What is DMSO and how is it used medically. What are the potential benefits and risks of DMSO treatment. How should DMSO be properly administered and what precautions should be taken. What does current research say about DMSO effectiveness for various conditions.

Understanding DMSO: Origins and Medical Applications

Dimethyl sulfoxide (DMSO) is a byproduct of paper production derived from wood pulp. Initially used as an industrial solvent in the mid-1800s, DMSO’s potential medical applications began to be explored around the mid-20th century. Its ability to penetrate the skin and potentially enhance the absorption of other substances has made it an intriguing compound in medical research.

The Food and Drug Administration (FDA) has approved DMSO as a prescription medication for treating symptoms of painful bladder syndrome. Under medical supervision, it’s also used to address several other conditions, including shingles. However, its use extends beyond these approved applications, with many people turning to DMSO for various health concerns.

Availability and Forms of DMSO

DMSO is available in several forms:

• Prescription medication (FDA-approved for specific conditions)
• Over-the-counter gels and creams
• Oral supplements (though safety is uncertain)

It’s important to note that while DMSO can be purchased without a prescription in health food stores, by mail order, and online, its use should be approached with caution due to potential risks and lack of regulation in some forms.

Common Uses and Claimed Benefits of DMSO

DMSO has been used or studied for a variety of conditions, though scientific evidence supporting many of these uses is limited. Some common applications include:

• Pain relief for osteoarthritis
• Wound healing
• Burns treatment
• Alternative cancer therapy (though not supported by scientific evidence)
• Various skin conditions
• Musculoskeletal disorders
• Inflammatory conditions

Is DMSO effective for treating osteoarthritis pain? A recent analysis of studies found that DMSO was not significantly more effective than placebo in relieving joint pain associated with osteoarthritis. This highlights the importance of approaching DMSO use with caution and skepticism, especially for conditions where scientific evidence is lacking.

Potential Risks and Side Effects of DMSO Use

While DMSO is sometimes touted as a miracle solution, it’s crucial to understand the potential risks and side effects associated with its use. These can range from mild discomfort to serious health issues.

Common Side Effects

When applied topically, DMSO may cause:

• Skin irritation
• Strong garlic-like odor
• Stomach upset

More Serious Risks

More severe side effects and risks include:

• Allergic reactions
• Headaches
• Dizziness
• Drowsiness
• Nausea and vomiting (when taken orally)
• Potential for deadly reactions at high concentrations

Can DMSO interact with other medications? Yes, DMSO can increase the effect of certain medicines, potentially leading to serious health issues. It’s particularly important to be cautious with blood thinners, steroids, and sedatives when using DMSO.

DMSO Dosage and Administration

Determining the proper dosage of DMSO can be challenging due to limited scientific guidelines. For osteoarthritis treatment, a typical concentration is 25%, applied three to four times daily. However, over-the-counter DMSO products can range from 10% to 90% concentration.

How should DMSO be applied safely? When using DMSO topically:

1. Ensure the application area is clean and dry
2. Apply a thin layer of DMSO to the affected area
3. Wash hands thoroughly before and after application
4. Monitor for any adverse reactions

It’s crucial to remember that DMSO can enhance the absorption of other substances on the skin, so proper cleaning before application is essential.

Special Precautions and Contraindications

Certain groups should exercise extra caution or avoid DMSO altogether:

• Pregnant and breastfeeding women (due to unknown effects on fetus or infant)
• Individuals with liver or kidney disease
• Those with a history of asthma or allergies

Are there specific medical conditions that contraindicate DMSO use? Yes, individuals with the following conditions should consult a healthcare provider before using DMSO:

• Diabetes
• Heart conditions
• Bleeding disorders
• Glaucoma

DMSO in Cancer Treatment: Separating Fact from Fiction

DMSO has been promoted by some as an alternative cancer treatment. However, it’s crucial to understand the scientific perspective on this claim.

Does scientific evidence support DMSO as a cancer treatment? According to the American Cancer Society, there is no evidence to support the use of DMSO in treating cancer. In fact, relying on DMSO as a cancer treatment could lead to dangerous delays in receiving proper and effective treatment.

While DMSO may have some properties that make it interesting to researchers, its role in cancer treatment remains unproven. Patients considering DMSO for cancer should always consult with their oncologist and primary care physician before pursuing any alternative treatments.

Regulatory Status and Quality Concerns

The regulatory status of DMSO varies depending on its intended use and how it’s marketed. This can lead to significant differences in quality and safety between products.

Is all DMSO of the same quality? No, the quality of DMSO can vary significantly. Some DMSO products on the market may be industrial grade, containing impurities that could be harmful when absorbed through the skin. This underscores the importance of sourcing DMSO from reputable suppliers and preferably under medical supervision.

Unlike prescription drugs, supplements containing DMSO are not strictly regulated by the FDA. This means that manufacturers are not required to prove the safety or efficacy of their products before selling them. Consumers should be aware of this lack of oversight when considering DMSO supplements.

Current Research and Future Perspectives on DMSO

While DMSO has been studied for decades, much about its effects and potential uses remains unknown. Ongoing research continues to explore its properties and possible applications.

What areas of DMSO research show promise? Some areas of current interest include:

• DMSO’s potential as a delivery mechanism for other drugs
• Its use in cryopreservation of biological samples
• Possible neuroprotective effects in certain conditions

However, it’s important to note that much of this research is still in early stages, and more rigorous studies are needed to establish DMSO’s efficacy and safety in these areas.

As research progresses, our understanding of DMSO’s benefits and risks may evolve. For now, its use outside of FDA-approved applications should be approached with caution and under medical supervision.

DMSO: Uses and Risks

DMSO, or dimethyl sulfoxide, is a by-product of paper making. It comes from a substance found in wood.

DMSO has been used as an industrial solvent since the mid-1800s. From about the mid-20th century, researchers have explored its use as an anti-inflammatory agent.

The FDA has approved DMSO as a prescription medication for treating symptoms of painful bladder syndrome. It’s also used under medical supervision to treat several other conditions, including shingles.

DMSO is easily absorbed by the skin. It’s sometimes used to increase the body’s absorption of other medications.

DMSO is available without a prescription most often in gel or cream form. It can be purchased in health food stores, by mail order, and on the Internet.

While it can sometimes be found as an oral supplement, its safety is unclear. DMSO is primarily used by applying it to the skin.

Why Do People Use DMSO?

DMSO has been used to try to relieve the pain of osteoarthritis. It has also been promoted as an “alternative” cancer treatment.

People have used it to try to treat wounds, burns, and other injuries. People have also used it to try to treat such conditions as:

Other than its use as a prescription medicine, there is little or no scientific evidence to support other claims made about DMSO’s effectiveness.

The American Cancer Society says there is no evidence to support the use of DMSO to treat cancer. Using it that way could cause serious delays in getting proper and effective treatment.

A recent analysis of studies on the use of DMSO to relieve osteoarthritis pain found that it was not significantly more effective than placebo in relieving joint pain.

There are no studies that provide guidelines for determining the proper dose of DMSO. The gel used to treat osteoarthritis typically has a concentration of 25%. It is applied three or four times a day. But DMSO sold without a prescription can range from 10% concentration to 90%.

What Are the Risks of Using DMSO?

Some DMSO on the market may actually be industrial grade. Industrial grade DMSO may contain a number of impurities that can easily be absorbed into the skin with potentially serious health effects.

The most frequent side effects from using DMSO on the skin include:

• Stomach upset
• Skin irritation
• Strong odor of garlic

More serious side effects include:

DMSO can also cause a deadly reaction when used in high concentrations.

Using DMSO by mouth can cause:

DMSO can increase the effect of some medicines, which can lead to serious health issues. Examples of such medicines include:

The biggest concern of DMSO as a solvent is that when it gets on the skin it will cause anything on the skin to be absorbed. So be sure to wash your hands and skin well before using.

Pregnant women and women who are breastfeeding should not use DMSO, since little is known about its possible effects on the fetus or infant.

You should also not use DMSO without talking to your doctor if you have:

Always keep in mind that supplements are not regulated by the FDA the same was as drugs are. The manufacturer does not have to prove that a supplement is safe or effective before selling.

Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews

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Merlini G. Treatment of primary amyloidosis. Semin Hematol 1995;32:60-79.

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Rand-Luby L, Pommier RF, Williams ST, et al. Improved outcome of surgical flaps treated with topical dimethylsulfoxide. Ann Surg 1996;224:583-9. View abstract.

Rosenstein ED. Topical agents in the treatment of rheumatic disorders. Rheum Dis Clin North Am 1999;25:899-918. View abstract.

Rowley SD. Hematopoietic stem cell processing and cryopreservation. J Clin Apheresis 1992;7:132-4. View abstract.

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Salim AS. The relationship between Helicobacter pylori and oxygen-derived free radicals in the mechanism of duodenal ulceration. Intern Med 1993;32:359-64. View abstract.

Sant GR, LaRock DR. Standard intravesical therapies for interstial cystitis. Urol Clin North Am 1994;21:73-83. View abstract.

Sant GR. Intravesical 50% dimethyl sulfoxide (Rimso-50) in treatment of interstitial cystitis. Urology 1987;29:17-21.

Shirley SW, Stewart BH, Mirelman S. Dimethyl sulfoxide in treatment of inflammatory genitourinary disorders. Urology 1978;11:215-20. View abstract.

Simon LS, Grierson LM, Naseer Z, et al. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain 2009;143:238-45. View abstract.

Spremulli EN, Dexter DL. Polar solvents: a novel class of antineoplastic agents. J Clin Oncol 1984;2:227-41. View abstract.

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Thiers BH. Unusual treatments for herpesvirus infections II, herpes zoster. J Am Acad Dermatol 1983;8:433-6.

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Torres MA, Furst DE. Treatment of generalized systemic sclerosis. Rheum Dis Clin North Am 1990;16:217-41. View abstract.

Trice JM, Pinals RS. Dimethyl sulfoxide: a review of its use in the rheumatic disorders. Semin Arthritis Rheum 1985;15:45-60.

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Williams HJ, Furst DE, Dahl SL, et al. Double-blind, multicenter controlled trial comparing topical dimethyl sulfoxide and normal saline for treatment of hand ulcers in patients with systemic sclerosis. Arthritis Rheum 1985;28:308-14. View abstract.

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Health Benefits, Side Effects, Uses, Dose & Precautions

Abdelkefi, A., Lakhal, A., Moojat, N., Hamed, L. B., Fekih, J., Ladeb, S., Torjman, L., and Othman, T. B. Severe neurotoxicity associated with dimethyl sulphoxide following PBSCT. Bone Marrow Transplant. 2009;44(5):323-324. View abstract.

