The therapeutic and prophylactic role of oral zinc sulfate in management of recurrent aphthous stomatitis (ras) in comparison with dapsone.

OBJECTIVE: To evaluate the therapeutic and prophylactic effectiveness of oral zinc sulfate in recurrent aphthous stomatitis (RAS) in comparison with dapsone. METHODS: A double-blind placebo controlled study, conducted in the Department of Dermatology, Baghdad Teaching Hospitals, Baghdad, Iraq between May 2005 and October 2006, in which 45 patients with RAS were recruited and divided into 3 equal groups: group A (on zinc sulfate 150 mg twice daily), group B (on dapsone 50 mg twice daily), and group C (on glucose 250 mg as placebo). The drugs were prepared in identical capsules, and the patients were instructed to take the capsules twice daily after meals (in a double-blind manner). Assessment of each patient was carried out by the Oral Clinical Manifestation Index (OCMI) and the diameter of the ulcers at day 0, day 4, and at the second, fourth, sixth, eighth, tenth, and twelfth weeks of therapy. RESULTS: Forty-five patients were included in the study (25 males and 20 females), and their ages ranged between 16-45 years (mean+/-SD 31.24+/-8.14). In group A, the mean of OCMI and diameter of ulcers improved, with a p=0.0001 for OCMI, and 0.0001 for the diameter for ulcers at the end of the twelfth week of therapy, which was statistically significant. Group B, also showed significant improvement, however, the action was lower and slower (p=0.0001 for OCMI, and 0.001 for the diameter for ulcers). Group C revealed slight non-significant improvement (p=0.028 for OCMI, and 0.034 for the diameter of ulcers). In the sixth week of therapy, zinc sulfate was more effective than dapsone in reducing the OCMI of the ulcers (p=0.007). CONCLUSION: The present study showed that both zinc sulfate and dapsone had significant therapeutic and prophylactic effects in controlling RAS, however, zinc sulfate had much more rapid and sustained action.

Oxidative stress in patients with Behcet's disease: I correlation with severity and clinical parameters.

The study was designed to investigate the possible correlation between some oxidative stress parameters in Behcet's disease and the clinical manifestations of the disease as well as the possible correlation with the disease severity. Seventy-six patients diagnosed according to the International Study Group criteria for Behcet's disease were included in the study. Sixty patients had mild-to-moderate disease and 16 patients had severe disease. Sixty matched control subjects were also included. After a full history and examination from each subject, 10 mL blood was drawn from each for analysis. Serum malondialdehyde, glutathione, ceruloplasmin, copper and zinc levels were determined. Patients with Behcet's disease showed increased levels of serum malondialdehyde and copper while glutathione and zinc levels were decreased. Comparison between these parameters in patients with mild-to-moderate disease with those with severe disease showed only that serum zinc levels were lower in severe Behcet's disease. Serum malondialdehyde levels were found to be significantly positively correlated with oral ulcer size, duration and frequency. Glutathione levels were found to be inversely correlated with the clinical manifestation index and all oral ulcer parameters. Zinc levels were found to be inversely correlated with the clinical manifestation index and pathergy test positivity grades. Copper levels were found to be positively correlated with oral ulcer number. Although the parameters of oxidative stress did not show correlation with disease severity, they were correlated with the disease manifestations. This points out the importance of oxidative stress in Behcet's disease.

Oral zinc sulfate in the treatment of Behcet's disease: a double blind cross-over study.

This was a randomized, controlled, double-blind trial of zinc sulfate in the treatment of Behcet's disease. Patients with Behcet's disease were recruited in this study between November 2001 and February 2003. A clinical manifestations index (CMI) was calculated for each patient. Serum zinc was estimated in all patients both at the beginning and monthly throughout the trial. Serum zinc levels were estimated from 30 healthy normal subjects matched for age and sex as a control group. Patients were randomly allocated to receive either 100 mg zinc sulfate or identical placebo tablet three times daily in a double-blind manner. After 3 months of starting treatment, patients were crossed over, that is, patients on placebo received zinc sulfate and vice versa. Mean serum zinc level in Behcet's disease patients was statistically significantly lower than mean serum zinc levels in healthy the control. In group A (started with zinc sulfate), the mean CMI started to decline directly after the first month of therapy with zinc sulfate to significantly lower levels. After shifting to placebo treatment in the fourth month, the mean of CMI started to rise again gradually but remained significantly lower than levels before therapy for the fourth and fifth months. In group B (started with placebo), the mean of CMI remained high for the first 3 months. After crossing over to zinc sulfate in the fourth month, the mean of CMI started to decrease after the fourth month. An inverse correlation between CMI and serum zinc level was found. No side-effects were seen in either group. In conclusion, zinc sulfate was found to be a good option in the treatment of Behcet's disease.

