Comparison of pro-inflammatory cytokines of non-healing and healing cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) heals spontaneously within several weeks or months, but, in rare cases, CL-active lesions last for many years. In this study, we assessed cell-mediated immunity in non-healing CL through the measurement of three pro-inflammatory cytokines: Interferon-γ (IFN-γ), IL-17a and CXCL-11. For this, 32 patients afflicted with healing or non-healing CL were recruited in this study. Peripheral blood mononuclear cells (PBMCs) of every patient were treated with three antigens: purified protein derivative (PPD), soluble Leishmania antigen (SLA) and phytohaemagglutinin (PHA). Cytokine quantification was performed using enzyme-linked immunosorbent assay (ELISA) method. Results of our study showed that neither cytokine produced in the presence of a PPD stimulator (as an irrelevant antigen) significantly differed between the healing and non-healing groups (P-value ≥0.05 for all of them). However, IFN-γ, CXCL-11 and IL-17a levels produced in the presence of PHA or SLA were significantly higher within the healing than in the non-healing group (P-value <0.01 for all of them). It seems that appropriate levels of IFN-γ, as well as IL-17a and CXCL-11, contribute to the control of Leishmania infection.

Treatment of localized psoriasis with a topical formulation of zinc pyrithione.

BACKGROUND: Psoriasis is a common chronic condition of the skin that is resistant to many therapies. AIM: To test the efficacy of a topical formulation of zinc pyrithione in an emollient base compared with an emollient alone in the treatment of psoriasis. METHODS: This was a randomized double-blind clinical trial. Patients with localized psoriasis involving less than 10% of body skin areas were enrolled in the study. They were randomly allocated to one of two treatment groups. Group A was treated with emollient cream containing 0.25% zinc pyrithione and group B was treated with emollient cream alone twice daily for 3 months. Response to treatment was assessed using PASI scores. RESULTS: Of 60 participants, 30 patients in group A and 30 patients in group B completed the study. The mean PASI scores before and after treatment were 3.4±1.8 and 0.9±1.3 in group A (p<0.01), and 4.3±2 and 3.9±1.3 in group B (p>0.05), and there was a significant difference between the two groups' mean PASI scores at the end of the study (p<0.01). The differences in the mean PASI scores before and after treatment were 2.4±2 and 0.4±0.1 in groups A and B, respectively (p<0.01). CONCLUSION: A topical formulation of zinc pyrithione can be used to treat localized psoriasis.

Cloning, expression and dynamic simulation of TRYP6 from Leishmania major (MRHO/IR/75/ER).

Leishmania, a digenetic protozoan parasite causes severe diseases in human and animals. Efficient evasion of toxic microbicidal molecules, such as reactive oxygen species and reactive nitrogen species is crucial for Leishmania to survive and replicate in the host cells. Tryparedoxin peroxidase, a member of peroxiredoxins family, is vital for parasite survival in the presence of antioxidant, hence it is one of the most important molecules in Leishmania viability and then, it may be an appropriate goal for challenging against leishmaniasis. After cloning and sub-cloning of TRYP6 from Leishmania major (MRHO/IR/75/ER), homology modeling of the LmTRYP6 was proposed to predict some functional property of this protein. The refined model showed that the core structure consists of a seven ß stranded ß-sheet and five α helices which are organized as a central 7-stranded ß2-ß1-ß5-ß4-ß3-ß6-ß7 surrounded by 2-stranded ß-hairpin, α helices A and D on one side, and α helices B, C and E on the other side. The peroxidatic active site is located in a pocket formed by the residue Pro45, Met46, Thr49, Val51, Cys52, Arg128, Met147 and Pro 148. The catalytic Cys52, located in the first turn of helix αB, is in van der Waals with a Pro45, a Thr49 and an Arg128 that are absolutely conserved in all known Prx sequences. In this study, an attractive molecular target was studied. These results might be used in designing of drugs to fight an important human pathogen.

Karyosystematic and morphometric characterization of the rodents as reservoir hosts of zoonotic cutaneous leishmaniasis in an endemic focus of Isfahan Province, Iran.

BACKGROUND & OBJECTIVES: Rodents belonging to Gerbillinae subfamily are the main reservoir hosts of zoonotic cutaneous leishmaniasis (ZCL) in Iran. Regarding the important role of these rodents in the maintenance of Leishmania major in the nature, their identification with morphometric, cytogenetic and molecular methods seems to be essential. The karyotype study of these species, captured from a new focus of zoonotic cutaneous leishmaniasis located in the south of Isfahan Province was carried out in 2007. METHODS: Twenty specimens containing seventeen Meriones persicus and three Nesokia indica were captured from Mobarakeh rural district south of Isfahan. Giemsa-stained karyotypes of these two species were prepared from bone marrow chromosome preparations. Systematic important characters of the body and cranium (incisors, molars, occipitonasal, condylobasal, zygomatic, tympanic bullae, etc.) of these rodents were studied. Cranium size was measured using a Vernier calipers. RESULTS: Specimens of M. persicus and N. indica had 2n = 42. The karyotype study of these species included metacentric, sub-metacentric and acrocentric chromosomes. Morphological studies were completely matched with the reported characters of these species and further confirmed the diagnoses. INTERPRETATION & CONCLUSION: Based on the results of this study, M. persicus and N. indica are two completely differentiated rodents species that were collected from a new focus and they can also be differentiated morphologically.

A comparative study between the efficacy of systemic meglumine antimoniate therapy with standard or low dose plus oral omeprazole in the treatment of cutaneous leishmaniasis.