Akkok, C. A., Holte, M. R., Tangen, J. M., Ostenstad, B., and Bruserud, O. Hematopoietic engraftment of dimethyl sulfoxide-depleted autologous peripheral blood progenitor cells. Transfusion 2009;49(2):354-361. View abstract.

Aliaga, A., Armijo, M., Camacho, F., Castro, A., Cruces, M., Diaz, J. L., Fernandez, J. M., Iglesias, L., Ledo, A., Mascaro, J. M., and . [A topical solution of 40% idoxuridine in dimethyl sulfoxide compared to oral acyclovir in the treatment of herpes zoster. A double-blind multicenter clinical trial]. Med.Clin (Barc.) 2-22-1992;98(7):245-249. View abstract.

Amato, R., Ho, D., Schmidt, S., Krakoff, I. H., and Raber, M. Phase I trial of a 72-h continuous-infusion schedule of fazarabine. Cancer Chemother.Pharmacol. 1992;30(4):321-324. View abstract.

Amorim, C. A., David, A., Van, Langendonckt A., Dolmans, M. M., and Donnez, J. Vitrification of human ovarian tissue: effect of different solutions and procedures. Fertil.Steril. 3-1-2011;95(3):1094-1097. View abstract.

Antherieu, S., Chesne, C., Li, R., Camus, S., Lahoz, A., Picazo, L., Turpeinen, M., Tolonen, A., Uusitalo, J., Guguen-Guillouzo, C., and Guillouzo, A. Stable expression, activity, and inducibility of cytochromes P450 in differentiated HepaRG cells. Drug Metab Dispos. 2010;38(3):516-525. View abstract.

Ashkenazi, A. and Marks, R. S. Luminol-dependent chemiluminescence of human phagocyte cell lines: comparison between DMSO differentiated PLB 985 and HL 60 cells. Luminescence. 2009;24(3):171-177. View abstract.

Atas, E., Kesik, V., Sari, E., Kismet, E., Yaris, N., and Koseoglu, V. Temporary vision loss because of dimethyl sulfoxide in autologous stem cell transplantation. Pediatr.Transplant. 2012;16(3):302-303. View abstract.

Becker, D. P., Young, H. F., Nulsen, F. E., and Jane, J. A. Physiological effects of dimethyl sulfoxide on peripheral nerves: possible role in pain relief. Exp Neurol. 1969;24(2):272-276. View abstract.

Bertelli, G., Dini, D., Forno, G., Gozza, A., Venturini, M., Ballella, G., and Rosso, R. Dimethylsulphoxide and cooling after extravasation of antitumour agents. Lancet 4-24-1993;341(8852):1098-1099. View abstract.

Bertelli, G., Gozza, A., Forno, G. B., Vidili, M. G., Silvestro, S., Venturini, M., Del Mastro, L., Garrone, O. , Rosso, R., and Dini, D. Topical dimethylsulfoxide for the prevention of soft tissue injury after extravasation of vesicant cytotoxic drugs: a prospective clinical study. J.Clin Oncol. 1995;13(11):2851-2855. View abstract.

Binder, I. and van, Ophoven A. [The complexity of chronic pelvic pain exemplified by the condition currently called interstitial cystitis. Part 1: Background and basic principles]. Aktuelle Urol. 2008;39(3):205-214. View abstract.

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Bojanic, I., Cepulic, B. G., Mazic, S., Batinic, D., Nemet, D., and Labar, B. Toxicity related to autologous peripheral blood haematopoietic progenitor cell infusion is associated with number of granulocytes in graft, gender and diagnosis of multiple myeloma. Vox Sang. 2008;95(1):70-75. View abstract.

Bonnetblanc, J. M., Bordessoule, D., Fayol, J., and Amici, J. M. [Treatment of accidental extravasation of antitumor agents with dimethylsulfoxide and alpha-tocopherol]. Ann Dermatol Venereol. 1996;123(10):640-643. View abstract.

Brien, S., Prescott, P., Bashir, N., Lewith, H., and Lewith, G. Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis. Osteoarthritis.Cartilage. 2008;16(11):1277-1288. View abstract.

Brobyn, R. D. The human toxicology of dimethyl sulfoxide. Ann.N.Y.Acad.Sci. 1-27-1975;243:497-506. View abstract.

Bulum, T., Prkacin, I., Cavric, G., Sobocan, N., Skurla, B., Duvnjak, L., and Bulimbasic, S. [Secondary (AA) amyloidosis in Crohn’s disease]. Acta Med Croatica 2011;65(3):271-278. View abstract.

Caselli, D., Tintori, V., Messeri, A., Frenos, S., Bambi, F., and Arico, M. Respiratory depression and somnolence in children receiving dimethylsulfoxide and morphine during hematopoietic stem cells transplantation. Haematologica 2009;94(1):152-153. View abstract.

Chang, B. L., Chang, A., Strasser, J., Reinhardt, J. F., and Guarino, M. An unusual presentation of invasive squamous cell carcinoma of the upper extremities in a patient with a history of severe electrical burns and chronic thermal and chemical exposure. Del.Med J 2011;83(5):137-141. View abstract.

Chen-Plotkin, A. S., Vossel, K. A., Samuels, M. A., and Chen, M. H. Encephalopathy, stroke, and myocardial infarction with DMSO use in stem cell transplantation. Neurology 3-13-2007;68(11):859-861. View abstract.

Chinnadurai, M., Chidambaram, S., Ganesan, V., Baraneedharan, U., Sundaram, L., Paul, S. F., and Venkatachalam, P. Bleomycin, neocarzinostatin and ionising radiation-induced bystander effects in normal diploid human lung fibroblasts, bone marrow mesenchymal stem cells, lung adenocarcinoma cells and peripheral blood lymphocytes. Int J Radiat.Biol. 2011;87(7):673-682. View abstract.

Dawson, T. E. and Jamison, J. Intravesical treatments for painful bladder syndrome/ interstitial cystitis. Cochrane.Database.Syst.Rev 2007;(4):CD006113. View abstract.

Demir, E., Kilciler, M., Bedir, S., Erten, K., and Ozgok, Y. Comparing two local anesthesia techniques for extracorporeal shock wave lithotripsy. Urology 2007;69(4):625-628. View abstract.

Duimel-Peeters, I. G., Halfens, J. G., Ambergen, A. W., Houwing, R. H., Berger, P. F., and Snoeckx, L. H. The effectiveness of massage with and without dimethyl sulfoxide in preventing pressure ulcers: a randomized, double-blind cross-over trial in patients prone to pressure ulcers. Int J Nurs Stud 2007;44(8):1285-1295. View abstract.

Fall, M., Oberpenning, F., and Peeker, R. Treatment of bladder pain syndrome/interstitial cystitis 2008: can we make evidence-based decisions? Eur Urol. 2008;54(1):65-75. View abstract.

Fitzhugh, C. D., Unno, H., Hathaway, V., Coles, W. A., Link, M. E., Weitzel, R. P., Zhao, X., Wright, E. C., Stroncek, D. F. , Kato, G. J., Hsieh, M. M., and Tisdale, J. F. Infusion of hemolyzed red blood cells within peripheral blood stem cell grafts in patients with and without sickle cell disease. Blood 6-14-2012;119(24):5671-5673. View abstract.

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Geertzen, J. H., de Bruijn, H., Bruijn-Kofman, A. T., and Arendzen, J. H. Reflex sympathetic dystrophy: early treatment and psychological aspects. Arch.Phys.Med.Rehabil. 1994;75(4):442-446. View abstract.

Gonzalez-Lopez, T. J., Sanchez-Guijo, F. M., Ortin, A., Crusoe, E., Cordoba, I., Corral, M., Vazquez, L., and Caballero, M. D. Ischemic stroke associated with the infusion of DMSO-cryopreserved auto-PBSCs. Bone Marrow Transplant. 2011;46(7):1035-1036. View abstract.

Goris, R. J., Dongen, L. M., and Winters, H. A. Are toxic oxygen radicals involved in the pathogenesis of reflex sympathetic dystrophy? Free Radic.Res Commun. 1987;3(1-5):13-18. View abstract.

Grum-Tokars, V., Ratia, K., Begaye, A., Baker, S. C., and Mesecar, A. D. Evaluating the 3C-like protease activity of SARS-Coronavirus: recommendations for standardized assays for drug discovery. Virus Res 2008;133(1):63-73. View abstract.

Hay, D. C., Zhao, D., Fletcher, J., Hewitt, Z. A., McLean, D., Urruticoechea-Uriguen, A., Black, J. R., Elcombe, C., Ross, J. A., Wolf, R., and Cui, W. Efficient differentiation of hepatocytes from human embryonic stem cells exhibiting markers recapitulating liver development in vivo. Stem Cells 2008;26(4):894-902. View abstract.

Ho, J. W., Ngan Hon, P. L., and Chim, W. O. Effects of oxymatrine from Ku Shen on cancer cells. Anticancer Agents Med Chem 2009;9(8):823-826. View abstract.

Hoang, B. X., Levine, S. A., Shaw, D. G., Tran, D. M., Tran, H. Q., Nguyen, P. M., Tran, H. D., Hoang, C., and Pham, P. T. Dimethyl sulfoxide as an excitatory modulator and its possible role in cancer pain management. Inflamm.Allergy Drug Targets. 2010;9(4):306-312. View abstract.

Hoang, B. X., Tran, D. M., Tran, H. Q., Nguyen, P. T., Pham, T. D., Dang, H. V., Ha, T. V., Tran, H. D., Hoang, C., Luong, K. N., and Shaw, D. G. Dimethyl sulfoxide and sodium bicarbonate in the treatment of refractory cancer pain. J Pain Palliat.Care Pharmacother. 2011;25(1):19-24. View abstract.

Iyer, G., Morris, M. J., Rathkopf, D., Slovin, S. F., Steers, M., Larson, S. M., Schwartz, L. H., Curley, T., DeLaCruz, A., Ye, Q., Heller, G., Egorin, M. J., Ivy, S. P., Rosen, N., Scher, H. I., and Solit, D. B. A phase I trial of docetaxel and pulse-dose 17-allylamino-17-demethoxygeldanamycin in adult patients with solid tumors. Cancer Chemother. Pharmacol 2012;69(4):1089-1097. View abstract.

Jacobs, SW and Wood, DC. Dimethyl sulfoxide (DMSO) – A status report. Clin Med 1971;78(21)

Juel-Jensen, B. E., MacCallum, F. O., Mackenzie, A. M., and Pike, M. C. Treatment of zoster with idoxuridine in dimethyl sulphoxide. Results of two double-blind controlled trials. Br Med J 12-26-1970;4(5738):776-780. View abstract.

