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

12.07.202317.07.2023 by alexxlab

What are the health benefits of oral DMSO treatment for lipoid proteinosis. How effective is DMSO as a long-term therapy for this rare disorder. What side effects and precautions should patients be aware of when using oral DMSO.

Содержание

Understanding Lipoid Proteinosis: A Rare Genetic Disorder

Lipoid proteinosis, also known as Urbach-Wiethe disease, is an uncommon autosomal recessive disorder characterized by the deposition of hyaline material in the skin, mucous membranes, and internal organs. This rare condition affects both males and females equally and typically manifests in early childhood.

What are the main clinical features of lipoid proteinosis? The hallmark symptoms include:

Hoarseness of voice, often present from infancy
Thickening of the skin and mucous membranes
Beaded papules along the eyelid margins
Waxy yellow plaques on the skin
Neurological symptoms in some cases

The chronic and progressive nature of lipoid proteinosis presents significant challenges for patients and healthcare providers alike. While the condition is generally benign, it can significantly impact quality of life due to its effects on appearance and vocal function.

The Search for Effective Treatments: Exploring DMSO Therapy

Given the rarity of lipoid proteinosis, there is no universally accepted standard treatment. However, researchers and clinicians have explored various therapeutic options, including the use of dimethyl sulfoxide (DMSO).

What is DMSO and why has it been considered for lipoid proteinosis? DMSO is an organosulfur compound with anti-inflammatory and antioxidant properties. Its potential to penetrate biological membranes and interact with proteins has made it an intriguing candidate for treating disorders involving abnormal protein deposition.

Previous Reports on DMSO Treatment

Prior to the study discussed in this article, there had been limited reports on the use of DMSO for lipoid proteinosis. How did these earlier cases influence the decision to conduct a long-term study? Two notable instances had shown promising results:

A case report by Wong and Lin (1988) described a “remarkable response” to oral DMSO in a patient with lipoid proteinosis.
Another single case had demonstrated potential benefits from experimental oral DMSO use.

These isolated reports provided the impetus for a more comprehensive investigation into the long-term efficacy of oral DMSO treatment for lipoid proteinosis.

Long-Term DMSO Therapy: A Clinical Study

The study conducted by Ozkaya-Bayazit et al. aimed to assess the effectiveness of long-term oral DMSO treatment in patients with lipoid proteinosis. This research represents a significant contribution to the limited body of evidence on therapeutic approaches for this rare disorder.

Study Design and Participants

How was the study structured? The research involved three patients with confirmed diagnoses of lipoid proteinosis:

Two sisters
One unrelated male patient

What was the treatment protocol? The patients received oral DMSO at a dosage of 60 mg/kg/day. This regimen was maintained for an average duration of 3 years, allowing for a comprehensive evaluation of both short-term and long-term effects.

Assessing the Efficacy of Oral DMSO Treatment

The primary objective of the study was to determine whether long-term DMSO therapy could produce beneficial effects for patients with lipoid proteinosis. What specific outcomes were the researchers looking to improve?

Skin manifestations
Mucosal lesions
Hoarseness of voice

After an average treatment period of 3 years, what were the results of the DMSO therapy? Unfortunately, the study found no significant improvements in any of the targeted symptoms. The lack of positive outcomes led to the discontinuation of DMSO treatment for all three patients.

Unexpected Disease Progression

In addition to the absence of beneficial effects, did the study reveal any concerning developments? One patient experienced a worsening of symptoms during the course of DMSO treatment:

Increased hoarseness
Onset of dyspnea (difficulty breathing)
Progression of vocal cord infiltrates, necessitating surgical intervention

This unexpected deterioration raises important questions about the potential impact of long-term DMSO use in patients with lipoid proteinosis.

Implications for DMSO Treatment in Lipoid Proteinosis

The findings of this study have significant implications for the management of lipoid proteinosis and the use of DMSO as a potential therapy. How do these results compare to previous reports?

While earlier case reports had suggested promising outcomes with DMSO treatment, this longer-term study failed to replicate those positive results. The discrepancy between these findings highlights the importance of conducting more extensive clinical trials before drawing definitive conclusions about treatment efficacy.

Limitations and Considerations

When interpreting the results of this study, what factors should be taken into account?

Small sample size (only three patients)
Potential variability in disease severity and progression among individuals
Possible differences in DMSO formulation or administration compared to previous reports
Limited duration of follow-up beyond the treatment period

These limitations underscore the need for larger, more comprehensive studies to fully evaluate the potential of DMSO and other therapies for lipoid proteinosis.

Side Effects and Safety Considerations of Oral DMSO

While the study primarily focused on efficacy, it’s crucial to consider the potential side effects and safety profile of long-term oral DMSO use. What adverse effects should patients and healthcare providers be aware of?

Gastrointestinal disturbances
Skin irritation
Halitosis (bad breath) with a characteristic garlic-like odor
Potential for drug interactions

Although the study did not report significant safety concerns, the lack of benefit coupled with these potential side effects suggests that the risk-benefit ratio of oral DMSO for lipoid proteinosis may be unfavorable.

Precautions and Monitoring

For patients considering or currently using DMSO, what precautions should be taken?

Regular medical follow-ups to assess disease progression and potential side effects
Liver and kidney function tests to monitor for any systemic effects
Careful consideration of concurrent medications to avoid interactions
Immediate reporting of any new or worsening symptoms to healthcare providers

These precautions are essential to ensure patient safety and to detect any adverse effects early in the course of treatment.

