Oral DMSO Treatment for Lipoid Proteinosis: Efficacy, Side Effects, and Long-Term Outcomes

16.07.202317.07.2023 by alexxlab

How effective is oral DMSO treatment for lipoid proteinosis. What are the potential side effects and long-term outcomes of this therapy. Is DMSO a viable treatment option for patients with this rare genetic disorder.

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Understanding Lipoid Proteinosis: A Rare Genetic Disorder

Lipoid proteinosis, also known as Urbach-Wiethe disease, is an extremely rare autosomal recessive disorder characterized by the deposition of hyaline material in the skin, mucous membranes, and internal organs. This condition typically manifests in early childhood with hoarseness of voice, thickening of the skin, and various mucosal abnormalities.

The rarity of lipoid proteinosis poses significant challenges for both patients and healthcare providers. With limited treatment options available, researchers have explored various experimental therapies to manage the symptoms and progression of this disorder.

Key Features of Lipoid Proteinosis

Hoarseness of voice due to laryngeal involvement
Thickened, waxy skin
Beaded papules along the eyelid margins
Tongue and oral mucosal lesions
Neurological symptoms in some cases

The Potential of DMSO as a Treatment Option

Dimethyl sulfoxide (DMSO) has garnered attention as a potential therapeutic agent for lipoid proteinosis due to its unique properties. DMSO is an organosulfur compound with anti-inflammatory and antioxidant effects, as well as the ability to penetrate biological membranes easily.

Can DMSO effectively treat lipoid proteinosis? While some case reports have suggested promising results, the overall efficacy of DMSO in managing this condition remains uncertain. The study discussed in this article aimed to evaluate the long-term effects of oral DMSO treatment in three patients with lipoid proteinosis.

Proposed Mechanisms of Action for DMSO in Lipoid Proteinosis

Reduction of inflammation in affected tissues
Potential dissolution of hyaline deposits
Improved tissue penetration of other medications
Antioxidant effects to mitigate cellular damage

Long-Term Oral DMSO Treatment: A Clinical Study

The study conducted by Ozkaya-Bayazit et al. involved three patients with lipoid proteinosis – two sisters and an unrelated man. These patients underwent long-term oral DMSO treatment at a dosage of 60 mg/kg/day. The average treatment duration was approximately 3 years, providing valuable insights into the long-term effects and tolerability of this therapy.

What were the outcomes of this long-term DMSO treatment? Unfortunately, the results were disappointing. After an average of 3 years of treatment, the researchers observed no beneficial effects on the patients’ skin lesions, mucosal abnormalities, or hoarseness. In fact, one patient experienced a worsening of symptoms, including increased hoarseness and the onset of dyspnea, necessitating surgical intervention to remove vocal cord infiltrates.

Key Findings from the Study

No improvement in skin or mucosal lesions
Persistent hoarseness in all patients
Disease progression in one patient despite treatment
Lack of efficacy led to discontinuation of DMSO therapy

Contrasting Results: Previous Case Reports on DMSO Treatment

The findings of this study stand in contrast to earlier case reports that suggested potential benefits of DMSO treatment for lipoid proteinosis. A notable example is the case reported by Wong and Lin in 1988, where a patient showed a “remarkable response” to oral DMSO therapy.

Why did the results differ between these studies? Several factors could contribute to the discrepancy, including variations in patient characteristics, disease severity, dosage regimens, and duration of treatment. It’s also possible that individual genetic factors play a role in treatment response, highlighting the complex nature of this rare disorder.

Factors Influencing Treatment Outcomes

Individual genetic variations
Stage and severity of the disease
Dosage and duration of DMSO treatment
Potential placebo effect in single case reports
Differences in assessment methods and criteria

Safety Profile and Side Effects of Oral DMSO Treatment

While the study focused primarily on efficacy, it’s crucial to consider the safety profile of long-term oral DMSO treatment. Although the authors did not report significant adverse events, DMSO is known to have potential side effects that should be carefully monitored.

What are the common side effects of oral DMSO treatment? Patients may experience gastrointestinal discomfort, skin irritation, and a characteristic garlic-like body odor. In some cases, more serious side effects such as liver toxicity or allergic reactions have been reported with DMSO use in other conditions.

Potential Side Effects of Oral DMSO

Gastrointestinal disturbances (nausea, vomiting, diarrhea)
Skin rash or irritation
Garlic-like breath and body odor
Headache and dizziness
Potential for liver enzyme elevations

Alternative Treatment Approaches for Lipoid Proteinosis

Given the lack of efficacy observed with DMSO in this study, it’s important to consider alternative treatment options for patients with lipoid proteinosis. While there is no cure for the condition, several approaches have been explored to manage symptoms and improve quality of life.

Are there other promising treatments for lipoid proteinosis? Some studies have investigated the use of retinoids, such as acitretin, with varying degrees of success. Surgical interventions may be necessary to address specific complications, such as vocal cord infiltrates or airway obstruction. Additionally, supportive care and symptomatic management play crucial roles in the overall treatment strategy.