Junior, A. M., Arrais, C. A., Saboya, R., Velasques, R. D., Junqueira, P. L., and Dulley, F. L. Neurotoxicity associated with dimethylsulfoxide-preserved hematopoietic progenitor cell infusion. Bone Marrow Transplant. 2008;41(1):95-96. View abstract.

Kaidbey, K. H. Therapy of resistant psoriasis with topical corticosteroids and dimethylsulfoxide. Dermatologica 1976;152(5):316-320. View abstract.

Kneer, W., Kuhnau, S., Bias, P., and Haag, R. F. [Dimethylsulfoxide (DMSO) gel in treatment of acute tendopathies. A multicenter, placebo-controlled, randomized study]. Fortschr.Med. 4-10-1994;112(10):142-146. View abstract.

Koenen NJ, Haag RF Bia P Rose P. Perkutane therapie bei aktivierter Gonarthrose. Munch Med Wochenschr 1996;138:534e8.

Kumar, S., Kumar, S., Ganesamoni, R., Mandal, A. K., Prasad, S., and Singh, S. K. Dimethyl sulfoxide with lignocaine versus eutectic mixture of local anesthetics: prospective randomized study to compare the efficacy of cutaneous anesthesia in shock wave lithotripsy. Urol.Res 2011;39(3):181-183. View abstract.

Lawrence, H. J. and Goodnight, S. H., Jr. Dimethyl sulfoxide and extravasation of anthracycline agents. Ann.Intern.Med. 1983;98(6):1025. View abstract.

Lawrence, H. J., Walsh, D., Zapotowski, K. A., Denham, A., Goodnight, S. H., and Gandara, D. R. Topical dimethylsulfoxide may prevent tissue damage from anthracycline extravasation. Cancer Chemother.Pharmacol 1989;23(5):316-318. View abstract.

Layman, D. L. and Jacob, S. W. The absorption, metabolism and excretion of dimethyl sulfoxide by rhesus monkeys. Life Sci 12-23-1985;37(25):2431-2437. View abstract.

Lishner, M., Lang, R., Kedar, I., and Ravid, M. Treatment of diabetic perforating ulcers (mal perforant) with local dimethylsulfoxide. J.Am.Geriatr.Soc. 1985;33(1):41-43. View abstract.

Lopez-Otero, A., Ruiz-Delgado, G. J., and Ruiz-Arguelles, G. J. A simplified method for stem cell autografting in multiple myeloma: a single institution experience. Bone Marrow Transplant. 2009;44(11):715-719. View abstract.

Lundy, B., Miller, J. C., Jackson, K., Senchina, D. S., Burke, L. M., Stear, S. J., and Castell, L. M. A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance – part 25. Br J Sports Med 2011;45(13):1077-1078. View abstract.

Lv, X., Li, Y., Jiang, C., and Wu, Z. The incidence of trigeminocardiac reflex in endovascular treatment of dural arteriovenous fistula with onyx. Interv.Neuroradiol. 2010;16(1):59-63. View abstract.

MacCallum, F. O. and Juel-Jensen, B. E. Herpes simplex virus skin infection in man treated with idoxuridine in dimethyl sulphoxide. Results of double-blind controlled trial. Br Med J 10-1-1966;2(5517):805-807. View abstract.

Marcacci, G., Corazzelli, G., Becchimanzi, C., Arcamone, M., Capobianco, G., Russo, F., Frigeri, F., and Pinto, A. DMSO-associated encephalopathy during autologous peripheral stem cell infusion: a predisposing role of preconditioning exposure to CNS-penetrating agents? Bone Marrow Transplant. 2009;44(2):133-135. View abstract.

Matsugasumi, T., Kamoi, K., Harikai, S., Inagaki, T., Kimura, Y., Hirahara, N., Sou, J., Nakagawa, S., Kawauchi, A., and Miki, T. [Localized amyloidosis of the urinary bladder: a case report]. Hinyokika Kiyo 2011;57(8):439-443. View abstract.

Matsumoto, J. Clinical trials of dimethyl sulfoxide in rheumatoid arthritis patients in Japan. Ann.N.Y.Acad.Sci. 3-15-1967;141(1):560-568. View abstract.

McCammon, K. A., Lentzner, A. N., Moriarty, R. P., and Schellhammer, P. F. Intravesical dimethyl sulfoxide for primary amyloidosis of the bladder. Urology 1998;52(6):1136-1138. View abstract.

Murugesan, C., Saravanan, S., Rajkumar, J., Prasad, J., Banakal, S., and Muralidhar, K. Severe pulmonary oedema following therapeutic embolization with Onyx for cerebral arteriovenous malformation. Neuroradiology 2008;50(5):439-442. View abstract.

Nielsen, E. H. and Johansen, T. Effects of dimethylsulfoxide (DMSO), nocodazole, and taxol on mast cell histamine secretion. Acta Pharmacol.Toxicol.(Copenh) 1986;59(3):214-219. View abstract.

Nonoguchi, H., Kohda, Y., Fukutomi, R., Nakayama, Y., Naruse, M., Kitamura, K., Inoue, T., Nakanishi, T., and Tomita, K. A case with acute renal failure and subsequent nephrotic syndrome. Ren Fail. 2009;31(2):162-166. View abstract.

O’Donnell, J. R., Burnett, A. K., Sheehan, T., Tansey, P., and McDonald, G. A. Safety of dimethylsulphoxide. Lancet 2-28-1981;1(8218):498. View abstract.

Olver, I. N. and Schwarz, M. A. Use of dimethyl sulfoxide in limiting tissue damage caused by extravasation of doxorubicin. Cancer Treat.Rep. 1983;67(4):407-408. View abstract.

Olver, I. N., Aisner, J., Hament, A., Buchanan, L., Bishop, J. F., and Kaplan, R. S. A prospective study of topical dimethyl sulfoxide for treating anthracycline extravasation. J.Clin Oncol. 1988;6(11):1732-1735. View abstract.

Otrock, Z. K., Beydoun, A., Barada, W. M., Masroujeh, R., Hourani, R., and Bazarbachi, A. Transient global amnesia associated with the infusion of DMSO-cryopreserved autologous peripheral blood stem cells. Haematologica 2008;93(3):e36-e37. View abstract.

Ozkaya-Bayazit, E., Kavak, A., Gungor, H., and Ozarmagan, G. Intermittent use of topical dimethyl sulfoxide in macular and papular amyloidosis. Int.J.Dermatol. 1998;37(12):949-954. View abstract.

Patel, S., Trivedi, A., Dholaria, P., Dholakia, M., Devra, A., Gupta, B., and Shah, S. A. Recurrent multifocal primary amyloidosis of urinary bladder. Saudi.J Kidney Dis Transpl. 2008;19(2):247-249. View abstract.

Peeker, R., Haghsheno, M. A., Holmang, S., and Fall, M. Intravesical bacillus Calmette-Guerin and dimethyl sulfoxide for treatment of classic and nonulcer interstitial cystitis: a prospective, randomized double-blind study. J.Urol. 2000;164(6):1912-1915. View abstract.

Perez, R. S., Zollinger, P. E., Dijkstra, P. U., Thomassen-Hilgersom, I. L., Zuurmond, W. W., Rosenbrand, K. C., and Geertzen, J. H. Evidence based guidelines for complex regional pain syndrome type 1. BMC.Neurol. 2010;10:20. View abstract.

Perez, R. S., Zuurmond, W. W., Bezemer, P. D., Kuik, D. J., van loenen, A. C., de Lange, J. J., and Zuidhof, A. J. The treatment of complex regional pain syndrome type I with free radical scavengers: a randomized controlled study. Pain 2003;102(3):297-307. View abstract.

Perez-Marrero, R., Emerson, L. E., and Feltis, J. T. A controlled study of dimethyl sulfoxide in interstitial cystitis. J.Urol. 1988;140(1):36-39. View abstract.

Perez-Marrero, R., Emerson, L. E., Maharajh, D. O., and Juma, S. Prolongation of response to DMSO by heparin maintenance. Urology 1993;41(1 Suppl):64-66. View abstract.

Potter, P., Eisenberg, S., Cain, K. C., and Berry, D. L. Orange interventions for symptoms associated with dimethyl sulfoxide during stem cell reinfusions: a feasibility study. Cancer Nurs. 2011;34(5):361-368. View abstract.

Puri, A. S., Thiex, R., Zarzour, H., Rahbar, R., and Orbach, D. B. Trigeminocardiac reflex in a child during pre-Onyx DMSO injection for juvenile nasopharyngeal angiofibroma embolization. A case report. Interv.Neuroradiol. 2011;17(1):13-16. View abstract.

Rademaker-Lakhai, J. M., van den, Bongard D., Pluim, D., Beijnen, J. H., and Schellens, J. H. A Phase I and pharmacological study with imidazolium-trans-DMSO-imidazole-tetrachlororuthenate, a novel ruthenium anticancer agent. Clin Cancer Res. 6-1-2004;10(11):3717-3727. View abstract.

Ravid, M., Shapira, J., Lang, R., and Kedar, I. Prolonged dimethylsulphoxide treatment in 13 patients with systemic amyloidosis. Ann.Rheum.Dis. 1982;41(6):587-592. View abstract.

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Rossberger, J., Fall, M., and Peeker, R. Critical appraisal of dimethyl sulfoxide treatment for interstitial cystitis: discomfort, side-effects and treatment outcome. Scand.J Urol.Nephrol. 2005;39(1):73-77. View abstract.

Roth, S. H. and Fuller, P. Diclofenac sodium topical solution 1.5% w/w with dimethyl sulfoxide compared with placebo for the treatment of osteoarthritis: pooled safety results. Postgrad.Med 2011;123(6):180-188. View abstract.

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Ruiz-Delgado, G. J., Mancias-Guerra, C., Tamez-Gomez, E. L., Rodriguez-Romo, L. N., Lopez-Otero, A., Hernandez-Arizpe, A., Gomez-Almaguer, D., and Ruiz-Arguelles, G. J. Dimethyl sulfoxide-induced toxicity in cord blood stem cell transplantation: report of three cases and review of the literature. Acta Haematol. 2009;122(1):1-5. View abstract.

Sairanen, J., Leppilahti, M., Tammela, T. L., Paananen, I., Aaltomaa, S., Taari, K., and Ruutu, M. Evaluation of health-related quality of life in patients with painful bladder syndrome/interstitial cystitis and the impact of four treatments on it. Scand.J Urol.Nephrol. 2009;43(3):212-219. View abstract.

Salim, A. S. A new approach to the treatment of nonsteroidal anti-inflammatory drugs induced gastric bleeding by free radical scavengers. Surg.Gynecol.Obstet. 1993;176(5):484-490. View abstract.

