects in MS disease and other neroudegenerative disorders, but still more studies are needed to find various mechanisms and pathways that MS14 shows itʼs neuroprotective effects.

Cannabis sativa

Cannabis sativa L. (Bang, Marijuana, and Hachis) is a flowering plant in the genus Cannabis from the Cannabaceae family. C. sativa is native to Western and Central Asia, but extensively cultivated in Asia and Europe. 166C. sativa has traditionally been used for healing the different diorders such as allergies, inflammation and sexually transmitted diseases.167 Seeds, leaves and flowers of C. sativa was reported to have various therapeutic and medicinal values. There are numerous studies that indicated the pharmacological usage of C. sativa, including analgesic effect, anticancer activity, anti-inflammatory activity, central nervous system depressant activity and immunomodulatory effect.166

C. sativa is the most important and the most common plant which is using for treating of MS. There are numerous studies that indicated cannabinoids consumption reduced muscle stiffness, bladder disturbance, spasms, neuropathic pain and sleep disorders in MS patients.168,169 The major compound of C. sativa is ∆-9tetrahydrocannabinol (THC).170 THC binds to cannabinoid receptors (CBR) in the CNS and acts as a partial agonist to CB1 and CB2 receptors. 171 THC was shown to have anti-inflammatory and neuroprotective properties.167 Some studies have shown the applications of cannabinoids for improvments of spasticity in MS, consumption of cannabinoids led to significant improvement in patient-reported spasticity.172-174 Also, the combination of THC and cannabidiol (CBD) was more effective for treatment of moderate to severe refractory spasticity in MS patients.175 Cannabinoids and their synthetic drugs indicated attractive anti-inflammatory effects in animal models of MS.176 Synthetic cannabinoids can reduce inflammation by suppressing the TNF-α production in the brain. Also, Synthetic cannabinoids can improve motor function by preventing the infiltration of immune cells into the CNS, and can decrease the pro-inflammatory cytokines secretion such as IFN-µ, IL-17, IL-6, IL-1β and TNF-α.167 Sativex is a combination of the two derived cannabinoids of the C. sativa; THC and CBD, which has been formulated for oromucosal mouth spray to relief neuropathic pain, spasticity, sleeping difficulties, bladder disturbance and other symptoms associated with MS. 177 Orally administration of THC can decrease the intensity of several signs and symptoms of MS such as, decreasing spasticity, rigidity, tremor, as well as improving walking ability, performance of handwriting and bladder control.169 Smoking marijuana in patients with MS demonstrated to have some advantageous effects, including healing the spasticity, pain, tremor and emotional dysfunction.178 In one clinical trial, cannabinoids decreased the urinary symptoms, urinary incontinence, frequency of urination and nocturia in treated group.179 There are some adverse effects associated with C. sativa such as the risks of cancer, cardiovascular disease, nausea, vomiting and impaired driving.61

Multiple Sclerosis Foundation – Three Herbs and Supplements That May Help With MS

Adding healthy herbs and supplements to any diet can improve overall motor and cognitive functioning, but for those with multiple sclerosis, these natural additives can be especially helpful. Many doctors suggest naturally occurring herbs and minerals to help patients counteract common MS symptoms. Although they should not replace prescribed medications, taking these following herbs can help you manage your MS symptoms by reducing inflammation and strengthening the immune system.

 

Ginger

Ginger is a sweet substitute for honey that can help alleviate muscle and joint pain. As a naturally occurring anti-inflammatory, it can reduce the inflammation around the nerves and muscles that causes the stiffness and physical pain common with MS. Cutting up ginger root and adding it to some of your favorite meals or choosing to make a warm cup of tea out of it can bring delicious and healthy improvements to your daily lifestyle.

Chamomile

Like ginger, chamomile can ease tension and relax muscles by reducing inflammation. Because of its relaxing tendencies, many patients choose to drink it in a tea. This can prove to be especially effective at night if physical pain prevents you from getting a full night’s sleep. Its sweet taste also makes for a delicious cake or glaze which can be paired with fresh fruit for a refreshing summertime snack.

Dandelion

Dandelion is a fine substitute for caffeine and can help alleviate the fatigue that is brought on by the physical pain caused by MS symptoms. Dandelion comes in supplement form for those wary of eating a weed, but if you’re willing to take the risk, drinking it in a tea is a healthy option. Dandelion greens are also popular in salads, as they are rich in iron to help strengthen the immune system and provide energy. You can even mix them into hummus or pesto.

The list of herbs and supplements available to MS patients is extensive, but remember to moderate your consumption of these plants and vitamins until you are certain of how your body will react to them. They can never act as replacements for regularly prescribed medication but can be added to help alleviate tension, fatigue, and other conditions that are caused by or exacerbate symptoms.

Check with your doctor before you make any changes to your diet, and remember to stop eating something if it makes you feel ill. However, if your doctor gives you the green light, herbs can be a great alternative remedy to helping you reduce inflammation in your body and ultimately manage your symptoms.

 

Daryl H. Bryant has been successfully managing his MS for 14 years and is the author of MS – Living Symptom Free: The True Story of an MS Patient, a book that covers every aspect of living with multiple sclerosis, from common MS symptoms to the things doctors don’t tell you about MS. Today, Daryl is living a happy, healthy, and successful life, despite his MS, and he writes a weekly blog on how to manage MS symptoms.

Multiple Sclerosis: Alternative Treatments | HealthLink BC

Overview

There is no cure for multiple sclerosis (MS). So far, the only treatments proved to affect the course of the disease are disease-modifying medicines, such as interferon beta. Other types of treatment should not replace these medicines if you are a candidate for treatment with them.

Some people who have MS report that alternative treatments have worked for them. This may be in part due to the placebo effect. The placebo effect means that you feel better after getting treatment, even though the treatment may not have been proven to work. Some complementary therapies may help relieve stress, depression, fatigue, and muscle tension. And some may improve your overall well-being and quality of life.

A summary of evidence on complementary and alternative therapies suggests that some treatments may help relieve symptoms. For example:footnote 1

  • Some forms of natural or man-made substances related to cannabis (marijuana) may help with muscle stiffness (spasticity) and pain.
  • Ginkgo biloba or magnetic therapy may help relieve fatigue for some people.
  • Reflexology, where a therapist applies pressure to certain points on the feet, may help relieve skin feelings such as tingling and numbness.

The summary showed that several other complementary and alternative treatments are not likely to help. For example:footnote 1

  • Natural or man-made substances related to cannabis (marijuana) are unlikely to help relieve tremor.
  • Ginkgo biloba does not help people who have MS think more clearly.
  • The Cari Loder regimen (lofepramine plus phenylalanine with vitamin B12) is not likely to help improve general quality of life or to relieve depression or disability.
  • Magnetic therapy is unlikely to help relieve depression.

Some people think that certain things may increase the risk of having an attack of MS, including:

  • Dietary deficiencies.
  • Sensitivity to foods and environmental toxins (including mercury amalgam in dental work).
  • Sensitivity to stress and trauma.
  • Viral infection while at a young age that causes a permanent, partial breakdown in the immune system.
  • Blockage in the veins that drain blood from the brain.

Many people who have MS also experiment with their diets, in part because there are many claims about the effectiveness of certain diets and nutritional supplements in the treatment of MS.