Potential Treatment Options for Lipoid Proteinosis

Retinoids (e.g., acitretin)
Surgical removal of problematic lesions
CO2 laser therapy for cutaneous lesions
Speech therapy for voice-related issues
Psychological support and counseling

Implications for Future Research and Clinical Practice

The results of this long-term study on oral DMSO treatment for lipoid proteinosis highlight the need for continued research into effective therapies for this rare disorder. While DMSO may not be the answer for all patients, its potential benefits in certain cases cannot be entirely ruled out.

How can these findings inform future research and clinical practice? Researchers should consider conducting larger, controlled studies to further evaluate the efficacy of DMSO and other potential treatments. Additionally, efforts to identify biomarkers or genetic factors that may predict treatment response could help personalize therapeutic approaches for individual patients.

Future Directions in Lipoid Proteinosis Research

Larger, multicenter clinical trials
Investigation of combination therapies
Exploration of novel therapeutic targets
Development of gene therapy approaches
Improved diagnostic and monitoring techniques

In conclusion, while the long-term study of oral DMSO treatment in three patients with lipoid proteinosis did not demonstrate significant benefits, it provides valuable insights into the challenges of managing this rare disorder. As research continues, healthcare providers must work closely with patients to explore individualized treatment strategies that address their specific symptoms and needs. The quest for effective therapies for lipoid proteinosis remains ongoing, emphasizing the importance of continued scientific investigation and clinical innovation in the field of rare genetic disorders.

[Oral DMSO therapy in 3 patients with lipoidproteinosis. Results of long-term therapy]

Case Reports

. 1997 Jul;48(7):477-81.

doi: 10.1007/s001050050613.

[Article in

German]

E Ozkaya-Bayazit¹, G Ozarmağan, C Baykal, T Uluğ

Affiliations

Affiliation

¹ Dermatologische Abteilung, Medizinischen Fakultät Istanbul der Universität, Istanbul.

PMID:
9333627
DOI:
10.1007/s001050050613

Case Reports

[Article in

German]

E Ozkaya-Bayazit et al.

Hautarzt.

1997 Jul.

. 1997 Jul;48(7):477-81.

doi: 10.1007/s001050050613.

Authors

E Ozkaya-Bayazit¹, G Ozarmağan, C Baykal, T Uluğ

Affiliation

¹ Dermatologische Abteilung, Medizinischen Fakultät Istanbul der Universität, Istanbul.

PMID:
9333627
DOI:
10.1007/s001050050613

Abstract

Lipoid proteinosis is a rare autosomal recessive disorder with a chronic, benign course. There is no generally accepted systemic therapy apart from the experimental oral use of dimethyl sulphoxide (DMSO) and etretinate in two single cases. We treated two sisters and an unrelated man with lipoid proteinosis with longterm oral DMSO (60 mg/kg/d). At the end of an average treatment time of 3 years, DMSO was withdrawn because it produced no beneficial effects with regard to their skin, mucosal lesions or hoarseness. Additionally, one patient showed progression of her disease with worsening hoarseness and onset of dyspnea, requiring surgical removal of vocal cord infiltrates. Three patients with lipoid proteinosis failed to show any beneficial response to long term treatment with DMSO.

Cited by

Two Egyptian cases of lipoid proteinosis successfully treated with acitretin.
Bakry OA, Samaka RM, Houla NS, Basha MA.
Bakry OA, et al.
J Dermatol Case Rep. 2014 Mar 31;8(1):29-34. doi: 10.3315/jdcr.2014.1168. eCollection 2014 Mar 31.
J Dermatol Case Rep. 2014.
PMID: 24748909
Free PMC article.
Cryosurgery (N2O) Application to Remove Lip Lesions of Lipoid Proteinosis Syndrome: A Case Report.
Shirani AM.
Shirani AM.
J Dent Res Dent Clin Dent Prospects. 2008 Spring;2(2):68-70. doi: 10.5681/joddd.2008.014. Epub 2008 Aug 15.
J Dent Res Dent Clin Dent Prospects. 2008.
PMID: 23289062
Free PMC article.
Acitretin treatment for lipoid proteinosis.
Gündüz O, Sahiner N, Atasoy P, Senyücel C.
Gündüz O, et al.
Case Rep Dermatol Med. 2012;2012:324506. doi: 10.1155/2012/324506. Epub 2012 Aug 9.
Case Rep Dermatol Med. 2012.
PMID: 23259080
Free PMC article.

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DMSO (Dimethyl Sulfoxide): Uses, Benefits, Risks, and More

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Medically reviewed by Angelica Balingit, MD — By Jessica DiGiacinto and Joe Bowman — Updated on May 16, 2023

DMSO is a colorless chemical solvent that may have many medical uses but is currently only approved by the FDA to treat interstitial cystitis.

The story of dimethyl sulfoxide (DMSO) is an unusual one. This by-product of the paper making process was discovered in Germany in the late 19th century. It’s a colorless liquid that gained notoriety for its ability to penetrate the skin and other biological membranes.