Sams, W. M., Jr. The effects of dimethyl sulfoxide on nerve conduction. Ann.N.Y.Acad.Sci. 3-15-1967;141(1):242-247. View abstract.

Schlegel, P. G., Wolfl, M., Schick, J., Winkler, B., and Eyrich, M. Transient loss of consciousness in pediatric recipients of dimethylsulfoxide (DMSO)-cryopreserved peripheral blood stem cells independent of morphine co-medication. Haematologica 2009;94(10):1473-1475. View abstract.

Schroeder, T., Fenk, R., Saure, C., Czibere, A., Bruns, I., Zohren, F., Haas, R., and Kobbe, G. The Mexican way: a feasible approach to avoid DMSO toxicity. Bone Marrow Transplant. 2011;46(3):469-471. View abstract.

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Shainhouse, J. Z., Grierson, L. M., and Naseer, Z. A long-term, open-label study to confirm the safety of topical diclofenac solution containing dimethyl sulfoxide in the treatment of the osteoarthritic knee. Am J Ther 2010;17(6):566-576. View abstract.

Shirley, H. H., Lundergan, M. K., Williams, H. J., and Spruance, S. L. Lack of ocular changes with dimethyl sulfoxide therapy of scleroderma. Pharmacotherapy 1989;9(3):165-168. View abstract.

Sibert, L., Khalaf, A., Bugel, H., Sfaxi, M., and Grise, P. Intravesical dimethyl sulfoxide instillations can be useful in the symptomatic treatment of profuse hematuria due to eosinophilic cystitis. J.Urol. 2000;164(2):446. View abstract.

Simpson, J. R. Idoxuridine in the treatment of herpes zoster. Practitioner 1975;215(1286):226-229. View abstract.

Sokolov, M. V., Panyutin, I. G., and Neumann, R. D. Whole-genome gene expression profiling reveals the major role of nitric oxide in mediating the cellular transcriptional response to ionizing radiation in normal human fibroblasts. Genomics 2012;100(5):277-281. View abstract.

Souza, C. S., Felicio, L. B., Ferreira, J., Kurachi, C., Bentley, M. V., Tedesco, A. C., and Bagnato, V. S. Long-term follow-up of topical 5-aminolaevulinic acid photodynamic therapy diode laser single session for non-melanoma skin cancer. Photodiagnosis.Photodyn.Ther 2009;6(3-4):207-213. View abstract.

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van Dieten, H. E., Perez, R. S., van Tulder, M. W., de Lange, J. J., Zuurmond, W. W., Ader, H. J., Vondeling, H., and Boers, M. Cost effectiveness and cost utility of acetylcysteine versus dimethyl sulfoxide for reflex sympathetic dystrophy. Pharmacoeconomics. 2003;21(2):139-148. View abstract.

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Wang, W. J., Lin, C. S., and Wong, C. K. Response of systemic amyloidosis to dimethyl sulfoxide. J.Am.Acad.Dermatol. 1986;15(2 Pt 2):402-405. View abstract.

Wang, Y., Chen, G., Song, T., Mao, G., and Bai, H. Enhancement of cardiomyocyte differentiation from human embryonic stem cells. Sci China Life Sci 2010;53(5):581-589. View abstract.

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Yoshimitsu, K., Koga, N., Kitamura, Y., Fukuda, K., Kittaka, E., Horino, N., Sakura, N., Tanaka, T., Nishi, Y., Sakano, T., and . Favorable effect of dimethyl sulfoxide on secondary amyloidosis in juvenile rheumatoid arthritis. Pediatr.Pharmacol.(New York.) 1984;4(3):177-181. View abstract.

Zuurmond, W. W., Langendijk, P. N., Bezemer, P. D., Brink, H. E., de Lange, J. J., and van loenen, A. C. Treatment of acute reflex sympathetic dystrophy with DMSO 50% in a fatty cream. Acta Anaesthesiol.Scand. 1996;40(3):364-367. View abstract.

Barker SB, Matthews PN, Philip PF, Williams G. Prospective study of intravesical dimethyl sulphoxide in the treatment of chronic inflammatory bladder disease. Br J Urol 1987;59:142-4. View abstract.

Bertelli G. Prevention and management of extravasation of cytotoxic drugs. Drug Saf 1995;12:245-55. View abstract.

Birder LA, Kanai AJ, de Groat WC. DMSO: effect on bladder afferent neurons and nitric oxide release. J Urol 1997;158:1989-95. View abstract.

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Simon LS, Grierson LM, Naseer Z, et al. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain 2009;143:238-45. View abstract.

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Toren A, Rechavi G. What really cures in autologous bone marrow transplantation? A possible role for dimethylsulfoxide. Med Hypotheses 1993;41:495-8. View abstract.

Torres MA, Furst DE. Treatment of generalized systemic sclerosis. Rheum Dis Clin North Am 1990;16:217-41. View abstract.

Trice JM, Pinals RS. Dimethyl sulfoxide: a review of its use in the rheumatic disorders. Semin Arthritis Rheum 1985;15:45-60.

Wildenhoff KE, Esmann V, Ipsen J, Harving H, et al. Treatment of trigeminal and thoracic zoster with idoxuridine. Scand J Infect Dis 1981;13:257-62. View abstract.

Williams HJ, Furst DE, Dahl SL, et al. Double-blind, multicenter controlled trial comparing topical dimethyl sulfoxide and normal saline for treatment of hand ulcers in patients with systemic sclerosis. Arthritis Rheum 1985;28:308-14. View abstract.

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DMSO induces drastic changes in human cellular processes and epigenetic landscape in vitro

Human 3D microtissues (MTs) of a maturing cardiac model and a mature hepatic model were exposed to culture medium with or without 0.1% DMSO for two weeks with sampling time points at 2, 8, 72, 168, 240 and 336 hours. The proteome (approximately 2,000 measured proteins), the full transcriptome (including miRNAs) and whole-genome methylation were measured on material obtained from the same sample. Figure 1 contains a graphical overview of the experimental design. In order to obtain a first overview of DMSO-induced cross-omics effects, amounts of differentially changed entities (all corrected for multiple testing using FDR <0.05) are summarized for each platform. Numbers of differentially changed entities differed between the tissue types, with cardiac samples showing a larger effect of DMSO than hepatic, with the exception of mRNAs. This difference is especially noticeable for miRNAs and genome methylation. Because proteomics data was least informative due to its partial nature, these results were included in Supplementary Data. Furthermore, principal component analysis (PCA), using averages of triplicates, for each platform (Fig. 2 & Supplementary Data) depicts clear differences between 0.1% DMSO exposed (DMSO) and untreated (UNTR) samples, with the exception of methylation in hepatic MTs.

Figure 1

Graphical overview of experimental design combined with summary of differential entities of each analysis method. Tissue-specific information is depicted in orange for cardiac and green for hepatic. Furthermore, exposures are coloured blue and measurement platforms purple. Abbreviations: h = hours; mRNA = messenger RNA; miRNA = microRNA.

Figure 2

PCAs depicting differences between DMSO and UNTR for all measured platforms. (a) PCA of RNAs indicates clear differences in RNA expression between DMSO (triangle) and UNTR (circles). Cardiac samples (left) are more distinct from UNTR than hepatic samples (right). (b) PCA of miRNAs reveals clear separation between DMSO and UNTR in cardiac samples, while hepatic samples seem more susceptible to the duration of the exposure (as seen by colour pattern that corresponds to the specific time points, see legend). (c) PCA of promotor methylation indicates differences between DMSO and UNTR for cardiac samples but not for hepatic samples.

To study the molecular effects of DMSO, affected cellular processes were analysed using the full transcriptome. Thereafter, tissue-specific effects of DMSO on regulation of gene expression were investigated by analysing changes in miRNAs and genome-methylation.

DMSO effects on cellular processes

DMSO effects on mRNAs were depicted by of PCA (Fig. 2a,b). The clear separation between UNTR and 0.1% DMSO indicated that DMSO was able to affect cellular processes by altering gene expression. Comparison between DMSO and UNTR resulted in 2051 differentially expressed genes (DEGs = FDR <0.05; of which 871 with |log2FC| >1) in cardiac MTs and 2711 DEGs (of which 1879 with |log2FC| >1) in hepatic MTs, of which 60.7% and 62.9% DEGs were downregulated respectively.

Pathway analysis of DEGs

To identify cellular processes affected by DMSO exposure, DEGs were used for pathway overrepresentation analysis using ConsensusPathDB¹⁵ with the curated Reactome database¹⁶. Significantly overrepresented pathways (q-value < 0.05) were ordered using the hierarchical connections between (sub-) pathways obtained from the Reactome Pathway Browser (Supplementary Tables 1,2). A summary containing the highest hierarchical pathway levels (from now on referred to as clusters) is included in Table 1 for cardiac and Table 2 for hepatic MTs.

Table 1 Pathway analysis of Cardiac DEGs & DEPs detected after 0.1% DMSO exposure.Table 2 Pathway analysis of Hepatic DEGs & DEPs detected after 0.1% DMSO exposure.

Through pathway analysis on DEGs, 225 significantly overrepresented pathways (q-value < 0.05) were found in cardiac MTs, which corresponded to 19 clusters (out of a total of 25 clusters in the Pathway Browser), and 167 pathways corresponding to 16 clusters in hepatic MTs. There was substantial overlap between the tissue types, with 60 pathways and 15 clusters found in both. Although there were differences in magnitude of DMSO effect between tissue types, the affected biological processes by DMSO do not appear to be tissue-specific.

The most significantly affected cluster by DMSO is the “metabolism” cluster in hepatic MTs. Here, most effects were found in pathways “citric acid cycle and respiratory electron transport” (q-value: 3.5 * 10⁻¹⁰, 63 DEGs out of 171 genes, 76.2% downregulated), “glucose metabolism” (q-value: 9.9 * 10⁻⁹, 36 DEGs out of 77 genes, 80.5% downregulated) and “metabolism of lipids and lipoproteins” (q-value: 2.9 * 10⁻⁶, 165 DEGs out of 728 genes, 55.2% downregulated). Changes in lipid and lipoprotein metabolism were not detected in cardiac MTs using DEGs, but similar effects of DMSO were observed for “citric acid cycle and respiratory electron transport” (q-value: 1.3 * 10⁻¹², 58 DEGs out of 171 genes, 65.5% downregulated) and “glucose metabolism” (q-value: 2.8 * 10⁻³, 20 DEGs out of 77 genes, 55.0% downregulated), though less genes were downregulated in cardiac MTs compared to hepatic MTs.

