The use of dimethylsulfoxide (DMSO) for the treatment of intractable pain in surgical patients
William M. Rosenbaum, M.D.; Edward E. Rosenbaum, M.D.; Stanley W. Jacob, M.D.

Portland, OR. Department of Surgery, University of Oregon Medical School

The Effects of Dimethyl Sulfoxide on Post-traumatic Limb Swelling and Joint Stiffness
A Review and an Experimental Study in Rabbits
Robert C. More, M.D.; J. Michael Kabo, PH.D., Frederick J. Dorey, PH.D.; Roy A. Meals, M.D.

Dimethyl sulfoxide (DMSO) is an inorganic compound with many interesting in vitro properties, including the ability to scavenge oxygen-free radicals. DMSO has been used to treat a variety of clinical conditions, especially musculoskeletal trauma, but valid data regarding its effectiveness are lacking. This paper reviews the pharmacology of DMSO and reports on its effectiveness in reducing posttraumatic limb swelling and ankle joint stiffness in a rabbit hind limb model. The left and right hind limbs of the test and control animals were instrumented and fractured identically. DMSO was applied daily to the skin of only one limb in the test animals. DMSO reduced postinjury ankle stiffness in both ankles of the test rabbits by 41% but had no effect on limb swelling compared to control rabbits. Postulated mechanisms of decreased joint stiflness include oxygenfree radical scavenging and inhibition of fibroblast proliferation.

Self-Administration of Dimethyl Sulfoxide (DMSO) for Interstitial Cystitis
Lt. Col. Robert D. Biggers (MC), USAF

From the Urology Service, U.S. Air Force Academy Hospital, U.S. Air Force Academy, Colorado Springs, Colorado

Abstract: Ten patients with biopsy-proved interstitial cystitis were treated with a program of self-admintstered dimethyl sulfoxide (DMSO) using the technique of intermittent self-catheterization. Nine of the 10 patients responded favorably to the treatment and are on a maintenance program. The technique was well tolerated and without complications.

What Really Cures in Autologous Bone Marrow Transplantation? A Possible Role for Dimethyl sulfoxide
A. Toren and G. Rechavi

Medical Hypotheses (1993)41, 495-498

Institute of Hematology and the Pediatric Hemato-oncology Unit, The Chaim Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Israel (Correspondence to AT, The Institute of Hematology, The Sheba Medical Center, Tel-Hashomer 52 621, Israel).

Absbract-Dimethylsulfoxide has long been known to be a potent inducer of differentiation of various malignant cells in animals and human beings. It is a toxic agent, and high concentrations are needed to induce differentiation. Other compounds that also have methylene groups and a polar/apolar architecture, and are needed in much smaller concentrations to induce differentiation, like hexamethylene bisacetamide have been developed. They are already used in trials in human beings. However dimethylsulfoxide still has a very important role in bone marrow transplantation, being added to the frozen marrow as a cryoprotectant. We suggest that dimethylsulfoxide may induce differentiation of malignant cells present in the marrow or alternatively in the body when it is infused back with the transplanted marrow. This may be an additional factor contributing to the success rate achieved in various malignancies treated by transplantation, especially autologous, complementing the traditional explanations which are based mainly on the high dose chemotherapy and the immunological manipulations that occur during transplantation.

The Use of Dimethyl Sulfoxide (DMSO) in the Treatment of Interstitial Cystitis
A.EK.A. Engberg, L. Frodin and G. Jonson

Department of Urology, University Hospital, Uppsala and Department of Urology, University Hospital, Lund, Sweden

Scandinavian Journal of Urololgy and Nephrololgy 12:129-131, 1978

Abstract: Dimethylsulfoxide (DMSO) was used in 17 patients with interstitial cystitis. The diagnosis was made on the basis of clinical and laboratory findings and the characteristic picture with Hunner ulcera. The majority of the patients had responded poorly to other forms of conservative treatment. Subjective symptoms were controlled in 2/3 of the cases but repeated treatment was needed and 5 patients did not respond to the therapy. The DMSO treatment is an alternative worth to try and has, in some cases, a dramatic and lasting effect.