Scientists discovered that they could use DMSO as a transportation device to pass small molecules through skin in the 1960s. Since then, scientists have researched the potential benefits and risks of using DMSO to treat a variety of conditions. This research is ongoing.

DMSO was approved by the Food and Drug Administration (FDA)to treat interstitial cystitis (a chronic bladder issue) under the brand name RIMSO-50.

The compound has no other approved uses, but it’s been purported to be a treatment for:

arthritis
cancer
chemotherapy side effects
general pain

Because it absorbs easily into the skin, it’s also been studied as a vehicle for administering topical drugs.

In the late 70s, the FDA approved DMSO to help treat interstitial cystitis. It remains the only FDA-approved bladder installation (or bladder wash) for this condition. For individuals living with interstitial cystitis, DMSO has been shown to:

ease pain due to the condition
help relax the bladder
increase bladder capacity

When it comes to off-label uses, DMSO is often employed as an alternative treatment to reduce inflammation and pain.

Because it absorbs easily into the skin, DMSO may be a beneficial alternative to other pain medications. However, further investigation into this area is needed before any conclusions can be drawn.

DMSO has also been touted for its ability to reduce the amount of leakage during chemotherapy administration, but more studies, and real-world usage, need to be done before it can be labeled as a trusted method.

Additionally, there has been some research into DMSO’s benefits when it comes to inhibiting cancer cells. A 2020 study published in the Journal of Medical Discovery found evidence of benefit. However, research is just beginning in this area, so many more studies need to be done before any conclusions can be made.

While many of the reported side effects of taking DMSO are mild, the amount of DMSO someone takes is directly correlated to the severity of the reaction.

One common side effect is the taste of garlic in the mouth and throat.

More severe side effects include:

headache
nausea
vomiting
stomach ache
diarrhea
fever
chills
a lowered heart rate
itching
rash
rough or thickened skin

Risks

Because it’s seen as a more alternative treatment, DMSO is easy to find and buy online. However, buying this product and using it without a healthcare professional’s supervision could increase the likelihood of overuse.

DMSO may also increase the effect of a few medications, which could produce serious reactions in some people. A few medications DMSO may affect include:

sedatives
blood thinners
steroids

DMSO can be administered

topically, via a gel or solution
as a bladder wash, via a catheter (for interstitial cystitis)

As with any alternative treatment, it’s always advised to talk with a doctor before deciding to purchase any product that contains DMSO. Dosage is directly connected to the severity of possible side effects.

Dimethyl sulfoxide (DMSO) is a chemical solvent that is sometimes used to help reduce inflammation and pain, and may also be beneficial in reducing leakage during chemotherapy treatment.

It has been FDA approved to treat only one condition: interstitial cystitis.

Because of possible interactions with other common medications, and lack of definitive research into its benefits, DMSO should not be used without medical supervision.

Last medically reviewed on February 1, 2022

How we reviewed this article:

Healthline has strict sourcing guidelines and relies on peer-reviewed studies, academic research institutions, and medical associations. We avoid using tertiary references. You can learn more about how we ensure our content is accurate and current by reading our editorial policy.

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Elisia I, et al. (2016). DMSO represses inflammatory cytokine production from human blood cells and reduces autoimmune arthritis.
ncbi.nlm.nih.gov/pmc/articles/PMC4816398/
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Tang H, et al. (2020). DMSO inhibits growth and induces apoptosis through extrinsic pathway in human cancer cells.
https://www.proquest.com/openview/06527232a660b6867effa2ff8f68deed/1?pq-origsite=gscholar&cbl=2050635
Understanding unapproved use of approved drugs “off-label.” (2018).
fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/understanding-unapproved-use-approved-drugs-label
Wengström Y, et al. (2008). European oncology nursing society extravasation guidelines.
sciencedirect.com/science/article/abs/pii/S1462388908001002
What is interstitial cystitis(IC)/bladder pain syndrome? (n.d.).
urologyhealth.org/urology-a-z/i/interstitial-cystitis

Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available.

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May 16, 2023

Written By

Jessica DiGiacinto, Joe Bowman

Edited By

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Copy Edited By

Delores Smith-Johnson

Feb 1, 2022

Medically Reviewed By

Angelica Balingit, MD

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Medically reviewed by Angelica Balingit, MD — By Jessica DiGiacinto and Joe Bowman — Updated on May 16, 2023

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What Dermatologists Treat: Topical Skin Therapy

Methods

Ending. Beginning in #3/2015, #4/2015

Author: Ruppel VV, PhD, veterinary dermatologist. Veterinary Clinic of Neurology, Traumatology and Intensive Care, St. Petersburg.