Be careful about taking supplements. Some minerals and vitamins are toxic if they are taken in large amounts.

Discuss your treatment options with your doctor before trying any type of alternative treatment for MS. You can also get reliable advice from an MS treatment centre or the Multiple Sclerosis Society of Canada.

References

Citations

  1. Yadav V, et al. (2014). Summary of evidence-based guideline: Complementary and alternative medicine in multiple sclerosis: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology, 82(12): 1083–1092.

Credits

Adaptation Date: 7/17/2020

Adapted By: HealthLink BC

Adaptation Reviewed By: HealthLink BC

Adaptation Date: 7/17/2020

Adapted By: HealthLink BC

Adaptation Reviewed By: HealthLink BC

Yadav V, et al. (2014). Summary of evidence-based guideline: Complementary and alternative medicine in multiple sclerosis: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology, 82(12): 1083-1092.

A Controversial ‘Cure’ for Multiple Sclerosis

Arata said the Zamboni procedure resembles those he does on other vein disorders. The F.D.A. calls such practices off-label; once an intervention has been approved in one part of the body, doctors can perform it elsewhere in the anatomy. “All the treatments I’ve done my entire career have been pretty much based on the same thing,” Arata said. “We’re not a specialty that has these huge numbers of cases that we generate randomized control trials and everything’s evidence-based. And having a couple of catastrophic events also doesn’t deter me.” He added: “Radio-frequency ablation of tumors had small studies, no randomization, driven by patients. There were a couple of deaths early on; it’s now mainstream. Early on the critics were oncological surgeons, and guess what? They’re now doing it.”

Dr. Michael Haupts, a CCSVI doubter who heads neurology at Augustahospital M.S. Clinic in Germany, agrees with Arata — up to a point. “Lots of procedures and operations get evidence-based only after a while, and maybe some you can never prove in evidence,” Haupts told me. But, he said, treatment for a chronic and incurable disease like M.S., which can be survived for many years, has a high bar for safety and effectiveness. Even Zamboni agrees with this sentiment. “With this big attention in social networks, it has generated a black market with speculation, with not properly performed procedures,” he says. “It’s unethical to offer a treatment when it’s in an experimental phase.”

In May, the F.D.A. issued a warning about the CCSVI procedure, underscoring that “there is no reliable evidence from controlled clinical trials that this procedure is effective” and that “the criteria used to diagnose CCSVI has not been adequately established.” The agency went further, “alerting people with M.S. to the risks of serious injuries and death associated with procedures to treat” CCSVI. At least one person has died shortly after the procedure, and there are reports of paralysis, blood clots and nerve damage in the brain, hemorrhaging and emergency surgery after a stent came loose and headed to the heart (stents are normally placed in the arteries, which carry blood away from the heart). Dake and Stanford Hospitals and Clinics are being sued by two patients claiming injury from CCSVI operations. (Stanford says the claims are without merit.)

This summer, after the F.D.A. warning came out, Arata e-mailed me with a change of view, attaching a paper he wrote and submitted to The American Venous Forum. He had “come to the conclusion that what we are treating is autonomic dysfunction,” he said. The paper included a list of symptoms of autonomic dysfunction that closely track many symptoms of M.S. It’s unusual for a doctor to reach a conclusion that a condition for which he already treated more than 1,000 people is not what he thought he was treating them for.

The surgery may be doing something for Arata’s patients, but it’s hard to say exactly what. “We know every time you do something on a hopeless person — inject, cut something, even stimulate with electricity — you will change his or her endogenous being and hormonal state and will have biological effects,” Haupts, the German neurologist, says. “If I would operate on people’s veins, I’m quite sure I’d have effects. Yet I know those effects will disappear and will not be really clear.

That was essentially the message of a study of 462 patients presented this month at the major annual conference of European M.S. researchers and clinicians. Objective measures of disability showed there was no change after the surgery, and more than a fifth of the patients had relapses, some more than once. Yet more than half of all patients said their symptoms had improved. Researchers from the Italian Society of Neurology attributed the results to “high expectation.” CCSVI supporters took to the Web, criticizing the study; one Facebook post said it amounted to “huffing and puffing” and noted the scientists’ disclosures of relationships with pharmaceutical manufacturers. Whatever is happening to the patients, it seems to be temporary: many CCSVI patients return for a second (or even a third) operation several months after their initial procedures. Jeff Beal, who is one of these, says it’s “pretty common [to] need a tuneup or two.”

When I was in Arata’s office a year ago, I met Jack Karnes, a 53-year-old from the Seattle area, who had undergone the vein-clearing operation the previous day. Karnes uses a wheelchair and can barely speak as a result of M.S. He was elated that when his brother and caregiver, Randall, helped him out of bed that morning, his foot was able to move in a way it hadn’t in years. He demonstrated his newfound ability to touch the tips of his thumb and forefinger. “We’ll get you playing that guitar again in no time, Jackie,” Randall told him. “He used to be a hell of a guitar player.”

Multiple Sclerosis Foundation – 14 Natural Ways to Calm Dysesthesia Discomfort

While these sensations are unpleasant, they’re not usually dangerous and don’t necessarily require treatment. Sometimes they resolve on their own, only to reappear later. Sometimes they’re continuous. However, if you’re experiencing dysesthesia for the first time you should inform your doctor — in case the new symptom indicates a relapse. If dysesthesia begins to interfere with your day-to-day activities and quality of life, or pain becomes unbearable, you’ll probably want to seek relief.  

Just as your MS is different than other people’s MS, your response to treatments will be unique. It’s very likely you’ll find what works best for you through trial and error. Your doctor can prescribe medications, but natural remedies may also help calm the painful sensations of dysesthesia. Additionally, there are preventative steps you can take to try and keep dysesthesia at bay. Consider these 14 natural options:

1) Wear pressure stockings and/or pressure gloves. These accessories will often convert your sensation of pain to a less uncomfortable feeling of pressure. Basically, you’re tricking your brain. Most drugstores sell pressure stockings and gloves, or you might ask if your doctor will order ones that are right for you.

2) Apply warm or cold compresses to affected areas. Altering body temperature is another way to convert your pain to a different sensation. Experiment with the hot and cold compresses to determine what brings the most relief. 

3) Meditate to lower your sensitivity to uncomfortable sensations.

4) Practice deep breathing. The goal is to summon the relaxation response, which helps offset the affect of painful sensations.

5) Try acupuncture. More clinical trials are needed to prove acupuncture definitely improves MS symptoms. However, there have been studies of people with conditions other than MS who’ve successfully used acupuncture to treat pain. 

6) Use biofeedback. Electrical sensors give you information about your body so you can make small changes to ease pain. For example, you might learn to relax certain muscles or slow your breathing to calm the unpleasant sensations.

7) Apply skin-calming lotions, creams, and washes containing calamine or aloe.

8) Exercise – but not too strenuously. Walking, stretching, yoga, gentle swimming or other activities recommended by a physiotherapist are best. Becoming stronger and more flexible helps manage dysesthesia.

9) Wear loose-fitting, cool, clothing. Cotton clothing and bedding are good choices because the fabric is “breathable” and soft to the touch.

10) Close to bedtime, take a lukewarm bath with Epsom salts and colloidal oats, elements known to soothe the skin.

