Background: Malaria is caused by a parasitic protozoan called Plasmodium with an estimated mortality rate of one million people annually and it is estimated that half of the world’s population are at risk for this disease.Objectives: The current study aimed to compare the effect of hydroxychloroquine and PYRIMETHAMINE with sulfadoxinePYRIMETHAMINE to treat Plasmodium berghei infection in mice. PYRIMETHAMINE, hydroxychloroquine and sulfadoxinePYRIMETHAMINE were used in the current study.Methods: Four groups of mice each including nine mice were selected. The mice were infected by intraperitoneally injection of Plasmodium bergheiinfected red blood cells. One group was considered as a positive control and three other ones received each one of the drugs. On days 4, 7, 14, 21 and 28, a blood smear was prepared from each mouse, stained with Giemsa and the parasitemia rate was calculated.Results: Parasitemia in the positive control group showed an increaseondays fourandseven at a level of 5.9% and 23.7%, respectively, which was statistically significant compared with the other groups (P<0.05). The parasitemia remarkably decreased in the group receiving sulfadoxine-PYRIMETHAMINE than in the one taking PYRIMETHAMINE (P<0.05). In addition, the mortality rate in mice treated with sulfadoxine-PYRIMETHAMINE was lower than those of the other groups (P<0.05). The survival time in the group treated with sulfadoxine-PYRIMETHAMINE was 28 days on average and in the group treated with PYRIMETHAMINE and hydroxychloroquine were 15.56 and 26.44 days, respectively.Conclusions: The results of the article suggested that malaria treatment strategy shifts completely from the monotherapy; therefore, the combination drugs should be used for this purpose, especially in endemic areas.

Background: Although PYRIMETHAMINE (Tindurin™) appears to be effective in the prevention and treatment of some infectious diseases, very little information exists on its unpredictable properties. We design this study to evaluate its anti-tumoral effect on a model of cell line.Methods: The cytotoxic influence of PYRIMETHAMINE on prostate cell line was investigated using an in vitro colometric assay. The potential modulatory effects on metastasis, apoptosis, and immortality characteristics of cells were assessed with gelatin zymography, terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and telomeric repeat amplification protocol, respectively.Results: Cytotoxicity analysis of PYRIMETHAMINE revealed a dosedependent fashion. An apoptotic influence of PYRIMETHAMINE was also confirmed by data obtained from TUNEL assay. Dose-dependent inhibitory effect on matrix metalloproteinases (MMP) was seen in PYRIMETHAMINE. A potent inhibitory effect of PYRIMETHAMINE was also established by data achieved from TRAPeze telomerase detection kit.Conclusions: Collectively, as induction of apoptosis together with MMP and telomerase inhibition could be indicative of cancer treatment, PYRIMETHAMINE might be considered as a chemopreventative agent in cancer.

Despite recent advances in burn wound management, sepsis remains the main cause of death in patients resuscitated after major thermal injury. Increased susceptibility to infections has been related to severe suppression of the immune system. The aim of this study was to induce immune suppression with blister fluid injection, and to modulate immune response by use of cimetidine and PYRIMETHAMINE in animal model.Male Balb/c mice were injected with blister fluid intrapritoneally (ip). Fluids were collected from parital-thickness burn blisters and then the delayed type hypersensitivity (DTH) to sheep red blood cell (SRBC) and the effects of different doses of immunomodulators (Cimetidine and PYRIMETHAMINE) on this response were quantitated.A marked suppression of DTH was observed in mice injected with blister fluid. PYRIMETHAMINE and Cimetidine at all three doses caused a significant enhancement of DTH response to SRBC compared with blister fluid injected in control group.This finding represents evidence of a host defense defect within the burn wound and also indicates the blister fluid exhibit immunosuppressor factor that can modulate with immunomadulatory drugs like cimetidine and PYRIMETHAMINE.