Topical anti-inflammatory agents

Topical glucocorticoids

Physical exposure to cold is considered the simplest and safest method to help reduce itching. But more often, local glucocorticoids are used to eliminate itching (and inflammation). In high concentrations, when applied to inflamed and injured skin, glucocorticoids are absorbed into it. This rarely leads to serious adverse clinical effects if glucocorticoids are used for a short time.
Scientists have conducted a significant number of studies confirming that long-term topical use of corticosteroids can lead to systemic changes: for example, adversely affect the response of the adrenal cortex to exogenous corticotropin and lead to an increase in liver enzymes. And therefore, despite the significant number of products containing various glucocorticoid compounds in their composition, the search for safe agents for topical application to the skin continues to this day.
So, relatively recently, Virbac offered a Cortavance spray containing hydrocortisone aceponate, which belongs to the diester class of glucocorticoids. Diesters are lipophilic components that provide enhanced penetration into the skin. Hydrocortisone aceponate, which accumulates in the skin of dogs, is effective locally at low doses. Topical application of diesters results in a high therapeutic index – high local activity with reduced systemic secondary effects. In addition, the product has a minimal effect on the cells of the epidermis and on the synthesis of collagen, which is a condition that prevents pronounced atrophogenicity when used. But, despite this, the drug should be applied with caution to those areas where the skin is physiologically thinned (scrotum, groin, armpits, sides).
If we talk about possible side effects that occur against the background of the use of glucocorticoids, then their list includes atrophy, peeling, comedones, alopecia and pyoderma, as well as skin calcification, which can occur on their own, without concomitant systemic effects.
The most powerful are fluoride steroids. They penetrate the skin better and are therefore more effective. Even a single application to the skin during the day may be sufficient to achieve the expected effect. However, their use may be associated with a large number of side effects (see above).
Topical glucocorticoid therapy should follow the same principles as systemic therapy. That is, strong drugs at the initial stage should be used twice a day to relieve inflammation, then once a day, and finally, subject to the expected long-term therapy, they should be replaced with softer glucocorticoids. In the future, maintenance therapy with these local agents should be continued, if possible, on a daily basis.
In some cases, with maintenance therapy with local glucocorticoids, it is enough to use them twice a week. Pet owners should wear gloves to avoid adverse consequences.

Local immunomodulators

Tacrolimus
Tacrolimus (Protopic) is a 23-mer macrolide that is similar in action to cyclosporine and results in calcineurin inhibition. It inhibits the production of cytokines by T-lymphocytes, has an effect on antigen-presenting cells and keratinocytes.
Tacrolimus reduces the clinical symptoms of manifestation in atopic dermatitis, in some cases it can be effective in discoid lupus erythematosus, perianal fistulas, ulcerative nasal dermatitis of Bengal cats, metatarsal fistulas of German shepherds.
In some cases, the authors have also used it in the treatment of vasculitis, vitiligo, alopecia areata, allergic contact dermatitis, erythema multiforme, and other inflammatory skin conditions.
More effective form of the drug with a content of 0.1% tacrolimus. Owners are advised to wear gloves when applying this product to the skin of animals.

Pimecrolimus
Pimecrolimus (Elidel) is an ascomycin macrolactam derivative that acts similarly to tacrolimus. Pimecrolimus is worse than tacrolimus at penetrating the skin of patients, so it is less effective.
Precautions for handling it are the same as for tacrolimus (use of gloves).

Imiquimod
Imiquimod (Aldara) is a relatively new drug with great potential for use in veterinary dermatology.
Imiquimod is a synthetic amine-based imidazoquinoline immune response modifier with potent antiviral and antitumor effects in animals and humans.
Antiviral and antitumor effects primarily result from activation of Toll-like receptors (TLR)-7, leading to the secretion of cytokines from monocytes/macrophages (interferon [IFN]-α, interleukin [IL]-12, tumor necrosis factor [TNF]-α ).
The local immune response leads to the predominance of Th2 and the development of the so-called cellular immune response. The latter is important for the treatment of viral infections, such as human papillomavirus, herpes simplex virus, actinic keratosis,
superficial basal cell carcinoma, human and feline squamous cell carcinoma in situ. The drug has also been used to treat feline herpesvirus dermatitis with varying efficacy.
For most conditions, imiquimod is applied two to three times per week in varying courses of duration; but usually, as noted, results are observed after a 4-week course of therapy.
The frequency of application may depend on whether skin irritation occurs at the site of imiquimod application. And if such reactions occur, then the drug can be used with longer intervals.

Other local agents

Sulfur
Sulphurous (sulphated) lime is prepared by boiling a suspension of sublimated sulfur, lime (Ca[OH]2) and water, which produces calcium pentasulfide and calcium thiosulfate. Sulfur is a degreasing agent. Sulfur is keratoplastic at low concentrations and keratolytic at high concentrations (h3S breaks down keratin). In this case, it acts synergistically with salicylic acid. Sulfur is antifungal and antibacterial mainly due to the conversion of pentathionic acid and h3S (this conversion can be supplemented by skin bacteria and keratinocytes).
Lime sulfide inhibits the growth of Microsporum canis more effectively than chlorhexidine, captan, povidone-iodine, and ketoconazole shampoo.
Lime sulfide is inexpensive and non-toxic and is now available in Russia. Side effects include rare excessive dryness or irritation of the skin.
The disadvantages of its use include an unpleasant odor (reminiscent of the smell of rotten eggs) and staining of light wool and skin in yellow.