11) Stay cool. Heat can stimulate sensations and intensify steady pain. If you must go out in hot weather, wear a cooling vest, hat, and scarf. Don’t take very hot baths or showers. Always be aware of your body temperature during exercise. 

 12) Avoid drastic temperature changes. Even something as simple as a sudden blast of cold air from your car’s air conditioner or stepping into a sauna could set off abnormal sensations.

 13) Keep a daily diary of foods and activities. Describe how you’re feeling, along with any new symptoms or symptom flares. Over time, you may be able to identify what triggers your dysesthesia.

 14) Get a good night’s sleep. Fatigue can heighten sensitivity to pain. MS symptoms as well as conditions not related to MS can interfere with sleep. An overnight study done at a sleep clinic will help pinpoint the underlying problems keeping you from resting well.

Fruit Compound Reduces and Helps Repair Damage in MS Models

Scientists report that a compound found in the peels of fruits such as apples and prunes, and some herbs, can reduce further damage to neurons from multiple sclerosis, and also help rebuild the protective sheaths covering neurons, reversing the damage.

“Although the evidence is preliminary—our data is from animal models of disease—it’s encouraging to see a compound that both halts and repairs damage in MS, in the lab,” says Guang-Xian Zhang, PhD, co-senior author and professor of neuroscience at the Sidney Kimmel Medical College at Thomas Jefferson University.

The study, “A dual effect of ursolic acid to the treatment of multiple sclerosis through both immunomodulation and direct remyelination” appears in PNAS.

“Current multiple sclerosis (MS) medications are mainly immunomodulatory, having little or no effect on neuroregeneration of damaged central nervous system (CNS) tissue; they are thus primarily effective at the acute stage of disease, but much less so at the chronic stage. An MS therapy that has both immunomodulatory and neuroregenerative effects would be highly beneficial,” write the investigators.

“Using multiple in vivo and in vitro strategies, in the present study we demonstrate that ursolic acid (UA), an antiinflammatory natural triterpenoid, also directly promotes oligodendrocyte maturation and CNS myelin repair. Oral treatment with UA significantly decreased disease severity and CNS inflammation and demyelination in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Importantly, remyelination and neural repair in the CNS were observed even after UA treatment was started on day 60 post immunization when EAE mice had full-blown demyelination and axonal damage.

“UA treatment also enhanced remyelination in a cuprizone-induced demyelination model in vivo and brain organotypic slice cultures ex vivo and promoted oligodendrocyte maturation in vitro, indicating a direct myelinating capacity. Mechanistically, UA induced promyelinating neurotrophic factor CNTF in astrocytes by peroxisome proliferator-activated receptor γ(PPARγ)/CREB signaling, as well as by up-regulation of myelin-related gene expression during oligodendrocyte maturation via PPARγ activation. Together, our findings demonstrate that UA has significant potential as an oral antiinflammatory and neural repair agent for MS, especially at the chronic-progressive stage.”

“There is additional work we must do to test the safety of this compound, ursolic acid” says co-senior author A.M. Rostami, MD, PhD, chair of the department of neurology at the Vickie and Jack Farber Institute for Neuroscience – Jefferson Health. “But this is a great new lead for disease treatment.”

The researchers used a lab-grade purified form of ursolic acid in mice that had established MS disease.

Many experiments have looked at mice in the acute phase, when disease is just starting or at the peak,” says Zhang. “Instead, we tested whether this compound was effective in chronic disease, once there has already been chronic damage to tissues of central nervous system.”

The researchers and colleagues used an established mouse model of multiple sclerosis that develops the disease slowly over the course of its life, mimicking human disease. At about day 12, the mouse begins the acute phase of the disease, when signs of MS, partial paralysis, appear, and when currently-available medications are most effective.

The researchers, however, started treating mice at day 60, a far more advanced stage of the disease when chronic tissue damage has been formed in brain and spinal cords, which needs to be repaired and regenerated.

Researchers treated the mice for 60 days, and began to see an improvement at day 20 of treatment. The mice which were paralyzed at the start of the experiment, regained the ability to walk around again, although with weakness, after treatment.

“It’s not a cure, but if we see a similar response in people, it would represent a significant change in quality of life. And most significantly, it’s a reversal, which we really haven’t seen before with other agents at such a late stage of disease,” says Zhang.

The scientists also investigated just how ursolic acid acted on cells. They observed that it suppressed Th27 cells, a type of immune cell that is one of the main drivers of the pathological autoimmune response in MS. Many currently active therapies appear to suppress Th27. But the Jefferson researchers showed that the compound could activate precursor cells to mature into much needed myelin-sheath-making cells (oligodendrocytes).

“This maturation effect is the most crucial,” stated Zhang. “Myelin-sheath-making oligodendrocytes are depleted in MS. And the stem cells that produce new oligodentrocytes are dormant and unable to mature. This compound helps activate those stem cells into making new oligodendrocytes, and is likely responsible for the reversal of symptoms we saw.”

The next steps for the investigators include testing the compound for safety. Although ursolic acid is available as a dietary supplement, it could be toxic at high doses.

“There are still a number of tests to complete before the first clinical trials,” says Rostami. “However, we are moving quickly with this promising approach.”

Sexual Dysfunction in MS Fact Sheet

Framework:
Sexual dysfunction is a common symptom of MS. However, it is an underappreciated condition that often goes unreported by both the patient and clinician. Sexual dysfunction can affect a person’s mood, relationships, daily functioning, and quality of life. At the Mellen Center our approach is to assess for sexual dysfunction symptoms in patients, identify factors contributing to the problem, and treat from a multidisciplinary perspective.

Q: What are common sexual dysfunction problems in MS?

A: Common problems related to sexual functioning in this population include decreases in genital sensation, decreases in libido and vaginal lubrication, erectile dysfunction, and difficulties with orgasm.

Q: What are the gender differences in sexual dysfunction in adults with MS?

A: In terms of gender differences, the most prevalent problems for men include erectile dysfunction, loss of sexual confidence, orgasmic dysfunction, and genital numbness. For women, the most common presentations include orgasmic dysfunction, loss of libido, inadequate vaginal lubrication, and genital numbness.

Q: How prevalent is sexual dysfunction in adults with MS?

A: Though research in this area is still fairly limited, studies indicate prevalence rates of 40 to 80% in women and from 50 to 90% in men. A survey of MS patients (n=5868) found that 67.2% of participants endorsed sexual dysfunction symptoms that were present always or almost always in the previous six months. Moreover, a clinical sample from the Mellen Center revealed that 60% of patients endorsed some form of sexual dysfunction (n=105).

Q: What causes sexual dysfunction in adults with MS?

A: In the general population, sexual dysfunction is usually evaluated according to different aspects of the sexual response cycle (i.e., disorders of libido, arousal, and orgasm). Though the etiology of sexual dysfunction in MS patients is still not entirely understood, a common conceptualization is that the nature of sexual changes in this disease can be attributed to primary, secondary, or tertiary causes.

Primary causes of sexual dysfunction in MS include those due to physiological impairment associated with lesions in the cortex and spinal cord which can lead to numbness or paresthesias that directly affect the genitals; loss of libido; decreased vaginal lubrication in women; and difficulty initiating or maintaining an erection in men. Certain medications can also have an impact on primary causes. Secondary causes are likely associated with non-sexual physical changes, such as fatigue, spasticity, pain, and bladder and bowel dysfunction. Tertiary causes refer to psychosocial variables that can interfere with sexual performance or satisfaction, including changes in social roles, depression, demoralization, and interpersonal difficulties.