Another highly affected cluster by DMSO treatment in both tissue types was “vesicle-mediated transport”. DMSO effects in this cluster were mainly detected in processes related to Golgi-mediated protein transport and secretion. Of this process, “ER-to-Golgi anterograde transport” was the most affected (Cardiac: q-value: 2.4 * 10⁻⁶, 38 DEGs out of 134 genes, 68.4% downregulated; Hepatic: q-value:1.0 * 10⁻⁵, 44 DEGs out of 134 genes, 44.4% downregulated). This pathway was also part of the cluster “metabolism of proteins”, which additionally revealed DMSO effects on “Asparagine N-linked glycosylation” (Cardiac: q-value: 2.1 * 10⁻⁶, 64 DEGs out of 283 genes, 76.6% downregulated; Hepatic: q-value: 1.2 * 10⁻⁷, 83 DEGs out of 283 genes, 54.8% downregulated), which were post-transcriptional protein modifications necessary for transport of proteins from the ER to the Golgi¹⁷.

Though the cluster of “cellular responses to stress” was detected in both tissue types, overrepresented pathways differ. “Cellular senescence” was significantly affected in cardiac MTs (q-value: 2.6 * 10⁻⁴, pathway size: 192, 42 DEGs, 64.3% downregulated), but not detected during pathway analysis in hepatic MTs. Finally, additional cardiac-specific clusters affected by DMSO were “cell cycle”, “DNA repair”, “organelle biogenesis and maintenance”, but also the highly significant cluster (q < 0.01) of “chromatin organization”. Since the most significantly affected pathways were found in both tissue types, this indicates robust actions of DMSO.

DMSO effects observed in regulation of gene expression and translation

Pathways related to regulation of gene expression and translation were already detected during the pathway analysis of cardiac MTs (Table 3). Though these pathways were not overrepresented in hepatic MTs, the amounts of DEGs detected indicated that DMSO was able to influence these processes and could induce biological alterations to the cell model.

Table 3 Pathways related to transcriptional regulation.

DMSO effects observed in regulation by microRNAs

Tissue-specific influence of DMSO was observed in the sequencing data of miRNAs. Out of 1,105 sequenced cardiac miRNAs, 704 (=63.7%) were differentially expressed (DE, FDR <0.05) with 59.5% showing downregulation. Furthermore, the PCA plot (Fig. 2c) revealed a clear difference between the miRNAs of the treatment groups. In hepatic MTs, out of 1,033 sequenced miRNAs, 186 (=18%) were DE with approximately half of the miRNAs being upregulated (47.3%). Furthermore, the PCA plot not only revealed a clear separation between miRNAs of the treatment groups, but indicated also a time-dependent effect. The two principal components (time and dose) represented together more than 95% of the total variation, leaving only minor effect for other factors.

To investigate the source of tissue-specific difference, gene expression changes in the process of miRNA biogenesis were investigated in more detail (Fig. 3). MiRNA biogenesis starts by the transcription of the primary miRNA transcribed by polymerase II (a complex of 11 subunits) or polymerase III (a complex of 10 subunits). In cardiac MTs, polymerase II contained 1 upregulated and 8 downregulated genes. In hepatic MTs, 5 genes were downregulated and 1 was upregulated. Though fewer genes were downregulated in hepatic MTs, the fold changes were larger compared to cardiac MTs. The cleavage of the pri-miRNA into pre-miRNA did not appear affected by DMSO exposure. DICER1 (which cleaves pre-miRNAs) was downregulated in cardiac MTs and upregulated in hepatic MTs, depicting a clear tissue-specific difference in the response to DMSO exposure. Finally, AGO2 (encoding the main component of the miRNA-RISC) was downregulated in cardiac MTs. The changes in this process could induce differences in the cells miRNA content and therefore affect their regulatory function.

Figure 3

DMSO effect in the process of Gene silencing by RNAs. DEGs in biogenesis of miRNA. The complete process is divided in sub-processes (purple ovals) and depicting involved genes (blue rectangles) and detected DEGs for cardiac (orange rectangles) and hepatic (green rectangles) samples.

In cardiac MTs, the downregulated genes in miRNA biogenesis could explain the extremely high amount of downregulated DE miRNA and indicate extreme deregulation of gene silencing by miRNAs. In hepatic MTs, where the only significant change was the upregulation of DICER1 (Table 3), miRNA biogenesis was not disrupted by DMSO exposure.

To get an indication of the DMSO effects on gene silencing by miRNAs, the miRTarBase database¹⁸, containing experimentally validated microRNA-target interactions (MTI), was used to obtain gene targets of detected DE miRNAs. We only included MTIs with strong evidence (validated by reporter assay, Western blot or qPCR). Of the 704 DE cardiac miRNAs, only 281 (=40%) could be found in the database, resulting in a total of 2051 gene targets potentially affected by DMSO-induced changes in miRNA gene silencing. For hepatic MTs, targets for 106 DE miRNAs (=57%) were obtained, with a total of 545 potentially affected genes. The obtained gene targets were used to visualize overrepresented pathways using the Reactome Pathway Browser (Supplementary Fig. 3). Unexpectedly, overrepresented pathways were located in the same clusters for both tissue types. Most effects were observed for “Signal Transduction”, “Immune System” and “Gene Expression”. However, extreme deregulation of cardiac MTs and limited information about MTIs is making any downstream analysis on putative affected mRNA irrelevant.

DMSO effects observed in epigenetics

In order to assess epigenetic alterations introduced by DMSO, we focus on genome wide DNA methylation. Pathway analysis of cardiac gene expression revealed deregulation of DNA methylation pathways. Methyltransferases DNMT1, a key factor for maintenance of DNA methylation, and DNMT3A, facilitating both de novo and maintenance of DNA methylation, were upregulated while TET1, which plays a key role in active de-methylation, was downregulated in cardiac MTs (Fig. 4a). Upregulation of epigenetic writers and downregulation of erasers after DMSO treatment pointed towards genomic hypermethylation, which potentially reduced transcriptional activity. In contrast, in hepatic pathway analysis, deregulation of DNA methylation was not observed. Note that, in both tissue types, transcriptional evidence for deregulation of other related epigenetic mechanisms were observed, such as histone methylation, where 16 genes and 13 genes were differentially expressed in cardiac and hepatic MTs respectively.

Figure 4

Epigenetic regulation of gene expression. (a) DEGs involved in DNA methylation. The process is divided in sub-processes (purple ovals) and depicting involved genes (blue rectangles) and detected DEGs for cardiac (orange rectangles) and hepatic (green rectangles) samples. (b) Relative enrichment of DMRs (DMSO vs UNTR, FDR 5%) within genomic features. For each feature, the number of overlapping DMRs over the total number of tested windows for the respective feature is depicted. Compared to all genomic regions, hypermethylated regions are enriched for satellites, simple repeats, and CGIs distal to promoters without known regulatory evidence and hypomethylated regions are enriched for simple repeats.

Whole genome methylation profiling by MeDIP-seq revealed 66,178 differentially methylated regions (DMRs; q-value < 0.05) in cardiac MTs. These alterations affected 1.1% of the covered genome. In line with the observed transcriptional changes of writers and erasers of DNA methylation, 71% of the DMRs corresponded to gain of methylation (46,984 hypermethylated regions vs 19,194 hypomethylated regions). In contrast, in hepatic MTs, no DMRs passed correction for multiple testing. Furthermore, the PCA plot (Fig. 2d) indicated a difference between treatment groups in cardiac MTs but not in hepatic MTs. Together, this illustrated tissue-specific impact of DMSO on the methylome in maturing cardiac MTs, while the mature hepatic MTs appeared unaffected.

In order to analyze the regulatory effects of the DMRs, the regions were annotated with known regulatory features, such as promoters, CpG Islands (CGIs), transcription factor binding sites (TFBS), and different classes of repetitive elements (Fig. 4b). Both hypo- and hypermethylated regions enriched specific repeat classes such as satellites (odds ratio of hyper/hypomethylation: 4.4/2.4) and simple repeats (hyper/hypomethylation 6.0/9.4 odds ratio), while repetitive elements in general were not enriched. The effect of DMSO on the upregulation of DNMTs and subsequent hypermethylation of repeat sequences was in line with previous findings in mouse embryoid bodies¹⁹. As expected, hypermethylated regions were also highly enriched in CGIs without regulatory evidence, e.g. not overlapping with TFBS and distal to transcription start sites. The odds ratio of these regions over the genome was 5.5. While CGIs in general had an odds ratio of 3.2, there was no enrichment of CGIs overlapping known TFBS at promoters, the regions with the best studied regulatory potential. Just as promoter regions, other features such as exons, introns, and TFBS were affected by hypermethylation at approximately the odds of the captured genomic background (Fig. 4b). Although we found specific examples where promoter hypermethylation co-occurs with transcriptional repression, no global correlation between differential promoter methylation and gene expression was observed. Only 148 of the 1,436 genes (10.3%) featuring hypermethylated promoters were downregulated in DMSO treated cardiac MTs. 86 of the genes (6%) were overexpressed, contrary to the expected repressive effect of methylation.

Taken together, our data implied a fundamental influence of DMSO on DNA methylation in cardiac MTs, but not in hepatic MTs. The induced alterations affected preferentially satellites and simple repeats, as well as CGIs distal to promoters without known regulatory evidence. The expression of neighboring genes was not significantly correlated to methylation differences. We therefore conclude that transcriptional repression by promoter hypermethylation was not the primary regulatory effect of the altered methylation marks, but the findings indicate a global disruption of DNA methylation mechanisms.

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For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

DMSO may help relieve pain but more studies are needed to confirm its safety and efficacy. There is no evidence that DMSO can treat cancer in humans.

DMSO is a widely used chemical solvent. It is rapidly absorbed when applied to the skin, and has been shown to reduce pain and inflammation. DMSO is used as a prescription drug to treat inflammation and pain of the bladder. Small studies suggest that DMSO may help relieve peripheral neuropathy^{and post-thoracotomy pain. It has also been studied for its effects on painful bladder syndrome/interstitial cystitis, but definitive evidence is lacking. More research is also needed to determine its effects in patients with osteoarthritis.}

DMSO is approved for the treatment of interstitial cystitis, when administered intravesically.

• As a cancer treatment
  Some laboratory studies have shown that DMSO may slow down the progression of cancer; however, clinical studies have not been performed.

• To treat chemotherapy extravasations (chemotherapy that has leaked and become trapped in surrounding tissue)
  DMSO may be used to treat this condition in a hospital setting.

• To reduce pain
  Applying DMSO to the skin appears to reduce pain in humans.

• To treat arthritis and osteoarthritis
  A few studies show that application of DMSO to the skin reduces pain and inflammation in humans; however, more studies are needed to determine the optimal dose.

• To treat interstitial cystitis (inflammation and pain of the bladder of unknown origin)
  Intravesical DMSO is an accepted treatment for interstitial cystitis; however, more studies are needed to establish this use.