Vitamin A
Retinoic acid at a concentration of 0.05%, tretinoin (Retin-A) , is popular in humane dermatology abroad (used to treat acne, pimples and ichthyosis). Although quite expensive, this concentration has been used by the authors in dogs and cats for the treatment of acne and some localized keratinizing diseases.
Usually, at the initial stage, a gel with a concentration of 0.01% is used, since it is less irritating than, for example, if the concentration of the active substance is 0.025%.
Retinoic acid increases the turnover time of the epidermis, reduces the cohesiveness of keratinocytes, normalizes the maturation of the follicular epithelium, and also has comedolytic properties. It has also been used in animals to prevent skin atrophy caused by corticosteroids. Retinoic acid can cause local skin irritation, which is a significant problem for many people and many animals (cats). Such side effects have been observed by scientific publications with Retina-A.
The preparation in the form of microspheres (Retin-A MICRO) is also available for sale abroad, which causes skin irritation in humans to a much lesser extent, as noted in the literature.
Synthetic retinoids are also available as local preparations (and in Russia). Adapalene is a topical retinoid with specific receptor activity for intranuclear retinoic acid receptors and is less irritating than retinoic acid. It also inhibits the activation of neutrophils and lipoxygenase enzymes. Tazarotene is a relatively new acetylene retinoid topical agent that is available in 0.1% cream and gel form. As a topical treatment, it is likely to have minimal absorption and no side effects have been reported so far. Tazarotene acts on retinoic acid receptors, which leads to the regulation of keratinocyte differentiation processes and inhibition of inflammation mechanisms in the skin (for example, by antagonizing the effects of IFN-γ).
Bexarotene is a relatively new synthetic retinoid X receptor (RXR) – a selective retinoid that inhibits proliferation, stimulates terminal differentiation, activates caspase-3, and also induces apoptosis. It also inhibits IL-2 secretion, prevents T cells from escaping from vessels into tissues, controls epidermal differentiation, and suppresses inflammation. It is available in dosage forms as a 1% gel for oral and topical use. Human medicine uses include the treatment of hand dermatitis, lymphomatoid papulosis, alopecia areata, follicular mucinosis, and mycosis fungoides. It is assumed that it can be used as one of the components in the complex treatment of T-cell lymphoma in dogs.
Zinc
Zinc has been valued in human medicine for its effects in wound healing, treating viral infections such as the herpes simplex virus. It is found in some veterinary shampoo products and has antimicrobial and antiseborrheic effects.
Urea
Urea has hygroscopic and keratolytic properties that contribute to the normalization of the epidermis, especially the quality of the stratum corneum. The application of urea as part of a cream or ointment to the stratum corneum has a softening and moisturizing effect, and the basis of the drug is perceived as less oily. It acts as a humectant at concentrations between 2% and 20%, but above this level, urea is a keratolytic. This action is the result of the dissolution of prekeratin and keratin, as well as the possible destruction of hydrogen bonds that keep the stratum corneum intact. It is a powerful keratolytic agent used to treat nasal hyperkeratosis, calluses, dermatosis of the auricle margins and acne.
a-hydroxy acids 2%-10%
a-hydroxy acids include lactic, malic, citric, tartaric, glutamic, glycolic and tartaric acids. They are effective in regulating keratinization, being keratoplastic substances, delaying final differentiation and weakening the forces of intercellular cohesion of the stratum corneum.
Ethyl lactate
The action of ethyl lactate is similar to that of benzoyl peroxide at a reduced skin pH. It is hydrolyzed in the skin by bacterial lipases to ethanol and lactic acid. Ethyl lactate is lipid soluble and has the ability to penetrate hair follicles and sebaceous glands.
Fatty acids
Fatty acids are important in moisturizing and controlling transepidermal water loss and epidermal barrier function.
Several new products have recently been developed that function by direct topical application of fatty acids to the skin and coat. These products have worked well for seborrheic skin conditions and allergic diseases. Among the available products in Russia, one can consider such as Dermoscent Essential 6 Spot-on (Laboratoire de Dermo-Cosmetique Animale) and Allerderm Spot-on (Virbac).
Essential 6 Spot-on contains a combination of fatty acids and emollients. It hydrates the skin, controls transepidermal water loss, and helps reduce inflammation as it also contains antioxidants. Overall, this product contains natural botanical ingredients including hemp seed and neem seed oils to achieve high concentrations of essential fatty acids with a 4:1 omega-6/omega-3 ratio. Additionally, other essential oils (rosemary, lavender, melaleuca, cedarwood, oregano, cloves, camphor, wintergreen, peppermint, turmeric) are included in the product along with vitamin E to restore the water-lipid film, moisturize the skin and control odor. Essential 6 Spot- on helps improve coat quality and control itching in dogs with atopic dermatitis, which can be used as part of the treatment of atopic dermatitis in dogs.
Allerderm Spot-on has similar properties. It contains a dermal lipid complex composed of a mixture of ceramides and fatty acids similar to those found in healthy skin of dogs and cats. It is believed that treatment with Allerderm Spot-on may also stimulate the production of endogenous stratum corneum lipids.
Polypropylene Glycol
Polypropylene glycol was originally used as a solvent and filler in the dosage form. At higher concentrations (>75%) it sometimes causes irritation or sensitization. It may also increase contact sensitization to other drugs or chemicals combined with it. It is an excellent lipid solvent and degreaser of the skin, but the main value of propylene glycol is probably its ability to increase the penetration of drugs through the skin. Propylene glycol is a powerful and reliable antibacterial agent, also possessing antidermatophyte and anticonidial properties. For most dermatological cases, it is used in concentrations of 30% to 40%. Propylene glycol is an excellent humectant (desiccant) and can induce keratolysis. Thus, higher concentrations are practically helpful in hyperkeratotic conditions, and 75% propylene glycol spray is effective in treating sebaceous adenitis.
Dimethyl Sulfoxide (DMSO)
DMSO is a simple hygroscopic organic solvent. Since it is easily miscible with lipids, organic solvents and water, it is an excellent dosage form excipient. Upon contact with air, concentrated solutions take on water and become hydrated at 67%. Higher concentrations tend to penetrate the skin barrier better. DMSO penetrates the skin (within 5 minutes), mucous membranes and the blood-brain barrier, as well as cells, organelles and membranes of microorganisms. Unlike most solvents, DMSO does not damage membranes upon penetration. It promotes membrane absorption of many other substances, especially corticosteroids. At the cellular level, DMSO and steroids show a synergistic effect.
DMSO has the properties of a cryoprotective, radioprotective, anti-ischemic, anti-inflammatory agent (binds free radicals, reduces prostaglandin synthesis, stabilizes lysosome membranes). Although its mechanism of action is not fully understood, the systemic toxicity and teratogenicity of this solvent in its pure form is considered to be low. Toxicity may be a concern depending on dose, route of administration, species and individual response of the animal. Admixtures or combinations with other agents can make DMSO dangerous due to its ability to enhance transepidermal absorption. Well-known minor side effects with DMSO include garlic odor, local fever (due to exothermic reaction with water) and/or itching (due to histamine release), and dehydration (very hygroscopic).
Possible uses may include topical application to skin ulcers, burns, insect bites, interdigital granulomas, open wounds, and skin grafts; reduction of excess granulation tissue and skin calcification; and treatment of acral dermatitis due to licking. The commercial name of the drug in Russia is Dimexide.
Aloe Vera
The bulk of the information regarding aloe vera is anecdotal. There are more than 300 species of Aloe plants, which vary in chemical composition depending on the species, climate and growing conditions. The terms “aloe”, “aloe vera” and “aloe extract” refer to the end products of juice extraction by various methods from aloe plants. The result of this heterogeneity in collection or extraction is a large difference between the composition, consistency and appearance of different products. Therefore, interpretation and comparison of different studies is often impossible, as the authors point out.
Aloe vera is used to treat pain, itching, fungal and bacterial infections, insect bites, burns, wound healing, and excessive growth of granulation tissue.
Melaleuca oil
Melaleuca oil is extracted from the leaves of the tea tree (Melaleuca alternifolia). It is antibacterial (eg against coagulase-positive staphylococci) and fungicidal (eg against Candida albicans,
T. mentagrophytes) properties.
Excessive application of melaleuca oil to the skin can lead to toxicosis, symptoms that include hypersalivation, incoordination, weakness, hypothermia, and liver toxicity.