Q: Why is it important to assess for and treat sexual dysfunction?

A: Despite the high frequency of sexual dysfunction in individuals diagnosed with MS, it is an often overlooked and not addressed by healthcare providers. Patients also tend to underreport this problem. In addition, research in this area is limited. Sexual dysfunction affects young and older adults and it can have a significant impact on an individual’s relationships and quality of life.

Q: How do we assess for sexual dysfunction in patients with MS?

A: A clinician can screen for sexual dysfunction symptoms as part of routine review of systems when inquiring about bladder and bowel function. It is always helpful to conduct a review of current medications and potential side effects that may impair sexual functioning.

Another option would be to utilize the Multiple Sclerosis Intimacy and Sexuality Questionnaire 19 (MSISQ-19), a 19-item self-report measure that addresses the three dimensions of sexual dysfunction (i.e., primary, secondary, and tertiary causes). The questionnaire, using a 5-point Likert scale ranging in order of frequency of experience (1 never, 2 almost never, 3 occasionally, 4 almost always, and 5 always), assesses the level in which MS symptoms have interfered with the individual’s sexual functioning in the previous 6 months. It is the only scale specifically designed and validated for an MS population. One of the advantages of the MSISQ-19 is that it only takes about 2 minutes to complete and can be done prior to the visit. If the screening is positive for sexual dysfunction symptoms, the practitioner can then follow up and inquire whether the patient would like help with these symptoms.

Q: What are barriers for providers to assess sexual dysfunction?

A: A study conducted by Griswald (2003) surveyed a group of MS specialty health-care professionals and found that the primary reason for not assessing for sexual dysfunction is limited time with patients (44%). Other barriers included having the issue be “outside of my role” (15.3%), patient discomfort (12.5%), lack of professional training or comfort (6.9%), other priorities (5.6%), limited medical coverage so they cannot afford treatment (2.8%), too intrusive for patients (2.8%).

Adequate training in healthcare provider and practice in assessment will increase providers comfort levels. Patients typically rely on the clinician to discuss issues in sexual functioning and many are grateful when the topic is addressed. (Foley, 2006).

Other barriers may include available resources and scope of practice. Having a list of physician and health psychology referrals that specialize in sexual dysfunction can be helpful in these cases. In addition, providing educational materials have been shown to be beneficial in some cases (Christopherson et al., 2006).

Q: How do we treat sexual dysfunction in the context of MS?

A: Treatment will depend on the nature of the symptoms and whether they are classified as primary, secondary, or tertiary, or likely a combination of these. Approaching treatment from a multidisciplinary model can be helpful, which can include neurologists, urologists, nurse practitioners, and health psychologists. Specific recommendations can be found below.

Treatment of Primary Causes

1) Orgasmic dysfunction, Premature/delayed ejaculation

Treatment:

  • Assess current medications that could be contributing (e. g., antipsychotics, SSRIs, and TCAs).
  • Gain an understanding of the different factors that could be contributing (i.e. other secondary or tertiary symptoms).
  • Focus is on appropriate contributing symptom management.

2) Decreased vaginal lubrication

Treatment:

  • Incorporate water-soluble lubricants prior to and during sexual activity and/or lubricants that contain menthol or other vasoactive agents as these can sometimes improve sensation (e.g., K-Y Jelly, Replens, or Astroglide).

3) Decreased libido

Treatment:

  • Cognitive Behavioral Therapy (CBT) to address unhelpful beliefs about sexual functioning/sexuality.
  • Couples therapy/Counseling.
  • Consider reducing/changing SSRIs and other medications that could be contributing.
  • Consider use of Flibastin for female patients.
  • Body mapping exercises.

4) Decreased genital sensation and paresthesias

Treatment:

  • Genital sensation can be improved with more vigorous genital stimulation and the use of vibrators.
  • Adequate management of paresthesias.
  • Cognitive Behavioral Therapy (CBT).
  • Couples therapy/Counseling.

5) Erectile dysfunction

Treatment:

  • Use of PDE-5 (phosphodiesterase-type5) inhibitors*.
  • Injectable medications for ED in MS such as prostaglandin**.
  • Consider reducing/changing SSRIs and other medications that could be contributing.
  • Consider adding Wellbutrin to antidepressant regimen.
  • Use of a vacuum assistive device (cannot be used for longer than 30 minutes).
  • Cognitive Behavioral Therapy (CBT) to address unhelpful beliefs about sexual functioning/sexuality.

Treatment of Secondary Causes

1) Fatigue

Treatment:

  • Energy conservation strategies such as planning sexual activity during a time of the day when MS fatigue is at its lowest; taking naps; using ambulation aids.
  • Pharmacologic treatment of fatigue as outlined in the Mellen Center Approach on management of fatigue.

2) Bladder and Bowel Symptoms

Treatment:

  • Behavioral strategies include restricting fluid intake before sexual activity, selfcatherization just before sexual activity, planned bowel movements twice a day and before sexual activity, use of condoms for concerns of urinary
    leakage in men.
  • Pharmacological interventions include the use of anticholinergic medications (may decrease vaginal lubrication which can be alleviated with the use of a water-soluble lubricant).

3) Spasticity

Treatment:

  • Active symptomatic management.
  • Physical therapy focusing on range of motion exercises.
  • Take antispasticity medication 30 minutes prior to sexual activity.
  • Explore alternative sexual positions to minimize discomfort or pain from spasticity.

4) Cognitive changes

Treatment:

  • To improve attention and concentration needed for successful sexual activity, the goal is to minimize nonsexual stimuli and maximize sensual and sexual stimuli.
  • Cognitive rehabilitation may be recommended.

Treatment of Tertiary Causes

1) Body image

Treatment:

  • Cognitive Behavioral Therapy (CBT).
  • Couples counseling or sex therapy.

2) Role reversal

Treatment:

  • If sexual partner is the primary caregiver, it may be helpful to incorporate other family members to perform caregiving duties for the patient to reduce “role conflict”.
  • Individual or couples counseling.

3) Depression

Treatment:

  • Cognitive Behavioral Therapy (CBT).
  • Consider SNRIs such as venlafaxine, desvenlafaxine, or duloxetine as opposed to SSRIs, such as fluoxetine, paroxetine, sertraline, or citalopram, which may result in more sexual side effects.
  • Consider adding Wellbutrin to antidepressant regimen as this medication has a lower profile of sexual dysfunction as a side effect.

* Sildenafil (Viagra) is the only medication evaluated in clinical trials in men with MS.

**Contraindicated when patient is on nitrate-based cardiac medications, as they can lower blood pressure excessively.

**It is recommended to refer the patient to a specialist in this area.

Note: All patients should be evaluated by their physician to be sure they are healthy enough for
sexual activity.

