Melatonin exacerbates acute experimental autoimmune encephalomyelitis by enhancing the serum levels of lactate: A potential biomarker of multiple sclerosis progression

Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS). In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5‐6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis (EAE) followed by assessing serum levels of lactate and melatonin. Results showed that clinical outcomes were exacerbated in melatonin‐ (neurological score = 6) vs PBS‐treated EAE rats (score = 5). Melatonin caused a significant increase in serum IFN‐γ, in comparison to PBS‐treated EAE rats whereas no considerable change in IL‐4 levels were found, although they were significantly lower than those of controls. The ratio of IFN‐γ/IL‐4, an indicator of Th‐1/Th‐2, was significantly higher in PBS‐ and melatonin‐ treated EAE rats, in comparison to controls. Moreover, results showed increased lymphocyte infiltration, activated astrocytes (GFAP+ cells) but also higher demyelinated plaques (MBP‐deficient areas) in the lumbar spinal cord of melatonin‐treated EAE rats. Finally, serum levels of lactate, but not melatonin, significantly increased in the melatonin group, compared to untreated EAE and normal rats. In conclusion, our results indicated a relationship between age and the development of EAE since a negative impact was found for melatonin on EAE recovery of young rats by enhancing IFN‐γ, the ratio of Th1/Th2 cells, and astrocyte activation, which seems to delay the remyelination process. While melatonin levels decline in MS patients, lactate might be a potential diagnostic biomarker for prediction of disease progression. Early administration of melatonin in the acute phase of MS might be harmful and needs further investigations.     

Study of the Cytotoxic and Bactericidal Effects of Sila‐substituted Thioalkyne and Mercapto‐thione Compounds based on 1,2,3‐Triazole Scaffold

A series of sila‐organosulphur compounds containing 1,2,3‐triazole cores were screened for their cytotoxic activity on human breast cancer cell line MCF‐7. Most of the tested compounds exhibited moderate‐to‐good activity against the cancer cells. Especially, the compound 4‐((2‐(trimethylsilyl)ethynylthio)methyl)‐1‐benzyl‐1H‐1,2,3‐triazole ( 3a) from series of sila‐substituted thioalkyne 1,2,3‐triazoles (STATs) and the compounds 3‐(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)‐1‐mercapto‐1,1‐bis(trimethylsilyl)propane‐2‐thione ( 4a) and 1‐mercapto‐1,1‐bis(trimethylsilyl)‐3‐(1‐phenethyl‐1H‐1,2,3‐triazol‐4‐yl)propane‐2‐thione ( 4e) from series of sila‐substituted mercapto‐thione 1,2,3‐triazoles (SMTTs) exhibited promising cytotoxicity against MCF‐7 with IC₅₀ values of 35.17, 32.63 and 30.3 μg/mL, respectively. In addition, the possible mechanisms for inhibition of cell growth and induction of apoptotic cell death were explored by DAPI staining, cell cycle analysis and qRT‐PCR. The synthetic compounds were evaluated for their in vitro antibacterial activities, and as a result, the most prominent effects were observed for 3e and 4e . Especially, 3e was found to be quite active against all the tested strains with the MIC values ranging from 15 to 62 μg/mL, except P. aeruginosa. The results of the time‐kill assay suggested that the compound of 3e completely inhibited the growth of both gram‐negative bacteria, A. baumannii, and gram‐positive bacteria, S. aureus. In addition, SEM analysis confirmed morphostructural damage of the bacteria. Our findings could be applicable for developing dual‐targeting anticancer/antibacterial therapeutics.     

Cancer incidence in patients with type 1 diabetes mellitus: a population-based cohort study in Sweden

Although patients with type 2 diabetes have elevated risks of liver, pancreatic, kidney, and endometrial cancer, little is known about the risk of cancer for patients with type 1 diabetes. We conducted a cohort study to examine cancer incidence among 29 187 patients in Sweden who were hospitalized for type 1 diabetes from 1965 through 1999. Relative risks of cancer were estimated by age-, sex- and calendar year of follow-up--adjusted standardized incidence ratios (SIRs), using data for the entire Swedish population as a reference. After excluding cancers diagnosed during the first year after hospital discharge, we observed 355 incident cases of cancer, which corresponded to a 20% increase in overall cancer incidence among type 1 diabetes patients (SIR = 1.2, 95% confidence interval [CI] = 1.0 to 1.3). Patients with type 1 diabetes had elevated risks of cancers of the stomach (SIR = 2.3, 95% CI = 1.1 to 4.1), cervix (SIR = 1.6, 95% CI = 1.1 to 2.2), and endometrium (SIR = 2.7, 95% CI = 1.4 to 4.7). Type 1 diabetes is associated with a modest excess cancer risk overall and risks of specific cancers that differ from those associated with type 2 diabetes.     