Literature:

Muller and Kirk’s Small Animal Dermatology, 7th Edition, P.114-134.
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Efficacy of some antiviral agents against COVID-19: in vitro studies

Authors: Xi Wang, Ruiyuan Cao, Huanyu Zhang, Jia Liu, Mingyue Xu, Hengrui Hu, Yufeng Li, Lei Zhao, Wei Li, Xiulian Sun, Xinglou Yang, Zhengli Shi, Fei Deng, Zhihong Hu, Wu Zhong, Manli Wang

Translation: Cancer Prevention Foundation

Since December 2019, the new COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread to more than 200 countries, infecting more than 1. 5 million people, caused 92,798 deaths (data as of April 10, 2020). The World Health Organization (WHO) declared the COVID-19 pandemic on March 11 and called for accelerated development of diagnostic procedures, vaccines and drugs to combat this new disease. In addition to the novel coronavirus infection, influenza viral infections have been a persistent threat to global public health for many years. In the United States only, as estimated by the Centers for Disease Control and Prevention (CDC), during the 2019 winter season-2020, there were at least 39 million cases, 400,000 hospitalizations, and 24,000 influenza deaths (https://www.cdc.gov/flu/weekly/index.htm). Considering that the current circulation of SARS-CoV-2 is accompanied by other influenza viral infections, the study of available and effective drugs for the treatment of both diseases is of great interest.