References:

  1. Christopherson JM, Moore K, Foley FW, Warren KG. A comparison of written materials vs. materials and counseling for women with sexual dysfunction and multiple sclerosis.
  2. Domingo S, Gales S, Thompson N, Stone L, Sullivan AB. Factors associated with sexual dysfunction in patients with multiple sclerosis: An exploratory study. Poster presented at: The 30th Annual Meeting for the Consortium of Multiple Sclerosis Centers, June 2016; National Harbor, MD.
  3. Foley FW. Assessment and treatment of sexual dysfunction in multiple sclerosis. In: Primer on Multiple Sclerosis. 1st ed. New York, NY: Oxford University Press; 2016:249-258.
  4. Foley FW & Iverson J. Sexuality. In: Multiple sclerosis: A Guide for Families. 3rd ed. New York, NY. Demos Medical Publishing; 2006.
  5. Sanders A, Foley FW, LaRocca NG, Zemon V. The multiple sclerosis intimacy and sexuality questionnaire-19. Sexual DisabiL. 2000; 18(1):3-26.
  6. Griswald G, Foley FW, Zemon V, LaRocca NG, Halper J. MS health professionals’ comfort, training, and practice patterns regarding sexual dysfunction. Int J Mult Scler Care. 2003; 5(2):3-10.

90,000 It won’t hurt. They put America on drugs and get billions. It is absolutely legal: Business: Economy: Lenta.ru

Tens of thousands of Americans die every year from overdoses of painkillers. The problem has grown to a national scale – even US President Donald Trump is seriously talking about the opioid crisis. Most addicts have become addicted to drugs prescribed by their attending physicians. And the main one among them was and remains a medicine produced by a family company with a half-century history.The Sackler Brothers became billionaires by drug addiction all of America; their descendants promise to cure American citizens of addiction, but they are driven by an exclusively mercantile interest. About the legal drug business in the United States – in the material “Lenta.ru”.

Members of the Sackler family are known throughout the world as major philanthropists who have spent millions of dollars helping museums and galleries. The halls in the Parisian Louvre, the New York Metropolitan Museum and the Guggenheim Museum, the London Museum of Natural History are named after them.The Sacklers have been repeatedly recognized as one of the richest people in America. In 2016, their total fortune was estimated at $ 13 billion, but most grateful art lovers still do not realize what was its source. The patrons themselves also do not like to dwell on this topic, and for good reason.

The main business of the Sacklers is in the pharmaceutical industry. In 1952, three physicist brothers – Arthur, Mortimer, and Raymond – bought the Manhattan-based Purdue Frederick Company and renamed it Purdue Pharma.Before new investors came, she specialized in laxatives and ear cleaners, but under the Sacklers she changed her profile abruptly, switching to pain relievers. Already in the 1960s, the company expanded, opening factories in New Jersey and Connecticut, and 20 years later released its first hit, MS Contin.

Raymond Sackler and his wife Beverly

It differed from the rest of the painkillers of the time with a breakthrough technology, which was called the controlled release mechanism.Its essence was that the active substance (the basis of any medicine) did not enter the bloodstream immediately, but gradually, and thanks to this, retained its effect for long hours. MS Contin broke sales records, but by the mid-1990s the patent was expiring, which meant that Purdue Pharma would have lost its monopoly on the market: anyone could produce the drug.

The exit was found pretty quickly. The active ingredient MS Contin was based on traditional morphine, and the Sackler brothers decided to see what would happen if it was further enhanced.The alternative was oxycodone, an opioid developed in Germany at the beginning of the 20th century that is twice as strong as morphine. By that time, painkillers based on it already existed, but they were all a mixture of oxycodone with another substance – for example, with aspirin. Purdue decided not to dilute it with anything and in 1995 introduced a new product – OxyContin. The result exceeded even the expectations of the creators: the drug quickly gained popularity, and its name became a household name.

True, some doctors doubted his safety, but the Sacklers quickly found a competent approach to them.Skeptics were invited to conferences, coaxed with gifts, paid for internships and expensive research. Purdue spared no expense in marketing, and it paid off: the US Food and Drug Administration (FDA) couldn’t find fault with it and licensed OxyContin.

Photo: t14 / ZumaPress / Globallookpress.com

According to some estimates, sales of the new drug brought the Sacklers a billion dollars annually, which was a fabulous result at the time.Among other things, the low cost helped to achieve it: oxycodone is much cheaper than morphine. Doctors were advised to prescribe OxyContin not only for acute chronic pain and incurable diseases at the last stage, as was the case with MS Contin and other competitors, but also for household injuries and sports injuries.

The drug became the most popular drug in hospitals, but it quickly became clear that it is highly addictive, which the manufacturers initially tried to play down.They argued that you can only get hooked on pills if you do not take them according to instructions, and referred to the experience of British doctors. In the United Kingdom, it is indeed common practice to prescribe potent opioids up to pure heroin to severely ill patients, but in the vast majority of cases this does not lead to dependence, since the administration is carried out under the strict supervision of doctors.

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Due to the availability and cheapness, OxyContin was nicknamed “country heroin”, which was not so far from the truth.Manufacturers wrote on the packaging that one tablet would last for 12 hours, but in reality the effect lasted no more than eight. On the recommendation of Purdue, doctors increased dosages and thus made patients even more active. Many doctors have noticed that from a certain point people begin to need not pain relief, but a new dose of the drug. From 1999 to the late 2000s, about 200,000 Americans died of OxyContin overdoses, and many switched to heroin and other “real” drugs.The latest statistics looked even more frightening: in the six years from 2001 to 2007, two-thirds of US overdose deaths took drugs prescribed by doctors; and in the first ten years of the new century, the number of babies dependent on opioids from birth increased threefold, due to the addiction of mothers.

But the Sackler brothers, who by that time there were only two (Arthur died several years before the release of the medicine), denied their guilt. They continued to insist that it was all about misapplication: allegedly due to the fact that patients crush tablets, inhale the resulting powder or use it for injections, the controlled release mechanism stops working.

Competitors also played into the hands of Purdue, producing an even stronger drug – fentanyl. Unlike oxycodone, it is not an opioid, but an opiate – that is, a substance obtained synthetically. It is not two times more powerful than morphine, but a hundred times at once, which did not prevent pharmacies from selling it by prescription. Because of its resemblance to heroin, fentanyl is often sold under the guise of this drug, and buyers do not calculate the dosage. All of this forced the public to take a break from OxyContin and Purdue for a while. So, in 2015, fentanyl was recognized as a national health threat in Canada.

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These circumstances helped the company in court. In 2007, the District Court of West Virginia considered several lawsuits at once, combined into one case. Among them were civil claims and criminal charges from state authorities. Purdue was charged with “misbranding,” meaning that the company misinformed consumers about the dangers of the drug.In addition, OxyContin in some cases was allowed to be sold even without a license.

The prosecution alleged that Purdue inappropriately obtained such approval from the FDA. However, in the end, the Sacklers managed to get off with little blood – a fine of $ 600 million (130 million of them – in private lawsuits). The amount is relatively small (for comparison: ten years earlier, the authorities sued the Big Five tobacco companies $ 246 billion), just over half of Purdue’s annual revenue from the sale of OxyContin.Separately, $ 34.5 million had to be paid to two top managers of the company and its lawyer. It is noteworthy that neither Mortimer nor Raymond Sackler was among them – the brothers always preferred to keep in the background and not to occupy managerial positions.

Lawsuits continued to come in after 2007 — both victims and entire states — but Purdue has learned to make pre-trial agreements with them. In response to criticism, the company explicitly states that it has not lost a single lawsuit over the past ten years.In reality, she simply did not bring a single case to a public hearing or delayed the process in such a way that the claims have been in the courts for years. True, one of these cases nevertheless leaked to the press – largely due to the fact that, under the terms of an agreement with the lawyers of the victims, Richard Sackler, 70-year-old son of Raymond, was forced to resign as president of the company. Purdue also paid the plaintiffs $ 24 million in damages.

