The use of sulfasalazine and pentoxifylline (low-cost antitumour necrosis factor drugs) as adjuvant therapy for the treatment of pemphigus vulgaris: a comparative study.

BACKGROUND: Pemphigus vulgaris (PV) represents a potentially life-threatening autoimmune blistering disease in which IgG autoantibodies are directed against cell-cell adhesion molecules. Tumour necrosis factor (TNF)-alpha has been suggested to have a possible role in the mechanism underlying acantholysis. OBJECTIVES: This comparative double-blinded study was carried out to estimate the use of both sulfasalazine (SSZ) and pentoxifylline (PTX) (low-cost anti-TNF drugs) as an adjuvant therapy for PV. METHODS: The study included 64 patients with PV: 42 patients received the full treatment regimen (with SSZ and PTX) and 22 patients followed the same regimen except they received placebo instead of PTX and SSZ. Five healthy subjects were included as controls. Serum samples were taken to measure TNF-alpha levels in the control group and before starting treatment in both the patient groups and this was repeated every 2 weeks for 8 weeks; a clinical assessment was made every week for all the patients. RESULTS: The serum level of TNF-alpha was statistically higher in both groups of patients than in the healthy individuals. There was a statistically significant decrease in the serum levels of TNF-alpha in patients in group 1 compared with those in group 2 at 6 and 8 weeks. There was also a significant clinical improvement in patients in group 1 compared with those in group 2. CONCLUSION: The use of PTX and SSZ as adjuvant therapy in the treatment of PV induced a faster and more significant decrease in the serum level of TNF-alpha, and this decrease was associated with rapid clinical improvement.

Evaluation of the therapeutic and protective effects of ivermectin and permethrin in controlling of wound myiasis infestation in sheep.

The aim of this study was to evaluate the therapeutic and protective efficacy of ivermectin and permethrin against wound myiasis induced by fleshflies in Riyadh region in sheep. Three different protocols were planned to evaluate efficacy of the selected drugs in addition to recording the myiasis incidence and prevalence among infested farms. The obtained results revealed that genital organs were the most common sites of infestation with myiasis in male and females, with high prevalence in spring and autumn seasons and complete disappearance in summer and winter seasons. Application of permethrin and ivermectin resulted in significant reduction in the number of live larvae in comparison with control, untreated group. Both drugs significantly protected sheep against re-infestation, with full protection recorded for 22 days in ivermectin-treated group, whereas permethrin only produced partial protection for 13 days. Ivermectin appeared more effective than permethrin in eradication of larvae from infested wounds. In addition, ivermectin significantly protected sheep from fatal outcomes of the infestation, and the emergence rate of pupa to adult was significantly reduced in ivermectin-treated animals.

Central serotonin level-dependent changes in body temperature following administration of tryptophan to pargyline- and harmaline-pretreated rats.

1. The effect of tryptophan on body temperature was studied in rats pretreated with pargyline, an irreversible monoamine oxidase inhibitor (MAOI), and harmaline, a reversible MAOI. 2. Tryptophan (100 mg/kg IP) produced hypothermia followed by hyperthermia in pargyline-pretreated rats, and hypothermia in harmaline-pretreated rats, but tryptophan did not cause body temperature changes by itself. 3. The tryptophan-induced hypo- and hyperthermic effects, which peaked at about 1 and 6 hr after tryptophan administration, respectively, were accompanied by a significant increase in serotonin (5-HT) levels in the pargyline-pretreated rat brain (75%-138.7% and 207%-240.9% increase, respectively), and the 5-HT levels in the hyperthermic state were significantly higher than those in the hypothermic state. 4. In harmaline-pretreated rats, tryptophan also increased the central 5-HT levels (80.5%-95.5% increase) in the hypothermic state, and the effect peaked at about 1 hr after tryptophan administration. The central 5-HT levels in harmaline-pretreated rats slightly decreased at 6 hr after tryptophan administration and were significantly lower than those in the hyperthermic state in the pargyline-pretreated rats. 5. Tryptophan (100 mg/kg IP) administration decreased 5-hydroxy indole acetic acid (5-HIAA) levels, 5-HT turnover, and dopamine (DA) turnover in the brain of pargyline-pretreated rats, but these parameters were not significantly different between the hypothermic and hyperthermic states (i.e., at 1 and 6 hr after tryptophan administration, respectively). 6. These results suggest that the tryptophan-induced body temperature change depends on the different 5-HT levels in the brain and that the 5-HT level needed to induce hyperthermia is higher than that needed to induce hypothermia.

Hypothermic effect of harmala alkaloid in rats: involvement of serotonergic mechanism.

The effect of total alkaloid extracted from Peganum harmala seeds collected in Egypt on body temperature was studied in rats. Intraperitoneal administration of the Peganum harmala extract produced significant and dose-dependent hypothermia. Similarly, harmine and harmaline, major constituents of the harmala alkaloid, lowered the body temperature. Pretreatment with p-chlorophenylalanine (100 mg/kg/day for 3 days), a 5-HT synthesis inhibitor, significantly attenuated the hypothermic effect of the total alkaloid and harmine, while it tended to block the hypothermic action of harmaline. Methysergide (2 mg/kg), a 5-HT antagonist, significantly attenuated the hypothermia induced by harmala alkaloids. Pindolol (0.05-2 mg/kg), a 5-HT1A receptor and beta-adrenoceptor antagonist, partly blocked the hypothermic effect of the harmala alkaloids in a dose-dependent manner, whereas propranolol (10 mg/kg), a beta-adrenoceptor antagonist, failed to alter it, suggesting that beta-adrenoceptor is not involved in the hypothermia caused by the alkaloids. Pretreatment with a dopamine receptor antagonist haloperidol (5 mg/kg, s.c. and 2 mg/kg, i.p. 24 and 2 h before the experiment, respectively) significantly attenuated the hypothermic effect of harmala alkaloids. Moreover, in haloperidol pretreated rats, methysergide (2 mg/kg, i.p.) and pindolol (0.05 and 2 mg/kg) completely attenuated the hypothermic effect of the alkaloids. These data suggest that harmala alkaloids produce hypothermic effect mainly through endogenous 5-HT stimulation of 5-HT1A receptor.