DMSO is approved for the treatment of interstitial cystitis, when administered intravesically. But it is not approved for over-the-counter use in any form due to insufficient evidence of efficacy and potential toxicities. The industrial form of DMSO may be contaminated with other chemicals.

• Garlic taste in mouth, dry skin, erythema and pruritis, urine discoloration, halitosis, agitation, hypotension, sedation and dizziness have been reported following use of DMSO.

• A systematic review of 109 studies showed that the most common adverse effects of DMSO were mild, transient gastrointestinal and skin reactions, and that small doses appear to be safe.
   

• DMSO was shown to cause neural damage in mice. Clinical relevance is not known.

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For Healthcare Professionals

Dimethylsulfoxide (DMSO) is a widely used chemical solvent because of its high polarity. It is also employed as a cryopreservative ^(15) (16). DMSO is readily absorbed by the skin and has been studied as a vehicle for topical drugs. It is thought to have analgesic and anti-inflammatory properties, and has been used topically to relieve pain and to treat arthritis.

Small studies suggest that DMSO may help relieve peripheral neuropathy ⁽¹⁾ and post-thoracotomy pain ⁽²⁾. It has also been investigated for its effects on painful bladder syndrome/interstitial cystitis ^(17) (18), but definitive evidence is lacking ^{(4) (5) (14)}. More research is also needed to determine its benefits in patients with osteoarthritis ⁽³⁾.
In oncology settings, DMSO has been used to prevent and manage extravasations of chemotherapeutic agents ^(6) (7). It may also slow down the progression of cancer cells, but data are inconsistent ^(2) (8).

DMSO is approved for the treatment of interstitial cystitis, when administered intravesically.

• Cancer treatment

• Chemotherapy side effects

• Pain

• Arthritis

• Interstitial cystitis

DMSO is diluted on exposure to air. Upon topical application, it rapidly penetrates the skin; however, unlike most penetrating solvents, it is not associated with irreversible membrane damage. DMSO can enhance the skin penetration of other drugs. Analgesic and anti-inflammatory effects may benefit patients with rheumatoid arthritis ⁽²⁾. In addition, DMSO traps free radical hydroxide; its antioxidant properties are thought to be responsible for the prevention of chemotherapy extravasations ⁽⁷⁾. A strong garlic taste in the mouth following DMSO administration is due to the exhaled dimethylsulfide (DMS) metabolite ⁽¹¹⁾.

DMSO is approved for the treatment of interstitial cystitis, when administered intravesically. But it is not approved for over-the-counter use in any form due to insufficient evidence of efficacy and potential toxicities. The industrial form of DMSO may be contaminated with other chemicals.

Pregnant women should avoid DMSO ⁽¹²⁾.

• Garlic taste in mouth, dry skin, erythema and pruritis (2), urine discoloration, halitosis, agitation, hypotension, sedation and dizziness (13) have been reported following use of DMSO.

• A systematic review of 109 studies showed that the most common adverse effects of DMSO were mild, transient gastrointestinal and skin reactions, and that small doses appear to be safe (19).
   

• DMSO was shown to cause neural damage in murine models (9). Clinical relevance is not known.

1. Kingery WS. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain 1997;73:123-39.

2. Brayton CF. Dimethyl sulfoxide (DMSO): a review. Cornell Vet. 1986;76:61-90.

3. Brien S, Prescott P, Bashir N, Lewith H, Lewith G. Systematic review of the nutritional supplements dimethyl sulfoxide (DMSO) and methylsulfonylmethane (MSM) in the treatment of osteoarthritis.Osteoarthritis Cartilage. Nov 2008;16(11):1277-1288.

4. Dawson TE, Jamison J. Intravesical treatments for painful bladder syndrome/ interstitial cystitis. Cochrane Database Syst Rev. 2007(4):CD006113.

5. Dimitrakov J, Kroenke K, Steers WD, et al. Pharmacologic management of painful bladder syndrome/interstitial cystitis: a systematic review. Arch Intern Med. Oct 8 2007;167(18):1922-1929.

6. Bertelli G. Prevention and management of extravasation of cytotoxic drugs. Drug Saf 1995;12:245-55.

7. Dorr RT. Antidotes to vesicant chemotherapy extravasations. Blood Rev. 1990;4:41-60.

8. Jacob SW,.Herschler R. Pharmacology of DMSO. Cryobiology 1986;23:14-27.

9. Hanslick JL, Lau K, Noguchi KK, et al. Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system. Neurobiol Dis. Apr 2009;34(1):1-10.

10. Prior D, Mitchell A, Nebauer M, Smith M. Oncology nurses’ experience of dimethyl sulfoxide odor. Cancer Nurs 2000;23:134-40.

11. Rosenstein ED. Topical agents in the treatment of rheumatic disorders. Rheum.Dis.Clin North Am 1999;25:899-918, viii.

12. Physicians’ Desk Reference. Montvale, NJ: Thomson, 2004.

13. MICROMEDEX(R) Healthcare Series. 120. Thomson, 2004.

14. French LM, Bhambore N. Interstitial cystitis/painful bladder syndrome. Am Fam Physician. 2011 May 15;83(10):1175-81.

15. Slichter SJ, Dumont LJ, Cancelas JA, et al. Safety and efficacy of cryopreserved platelets in bleeding patients with thrombocytopenia.Transfusion. 2018 Sep;58(9):2129-2138.

16. Mitrus I, Smagur A, Fidyk W, et al. Reduction of DMSO concentration in cryopreservation mixture from 10% to 7.5% and 5% has no impact on engraftment after autologous peripheral blood stem cell transplantation: results of a prospective, randomized study. Bone Marrow Transplant. 2018 Mar;53(3):274-280.

17. Tutolo M, Ammirati E, Castagna G, et al. A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroïtin sulphate 2% for painful bladder syndrome/interstitial cystitis. Int Braz J Urol. 2017 Jan-Feb;43(1):134-141.

18. Cervigni M, Sommariva M, Tenaglia R, et al. A randomized, open-label, multicenter study of the efficacy and safety of intravesical hyaluronic acid and chondroitin sulfate versus dimethyl sulfoxide in women with bladder pain syndrome/interstitial cystitis. Neurourol Urodyn. 2017 Apr;36(4):1178-1186.

19. Kollerup Madsen B, Hilscher M, Zetner D, Rosenberg J. Adverse reactions of dimethyl sulfoxide in humans: a systematic review. Version 2. F1000Res. 2018 Nov 5 [revised 2019 Jan 1];7:1746.

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Wednesday, March 11, 2020

Dimethyl Sulfoxide – an overview

DMSO tolerance is another important factor to consider in assays, because DMSO is a solvent widely used for compounds in drug discovery, including the compounds used in this study. In the DMSO tolerance test, the TR-FRET signals from the FAM-SRC1-B-mediated PXR coactivator recruitment assays were measured after 120 min of incubation with either DMSO vehicle control or various concentrations of T0901317 in final DMSO concentrations of 0.2%, 0.5%, 1%, 1.1%, 2%, 5%, or 10% plus 100 nM FAM-SRC1-B, 5 nM GST-hPXR-LBD, and 5 nM Tb-anti-GST. The total binding signal in the presence of 10 μM T0901317 remained stable at 5017, 4977, 4907, 5101, 5059, and 4959 with DMSO concentrations of 0.2%, 0.5%, 1%, 1.1%, 2%, and 5%, respectively, and then decreased to 4241 when the DMSO concentration was increased to 10% (Fig. 7A). The background binding signal (in the presence of the same concentration of DMSO) remained constant over the entire DMSO concentration range at 909, 917, 920, 950, 966, 972, and 901 with DMSO concentrations of 0.2%, 0.5%, 1%, 1.1%, 2%, 5%, and 10%, respectively (Fig. 7A). The signal-to-background ratio (the ratio of the signal from the 10 μM T0901317 group to that from the DMSO group) was also relatively stable, ranging from 5.5 to 5.1 at DMSO concentrations at or below 5% and falling to 4.7 when the DMSO concentration was 10% (Fig. 7B). In the 100 nM FAM-SRC1-B-mediated hPXR TR-FRET coactivator recruitment assay, the EC₅₀ values of T0901317 at DMSO concentrations of 0.2%, 0.5%, 1%, 1.1%, and 2% remained constant at 114.8, 111.5, 115.4, 111.3, and 118.6 nM, respectively, and then increased to 146.3 and 431.0 nM at DMSO concentrations of 5% and 10%, respectively (Fig. 7C). For the putative hPXR agonist T0901317, slight EC₅₀ deviation was observed with 5% DMSO (146.3 nM vs a typical 110–120 nM), and relatively substantial EC₅₀ deviation was observed with 10% DMSO (431.0 nM vs a typical 110–120 nM). Therefore, the FAM-SRC1-B-mediated PXR TR-FRET coactivator recruitment assay can tolerate a wide range of DMSO concentrations up to at least 2%. The DMSO concentration of 1.1% or 1.2% was used in further characterizing hPXR ligands for their agonistic or antagonistic activities.

Fig. 7. DMSO tolerance in the interaction of 100 nM FAM-SRC1-B with 5 nM GST-hPXR-LBD and 5 nM Tb-anti-GST after 120 min of incubation. (A) Interaction of 100 nM FAM-SRC1-B with 5 nM GST-hPXR-LBD and 5 nM Tb-anti-GST in the presence of DMSO control or T0901317 (10 μM) at the indicated final DMSO concentrations. (B) Signal-to-background ratios for the interaction of 100 nM FAM-SRC1-B with 5 nM GST-hPXR-LBD and 5 nM Tb-anti-GST in the presence of the indicated DMSO concentrations, with the signal and background being defined as 10,000 × the 520 nm/490 nm ratios obtained with T0901317 (10 μM) and DMSO, respectively. (C) T0901317 dose–response curves in the presence of 100 nM FAM-SRC1-B, 5 nM GST-hPXR-LBD, and 5 nM Tb-anti-GST at the indicated DMSO concentrations.

Dimethyl Sulfoxide, DMSO bladder irrigation

What is this medicine?

DIMETHYL SULFOXIDE (dye meth il suhl FOK sahyd) is a solution for your bladder. It is used to treat the bladder pain or discomfort caused by interstitial cystitis.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

COMMON BRAND NAME(S): Rimso-50

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:

• bladder cancer
• cataracts
• an unusual or allergic reaction to Dimethyl Sulfoxide, other medicines, foods, dyes, or preservatives.
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

This medicine is given by a catheter or syringe infusion into the bladder. It is given by a health care professional in a hospital of clinic setting. Try to hold this medicine in your bladder for 15 minutes after treatment.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.

NOTE: This medicine is only for you. Do not share this medicine with others.

What if I miss a dose?