Alternative Treatment Approaches for Lipoid Proteinosis

Given the disappointing results of long-term DMSO therapy, what other treatment options are available for patients with lipoid proteinosis? While there is no cure, several approaches have been explored:

Retinoids: Drugs like acitretin have shown some promise in managing skin and mucosal symptoms
Laser therapy: Used to treat specific skin lesions
Speech therapy: To help manage voice-related symptoms
Surgical interventions: For severe cases, particularly those affecting the airway

Each of these approaches targets specific aspects of the disease, and treatment plans are often individualized based on the patient’s presenting symptoms and disease severity.

Emerging Research and Future Directions

What new avenues are researchers exploring for the treatment of lipoid proteinosis? Current areas of interest include:

Gene therapy: Targeting the underlying genetic defect
Novel pharmacological agents: Drugs that may inhibit or reverse the abnormal protein deposition
Combination therapies: Exploring synergistic effects of multiple treatment modalities

These emerging approaches offer hope for more effective management of lipoid proteinosis in the future, although significant research is still needed to validate their efficacy and safety.

The Importance of Comprehensive Care and Support

While the search for effective treatments continues, how can healthcare providers best support patients with lipoid proteinosis? A multidisciplinary approach is crucial, encompassing:

Regular dermatological and ENT evaluations
Psychological support to address the emotional impact of the disease
Genetic counseling for affected families
Patient education and support groups

By addressing both the physical and psychological aspects of lipoid proteinosis, healthcare teams can help improve overall quality of life for affected individuals.

The Role of Patient Advocacy and Research Funding

How can the broader community contribute to advancing care for lipoid proteinosis? Key areas of focus include:

Raising awareness about this rare disorder
Advocating for increased research funding
Supporting patient organizations and registries
Encouraging participation in clinical trials and research studies

These efforts are essential for driving progress in understanding and treating lipoid proteinosis, ultimately leading to improved outcomes for patients.

In conclusion, while the long-term study of oral DMSO treatment for lipoid proteinosis did not yield the hoped-for benefits, it has provided valuable insights into the challenges of managing this rare disorder. As research continues, a multifaceted approach combining symptomatic treatment, supportive care, and ongoing investigation into novel therapies offers the best hope for patients living with lipoid proteinosis.

[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.

Current Version

May 16, 2023

Written By

Jessica DiGiacinto, Joe Bowman

Edited By

Jessica DiGiacinto

Copy Edited By

Delores Smith-Johnson

Feb 1, 2022

Medically Reviewed By

Angelica Balingit, MD

VIEW ALL HISTORY

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

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 Wang2020, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease COVID-19 rapidly spread to more than 200 countries, infected more than 1. 5 million people, and caused 92,798 deaths (data as of April 10, 2020). of the year). 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. However, the current dose of umifenovir (200 mg, 3 times/day) recommended by Chinese guidelines may not be sufficient to achieve ideal therapeutic efficacy to inhibit SARS-CoV-2 infection and should be increased. This assumption needs to be confirmed by further clinical trials.

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Oil industrial C.N.R.G. I40A (20 l.)

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General purpose industrial oil obtained by selective refining without additives. Designed for lubrication of the most common components and mechanisms of equipment in various industries. It is used as a working fluid in hydraulic systems of industrial equipment, road construction machines, automatic lines, presses, for lubrication of light and medium-loaded gears, rolling and sliding guides of machine tools, where special oils are not required.

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Industrial oil Condor Oil I8A (180 kg, 205 l.)

34`097.50 ₽

Used in various industries for lubrication of the most widely used light-loaded, high-speed units and mechanisms, lubrication of fibers and in the production of oils, lubricants and rubbers. In addition, I-8A is used for greasing leather, making pastes, mastics, window putty, etc.

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Industrial oil Devon I12A (180 kg, 216.

5 l.)

39`750.25 ₽

I-12A industrial oils are oils made from a mineral base, used in machines and mechanisms of industrial equipment, the operating conditions of which do not
impose special requirements on the antioxidant and anticorrosion properties of oils, as well as hydraulic fluids and base oils.

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Transmission oil ADDINOL ATF DCT (1 l.)

1`958.75 ₽

The latest development of ADDINOL ATF DCT is a synthetic automatic transmission oil specially developed for use in passenger cars with dual clutch transmissions (DSG, DCT).

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Transmission oil ADDINOL ATF DCT (4 l.)

7`240.00 ₽

The latest development of ADDINOL ATF DCT is a synthetic automatic transmission oil specially developed for use in passenger cars with dual clutch transmissions (DSG, DCT).

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Transmission oil ADDINOL ATF XN 2 Dexron II (1 l.)

1`345.00 ₽

Automatic transmission fluid ADDINOL Automatikgetriebefluid ATF XN 2 is made on the basis of high-quality fractions of refined mineral oils with the addition of well-proven complexes of active substances.

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

Understanding Lipoid Proteinosis: A Rare Genetic Disorder

The Search for Effective Treatments: Exploring DMSO Therapy

Previous Reports on DMSO Treatment

Long-Term DMSO Therapy: A Clinical Study

Study Design and Participants

Assessing the Efficacy of Oral DMSO Treatment

Unexpected Disease Progression

Implications for DMSO Treatment in Lipoid Proteinosis

Limitations and Considerations

Side Effects and Safety Considerations of Oral DMSO

Precautions and Monitoring

Alternative Treatment Approaches for Lipoid Proteinosis

Emerging Research and Future Directions

The Importance of Comprehensive Care and Support

The Role of Patient Advocacy and Research Funding

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

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Transmission oil ADDINOL ATF XN 2 Dexron II (1 l.)

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