Indeed, in the early stages of the COVID-19 outbreak, some influenza drugs (eg, oseltamivir) were used to treat patients with COVID-19[12]. We previously reported that favipiravir (T705), an anti-influenza drug approved in Japan and China, showed some efficacy against SARS-CoV-2 in in vitro studies [3]. In addition, umifenovir, an anti-influenza drug with the main antiviral component hemagglutinin (HA), is being used in a clinical trial against COVID-19 (ChiCTR2000029573) and has recently been added to the COVID-19 Diagnosis and Treatment Guidelines (sixth and seventh editions) in China. A recent retrospective study showed that treatment with umifenovir increased the number of recoveries and reduced mortality rates in patients with COVID-19[4]. However, to the best of our knowledge, no systematic analysis of the efficacy of influenza drugs against SARS-CoV-2 has been performed.

In this study, we evaluated the efficacy of six currently available and licensed influenza drugs in the treatment of SARS-CoV-2. These drugs include umifenovir, baloxavir, laninamivir, oseltamivir, peramivir, and zanamivir [5, 6]. M2 inhibitors (amantadine and rimantadine) are not included in this study as they were not recommended by the WHO for the treatment of influenza due to drug resistance. In a first step, the cytotoxicity of compounds in the African green monkey kidney cell line Vero E6 (ATCC-1586) was measured using the standard kit-8 (CCK8) cell scoring method. Cells were then infected with SARS-CoV-2 with a MOI of 0.05 in the presence of test compound or dimethyl sulfoxide (DMSO) control. Dose-response lines were constructed by quantifying the copy number of viral RNA in the infected cell supernatant 48 hours after infection (p. i.). As shown in Figure 1A, umifenovir effectively inhibited viral infection in in vitro studies; The 50% maximum effective concentration (EC 50 ) and 50% cytotoxic concentration (CC 50 ) of umifenovir were 4.11 (3.55-4.73) and 31.79(29.89-33.81) µm, respectively, and the selectivity index (SI = CC50/EC50) is 7.73. Baloxavir partially inhibited SARS-CoV-2 infection (~29%) at a high concentration of 50 μM (Figure 1A). In contrast, laninamivir, oseltamivir, peramivir, and zanamivir did not inhibit SARS-CoV-2 even at the highest drug concentrations (Figure 1A). The antiviral activity of the compounds was also assessed by observing cytopathic effects (CPE) and immunofluorescent staining of infected cells. As shown in Supplementary Figure S1, 48 hours post-infection, only in umifenovir-treated cells but not the other five drugs, viral genome expression and observed cytopathic effect (CPE) to SARS-CoV-2 were significantly reduced. It should be noted that we have also tested some human lung cell lines, such as MRC-5 human embryonic lung fibroblasts and the Calu-3 lung cancer cell line, however, they were not very efficient for SARS-CoV-2 replication and therefore were not used for this. research.

In addition to the influenza virus, umifenovir has been reported to inhibit a wide range of viruses by interfering with several steps in the viral replication cycle [7]. The effect of umifenovir on the stage of SARS-CoV-2 replication was investigated by conducting a preliminary experiment with time-based checkpoints with a frequency of infection (MOI) of 0. 05. Umifenovir was incubated with cells at the beginning of virus entry (Entry), post-entry (Post-entry) and during the entire infection process (Full-time), and the result of the virus was quantified by qRT-PCR. The data obtained showed that umifenovir effectively blocks the virus both at the stage of penetration and immediately after penetration. It has a strong effect on the rate of virus entry (~75% inhibition) with less effect on post-entry events (~55% inhibition) (Figure 1B). In addition, Western blotting (Figure 1C) and immunofluorescence microscopy (Supplementary Figure S2) confirmed that viral genome expression was drastically down-regulated throughout the full-time period (13% of the DMSO group, Figure 1C), and showed a more significant inhibitory effect at the stage of penetration (41%) than at the stage after the beginning of penetration (61%).

Next, a detailed study was carried out on how umifenovir blocks the entry of SARS-CoV-2 into cells. The virus (MOI = 0.05) was allowed to bind to Vero E6 cells at 4°C for 1 hour in the presence of umifenovir (10 μM) or DMSO control. Virus particles bound to the cell (bound virions) and in the supernatant (unbound virions) were analyzed by qRT-PCR. The results showed that treatment with umifenovir resulted in a significant decrease in binding efficiency (67%) compared with the control group (P < 0.05) (Fig. 1d). Accordingly, the proportion of unbound virions increased significantly to 156% of the control group after treatment with umifenovir (P < 0.001) (Figure 1d).