Oral zinc sulfate in the treatment of rosacea: a double-blind, placebo-controlled study.

BACKGROUND: Rosacea is a skin problem not uncommonly encountered world-wide. There is a need for an effective and well-tolerated treatment for this disease. OBJECTIVE: To evaluate the efficacy and side-effects of zinc sulfate in rosacea in a randomized, controlled, double-blind trial. PATIENTS AND METHODS: Patients with rosacea who attended the outpatient Clinic of Dermatology and Venereology in Baghdad Teaching Hospital were recruited into this study between October 2002 and August 2004. A disease severity score was calculated for each patient. The patients were randomly allocated to receive either zinc sulfate 100 mg or identical placebo capsules three times per day. Zinc sulfate and placebo capsules were given in a double-blind manner. Following 3 months of starting the treatment, the patients crossed over, i.e. patients on placebo crossed over to zinc sulfate and those on zinc sulfate crossed over to placebo. RESULTS: Twenty-five patients with rosacea were included in this study: 16 (64%) females and nine (36%) males. Nineteen patients completed the study: 11 (58%) females and eight (42%) males. Patient age ranged from 21 to 64 years with a mean +/- SD of 48.2 +/- 9.3 years. Duration of the disease ranged from 1 to 14 years with a mean +/- SD of 4.4 +/- 3.2 years. In the group started on zinc sulfate, the score before therapy ranged from 5 to 11 with a mean +/- SD of 8 +/- 2.0. The mean started to decrease directly after the first month of therapy with zinc sulfate to a significantly lower level. After shifting to placebo treatment, the mean started to rise gradually in the fifth month but remained significantly lower than the levels before therapy. In the group started on placebo, the score before therapy ranged from 5 to 9 with a mean +/- SD of 7 +/- 1.3. The mean remained high in the first 3 months of therapy while the patients were on placebo. After shifting to zinc sulfate, the mean started to decrease after the fourth month to significantly low levels. No important side-effects were reported apart from mild gastric upset in three (12%) patients on zinc sulfate. CONCLUSION: Zinc sulfate was found to be a good option in the treatment of rosacea, as it was safe, effective and lacking important side-effects.

Leishmania major and Leishmania tropica: II. Effect of an immunomodulator, S(2) complex on the enzymes of the parasites.

S(2) complex has been reported to have a direct antileishmanial effect. The possibility that the direct antileishmanial effect may be due to inhibition of key enzymes involved in glucose metabolism and/ or enzymes associated with virulence was investigated. Cell pellets were prepared from cultures of both axenic amastigotes and promastigotes of Leishmania major (MHOM/IQ/93/MRC6) and L. tropica (MHOM/IQ/93/MRC2). S(2) complex, at various concentrations, was added to the enzyme extracts prepared from the pellets. Results show that in the Embden-Meyerhof pathway, both hexokinase and glucose-phosphate isomerase but not fructophosphokinase were dose dependently inhibited. In the hexose-monophosphate shunt both glucose-6-phosphate dehydrogenase and ribose-5-phosphate isomerase were dose dependently inhibited. Malic dehydrogenase and malic enzyme from the citric-acid cycle were both dose dependently inhibited but succinate dehydrogenase from the same pathway was not inhibited. Both enzymes associated with virulence (protease and acid phosphatase), showed activation rather than inhibition at higher doses of S(2) complex. Thus, the direct antileishmanial effect of S(2) complex may result, partially or entirely, from the inhibition of enzymes that are necessary for the parasites' carbohydrate metabolism.