Dimethylsulfoxide with Heparin in the Treatment of Smoke Inhalation Injury
M. Brown, MD et al.

Journal of Burn Care Rehabilitation , Vol. 9 (1) 1988

DMSO significantly diminished the usual pulmonary lymphatic response to inhalation injury, presumably owing to inhibition of free radical-induced permeability changes.

Dimethyl Sulfoxide Antagonizes Hypotensive, Metabolic, and Pathologic Responses Induced by Endotoxin
Daniel J. Brackett, Megan R. Lerner, and Michael F. Wilson

Research Service, VA Medical Center and the Departments of Medicine and Anesthesiology, University of Oklahoma Health Sciences Center

Circulatory Shock 33:156-163 (1991)

There is evidence that free radical activity may be important in the development of endotoxemia. Dimethyl sulfoxide is a hydroxyl radical scavenger that readily penetrates cell membranes. Using the conscious, instrumented rat this study tests the ability of dimethyl sulfoxide to modify the course of endotoxemia by evaluating cardiovascular, metabolic, and tissue injury parameters for 4 hr after the toxic insult. Treatment with dimethyl sulfoxide (6.5 g/kg; i.p.) evoked significant decreases in cardiac output, stroke volume, and central venous pressure and increases in heart rate, systemic vascular resistance, mean aortic pressure, respiration rate, and concentrations of blood glucose and plasma lactate. Following endotoxin (40 mg/kg, i.v. LD90-24 hr), dimethyl sulfoxide pretreatment blocked the early hypotensive episode but all other cardiovascular and respiratory responses to endotoxin were essentially unaltered. The pH, PO2, PCO2, and hematocrit were the same for both treated and untreated groups; however, dimethyl sulfoxide prevented the endotoxin-induced hypoglycemia and significantly attenuated the hyperlacticemia at 4 hr. The severe hemorrhagic intestinal pathology characteristic of this model of endotoxemia was not present in the dimethyl sulfoxide treated group. From these results we conclude that dimethyl sulfoxide caused significant cardiovascular alterations conducive to impaired systemic blood flow. However, when administered prior to endotoxin, dimethyl sulfoxide induced significant beneficial modifications in the course of endotoxemia despite few improvements in cardiovascular function. The data indicate that the hydroxyl radical may be a mediator of tissue injury in this model of endotoxemia.

Dimethyl Sulfoxide in the Treatment of Scleroderma
Marvin F. Engel, MD,

Brunswick, Ga

The author reports a high rate of success in the management of the cutaneous manifestations of this disease by the topical use of this drug.

This paper can be considered a continuation of a study first reported before the Section on Dermatology of the Southern Medical Association in Houston in 1965; namely, "Dimethyl Sulfoxide (DMSO) in Clinical Dermatology." In that report I mentioned the remarkable improvement in 5 patients.with scleroderma treated with dimethyl sulfoxide.

Dimethyl Sulfoxide in the Treatment of Inflammatory Genitourinary Disorders
Sheridan W. Shirley, M.D.; Bruce H. Stewart, M.D.; Simon Mirelman, M.D.

From the Department of Urology, Cleveland Clinic Foundation, Cleveland, Ohio, and University of Alabama, Birmingham, Alabama

Abstract: Intravesical dimethyl sulfoxide (DMSO) has been used in the treatment of 213 patients with various inflammatory conditions involving the lower genitourinary tract, including intractable cystitis, radiation cystitis, chronic prostatitis, and chronic female trigonitis. Significant symptomatic relief has been achieved in the majority of patients so treated, and no systemic or local toxicity has been noted. Some patients failed to respond entirely, and others relapsed after DMSO treatment periods of several months, ultimately coming to augmentation cystoplasty or urinary diversion. However, because of its simplicity and ease of administration, intravesical DMSO therapy is recommended in all noninfectious or non-neoplastic inflammatory conditions presenting initially with severe symptoms, or that have failed to respond to conventional therapy.