Trichophyton mentagrophytes and T interdigitale genotypes are associated with particular geographic areas and clinical manifestations

The fungi Trichophyton mentagrophytes and T interdigitale account for significant amount of dermatophytosis cases worldwide. These two dermatophytes form a species complex and have a number of ribosomal internal transcribed spacer (ITS) region genotypes, allowing simultaneous species identification and strain typing. Our aim was to describe the geographic distribution of T mentagrophytes/T interdigitale ITS region genotypes and find an association between the genotypes and clinical presentations of respective infections. We performed rDNA ITS region sequencing in 397 Iranian T mentagrophytes/T interdigitale isolates and analysed all available in GenBank entries with sequences of this kind. For the study, 515 clinical annotations were available. Statistical analysis was performed by chi‐squared test and Spearman rank correlation analysis. A total of 971 sequences belonged to genotypes with at least 10 geographic annotations and were classified on the basis of exclusive occurrence in a particular region or high relative contribution to a regional sample. We discerned Asian and Oceanian (“ KU496915 ” Type V, “ KT192500 ” Type VIII, “ KU315316 ”), European (“ FM986750 ” Type III, “ MF926358 ” Type III*, “ KT285210 ” Type VI) and cosmopolitan (“ FM986691 ” Type I, “ JX122216 ” Type II, “ KP132819 ” Type II* and “ AF170453 ” Type XXIV) genotypes. There was statistically significant difference in the ITS genotype distribution between different affected body sites. Trichophyton mentagrophytes “ KT192500 ” Type VIII correlated with tinea cruris, T mentagrophytes “ KU496915 ” Type V correlated with tinea corporis, T interdigitale “ JX122216 ” Type II correlated with tinea pedis and onychomycosis. Trichophyton mentagrophytes and T interdigitale genotypes can be associated with distinct geographic locations and particular clinical presentations.     

Lack of Altered BECN1 Gene Expression in Iranian Patients with Acute Myeloid Leukemia

Acute myeloid leukemia (AML), one of the most prevalent leukemia types in adults, demonstrates great heterogeneity in molecular and clinical terms. Hence, there is a necessity to the mechanisms involved in AML generation in order to determine optimal treatment. This cross sectional study aimed to assess changes in BECN1 gene expression in with blood samples from 30 AML patients, compared with samples from 15 healthy persons. RNA was extracted and cDNA was synthesized and Real Time PCR applied to determine BECN1 gene expression. The results showed no significant differences in BECN1 gene expression between patients with AML and normal controls (P > 0.05). It appears that expression of BECN1 does not play a significant role in genesis of AML leukemia.     

Amelioration of cardio-respiratory perturbations following Mesobuthus eupeus envenomation in anesthetized rabbits with commercial polyvalent F(ab′)2 antivenom

Immunotherapy is the only specific treatment for scorpion sting. In the present study, protective effects of polyvalent antivenom against hemodynamic disturbances, biomarkers (troponin T, creatinine kinase isoenzyme MB, Lactate dehydrogenase) changes, electrocardiogram abnormalities and histopathological complications in heart and lung induced by Mesobuthus eupeus scorpion venom was investigated in anesthetized rabbits. Twenty four rabbits were randomized into four equal groups: six rabbits in control group received 1 ml ultra-pure water subcutaneously (group 1). Group two received LD50 of venom (4.5 mg/kg). In the third and fourth groups, 5 ml of scorpion antivenom was administrated intravenously simultaneous with venom injection and 60 min following envenomation, respectively. Results of the present study indicate significant decrease in hemodynamic parameters following envenomation in the second group of animals. Venom injection caused edema, myocytolysis, coagulation necrosis, hemorrhage in heart as well as edema, hemorrhage and vascular thrombus in lungs. Although envenomed rabbits presented rises in LDH and TnT but no alteration in CK-MB was observed. Electrocardiogram monitoring of rabbits showed ST elevation and inverted T waves. Simultaneous administration of antivenom and venom prevented entirely the clinical signs, hemodynamic disturbances, markers changes, ECG abnormalities and histopathological damages. Delayed immunotherapy gradually ameliorated clinical signs, hemodynamic disturbances and markers changes related to envenomation. Histopathological evaluation showed slight alterations such as mild myocytolysis in heart and mild edema in lung following delayed immunotherapy. In conclusion, scorpion antivenom administration has preventive, neutralizing and curative properties for M. eupeus scorpion envenomation, if it would be applied at optimum time, dose and route.