Clinical and radiological response and side effects of beta interferon in Iraqi patients with relapsing and remitting multiple sclerosis.

OBJECTIVE: To determine the efficacy and tolerability of subcutaneous Interferon beta 1a (IFNbeta-1a) among Iraqi patients with relapsing remitting multiple sclerosis (RRMS). METHODS: The study was held at the Multiple Sclerosis clinic at Baghdad Teaching Hospital, Baghdad, Iraq from January-October 2004. Thirty-seven patients with clinically definite RRMS and disability status scale below 6.5 were enrolled in this study. Patients received IFNbeta-1a, 22 ug subcutaneously 3 times a week. Clinical measures, including number of relapses and disability progression, with MRI measures including number, size activity of lesions, and brain atrophy were used for evaluation of response to treatment. Side effects were also looked for. RESULTS: Patient ages ranged between 17-60 years with a mean age of 34.85 years, with 20 female patients and 17 male patients. After 2 years of treatment, there was a significant reduction in relapse rate (54.1% were relapse free, and 21.6% had reduction in relapse rate). There was also a significant effect on disability progression (the mean expanded disability status scale (EDSS) before treatment was 3.22 and mean EDSS after treatment was 2.84). Significant effects on MRI measures were also shown, presented by a reduction in the number of lesions, which was seen in 64.9% of the patients, and a reduction in the size of lesions, which was seen in 64.9% of the patients. Also, significant effects on the activity of lesions was seen, as 67.6% of the patients had non-active lesions before treatment and remained non-active after treatment, and 29.7% of the patients had active lesions before treatment, which became non-active after 2 years of treatment. Mild adverse reactions were seen, mainly influenza like reactions and injection site reactions. CONCLUSION: Interferon beta-1a was effective in the treatment of RRMS with minimal side effects.

Acetylator phenotype in Iraqi patients with atopic dermatitis.

Atopic dermatitis (AD) is a common multifactorial disease which has an itchy, recurrent, flexural and symmetrical eczematous eruption. There are reports that indicate that AD is associated with a predominantly slow acetylator status. This study was designed to determine the acetylator status in children with AD and compare it to a matched group of normal children. The study included 36 AD patients diagnosed clinically and 42 healthy controls. Detailed history was taken from the parents of each patient and disease severity was assessed using the Hanifin-Rajka scoring system. After overnight fast, each control subject and patient received a single oral dose of 50 mg of dapsone; a blood sample was collected after 3 hours and plasma separated for determination of dapsone and monoacetyldapsone by HPLC. The frequency of slow acetylators in the control group was 69.4 percent, and the frequency of rapid acetylators was 30.6 percent. The frequency of slow acetylators in AD patients was 72.2 percent and the frequency of rapid acetylators was 27.80 percent. There were no statistically significant differences between the control and AD patients groups. There was an association in AD patients between the acetylator status and family history of allergy as well as the severity assessed the Hanifin-Rajka scoring system. Although slow acetylators had lesions predominantly on the limbs, the distribution of lesions on the skin of rapid acetylators favored the face and neck. Although a slow acetylator status does not predispose to AD, it is associated with a different severity and distribution of the disease.

Leishmania major and Leishmania tropica: I the in vitro effects of an immunomodulator, S2-Complex.

This study was undertaken to try to determine the possible anti-leishmanial activity of S2-Complex, an organic complex of copper chloride, ascorbic acid, and nicotinamide. The promastigotes, axenic amastigotes, and intracellular amastigotes of both Leishmania major and Leishmania tropica were incubated with different concentrations of S2-Complex. The EC50 for each form was calculated. Results show that all forms of the parasites were dose dependently inhibited by S2-Complex. The promastigotes of both parasites were the most resistant with highest EC50 followed by axenic amastigotes. While intracellular amastigotes were the most sensitive with the lowest EC50. These results indicate that S2-Complex has a direct anti-leishmanial effect. When mice were treated with S2-Complex or BCG for four days before harvesting the macrophages, and the macrophages infected with both L. major and L. tropica, they showed increased phagocytosis and increased parasite killing. The results of S2-Complex were not statistically different from the immunomodulating agent BCG. These results indicate that S2-Complex has an immunomodulating effect in addition to the direct anti-leishmanial effect.