Keep appointments for follow-up doses as directed. It is important not to miss your dose. Call your doctor or health care provider if you are unable to keep an appointment.

What may interact with this medicine?

Interactions are not expected.

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Tell your doctor or healthcare professional if your symptoms do not start to get better or if they get worse. Your condition will be monitored carefully while you are receiving this medicine. Your vision and blood may be tested before and during use of this medicine.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

• changes in taste
• pain when urinating

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

This drug is given in a hospital or clinic and will not be stored at home.

NOTE: This sheet is a summary. It may not cover all possible information. If you have questions about this medicine, talk to your doctor, pharmacist, or health care provider.

Dimethyl Sulfoxide | Memorial Sloan Kettering Cancer Center

This document, provided by Lexicomp ^® , contains all the information you need to know about the drug, including the indications, route of administration, side effects and when you should contact your healthcare provider.

Trade names: USA

Rimso-50

Trade names: Canada

Rimso-50

What is this drug used for?

• Used to relieve pain, reduce inflammation and reduce bladder irritation.
• If you got this drug for any other reason, ask your doctor about the benefits and risks. If you have questions or concerns about the use of this drug, talk to your doctor.

What should I tell my doctor BEFORE taking this drug?

• If you are allergic to this drug, any of its ingredients, other drugs, foods or substances. Tell your doctor about your allergy and how it manifested itself.

Combination of this drug with certain medications and medical conditions can be adverse.

Tell your doctor and pharmacist about all the medicines you take (prescription and over-the-counter, natural products and vitamins) and your health problems. You need to make sure that this drug is safe for your medical conditions and in combination with other drugs you are already taking.Do not start or stop taking any drug or change the dosage without your doctor’s approval.

What do I need to know or do while taking this drug?

• Tell all healthcare providers that you are taking this drug. These are doctors, nurses, pharmacists and dentists.
• Get a blood test and eye exam as recommended by your doctor.
• Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding.The benefits and risks for you and your child will need to be discussed.

What side effects should I report to my doctor immediately?

WARNING. In rare cases, some people with this drug can have serious and sometimes deadly side effects. Call your doctor or get medical help right away if you have any of the following signs or symptoms, which may be associated with serious side effects:

• Signs of an allergic reaction, such as rash, hives, itching, reddened and swollen skin with blisters or scaling, possibly associated with fever, wheezing or wheezing, tightness in the chest or throat, difficulty breathing, swallowing or speaking, unusual hoarseness, swelling in the mouth, face, lips, tongue, or throat.
• Changes in vision, eye pain or very severe eye irritation.

What are some other side effects of this drug?

Any medicine can have side effects. However, many people have little or no side effects. Call your doctor or get medical help if these or any other side effects bother you or do not go away:

• Irritation at the site of application of the medicinal product.
• The skin and breath smell like garlic when this drug was taken. Smell may persist for 72 hours after using this drug.

This list of potential side effects is not comprehensive. If you have any questions about side effects, please contact your doctor. Talk to your doctor about side effects.

You can report side effects to the National Health Office.

You can report side effects to the FDA at 1-800-332-1088. You can also report side effects at https://www.fda.gov/medwatch.

What is the best way to take this drug?

Use this drug as directed by your healthcare practitioner. Read all the information provided to you. Follow all instructions strictly.

• The drug is injected through a catheter into the bladder.
• You must urinate after taking this drug.This helps to flush the drug out of the bladder. Drink plenty of decaffeinated liquids during or immediately after taking this drug, unless your doctor tells you otherwise. Continue drinking fluids as directed by your doctor.

What should I do if a dose of a drug is missed?

• Call your doctor for further instructions.

How do I store and / or discard this drug?

• If you need to store this drug at home, ask your doctor, nurse, or pharmacist for information about how it is stored.

General information on medicinal products

• If your health does not improve or even worsens, see your doctor.
• You should not give your medicine to anyone and take other people’s medicines.
• Store all medicines in a safe place. Keep all medicines out of the reach of children and pets.
• Dispose of unused or expired drugs.Do not empty into toilet or drain unless directed to do so. If you have any questions about the disposal of your medicinal products, consult your pharmacist. There may be drug recycling programs in your area.
• Some medicines may come with other patient information sheets. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
• Some medicines may come with other patient information sheets. Check with your pharmacist. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
• If you think an overdose has occurred, call a Poison Control Center immediately or seek medical attention. Be prepared to tell or show which drug you took, how much and when it happened.

Use of information by consumer and limitation of liability

This summary information includes a summary of the diagnosis, treatment, and / or drug. It is not a comprehensive data source and should be used as a tool to help the user understand and / or evaluate potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects or risks that may apply to a particular patient.It should not be considered medical advice or a substitute for medical advice, diagnosis or treatment provided by a physician based on a medical examination and assessment of the patient’s specific and unique circumstances. Patients should consult a physician for complete information about their health, medical issues and treatment options, including any risks or benefits in relation to the use of the medication. This information does not guarantee that a treatment or drug is safe, effective, or approved for specific patients.UpToDate, Inc. and its subsidiaries disclaim any warranties or obligations related to this information or its use. Use of this information is governed by the Terms of Use found at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.

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Clinical Study Bladder Pain Syndrome: DMSO, Botox – Clinical Trials Registry

Tisol

Tizol (aqua complex of titanium glycerosolvate) is an original domestic drug, developed and produced by the pharmaceutical company OLIMP LLC (Society for Laboratory Research of Medicines, Yekaterinburg). Tizol has been successfully used for many years in various fields of medicine as a finished drug and as a base substance for the pharmaceutical production of soft dosage forms.

The high efficiency of the application of TISOL and its compositions is explained by the unique structure of Tizol, which ensures its deep penetration into biological tissues and environments.

Physical and chemical properties

Tizol (aqua complex of titanium glycerosolvate) is a metal complex compound, therefore it is sterile and has anti-inflammatory and antimicrobial effects.In the Tisol molecule, the titanium atom, chemically bonded to glycerol and water, is a complexing center for the fragments constituting the drug molecule: glycerol and water. This interaction determines the gel structure of the drug, which ensures its high conductivity through biological tissues and its pharmacological properties. Tizol mixes well and is capable of forming homogeneous stable complex compounds with microbiological purity and self-sustaining sterility due to intermolecular interactions with medicinal substances of various chemical nature.

Security

Tizol is safe, does not cause adverse reactions, which is confirmed by the results of pharmacological and clinical studies.

Efficiency

Medicinal compositions Tizol represent transdermal therapeutic systems that allow you to control the rate and amount of drugs administered through the skin and mucous membranes.Tizol quickly delivers medicinal substances unchanged to the pathological focus and releases them in full, enhancing the therapeutic effect of the substances, which allows a high therapeutic effect to be achieved. Comparative biopharmaceutical analysis showed that the rate of diffusion from the medical complex Tizol – drug substance is ahead of the petrolatum complex by 66%, and the complex of petroleum jelly – DMSO – drug by 30%. Tizol has 2-3 times higher transdermal conductivity compared to the widely used DMSO conductor and does not contain its drawbacks: it does not have an unpleasant “garlic” odor, does not cause dermatitis and allergic reactions, does not inhibit tissue respiration, and does not reduce tissue oxygenation.The high penetrating power of Tizol and its medicinal compositions and, as a result, more effective treatment have been confirmed in many areas of medicine (surgery, rheumatology, oncology, dermatology, dentistry, gynecology, etc.). The high conductive properties of medicinal compositions based on Tizol were confirmed by the method of emission spectral analysis with inductively coupled plasma, which was used to determine the quantitative content of titanium (Tizol label) in biopsy material or biological media obtained after the application of Tizol and medicinal compositions based on it.So, as a result of the applications of Tizol and Tizol with diclofenac for local treatment of arthritis on the knee joint area, the titanium level (Tisol label) in the synovial fluid increased tenfold from 0.04 μg / ml (without Tisol exposure) to 0.34-0, 51 μg / ml (p <0.001), which explains the deep penetration of the drugs and ensures high efficiency of treatment with Tizol and Tizol with diclofenac (in 75.9% and 80% of cases, respectively).

Literature
1.Modern aspects of the use of excipients in the technology of drugs. / Bagirova V.L., Demina N.B., Devyatkina I.A. et al. // Pharmateca. – 1998.- No. 6. – S. 34-36.
2. Smagina T.A. “Pharmacological research of complex preparations with Tizol”. Materials of the interregional scientific-practical conference “New technologies in medicine and pharmacy. Tizol “, Ekaterinburg, 2010
3. Medical technology “Treatment of patients with osteoarthritis using radon baths and local drug therapy.”(Registration certificate No. FS-2007/218 dated 22.10.2007).
4. Sokolova LA, “Reactive and rheumatoid arthritis; the triggering role of infectious factors and new approaches to diagnosis, assessment of severity and treatment.” Abstract of the thesis for the degree of Doctor of Medical Sciences, Yaroslavl, 2002
Emelyanov A.S. 1, Smirnova M.V. 1 *, Kovtun O.P. 2, Petrov A.Yu. 2, Emelyanova I.V. 1 LLC “OLIMP”, Yekaterinburg 1, GOU VPO “Ural State Medical Academy” Roszdrav,Yekaterinburg 2, “Solving the problem of targeted delivery of drugs to the pathological focus”

Dimethyl Sulfoxide – instructions for use, dosage, composition, analogs, side effects / Pillintrip

Inoculation of 50 ml 50 ml dimethyl sulfoxide directly into the bladder can be carried out with a catheter or syringe and left for 15 minutes. It is recommended to use an analgesic lubricant such as lidocaine jelly on the urethra before inserting the catheter to avoid seizures.The drug is excreted by spontaneous emptying.

It is recommended to repeat the treatment every two weeks until the maximum symptomatic relief is achieved. The time intervals between therapies can be increased accordingly.

Administration of suppositories for oral analgesics with belladonna and opium before instillation of dimethyl sulfoxide® (DMSO) solution may reduce bladder spasms.

In patients with severe interstitial cystitis with very sensitive blisters, initial treatment and possibly a second and third (depending on the patient’s response) should be performed under anesthesia.(A saddle was suggested.)

How Delivered

Bottles contain 50 ml of sterile and non-pyrogenic Dimethyl Sulfoxide® (DMSO) (50% DMSO aqueous solution).

Dimethyl sulfoxide is transparent and colorless.

Protect from strong light. Store at room temperature 59 ° to 86 ° F (15 ° to 30 ° C).

NDR # 67457-177-50

REFERENCES

1. Photos courtesy of the Interstitial Cystitis Association and K.Lowell Parsons, M.D.

Second. Erickson DR. Interstitial cystitis: an update on etiology and therapeutic options. J Women’s Health and Gender Environment Med 1999; 6: 745.