Next, the intracellular movement of the virus was analyzed. As we recently reported, inside infected cells, SARS-CoV-2 underwent vesicle transport, which was first carried out by early endosomes (EEs) and then further transported to endolysosomes (ELs) [8]. Co-localization of virions with endosomes (EEs) or endolysosomes (ELs) was visualized by immunofluorescence microscopy and analyzed statistically (n > 150 cells). As shown in Figure 1e and Supplementary Figure S3, at each time point monitored, there was no significant difference in the number of virions co-localized with EEs when comparing DMSO and umifenovir groups, although as infection progressed (30, 60 and 90 min p. i.), co-localization levels were significantly reduced in both DMSO (24.0%, 5.1% and 3.2%) and umifenovir groups (21.4%, 4.1% and 2.8%), indicating that some virions have already been transported from EEs to the next stage of vesicle transport. In contrast, at 60 min p.i. in the umifenovir group, a slightly higher percentage of virions were transported to ELs (22.4%) than in the DMSO group (18.3%) (P < 0.05) (Figure 1e, f). At 90 min after the start of treatment, significantly fewer virions (~13.5%) were found in the DMSO group, while significantly more virions remained in the umifenovir group (~23.6%), indicating that the drug captured the virus in the DMSO group (P < 0.001) (Fig. 1e, f). Taken together, these results indicated that umifenovir not only interfered with viral attachment, but also with the release of SARS-CoV-2 from intracellular vesicles (ELs).

Among the drugs tested, laninamivir, oseltamivir, peramivir, and zanamivir are the neuraminidase (NA) inhibitors most widely prescribed for the prevention and treatment of influenza. Despite the fact that SARS-CoV-2 does not contain NA analogues, NA inhibitors such as oseltamivir are nevertheless used clinically in the treatment of patients with COVID-19 [1, 2]. Our data indicate that these NA inhibitors were not active against SARS-CoV-2 (Figure 1A), consistent with the conclusion that oseltamivir and zanamivir were ineffective in inhibiting SARS-CoV-2. Baloxavir marboxil is a novel anti-influenza drug that selectively inhibits the endonuclease activity of the viral polymerase responsible for capturing droplet-coated primers from the host mRNA to initiate transcription of the viral mRNA. However, this capillary capture mechanism of endonuclease is not shared by coronaviruses, which encode their own enzymes for the formation of 5′-mRNA structures [10]. This may explain why baloxavir failed to block SARS-CoV-2 infection (Fig. 1a). During this study, Choi et al. also showed that oseltamivir and baloxavirne were able to inhibit SARS-CoV-2 in in vitro studies [11].

Umifenovir, an indole derivative, has been licensed in Russia and China as an antiviral for influenza for several decades. It is a broad-spectrum drug against a wide range of enveloped and non-enveloped viruses. Umifenovir interacts predominantly with aromatic amino acids, and affects several stages of the viral life cycle, either directly affecting viral proteins or virus-associated host factors [7]. For example, in the influenza virus, crystal structures have shown that umifenovir is introduced into the hydrophobic fusion pocket of the HA subunit, thereby preventing the low-temperature conformational change of HA and blocking the fusion process [12]. In hepatitis C virus, umifenovir disrupted both viral attachment and intracellular movement of vesicles [13]. In addition, we found that umifenovir plays a role in the interference between SARS-CoV-2 binding (Fig. 1d) and intracellular vesicle turnover (Fig. 1e, f). Umifenovir can also bind to lipid membranes and change the configuration of cytoplasmic or endosome membranes, which are critical for virus attachment and fusion [7]. Whether umifenovir infects virus and/or cells could be further investigated using a published method [14].

Thus, of the six influenza drugs, only umifenovir effectively suppressed SARS-CoV-2. Functionally, it blocks the spread of the virus, preventing it from attaching and spreading through the ELs. Although the SI of umifenovir is relatively low (SI = 7.73), as with any repurposed drug, its pharmacokinetic profile, including maximum concentration (Cmax), is more important in predicting efficacy. It is believed that if the maximum concentration of Cmax reaches EC 90 , the drug is likely to be effective; while if the Cmax reaches the EC 50 , the drug may be effective in in vivo studies. In humans, a single oral administration of 800 mg umifenovir results in a Cmax of ~4.1 µm [15], and this dosage is effective and safe against various influenza viruses with EC 50 values ranging from 2.5 to 20 µm [7, 16]. Umifenovir also exhibited anti-inflammatory activity, which may increase its efficacy in in vivo studies [16].

Given that the EC 50 (4.11 µm) of umifenovir against SARS-CoV-2 is comparable to or even lower than that of influenza viruses, we therefore suggest that umifenovir is potentially effective in the treatment of patients with COVID-19.

Oral DMSO Treatment for Lipoid Proteinosis: Efficacy, Side Effects, and Long-Term Outcomes

Understanding Lipoid Proteinosis: A Rare Genetic Disorder

Key Features of Lipoid Proteinosis

The Potential of DMSO as a Treatment Option

Proposed Mechanisms of Action for DMSO in Lipoid Proteinosis

Long-Term Oral DMSO Treatment: A Clinical Study

Key Findings from the Study

Contrasting Results: Previous Case Reports on DMSO Treatment

Factors Influencing Treatment Outcomes

Safety Profile and Side Effects of Oral DMSO Treatment

Potential Side Effects of Oral DMSO

Alternative Treatment Approaches for Lipoid Proteinosis

Potential Treatment Options for Lipoid Proteinosis

Implications for Future Research and Clinical Practice

Future Directions in Lipoid Proteinosis Research

[Oral DMSO therapy in 3 patients with lipoidproteinosis. Results of long-term therapy]

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Efficacy of some antiviral agents against COVID-19: in vitro studies

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