Acetylator phenotype in Iraqi patients with allergic contact dermatitis.

BACKGROUND: Few studies have been done on acetylator status in ACD. This study determined acetylator status in Iraqi patients with allergic contact dermatitis (ACD) in comparison to a matched control group. PATIENTS AND METHODS: The study included 35 ACD patients and 67 healthy volunteers. The ACD patients were diagnosed clinically and the diagnosis was confirmed by patch test. A detailed history wastaken from the patients. After an overnight fast, each control subject and each patient received a single oral dose of 100 mg of dapsone. A blood sample was collected after 3 hours and plasma was separated for determiination of dapsone and monoacetyldapsone by HPLC. RESULTS: Twenty-six of the 35 ACD patients returned for follow up. The frequency of slow acetylators in healthy individuals was 71.6%, while the frequency of rapid acetylators was 28.4%. The frequency of slow acetylators in ACD patients was 60.0% while the frequency of rapid acetylators was 40.0%. There was no association between the acetylator status, personal history of allergy, patch-test positivity or sites of dermatitis in ACD patients. CONCLUSION: A rapid acetylator status might predispose to ACD, but does not seem to influence other features of the disease.

Disseminated cutaneous leishmaniasis.

Disseminated cutaneous leishmaniasis DCL is a condition rarely seen in the Middle East. We report a case of disseminated cutaneous leishmaniasis in a 60-years-old lady. The patient first presented 1996 with an initial lesion, which started on the butterfly area of the face and spread, probably due to immunosuppression, to involve the whole face. The lesions consisted of nodules, which did not ulcerate. The histology showed abundance of macrophages filled with amastigotes L-D bodies. The patient was started on oral zinc sulphate 10 mg/kg in 3 divided doses daily. The condition showed gradual improvement. Repeated biopsies showed upgrading of the histopathological picture. After 6-months of treatment there was complete clearance of the condition. The patient was followed up for 6-years with no recurrence. However, she presented with a new lesion on the butterfly area again in February 2003. The biopsy again showed abundance of macrophages filled with amastigotes L-D bodies. A 4-months course of zinc sulphate 10 mg/kg in 3 divided doses daily resulted in complete clearance of the lesions. Zinc sulphate might represent a new treatment for this condition that has no adequate treatment until now.

Acetylator phenotype in Behçet's disease.

The purpose of this study was to determine the acetylator status in Behçet's disease (BD) patients and compare it to a matched group of normal individuals. Thirty-seven healthy volunteers and forty-one BD patients were included. Detailed history was taken from the patients. HLA-B51 was determined in the BD patients. In addition, the Clinical Manifestation Index (C.M.I.) was determined for each patient. Pathergy test was also done. After an overnight fast, each control subject and patient received a single oral dose of 100 mg of DDS. A blood sample was collected after 3 hours and the plasma was separated for determination of dapsone/monoacetyldapsone by HPLC. The frequency of slow acetylators in healthy individuals was 70.2%, while the frequency of rapid acetylators was 29.8%. The frequency of slow acetylators in BD patients was 53.7%, while the frequency of non-acetylators (undetected monoacetyldapsone MADDS in plasma) was 46.3%. There were no rapid acetylators among the BD patients. There was a strong negative association between the acetylator status and the severity of BD. In addition, acetylator status correlated with HLA-B51, in that BD patients with positive HLA-B51 were characterized by a very slow or non-acetylator status. Slow or non-acetylators had more severe BD. We conclude that BD patients have a unique acetylator status. This finding may have implications for the theories for the pathogenesis of the disease as well as for therapeutic aspects.

Drugs acting at the GABAA receptor attenuate ethanol-induced gastric mucosal damage in vitro.