3rd. Parkin J, et al. Intravinous dimethyl sulfoxide (DMSO) for interstitial cystitis – a practical approach. Urology, 1997; 49 (5A, Suppl): 106.

4th. Santana et al. Intravenous 50% dimethyl sulfoxide solution (dimethyl sulfoxide® (DMSO)) for the treatment of interstitial cystitis.Urology 1987; 29 (4, Suppl): 19.

Made for: Bioniche Pharma USA, LLC, Lake Forest, IL 60045. Made by: Bioniche Teo., Inverin, Co. Galway, Ireland.

Treatment of IC / PBS

Most guidelines, including the American Urological Association (AUA), agree that clinicians should start with the least invasive method and gradually move on to more invasive methods. [1]

Lifestyle changes and diet

Least invasive therapeutic options describe lifestyle change.Diet has a big impact on symptoms. Lists of food and beverages for IC / PBS are widely available on the Internet, [2], [3], [4] and scientific articles have been published on this topic. [5], [6] Most sources agree that certain types food irritates the damaged bladder wall. The following are usually mentioned in the lists:

• Caffeinated beverages
• Alcoholic drinks
• Hot and spicy dishes
• Acidic and acidic foods, including carbonated drinks.
• Certain fruits with a high acid content
• Tea or certain dietary supplements containing aromatic oils and / or volatile oil compounds.
• Herbal Products

Indeed, following an IC / PBS-friendly diet can help alleviate symptoms. However, lifestyle and dietary changes alone do not always work, especially in severe cases. It usually takes a long time for the effects to appear, and symptoms may worsen during this therapy.

Oral medicines

If no improvement is observed, oral therapy is the next mainstay of treatment. The most common medicines usually contain one or more of the following active ingredients:

• Antihistamines anti-inflammatory drugs.
• Non-steroidal anti-inflammatory drugs.
• Anti-inflammatory corticosteroid drugs.
• Tricyclic antidepressants
• Gabapentin relieves neuropathic pain.

It should be noted that the list of approved and available medicines varies greatly from country to country.

There have been many studies examining the effectiveness of these substances, and this is summarized on many pages. [7] These agents are anti-inflammatory, block a pain mediator, and have antidepressant effects. Therefore, oral formulations are an effective way to alleviate urinary symptoms and / or pain, thus improving the patient’s quality of life.

Alkalinizing urine is also an important part of oral treatment, as acidic urine can irritate the bladder and worsen symptoms. In many cases, avoiding foods that increase the acidity of urine is not enough. Therefore, alkalizing tablets (medications or dietary supplements) also play an important role in oral medication.

However, these agents practically do not affect the integrity of the mucous membrane. It is worth mentioning that there are certain drugs that do contain one or more active pharmaceutical ingredients (detailed below) used to replenish the mucous membrane.Many of them are widely known and available on the Internet. In this group, the most important drug is Pentosan Sodium Polysulfate (PPN, Elmiron, SP-54), which is approved by the FDA (USA) and is considered the only oral drug that actively helps to restore the mucous membrane.

Regardless of the use of agents that replenish the mucous layer, oral therapy has a number of significant disadvantages.To get into the bladder, drugs must be absorbed in the digestive system, enter the bloodstream, and reach other tissues. This reduces the effectiveness of drugs and increases the likelihood of side effects. PPN, for example, must be taken for 3 months or more to feel its effect on the mucous layer. Oral administration of PPN for a longer period can have serious side effects; [8] the recent discovery on this topic is of particular concern. [9]

Local treatment (intravesical instillation)

The next option is local treatment, that is, the introduction of certain substances directly into the bladder.

Many ingredients have been tested over the past 20 years. Some of them, such as BCG (Bacillus Calmette-Guerin), were ineffective. [10] Others who interacted with nerve growth factor had safety concerns. [11] With some substances, only partial improvement was achieved: for example, with vanilloids, pain decreased, but there was no improvement in urinary symptoms. [12] There are some agents that are currently being investigated, but the results are conflicting and / or inconclusive, or clinical trials have not yet been conducted.Blocking P2X3 receptors (which affect bladder activity) may be promising, but further experimentation will be required. [13] Botulinum toxin A (BTX-A, Botox) has been studied several times, but the results seem to be conflicting. [14], [15] Using liposomes to deliver various agents may be an effective method, [16] but, again, further experimentation will be required.

In terms of active ingredients, there are six main compounds that are associated with mucosal replenishment.These are as follows:

• Pentosan sodium polysulfate (PPS, Elmiron, SP-54)

• Dimethyl sulfoxide (DMSO, Rimso-50)

• Lidocaine (alkaline lidocaine, AL)

• Heparin

• Hyaluronic acid (HA)

• Chondroitin sulfate (HS)

On the other hand, the clinical data on these substances are contradictory.

The structure of PPN is similar to those compounds naturally present in the mucous membrane. Its mechanism of action is still unknown, but it may be an effective intravesical drug.[17]

DMSO is the only FDA-approved bladder instillation drug. According to some articles, it is more effective than some other agents, [18] while other sources point to problems with DMSO. [19]

Alkaline lidocaine (AL) is often used in various bladder cocktails. According to some reports, this medication itself is effective in rebuilding the mucous membrane.[20] Most therapists believe that it can enhance the effectiveness of other compounds, [21] even if there is research to deny it.

Heparin, hyaluronic acid and chondroitin sulfate are natural components of the mucous membrane.

Heparin, alone or with other compounds, is often used for topical treatment. [22] There is evidence that it is less effective than, for example, DMSO (see above). Hyaluronic acid may be the most abundant ingredient; its effectiveness has been tested several times with varying results.[23], [24], [25] The available data are also inconsistent for chondroitin sulfate. [26], [27], [28] According to some studies, HA + CS may be as effective as DMSO. [29]

In practice, different doctors use different bladder cocktails [30] in the hope that the patient will respond to treatment.

A large amount of conflicting data may be based on several facts. First, the etiology of IC / PBS is still unknown. If the disease can appear for different reasons, patients with different etiologies may respond differently to treatment.Secondly, in many countries only one or very few of these drugs are approved, which in itself prevents the construction of an objective and comparative picture. Third, in most countries only a few agents or cocktails are used for instillation, usually ex-tempore, making it difficult to conduct clinical trials with a large sample size.

It is worth investigating why topical treatments are less popular than oral medications, even though they are more effective when used with the correct medication.Invasiveness is an important factor. Many doctors try to avoid using a catheter unless absolutely necessary. Patients often refuse instillation therapy for fear of pain and the risk of further problems – microdamage and infections that the catheter can cause. To overcome these problems, Urosystem has developed the UroDapter® and UroStill®. The UroDapter® is a small catheter replacement device. UroStill® is a device that allows female patients to self-instill.With UroStill®, bladder treatments can be performed at home, without the direct assistance of a healthcare professional.

Combination therapy

It is undeniable that first lines of treatment – less invasive methods such as diet and oral medications – are needed. Unfortunately, not only is the diagnosis time-consuming, but the effect of less invasive treatments also appears later. This leads to the usual situation in which patients spend 1–3 years or more on life with difficult pain, severe urinary syndromes and gradually deteriorating quality of life.The more time spent doing this, the more likely it is that the patient will not respond at all to less invasive treatments.

Our recommendations are summarized in the following flow chart. In the case of severe symptoms, it is recommended to start a combination therapy with oral and intravesical treatment so that the patient’s condition improves as soon as possible.

Scheme of diagnostics and therapy of IC / PBS. A 100% mucosal integrity test should be understood as the mean value of urine portions measured on the first day (with low fluid intake) (described in the IC / PBS Diagnostics chapter).

As shown, the treatment used depends on the results of the cover integrity test. Lifestyle changes, diet, and oral treatment are effective and sufficient only in mild IC / PBS. In these cases, it is also necessary to monitor the patient, because, despite the treatment carried out, a worsening of the condition cannot be ruled out. (The patient monitoring system has not yet been implemented on this website.)

In more severe cases, mucosal repair with bladder instillations should be started immediately, but less invasive methods are usually performed simultaneously.

More invasive treatments – including botulinum toxin injections, neuromodulation, fulguration of damaged areas of the mucous layer, or cystectomy – are performed only if all other treatments have failed. Alternative therapies, including acupuncture and high pressure oxygen therapy, are generally recommended as adjunctive treatments due to their inadequate cost-benefit ratio.

Used literature

[1] https: // www.auanet.org/guidelines/interstitial-cystitis/bladder-pain-syndrome-(2011-amended-2014)

[2] https://docplayer.net/20821777-Eating-with-ic-www-ichelp-org-interstitial-cystitis-association.html

[3] https://www.ic-network.com/bev/

[4] https://ic-diet.com/IC-diet-food-list.html

[5] https://pubmed.ncbi.nlm.nih.gov/17499305/

[6] https://pubmed.ncbi.nlm.nih.gov/22453670/

[7] https://www.ic-network.com/interstitial-cystitis-treatments/oral-medication/

[8] https: // www.webmd.com/drugs/2/drug-14053/pentosan-polysulfate-sodium-oral/details

[9] https://www.ncbi.nlm.nih.gov/pubmed/29801663

[10] https://www.ncbi.nlm.nih.gov/pubmed/15758738/

[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756823/

[12] https://www.ncbi.nlm.nih.gov/pubmed/24376550/

[13] https://www.ics.org/2015/abstract/23

[14] https://www.ncbi.nlm.nih.gov/pubmed/24276074

[15] https://www.ncbi.nlm.nih.gov/pubmed/256

[16] https: // www.ncbi.nlm.nih.gov/pmc/articles/PMC4708561/

[17] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522791/

[18] https://www.ncbi.nlm.nih.gov/pubmed/28150028

[19] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293394/

[20] https://www.ncbi.nlm.nih.gov/pubmed/1

19/

[21] https://www.ncbi.nlm.nih.gov/pubmed/22576327/

[22] https://www.ncbi.nlm.nih.gov/pubmed/22082303/

[23] https://www.ncbi.nlm.nih.gov/pubmed/22576327/

[24] https: // www.researchgate.net/publication/47396396_Long-term_results_of_intravesical_hyaluronan_therapy_in_bladder_pain_syndromeinterstitial_cystitis

[25] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708541/

[26] https://www.ncbi.nlm.nih.gov/pubmed/20494413/

[27] https://www.ncbi.nlm.nih.gov/pubmed/18778342/

[28] https://www.ncbi.nlm.nih.gov/pubmed/22516357/

[29] https://www.ncbi.nlm.nih.gov/m/pubmed/27654012/

[30] https: // www.ic-network.com/interstitial-cystitis-treatments/bladder-instillations/

References / Consultant Plus

References

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