Background: Toxoplasmosis is a public health problem worldwide. This complication principally affects immunodeficient patients and pregnant women. Toxoplasma gondii is an opportunistic parasite, causing severe illness among and death of high-risk individuals and treatment is becoming increasingly difficult owing to side effects and low efficacies of drugs.Objectives: In this study, we investigated the anti-Toxoplasma gondii efficacy of propranolol in vivo.Materials and Methods: This study was performed in two separate pre-treatment and post-treatment groups. In each group, 18 female Balb/c mice in six subgroups (n=3) were used to assess the anti-Toxoplasma effect of propranolol at 2 and 3 mg/kg/day, PYRIMETHAMINE at 50 mg/kg/day, propranolol at 2 and 3 mg/kg/day plus PYRIMETHAMINE, and phosphate-buffered saline (PBS; as negative control). Treatment was performed 4, 24, and 48 hours before and after an intraperitoneal challenge of 1×103 tachyzoites of the virulent RH strain of T. gondii, in pre-treatment and post-treatment groups. Mice peritoneal exudates were collected on the seventh day after the challenge and parasite numbers were recorded as percent of growth inhibition and survival rate.Results: In the pre-treatment group, results showed that propranolol at 2 and 3 mg/kg combined with PYRIMETHAMINE was more effective in inhibiting growth of tachyzoites (86% and 98%, respectively) when compared with propranolol at 2 and 3 mg/kg (37% and 39%, respectively) and PYRIMETHAMINE (41%) alone. In the post-treatment group, all combined treatments significantly reduced parasite load. The growth inhibition of tachyzoites in mice receiving propranolol (2 and 3 mg/kg) was 75% and 51%, with the mean tachyzoites count being 1526±171.4 and 2948±1452.8, respectively, compared with PYRIMETHAMINE treatment outcome, which represents 99.9% growth inhibition.Conclusions: Our results demonstrated the promising prophylactic and therapeutic effects of propranolol against T. gondii infection. Propranolol also increases the efficacy of PYRIMETHAMINE in combination therapies.

Despite extensive world-wide research no effective therapy has been devised for the treatment and cure of patients exposed to sulfur mustard (S-M). A severe suppression of the immune system still remains the major cause of opportunist infections, septicemia and death in patients injured by S-M. In this report we present a model of S-M contamination in mice which is suitable for immunomodulation studies. Results show that differing doses of S-M caused an overall suppression of the immune response to SRBC as indicated by agglutination titers, (DTH) tests, spleen histology and spleen weight indices. In the second stage two immunomodulating agents; PYRIMETHAMINE and cimetidine were employed and their effectiveness in augmenting immune responses after S-M induced immunosuppression was evaluated. PYRIMETHAMINE, at all doses employed, enhanced antibody titers to SRBC, augmented DTH responses, and restored splenic follicles as compared with controls only ""posed to S-M. Cimetidine augmented antibody titers and enhanced DTH responses at doses of 10 and 15 mg/kg as compared with controls. At a dose of 5 mg/kg cimetidine did not exhibit any effect on titers or DTH responses. Histological studies revealed that cimetidine restored splenic follicles and increased macrophage numbers and phagocytic activity at all three doses. Spleen weight indices were not augmented by either drug. These data provide evidence that immunomodulating drugs may prove effective in countering the immunosuppressive effects of S-M.

Purpose: To compare the efficacy of classic treatment for ocular toxoplasmosis (PYRIMETHAMINE, sulfadiazine and predinsolone) with a regimen consisting of trimethoprim/sulfamethoxazole (TMP/SMX) [co-trimoxazole] plus predinsolone. Methods: In a prospective randomized single-blind clinical trial, 59 patients with activeocular toxoplasmosis were randomly assigned to two treatment groups: 29 were treated with PYRIMETHAMINE/sulfadiazine and 30 patients received TMP/SMX. Treatment consisted of six weeks treatment with antibiotics plus steroids. Anti-toxoplasmosis antibodies (IgM and IgG) were measured using ELISA. Outcome measures included changes in retinochoroidal lesion size after six weeks of treatment, visual acuity before and after intervention, adverse drug reactions during follow up and rate of recurrence. Results: Active toxoplasmosis retinochoroiditis resolved in all patients over six weeks of treatment with no significant difference in mean reduction in retinochoroidal lesion size between the two treatment groups (61% reduction in the classic treatment group and 59% in the TMP/SMX group, P=0.75). Similarly no significant difference was found in visual acuity after treatment between the two groups [mean visual acuity after treatment was 0.12 LogMAR (20/25) in classic treatment group and 0.09LogMAR (20/25) in TMP/SMX group, P = 0.56]. Adverse events were similar in both groups with one patient in each suffering from any significant drug side effects. The overall recurrence rate after 14 months of follow up was 6.7% with no significant difference between the treatment groups (P = 0.48).Conclusion: Drug efficacy in terms of reduction in retinal lesion size and improvement in visual acuity was similar between a regimen of TMP/SMX and the classic treatment of ocular toxoplasmosis with PYRIMETHAMINE and sulfadiazine. Therapy with TMP/SMX appears to be an acceptable alternative for the treatment of ocular toxoplasmosis.