Visceral leishmaniasis among children in an endemic area of northwestern Iran between 2016 and 2017: An epidemiological study

Objective: To clarify the epidemiological aspects of visceral leishmaniasis in Kaleybar and Khoda-Afarin districts, north-west of Iran.Methods: A total of 1 420 human(children under 12 years) samples, 101 domestic dogs samples(Canis familiaris), and 577 female sand fly samples were collected. Sera of human and dogs were tested using the direct agglutination test, and sand flies were identified at species level using the microscopic method. Furthermore, a structured questionnaire was applied to evaluate the correlation between the potential risk factors and the related clinical signs/symptoms with the human and dogs' seropositivity.Results: Totally, 2.18% of human samples were positive at titers≥1: 800; among them, 13 cases(41.94%) were above 1:3 200, and clinical symptoms were observed in all of them except for an 11-year old girl. Anti-Leishmania infantum antibodies were found at titer≥1: 320 in 9.90% of dogs' samples, half of them had at least one sign of canine visceral leishmaniasis. Moreover, 10 Phlebotomus species were identified in the study areas, and Phlebotomus(Larroussius) major group was the predominant species. There are significant correlations between the presence of anti-Leishmania infantum antibodies and the fever(P0.001), anemia(P=0.001) and weight loss(P=0.016) in children. On the other hand, significant correlations were revealed between the Leishmania infection and the shelter(P=0.039), cutaneous lesion(P=0.005), lymphadenopathy(P=0.001) and weight loss(P0.001) in the infected dogs.Conclusions: Visceral Leishmania infection is prevalent in rural areas of Kaleybar and KhodaAfar districts located in East-Azerbaijan province, therefore active detection and treatment of visceral leishmaniasis cases should not be neglected.     

Effect of Zingiber officinale Supplementation on Obesity Management with Respect to the Uncoupling Protein 1 ‐3826A>G and ß3‐adrenergic Receptor Trp64Arg Polymorphism

The present study aimed to investigate the effect of ginger (Zingiber officinale) supplementation on some obesity‐associated parameters, with nutrigenetics approach. Accordingly, 80 eligible obese women (aged 18–45 years) were randomly assigned to receive either ginger (2‐g ginger rhizomes powder as two 1‐g tablets per day) or placebo supplements (corn starch with the same amount) for 12 weeks. Subjects were tested for changes in body weight, body mass index, waist and hip circumferences, body composition, appetite score, and dietary intake. Moreover, participants were genotyped for the ‐3826A>G and Trp64Arg polymorphisms of uncoupling protein 1 and ß3‐adrenergic receptor genes, respectively. Over 12 weeks, ginger supplementation resulted in a slight but statistically significant decrease in all anthropometric measurements and total appetite score as compared with placebo group, which were more pronounced in subjects with the AA genotype for uncoupling protein 1 and Trp64Trp genotype for ß3‐adrenergic receptor gene. However, there was no significant difference in changes of body composition and total energy and macronutrients intake between groups. In conclusion, our findings suggest that ginger consumption has potential in managing obesity, accompanying with an intervention–genotype interaction effect. However, further clinical trials need to explore ginger's efficacy as an anti‐obesity agent in the form of powder, extract, or its active components. Copyright © 2015 John Wiley & Sons, Ltd.     

Hepatoprotective effect of silyamarin in individuals chronically exposed to hydrogen sulfide; modulating influence of TNF-α cytokine genetic polymorphism

Background and the purpose of the study

Silymarin, a standardized extract of the milk thistle (Silybum marianum), is believed to exert some of its hepatoprotective effects though inhibition of free radicals and inflammation. In this study the effect of some pro- and anti-inflammatory cytokines and also antioxidant genes polymorphisms on the hepatoprotective effects of silymarin in the occupationally exposed individuals to hydrogen sulfide (H₂S) in the sour natural gas refinery was investigated.

Methods

We genotyped seven polymorphisms in six genes reported by others as modifiers of oxidative stress (NQO1, mEPXH1, GSTT1 and GSTM1) and inflammation (TNF-α and TGF-β1) for an association in effect of decreasing in liver function tests (LFTs). The LFTs of 77 sour gas refinery workers were measured before and after administration of silymarin (140 mg, three times per day for 1 month).

Results

A significant reduction of blood AST, ALT and ALP was observed after 30 days of consumption (p < 0.001). The decreasing effect of silymarin on ALT in the subjects with high producer genotype (A allele carriers) was less than low producers. There were no significant associations between TGF-β1 and the studied genes of oxidative stress pathway and the effectiveness of silymarin.