Dimethyl sulfoxide in the management of patient with brain swelling and increased intracranial pressure after severe closed head injury
A. Kulalt, M. Akar L. Baykut

Neurosurgical Clinic of Dicle-University School of Medicine Dyarbakir, Turkey

Summary: The results of a prospective study on the effects of dimethyl sulfoxide (DMSO) in patients with severe closed head injuries causing brain edema and increase in intracranial pressure (ICP) are presented. 10 patients were selected and carefully analyzed according to Glasgow coma scale (GCS) scores and severity of brain edema. The results demonstrate that DMSO rapidly reduces the raised ICP, increases the cerebral perfusion pressure (CPP) and improves the neurological course and outcome without affecting the systemic blood pressure and patient responsiveness except only in one patient. We also point out that the rebound effect does not occur.

Radioprotective Effects of Dimethyl Sulfoxide in Golden Hamster Embryo Cells Exposed to Gamma Rays at 77 K, Protection from Lethal, Chromosomal, and DNA Damage
Masami Watanabe, Masao Suzuki, Keji Suzuki, Yuji Hayakawa; and Tetsuo Miyazaki

Division of Radiation Biology, School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236, Japan, and Department of Synthetic Chemistry,, Faculty of Engineering. Nugoya University, Chikusu-ku Nagaya 464, Japan

Radiation Research. 124, 73-78 (1990).

Golden hamster embryo cells were exposed to 137 Cs gamma rays in the presence or absence of dimethyl sulfoxide at both 310 and 77 K. Dimethyl sulfoxide gave significant protection against cell killing at both 310 and 77 K. The extent of radioprotection with 1.28 M dimethyl sulfoxide at 77 K was 85-89% of the lethal effects observed in the absence of dimethyl sulfoxide at 310 K: the dose modifying factor was 5.7. Dimethyl sulloxide also exerted protected against y-ray-induced DNA single-strand breaks and ehromosomal aberrations with a maximum protection of 8O-100'%, at a dimethyl sulfoxide concentration of 1.28 M at 77 K. At 77 K, H atoms. ion holes, and electrons can migrate through frozen cells but OH radicals cannot diffuse. thus the protective effects of dimethyl sulfoxide against cell killing, chromosomal aberrations, and DNA single-strand breaks at 77 K may be due to the scavenging of H atoms or other ions, rather than OH radicals. (1990 Academic Press, Inc.)

Pretreatment with catalase or dimethyl sulfoxide protects alloxan-induced acute lung edema in dogs
Tomoo Kawada, Kenjiro Kambara, Michio Arakawa, Takashi Segawa, Fumio Ando, Senri Hirakawa, Shoichi Emura, Shizuko Shoumura, and Hideo Isono

Second Department of Internal Medicine and First Departrnent of Anatomy, Gifu University School of Medicine, Gifu City, Gifu 500, Japan

Journal of Applied Physiololgy 73(4): 1326-1333, 1992.

Abstract: We tested the preventive effects of catalase, an enzymatic scavenger of hydrogen peroxide, or dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, on intravenous alloxan-induced lung edema in four groups of pentobarbital sodium-anesthetized, ventilated dogs for 3 h: saline (20 ml · kg-l · h-1) infusion alone (n = 5), alloxan (75 mg/kg) + saline infusion (n = 5), catalase (150,000 U/kg) + allaxan + saline infusion (n = 5), or DMSO (4 mg/kg) + alloxan + saline infusion (n = 5). Catalase or DMSO significantly prevented the increase in plasma thromboxane B2 and 6-keto-prostaglandin F, over 3 h after alloxan and the accumulation of extravascular lung water after 3 h [3.95 + 0.52 (SE) g/g with catalase, 3.06 + 0.42 g/g with DMSO, but not early pulmonary arterial pressor response. An electron microscopic study indicated that catalase or DMSO significantly reduced the endothelial cellular damages after alloxan. These findings strongly suggest that hydrogen peroxide and hydroxyl radical are major mediators responsible for intravenous alloxan-induced edematous lung injury in anesthetized ventilated dogs.