In 2013, the patent for OxyContin expired. But Purdue was not taken aback and managed to register a new drug with the FDA in time – with a slightly modified formula, but similar properties.However, after that, about a third of patients who used OxyContin switched to drugs, mainly heroin. Two years later, the FDA took an unprecedented step: it allowed the sale of drugs to children from 11 years old.

Photo: Spencer Platt / Getty Images

In 2017, a few months after his inauguration, US President Donald Trump declared an opioid emergency in the country. “This is a serious problem, we have not yet encountered such a problem,” the head of state said.According to official statistics, in America about 60 thousand people die from overdoses every year – more than in car accidents. And this number began to grow precisely with the entry into the market of OxyContin. Economic losses are estimated at $ 504 billion a year (2.8 percent of GDP). This includes federal and state government spending on MedicAid and Medicare opioids and drug addiction treatment.

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Neither continued attacks nor lawsuits have had any impact on Purdue Pharma’s business.The company has earned about $ 35 billion from OxyContin alone, and now continues to release its “successor” under the old brand. The only change is the warning labels on the packaging and in the instructions. The company’s website features a section on social responsibility that highlights how Purdue is actively investing in medical research and helping the country cope with the opioid crisis.

But the real sensation broke out in September this year. As a result of the journalistic investigation, it turned out that the first serious problems with the law prompted the Sacklers to take action.A few months after the same court that fined Purdue $ 600 million, the brothers founded a new company, Rhodes Pharma. This time they decided to occupy a niche in the production of generics (this is the name for drugs that are close in composition to the original, but released after the expiration of the patent). Thus, in 2013, Rhodes began producing a generic oxycontin called oxycodone. MS Contin returned to the market even earlier.

In scale, the second Sackler company quickly surpassed the first.By 2016, she managed to sell over 14 million packs. This fact negates Purdue’s assurances that its blame for the opioid crisis is not all that great. Moreover, according to former Purdue and Rhodes employees, their bonuses were often based on the two companies’ combined share of the opioid market.

In parallel, in early September, Richard Sackler (with a doctorate in medicine), along with five colleagues, patented a new drug for the treatment of drug addiction. Rather, the new formula of the already known and approved by the FDA medicine – buprenorphine (Buprenorphine).It has been used in Europe since 1996, in the USA since 2002. The principle of its modified formula is the opposite of what was once used in MS Contin. Now the active substance enters the body faster than usual, which allows it to quickly enter the body and leave it just as quickly. It is believed that this will allow patients to gradually reduce the dose until the drug is completely abandoned.

Until now, buprenorphine (with the old formula) has been sold primarily under the Suboxone brand.Its annual sales in America range from $ 1.4 billion to $ 1.55 billion. It has been established that it affects patients in different ways: both cases of complete recovery from addiction and death from an overdose are known. Rhodes intends to market it under the original name Buprenorphine in two forms: tablets and patches. The company is likely looking at revenues comparable to those from OxyContin.

The entire current range of Rhodes Pharma looks like a cruel joke. The company continues to produce opioid pain relievers that have led the US to an epidemic of drug addiction, while at the same time offering its clients to get rid of addiction.Courts across the country are still accepting claims. The largest of the latter is from the Ohio state, but it does not already mention the ban on Purdue or Rhodes products, the claims are limited to compensation for damage to the budget.

None of the Sackler brothers are already dead (Mortimer lived to be 93 years old, and Raymond – to 97), numerous descendants continue to dispose of their common fortune. Some of them connected life with art and try to distance themselves from the business of their ancestors. For example, Arthur Sackler’s daughter Elizabeth runs a feminist art center at the Brooklyn Museum.Once her father, who was called “modern Medici” for his charity, bequeathed to his children “to leave the world in a better state than it was before them.” Neither he himself nor his relatives coped with this task.

XXXVII International Scientific and Practical Conference “Natural Sciences and Medicine: Theory and Practice”

Unified format for the design of article bibliographic lists in accordance with GOST R 7.05-2008 “Bibliographic reference” (Examples of the design of references and article lists of literature)

Abstracts

Glukhov V.A. Research, development and construction of a system for electronic delivery of documents in the library: Avtoref. dis. Cand. tech. sciences. – Novosibirsk, 2000 .– 18 p.

Analytical reviews

Economics and politics of Russia and neighboring countries: analyt. review, apr. 2007, Ros. acad. Sciences, Institute of World Economy and International. relationship. – M.: IMEMO, 2007 .– 39 p.

Theses

Fenukhin V.I. Ethnopolitical conflicts in modern Russia: on the example of the North Caucasus region: dis…. Cand. polit. sciences. – M., 2002. – S. 54-55.

Internet documents

Official periodicals: electronic guide / Ros. nat. library, Legal Information Center. [SPb], 200520076. URL: http://www.nlr.ru/lawcrnter/izd/index.html (date of access: 18.01.2007)

Loginova L.G. The essence of the result of additional education for children // Education: researched in the world: international. scientific. ped. internet journal. 21.10.03. URL: http: // www.oim.ru/reader.asp?nomer=366 (date of access: 17.04.07)

The market of trainings in Novosibirsk: its own game [Electronic resource]. – Access mode: http://nsk.adme.ru/news/2006/07/03/2121.html (date of access: 17.10.08)

Litchford E.W. With the White Army across Siberia [Electronic resource] // Eastern Front of the Army of General A.V. Kolchak: website. – URL: http://east-front.narod.ru/memo/latchford.htm (date of access: 23.08.2007)

Conference proceedings

Archeology: history and prospects: collection of articles.Art. The first interregional conference. – Yaroslavl, 2003 .– 350 p.

Maryinskikh D.M., Development of a landscape plan as a necessary condition for sustainable development of the city (on the example of Tyumen) // Landscape ecology and land use planning: abstracts of the reports. Vseros. conf. (Irkutsk, 11-12 Sept. 2000). – Novosibirsk, 2000. – pp. 125–128.

Monographs

Tarasova V.I. Political history of Latin America: textbook. for universities. – M .: Prospect, 2006.- pp. 305–412.

The prescribed dot and dash separating the areas of the bibliographic description is allowed, replaced by a dot:

Philosophy of culture and philosophy of science: problems and hypotheses: interuniversity. Sat. scientific. tr. / Sarat. state un-t; [ed. S.F. Martynovich]. Saratov: Publishing house Sarat. University, 1999 .– 199 p.

It is allowed not to use square brackets for information borrowed not from a prescribed source of information.

Raisberg B.A. Modern economic dictionary / B.A. Raisberg, L. Sh. Lozovsky, E.B. Starodubtseva. – 5th ed., Rev. and add. – M .: INFRA-M, 2006 .– 494 p.

The title of the entry in the article can contain the names of one, two or three authors of the document. The names of the authors mentioned in the title are not repeated in the statement of responsibility. Therefore:

Raizberg B.A., Lozovsky L.Sh., Starodubtseva E.B. Modern economic dictionary. 5th ed., Rev. and add. M .: INFRA-M, 2006.- 494 p.

If there are four or more authors, then the title is not used (GOST 7.80-2000)

Patents

RF Patent No. 2000130511/28, 04.12.2000.