Conclusion

This is the first report about the effectiveness of silymarin in the subjects exposed chronically to H₂S. Meanwhile, the modulatory effect of TNF-α on the effectiveness of silymarin might be used for individualize therapy.     

Familial breast cancer registry program in patients referred to the cancer institute of Iran

Introduction: Annually a considerable number of people die because of breast cancer, a common diseaseamong women also in Iran. Identifying risk factors and susceptible people can lead to prevention or at leastearly diagnosis. Among susceptibility risks, 5-10% of patients have a family history predisposing factor whichcan influence the risk of incidence among the family. Having a registry program can be a more practical wayto screen high risk families for preventive planning. Method: Based on inclusion criteria, a questionnaire wasprepared and after a pilot study on a small number of patients, actual data were collected on 400 patients andprocessed in SPSS 16.0. Results: Totally, 28.2%of the patients were younger than 40 years old and 36.8% hadthe included criteria for familial breast cancer (FBC). 102 patient’s samples could be compared for receptorpresentation. Similar to other studies, the number of triple negative breast cancers increased as the age decreased.Conclusion: The high percentage of patients with FBC among 400 cases in this study demonstrates that in orderto design an infrastructural diagnostic protocol and screening of patients with FBC, a precise survey related tofrequency and founder mutations of FBC is needed nationwide.     

Characterization of agonist-induced motilin receptor trafficking and its implications for tachyphylaxis

The motilin receptor (MR) is a member of the seven-transmembrane receptor family and is expressed throughout the gastrointestinal tract of humans and other species. Motilin, the natural MR peptide ligand, has profound stimulatory effects on gastrointestinal contractility, indicating a therapeutic potential for MR modulators. However, long-term clinical use of certain MR agonists is limited by tachyphylaxis, a reduced responsiveness to repeated compound exposure. This study was meant to characterize the ligand-induced endocytosis of MR and to test whether receptor trafficking contributes to tachyphylaxis. A cell-based assay was developed by fusing a green fluorescent protein (GFP) moiety to the motilin receptor, and high-content biology instrumentation was used to quantify time and dose dependence of MR-GFP endocytosis. Maximal internalization of MR-GFP was induced after 45 min of constant exposure to 80 nM motilin. This process was disrupted by nocodazole, suggesting an essential role for microtubules. Internalized MR-GFP vesicles disappeared within 15 to 45 min of motilin withdrawal but did not overlap with the lysosomal compartment, indicating that MR-GFP escaped degradation and was recycled back to the plasma membrane. It is noteworthy that the kinetics of MR-GFP redistribution varied substantially when stimulated with motilin, erythromycin, 6,9-hemiacetal 8,9-anhydro-4'-deoxy-3'-N-desmethyl-3'-N-ethylerythromycin B (ABT-229), or N-[(1S)-1-[[[(1S)-1-(aminocarbonyl)-3-phenylpropyl]amino]carbonyl]-3-phenylpropyl]-2'-(1,3-benzodioxol-5-ylmethyl)tetrahydro-1',3'-dioxo-spiro[piperidine-4,5'(6'H)-[1H][1,2,4]triazolo[1,2-a]pyridazine]-8'-carboxamide (BMS-591348) at equipotent doses for Ca(2+)-mobilization. Retardation of the intracellular MR-GFP sorting cycle seemed to correlate with the tachyphylaxis-inducing properties of each compound, but not its EC(50). These results indicate that MR internalization, desensitization, and resensitization are ligand-dependent and that appropriate screening strategies may enable the development of small molecule agonists with ideal combinations of these distinct properties.     

Effects of rutin on acrylamide-induced neurotoxicity

Background

Rutin is an important flavonoid that is consumed in the daily diet. The cytoprotective effects of rutin, including antioxidative, and neuroprotective have been shown in several studies. Neurotoxic effects of acrylamide (ACR) have been established in humans and animals. In this study, the protective effects of rutin in prevention and treatment of neural toxicity of ACR were studied.

Results

Rutin significantly reduced cell death induced by ACR (5.46 mM) in time- and dose-dependent manners. Rutin treatment decreased the ACR-induced cytotoxicity significantly in comparison to control (P <0.01, P < 0.001). Rutin (100 and 200 mg/kg) could prevent decrease of body weight in rats. In combination treatments with rutin (50, 100 and 200 mg/kg), vitamin E (200 mg/kg) and ACR, gait abnormalities significantly decreased in a dose-dependent manner (P < 0.01 and P < 0.001). The level of malondialdehyde significantly decreased in the brain tissue of rats in both preventive and therapeutic groups that received rutin (100 and 200 mg/kg).

Conclusion

It seems that rutin could be effective in reducing neurotoxicity and the neuroprotective effect of it might be mediated via antioxidant activity.