Regulation of Β-Adrenergic Responses during in Vitro Differentiation of Mouse Erythroleukemia Cells
Radmila Moudry and Hartmut Porzig

Department of Pharmacology, University of Bern, CH-3010 Bern, Switzerland

Experimental Cell Research 191, 278-285 (1990)

Dimethyl sulfoxide (DMSO)-induced erythroid differentiation of Friend mouse erythroleukemia (MEL) cells is associated with a marked transient modulation of catecholamine sensitivity. Within 24 h after induction and well before the onset of hemoglobin synthesis, we observed a 3-fold increase in Β-receptor density and a more than 10-fold increase in receptor-coupled cAMP formation. During the following 4 days, in parallel with the development of normoblast-like cells, receptor numbers returned to preinduction levels while catecholamine-dependent cAMP formation remained significantly elevated. Simultaneously, the apparent potency of the Β-adrenoceptor agonist isoprenaline increased 10-fold. Improved receptor-cyclase coupling is probably due to a major shift in the expression of G; and G. regulatory proteins. Bacterial toxin-mediated ADP-ribosylation of membrane proteins suggests that the dominating species in native cells is Gi (G,`~:Gi,, = 1:7). By contrast, G. predominates in differentiated cells (G,~,:G~, = 1.8:1). Receptor-independent forskolin-stimulated cAMP formation showed a pronounced, albeit transient, decrease during differentiation. We suggest that these changes in cellular cAMP responses may be important for transient positive or negative cooperative interactions between hormones and growth factors in the course of erythroid cell development.

Effect of dimethyl sulphoxide and some antibiotics on cultured human T-lymphoma cells as measured by microcalorimetry
Per Lonobro and Ingemar Wadso

Thermochemistry, Chemical Centre, University of Lund, Lund, Sweden

Journal of Biochemical and Biophysical Methods, 22 (1991) 331-336 331

Summary: The influence of dimethyl sulphoxide (1), penicillin/streptomycin (11). gentamicin (111), and amphotericin B (IV) on growing human T-lymphoma cells was measured by microcalorimetry. There was a dose-dependent decrease in the heat production rate of the cells after 24 h of incubation with I in concentrations ranging from 0-2% (v/v) At 3.6~, about half of the cells died. 11 and 111 had no effect on the cells after incubation for 6 days, at concentrations from I to 10 times that of the normal (50-500 lU/ml; 50-500 ~g/ml). IV was used in combination with 11 (50 lU/ml; 50 ~g/ml) and 111 (50 lig/ml), respectively, at concentrations between 0.25 and 7.5 lig/ml. After 6 days of incubation. the results were similar to those obtained with 11 and 111 separately.

Preliminary Test Using DMSO as a Vehicle for Drugs in Leprosy
Roy O. Yeats

Sopas Hospital, Wabag, New Guinea

Seventy per cent DMSO was employed as a vehicle to test the effect of three drugs on tuberculoid markings and other lesions of patients already receiving oral treatment with Dapsone. All were outpatients and were given two treatments weekly. This study was preliminary, with the intent to employ hospitalized patients for larger and more exact trials at a later period. The evaluation was unfortunately stopped when the United States Food and Drug Administration discontinued studies on dimethyl sulfoxide.

Ten mg per ml of Dapsone, Isoniazid, and Paraaminosalicylic Acid, respectively, were used in the tests. The solutions were applied with cotton applicators, leaving the skin wet and dripping. All patients were stationary; some had been under Dapsone treatment for as long as five years, some for only six months.

Dapsone-Eight Patients

In this group, one patient was found to have albuminuria, and was eliminated before application of DMSO. He was given three months without treatment, and was then able to take Dapsone orally. The remaining seven patients in the group received an average of 16 applications. Of these seven, four lost all traces of tuberculoid markings. One lost the tuberculoid markings on the buttocks, but not on the face. One patient, a late neural leper, showed no improvement. One, a late neural leper with leonine brows, lost all tuberculoid markings except a nodular area on the left forehead. One showed no change in tuberculoid markings.

Paruaminosalicyclic Acid-Seven Patients

This group had an average of 16 treatments. One patient after ten treatments is said to have died away from home, but no particulars were obtained. One, with a heavy leonine brow, had a marked reduction in the folds. One patient lost the tuberculoid markings on the back, but not on the abdomen. One with many neurofibromata on the legs lost several of these and other neurofibromata were reduced in size. One with fissures and ulcers on the feet seemed to be completely healed, and two lost all tuberculoid markings.