Eskov D.N., Bonstedt B.E., Koreshev S.N., Lebedev G.I., Seregin A.G. Optoelectronic apparatus // Patent of Russia No. 2122745. 1998. Bul. No. 33.

Article from journals or collections

TV Adorno To the logic of social sciences // Vopr.philosophy. – 1992. – No. 10. – S. 76–86.

Crawford P.J. The reference librarian and the business professor: a strategic alliance that works / P.J. Crawford, T.P. Barrett // Ref. Libr. – 1997. Vol. 3. No. 58. – P.75–85.

The title of the record in the link can be the names of one, two, or three authors of the document. The names of the authors mentioned in the title may not be repeated in the disclaimer.

Crawford P.J., Barrett T.P. The reference librarian and the business professor: a strategic alliance that works // Ref.Libr. 1997. Vol. 3. No. 58. P.75–85.

If there are four or more authors, then the title does not apply (GOST 7.80-2000):

Kornilov V.I. Turbulent boundary layer on a body of revolution with periodic injection / suction // Thermophysics and aeromechanics. – 2006. – T. 13, No. 3. – S. 369–385.

Kuznetsov A.Yu. Consortium as a mechanism for organizing subscription to electronic resources // Russian Foundation for Basic Research: ten years of service to Russian science.- M .: Scientific. mir, 2003. – pp. 340–342.

Electronic resource

Artistic encyclopedia of foreign classical art [Electronic resource]. – M.: Big Ros. encyclopedia. [et al.], 1996. – 1 electron. wholesale disc (CD-ROM).

Examples of the design of references and cited references

Download GOST R 7.05-2008

Security Week 19 | Kaspersky blog

Let’s start with the production news: IBM intends to use the Watson supercomputer to solve information security problems (news, official press release).Let me remind you that Watson is, as the official documents say, a software and hardware complex (a cluster of 90 servers) capable of answering questions in natural language, or a kind of implementation of artificial intelligence. In 2011, Watson defeated pathetic people multiple winners in the Jeopardy game (we have it “Own Game”).

IBM wants to teach Watson to process a large flow of information related to information security – so that the supercomputer can “distinguish viruses from Trojans.”To this end, IBM will partner with a number of American universities, whose students will prepare information accordingly for further processing. There will be a lot of data, we are talking about billions of records.

However, it is too early to say that artificial intelligence and humanoid robots will protect us from all cyber threats. The final goals in the announcement are given in very broad strokes: “to automate the finding of relationships between data [about incidents], potential threats and defense strategies.”

Read here’s what the past week was interesting for: about Android, about Slack and that’s all https://t.co/ZpNQUKe4ft pic.twitter.com/OOZX02H5vB

– Kaspersky Lab (@Kaspersky_ru) May 9, 2016

On the one hand, the topic of machine learning, artificial intelligence and searching for anomalies in a huge data stream (for example, in network traffic) is very promising; Yes, in fact, such algorithms are already widely used now: from detecting new threats based on information about previous incidents to identifying complex, targeted attacks.

On the other hand, almost everyone in the industry agrees that absolutely everything cannot be automated, even if every large enterprise is equipped with a pair of Watsons. The share of “manual labor”, or rather, the need for highly qualified experts to investigate threats remains very high. The human factor plays an important role in security, and this is a very poorly algorithmic task.

However, IBM formulates the task correctly: “to give new opportunities to security experts.”Don’t replace them. This is the key difference between this initiative and other attempts to advertise on the topic of machine learning, promising that “the computer will understand everything” and will learn to detect any attacks on its own. Will not learn. Why – I’ll explain now.

Previous episodes of the series – here.

Of all the recent advances in artificial intelligence, the heralded most is the victory of machines over humans in mind games. Deep Blue versus Kasparov in chess, Watson in his own game, and most recently the victory of a supercomputer in Go.In March, when I was at the RSA conference, winning Go was mentioned in almost every second talk. To quote RSA President Amit Goran on this topic: “AI is cool, but you shouldn’t expect any breakthroughs in this direction in relation to IT security, based on today’s successes.”

It is one thing to win, even in a complex “human” game, it is another thing to be able to predict and prevent cyberattacks. In the first case, the game is played by the rules.In the second, there are no rules. AI in information security helps only in solving certain problems, and the more such “learnable” technologies are available, the more time an expert will have to deal with other problems: assess risks, predict attack vectors and prevent the most complex incidents. It is not yet possible to completely replace a person, and is unlikely to succeed.

Dangerous vulnerabilities in Windows and Adobe Flash are already being exploited to attack users and retail networks

News about Microsoft.News about Adobe.

The vulnerability in Windows was patched twice: a partial hole allowing arbitrary code execution with system privileges was closed in one of the April patch packs, and finally in a fresh update released this Tuesday. The vulnerability affects all current versions of Windows, from 7 to 10, and was discovered, alas, during the analysis of a series of successful attacks. Moreover, cybercriminals were looking for companies and devices used to process payments from credit cards.

The campaign was discovered in March by FireEye: the initial penetration into the victim’s network was carried out traditionally, using a “prepared” Word document sent by e-mail. In general, the season of attacks on American retail chains I mentioned earlier continues: cybercriminals are trying to catch up with the introduction of EMV payments (with a chip and a PIN, as in all normal countries), with which interception of credit card data becomes much more difficult.

Summed up the week: hacking Swift, extortion in Android, bypassing AppLocker, etc. https: // t.co / uhfyJm6hiK pic.twitter.com/ENHAnswqN4

– Kaspersky Lab (@Kaspersky_ru) May 2, 2016

A critical vulnerability in Adobe Flash is either exploited or not: Adobe claims they have not seen an attack, and independent sources deny it. Considering the potential danger of the vulnerability (exploitation can cause the application to crash and gain control over the system), Adobe warned in advance about its detection on May 10, and on the 12th – released a cumulative patch.

Cryptolockers: a view from the victim’s side

Threatpost article.

The most popular Threatpost post this week is not news, but shows the ransomware problem from an unexpected angle. An IT specialist from the online casino company shared a look at the problem from the victim’s side. Before publication, he asked not to be named. The company employs about a thousand employees. Despite the fact that such a business is very vulnerable to cyberattacks, as is often the case, IT security is not the top priority – there are enough other problems.

The article provides an example of a real cryptolocker attack on a company’s infrastructure. The entry point is an external consultant – a specialist working remotely on a laptop provided by the company. For some reason, the laptop is not protected by anything, but it has a connection to corporate network folders, allegedly due to a misconfiguration (file balls are mounted in the Public folder of the user partition – not the best option). After trying to open an attachment in a letter that looks like a familiar invoice, data encryption begins.And here you can clearly see how slow both the user and the IT specialists react to this problem, while it is necessary to react quickly.

The owner of the laptop calls support for half an hour, it still seems to him that there was some kind of technical malfunction. While he explains what is happening, the encryption of the data continues, he finally gets the right advice: disconnect the laptop from the network, right now. In the meantime, files on the server and some other computers of employees, also crookedly connected to network folders, are being encrypted.

In general, the story is typical: an attack through the most vulnerable link, which usually turns out to be a contractor or freelancer, encryption of data on the computer and in network folders, the rapid spread of the problem over the network. Fortunately, in this case, important data was not lost and the work of the company was not disrupted. Finally, an interesting private observation: if six months ago, the company’s admins recorded one attempt to attack a cryptolocker per day, now they block at least three. The company was attacked by the TeslaCrypt Trojan, which we wrote about in detail last year.