1. Benzodiazepines (BZ) have been reported to protect against ethanol-induced gastric damage in rats in both in vivo and in vitro models. However, the effects of some drugs in the new in vitro model do not agree with results reported previously in in vivo studies. 2. Therefore, the aim of the present study was to modify the new in vitro model to a model that more closely resembles the in vivo model and, using the new in vitro model, to reassess the gastroprotective effects of some BZ and to assess the effects of some new compounds. 3. The rat stomach was isolated from the whole animal and kept in aerated Krebs' solution at 37 degrees C in an organ bath. Gastric mucosal damage was induced by instillation of 1 mL of 100% ethanol into the stomach. Drugs or their vehicle were administered inside the bath 15 min before ethanol instillation into the stomach. One hour after the instillation of ethanol, the stomach was removed from the organ bath, opened along the greater curvature and then examined for gastric mucosal damage. 4. The results indicate that, compared with vehicle pretreatment, ethanol-induced gastric mucosal damage was significantly reduced in a dose-dependent manner by pretreatment with clonazepam, a drug that acts as an agonist at central BZ sites of the GABAA receptor, and Ro 15-4513, a partial inverse agonist at BZ sites of the GABAA receptor. Flumazenil (an antagonist of central BZ sites of the GABAA receptor) did not affect gastric mucosal lesions provoked by ethanol. However, flumazenil significantly reversed the mucosal protective effects of clonazepam and Ro 15-4513. 5. CGS 9896 (a partial agonist at BZ sites of the GABAA receptor, with anxiolytic and anticonvulsant but no sedative effects) did not offer any protection against ethanol-induced gastric mucosal damage. Ro 5-3663, an atypical BZ that binds to the picrotoxin site of the GABAA receptor and reported to be a potent convulsant and only a weak antagonist of GABA, did not show any protection against the development of lesions. 6. The results suggest local gastric mediation of the effects of ethanol, as well as the gastric protective effects of BZ, through an action at local central-type BZ sites of the GABAA receptor located in the rat stomach.

Dapsone in Behçet's disease: a double-blind, placebo-controlled, cross-over study.

The study was designed to investigate the effects of dapsone in the treatment of mucocutaneous manifestations of Behçet's disease and the possible prophylactic role of dapsone in a double blind/placebo controlled clinical trial. Twenty patients diagnosed according to the International Study Group criteria as Behçet's disease were included in the study. Patients were randomly allocated to receive either dapsone 100 mg daily or placebo for three months in a double-blind manner. After three months, patients were crossed over and followed for a further three months. Patients were followed up in each visit by assessing the number, size, duration and frequency of oral and genital ulcers, other cutaneous manifestations, and systemic manifestations of the disease. A pathergy test was done on each visit. Laboratory investigations included hemoglobin concentration, white blood cell count, ESR, and C-reactive protein. In dapsone-treated patients, there were significant reductions in the oral and genital ulcer parameters as well as the incidence of other cutanous and systemic manifestations. In the placebo-treated group, there were no significant changes in these parameters. The pathergy test result as well as those of other laboratory tests were all decreased in the dapsone-treated group. Although this study was a small scale study, it shows that dapsone was effective in treatment of mucocutaneous manifestations of Behçet's disease and possibly in prophylaxis against systemic manifestations of the disease. This result should lead to a larger scale study with a longer duration of follow-up.

Zinc sulphate in the treatment of cutaneous leishmaniasis: in vitro and animal study

This study was designed to evaluate the effectiveness of zinc sulphate both in vitro and in an animal model against both strains of old world cutaneous leshmaniasis. The in vitro sensitivities of promastigotes and axenic amastigotes of both Leishmania major and L. tropica to zinc suphate was determined, the LD50 calculated and compared to the standard treatment for cutaneous leishmaniais pentavalent antimony compounds. The results show that the two forms of both strains were sensitive to zinc sulphate and their respective LD50 were lower compared to the pentavalent antinomy compound. Furthermore the sensitivities of the forms of both strains were tested using a simple slide method and compared to results of the standard method. To confirm this result, zinc sulphate was administered orally to mice infected with cutaneous leishmaniasis both therapeutically and prophylactically. Results showed that oral zinc sulphate was effective in both treatment and prophylaxis for cutaneous leishmaniasis. These results encourage the use of oral zinc sulphate in the treatment of cutaneous leishmaniasis clinically.