Isoniazid-Eight Patients

This group underwent an average of 15 7/8 treatments. One, with only seven treatments, had lost all tuberculoid markings when seen two weeks after the treatment period had finished. Multiple nodules all over this patient's body became softer. The nodules had not been biopsied, so it is not known what they actually were. One patient in this group lost the tuberculoid markings from his back, but not from the arm and buttocks. Six others lost all of the tuberculoid markings.

Summary

Three groups of patients with leprosy were treated with drugs in 70 per cent dimethyl sulfoxide as a skin wash. All of these were on Dapsone orally. Improvement in all three groups was rapid and marked, but about equal. This was a preliminary study, and while no control on DMSO alone was tested, it is considered probable that the improvement in each group was due to the DMSO rather than to the drug in solution.

An Alternative Method for the Determination of Dimethyl Sulphide in Beer
G. E. Otter and A. S. Marsh

J. Inst Brew. March - April, 1982. Vol. 88. pp. 76-79

Abstract

A method for the determination of dimethyl sulphide (DMS) in beer and for total DMS precursor in malt is described. The DMS was extracted into chloroform and determined by glass capillary gas liquid chromatography (GLC) using a flame ionisation detector (FID) and diethyl ether as an internal standard. Errors arising from the use of 'head space' sampling were thereby avoided. The reproducibility of results and the recovery of DMS at the 100 ppb level were satisfactory but less so at levels below 50 ppb. Beers produced in a pilot brewery from malts containing high levels of total DMS precursor were not found to contain correspondingly high levels of DMS.

Conclusion

The new method is satisfactory for the analysis of DMS in beer and for the determination of total DMS precursor in malt. Reproducibility was good at the 100 ppb level but results below 50 ppb were less reliable because the limits of detection are being approached. However, for sorting or quality control purposes the results are satisfactory providing that the lack of precision is recognised.

The taste threshold for DMS in American beers is quoted at 25 ppb and at 30 ppb for British beers. This method indicates that the lowest level, at which it is perceptible in British beers, is about 40 ppb but at these low levels the accuracy of the method is only plus or minus 25%.

The results obtained in pilot scale brews did not support the practicability of controlling DMS levels in beer by using malts with known levels of DMS precursor. There was no significant difference either in DMS content or DMS flavour in beers produced from malts containing high, medium, or low DMS precursor levels.

MSM Studies

Effects of Oral Dimethyl Sulfoxide and Dimethyl Sulfone on Murine Autoimmune Lymphoproliferative Disease
Jane L. Morton and Benjamin V. Siegel

Division of Arthritis and rheumatic Diseases and Department of Pathology
Oregon Health Sciences University, Portland, Oregon 97221

Proceedings of the Society of Experimental Biology and Medicine 183, 227-230 (1986)

Abstract. The results from several studies examining the effects of DMSO on autoimmune phenomena have been inconclusive, possibly because of differences in experimental models, treatment regimens and doses employed. In the present investigation, autoimmune strain MRL/lpr, C3H/lpr, and male BXSB mice were placed on a continuous treatment regimen with 3% DMSO or 3% DMSO₂ in the drinking water, ad libitum, commencing at 1 to 2 months of age, before spontaneous disease development could be detected. This represented doses of 8-10 g/kg/day of DMSO and 6-8 g/kg/day of DMSO2. Both compounds were observed to extend the mean life span of MRL/lpr mice from 51/2 months to over 10 months of age. All strains showed decreased antinuclear antibody responses and significant diminution of Iymphadenopathy, splenomegaly, and anemia development. Serum IgG levels and spleen IgM antibody plaque formation, however, did not differ from control values. There was no indication of involvement of systemic immunosuppressive or antiproliferative effects, and treated animals were observed to remain healthy and vigorous with no signs of toxicity. These results demonstrate that high doses of both DMSO and its major in vivo metabolite, DMSO₂, provide significant protection against the development of murine autoimmune Iymphoproliferative disease. Possible mechanisms of protection are discussed. ~ 1986 Society for Experimental Biology and Medicine