What else happened:

Another vulnerability in the system software on Lenovo laptops.

An interesting longread on the complex relationship between the American FBI and Eastern European cybercriminals in Wired magazine.

Cryptolocker tried to attack the US Congress.

The creator of the anonymous payment system LibertyReserve was imprisoned for 20 years.

Antiquities:

“Something-658”

It is a very dangerous memory resident virus that writes itself to the beginning of COM files that are executed.On the 11th, monthly erases file C: /AUTOEXEC.BAT, writes DEL * .COM, DEL * .EXE commands to it, and then creates a zero-length SOME file. Intercepts int 21h. Contains the texts: “Something v1.1”, “some c: autoexec.bat del * .com del * .exe”.

Quote from the book “Computer Viruses in MS-DOS” by Eugene Kaspersky. 1992 year. Page 83.

Disclaimer: This column reflects only the personal opinion of its author. It may or may not coincide with the position of Kaspersky Lab.That’s how lucky you are.

90,000 TFOMS RH

What is IVF (In Vitro Fertilization)?

In vitro fertilization is one of the modern methods of fertility treatment for those couples who cannot conceive a child naturally. The name of the method comes from two Latin terms: extra (extra) – outside, outside and corpus (corpus) – the body, that is, the fusion of the sperm and the egg occurs outside the woman’s body – in laboratory conditions (“in vitro”).

How does IVF work?

The essence of the method is reflected in the name. The mother’s eggs and the father’s sperm are placed in a special environment, where they are connected independently or artificially, after which the fertilized egg is implanted into the woman’s uterus, where the pregnancy develops.

1. The oocyte is obtained by stimulating superovulation with the use of drugs. In this case, the process is monitored using ultrasound diagnostics.When the eggs are mature, an ovarian puncture is performed and the eggs are removed. The separated eggs are placed in special conditions where they are awaiting sperm fertilization.

2. Sperm can be obtained in two ways: naturally (masturbation) or by biopsy of the testicle and epididymis.

3. Fertilization. With IVF, fertilization is performed in a test tube. Sperm cells are added to the resulting eggs, which within a few hours penetrate the eggs and fertilize them.

4. Growing the embryo. After fertilization, specialists monitor the growth of embryos. Upon reaching the 46-cell stage (26 days after fertilization), the embryo can be transferred to the mother’s uterus.

5. Embryo transfer. Several embryos are transferred into the uterine cavity. In this case, the mother is additionally prescribed hormone therapy for successful implantation. Pregnancy is determined after two weeks using a blood test for human chorionic gonadotropin.If pregnancy occurs, then it goes exactly the same way as with natural conception. But not in all women the embryo takes root immediately, for many it does not happen on the first try.

Is it possible to undergo IVF under the compulsory medical insurance policy?

Since 2015, the provision of medical care in the field of “obstetrics and gynecology” in in vitro fertilization refers to specialized medical care and is payable at the expense of compulsory medical insurance.

In 2018, there was an increase in the number of stages financed by the CHI funds:

Carrying out the first stage of in vitro fertilization (stimulation of superovulation)

Carrying out I – III stages of in vitro fertilization (stimulation of superovulation, obtaining an egg, in vitro fertilization and embryo cultivation), followed by cryopreservation of embryos

Full cycle of in vitro fertilization without the use of embryo cryopreservation

Full cycle of in vitro fertilization with cryopreservation of embryos

Thawing of cryopreserved embryos with subsequent transfer of embryos into the uterine cavity (incomplete cycle)

(The storage of cryopreserved embryos is not carried out at the expense of compulsory health insurance).

How to get IVF referrals under the basic CHI program?

Step-by-step instructions for obtaining a referral for IVF (cryopreserved embryo transfer) within the framework of the basic CHI program are detailed on the official website of the Ministry of Health of the Republic of Khakassia mz19.ru in the section “Protection of mothers and children” – “IVF program”.

The main steps are:

1. Contacting the local doctor, obstetrician-gynecologist, antenatal clinic, passing the necessary medical examination.

2. Registration by the attending physician of an extract from the outpatient card, which is further considered by the medical commission (VC) of the medical organization with the provision of the VC decision.

3. Receipt by the patient of an extract from the outpatient card and an extract from the minutes of the VK meeting, as well as the collection of a complete package of documents.

4. Obtaining an opinion from the chief freelance specialist on reproductive health of the Ministry of Health of Khakassia, the deputy chief physician for outpatient care of the State Budgetary Healthcare Institution of the Republican Clinical Perinatal Center – Ph.M.Sc. Kamaeva Tatiana Alexandrovna.

Reception of women by the chief specialist in reproductive health T.A. Kamaeva, when issuing a quota for in vitro fertilization from 14.08.2018, will be held on Tuesdays from 17.00 to 18.00 at the Ministry of Health at the address: 72 Krylova, 3rd floor, room 330.

5. Submission of the full package to the commission of the Ministry of Health of Khakassia for the selection of patients for IVF

6. Consideration of the package of documents by the commission of the Ministry of Health of Khakassia (25 days).You will be informed about the decision of the commission by telephone.

7. After that, you will need to call the clinic of your choice operating in the CHI system to clarify the possibility of referral to them for IVF treatment (the list of clinics is also posted on the Mizdrav RH website https://mz19.ru/upload/iblock/c06 /kliniki-eko-v-sisteme-oms_-2018g.pdf).

8. To receive a referral, you need to come to the Ministry of Health of Khakassia (Abakan, Krylova st., 72, room 328) and provide the name of the clinic operating in the compulsory medical insurance system, which you have chosen for your IVF treatment.

9. After filling out the referral, you call the clinic and discuss the date of admission. With the necessary documents, you go on the appointed day to the clinic for IVF.

Can IVF be done only in clinics located outside the Republic of Khakassia?

No, since 2017, the medical organization GBUZ RH “Republican Clinical Perinatal Center” has also been carrying out in vitro fertilization.The first embryo transfer was made to a young resident of Khakassia on December 18, 2017.

Is it possible in the Perinatal Center of the Republic of Khakassia to undergo IVF procedure under compulsory health insurance for couples from the Republic of Tuva (or from other regions)?

On the issue of referring you to the procedure of in vitro fertilization in a medical organization State Budgetary Institution of Health of the Republic of Khakassia “Republican Clinical Perinatal Center”, you need to seek advice from the Ministry of Health of your subject.In case of compliance with all the requirements of the legislation on the part of the sending party, it is possible to provide medical care under the policy of compulsory medical insurance in medical organizations of the Republic of Khakassia.

Tell me, please, when conducting an examination before IVF, is it legitimate to assign partially paid tests to me and my husband?

If there are indications for the IVF procedure, if there is a referral from the attending physician, examinations are payable at the expense of the CHI funds.

Additionally, for advice on the legality of collecting funds or with an application for a refund, you can contact the Contact Center at the toll-free number: 8-800-350-42-25


Tell me, does the compulsory medical insurance policy cover only 1 IVF attempt? Suddenly, the embryo will not take root, then do it at your own expense?

In federal legislation, the number of IVF attempts under compulsory medical insurance is not limited.