BACKGROUND & OBJECTIVES: Pentavalent antimony compounds are the first line of drugs in the treatment of cutaneous leishmaniasis. However, because of their potential toxic effects, many investigations are performed to find an effective and safe treatment for cutaneous leishmaniasis patients. Our objective in this investigation was to compare the effect of oral omeprazole and low dose systemic meglumine antimoniate (MA) and standard dose of systemic MA in the treatment of cutaneous leishmaniasis. METHODS: This was a randomized double-blinded clinical trial. In 150 patients with cutaneous leishmaniasis who were randomly divided into three groups and were treated with: (i) MA 60 mg/kg/day/ IM and oral placebo for three weeks; (ii) MA 30 mg/kg/day/IM and oral omeprazole 40 mg/day for three weeks; and (iii) MA 30 mg/kg/day/IM and oral placebo for three weeks. All the patients were visited every two weeks from the beginning of the trial up to six weeks and then at 8 and 12 weeks. The effectiveness of the treatment was classified in three levels as complete response, partial response and no response. Data were analyzed by SPSS 10 using KI square, Mann-Whitney, Kaplan-Mayer and ANOVA tests. RESULTS: Rate of complete response for three months (12 weeks) after starting the treatments was 93% for the group treated with standard dose of glucantime and placebo, 89% for the group treated with omeprazole and low dose glucantime and 80% for the group treated with low dose glucantime and placebo and these differences were significant (p < 0.05). The highest response rate was for the group treated with standard dose of glucantime and placebo. INTERPRETATION & CONCLUSION: Although oral omeprazole and low dose of systemic MA showed less efficacy in comparison to standard dose of systemic MA in the treatment of cutaneous leishmaniasis, it still can be considered as a replacement therapy in high risk patients (such as patients with heart, kidney and/or liver disease) under close supervision of physician.

Comparison of Thymus vulgaris (Thyme), Achillea millefolium (Yarrow) and propolis hydroalcoholic extracts versus systemic glucantime in the treatment of cutaneous leishmaniasis in balb/c mice.

BACKGROUND & OBJECTIVES: Leishmaniasis is a parasitic disease transmitted by sand flies. Many investigations are performed to find an effective and safe treatment for leishmaniasis. In this study, we evaluated the efficacy of herbal extracts of Thymus vulgaris (Thyme) and Achillea millefolium (Yarrow), propolis hydroalcoholic extract and systemic glucantime against cutaneous leishmaniasis in Balb/c mice. METHODS: A total of 45 mice were randomised into five groups each including nine mice. They were treated with pure ethanol 70 degrees, systemic glucantime, Achillea millefolium hydroalcoholic extract, Thymus vulgaris hydroalcoholic extract and propolis hydroalcoholic extract for six weeks. The statistical tests including student t-test were used for analysis. Data were analyzed by SPSS software, ver 13.00. RESULTS: Mean of ulcer size reduction were -17.66, -22.57, 43.29, 36.09 and 43.77% for the alcohol, glucantime, yarrow, thyme and propolis groups, respectively. The results were suggestive that Thymus vulgaris, Achillea millefolium and propolis hydroalcoholic extracts were significantly more effective in reduction of ulcer size as compared with glucantime (p = 0.006, 0.002 and 0.008, respectively). INTERPRETATION & CONCLUSION: Our results are suggestive that Thymus vulgaris, Achillea millefolium and propolis extracts are effective for treatment of cutaneous leishmaniasis in mice. Regarding these results, we suggest that efficacy of these extracts alone or in combination are evaluated against human cutaneous leishmaniasis as a randomized clinical trial.

Effect of combination therapy with systemic glucantime and pentoxifylline in the treatment of cutaneous leishmaniasis.

INTRODUCTION: Cutaneous leishmaniasis is a common parasitic disease in Iran, especially in Isfahan. First line treatment for this disease is antimonial compounds; however, owing to the intermittent failure of this treatment and its significant side-effects alternative therapeutic measures have been advocated. OBJECTIVE: Evaluating the efficacy of pentoxifylline plus glucantime in the treatment of cutaneous leishmaniasis. METHODS: This double-blind, randomized, controlled clinical trial with simple sampling was performed on 64 patients with cutaneous leishmaniasis referred to the Skin Diseases & Leishmaniasis Research Center from an endemic foci of L. major in Isfahan. The patients randomly were divided into two groups. One group was treated with systemic Glucantime (20 mg pentavalent antimony/kg/day) combined with pentoxifylline (400 mg three times daily) and the other group were treated with Glucantime (20 mg pentavalent antimony/kg/day) plus placebo (three tablets daily) for 20 days. Follow up lasted 3 months. Response to treatment was grouped as complete improvement (lesions had been flattened, no induration, and epidermal creases had appeared), partial improvement (reduction in lesion size, but without the appearance of epidermal creases) and poor response (no reduction in lesion size). RESULTS: Of 64 participants, 32 patients in the trial group and 31 patients in the control group were followed for 3 months. One patient in group B discontinued withdrew. After this time, complete improvement, partial improvement and poor response to treatment were 81.3%, 12.5% and 6.2% in the trial group and 51.6%, 29% and 19.4% in the control group, respectively. We also observed no adverse effect resulting from pentoxifylline. DISCUSSION: The result obtained by two therapeutic methods indicates that combined therapy with Glucantime and pentoxifylline is more effective than Glucantime alone (P < 0.05).