Effect of metformin on clastogenic and biochemical changes induced by adriamycin in Swiss albino mice

Diabetes mellitus (DM) is a chronic disease that is characterized by deteriorating glycemic control. The disease is known to be caused by imbalance between reactive oxygen species (ROS) and antioxidant defense systems. Hyperglycemia is commonly observed in a wide variety of diseases, including cancer. Although, therapy against glycemic control, is used in all these diseases, the diabetic cancer patients are on additional therapy with anticancer drugs. The objective of present study was to study if Glucophage (metformin), a very popular antidiabetic agent can avert the mutagenicity and lipid peroxidation caused by adriamycin (ADR), which is a commonly used cytotoxic drug. The experimental protocol included oral treatment of mice with different doses (62.5, 125 and 250 mg/kg day) of metformin for 7 days. Some mice in each group were injected i.p. with ADR (15 mg/kg). In each case animals were killed, 30 or 24, 48 and 72 h after the last treatment and femurs were excised for cytological studies by micronucleus test. Additional experiments on estimation of glutathione (GSH) and malondialdehyde (MDA) were undertaken in blood and serum, respectively. Twenty-four hour after the treatment, blood from each mouse was collected from heart and preserved for analysis. The results obtained revealed that pretreatment with metformin: (i) reduced the ADR-induced frequency of micronuclei without any alteration in its cytotoxicity and (ii) protected against the ADR-induced increase and decrease of MDA and GSH, respectively. The exact mechanism of action is not known, however, the inhibition of ADR-induced clastogenicity and lipid peroxidation by metformin may be attributed to the antioxidant action of the latter. Our results demonstrate that metformin might be useful to avert secondary tumor risk by decreasing the accumulation of free radicals and inhibition of mutagenicity.     

Hematological toxicology following embryonic exposure to aflatoxin-B1

The influence of embryonic exposure to aflatoxin-B1 (AF-B1) upon the erythroid system of the maturing chicken was examined using a variety of assays. Since the chick embryo is known to possess mixed-function oxidase activity, this animal serves as an excellent model system for studies of human fetal toxicology. AF-B1 (0.1 microgram) was administered to either 6- or 12-day embryos by the air sac method. This level of AF-B1 was highly mutagenic and was found to induce an average of 10.6 sister chromatid exchanges (SCEs) per cell compared with 1.8 SCEs per cell for the acetone control solvent. Despite selection against treated embryos through acute and chronic embryonic toxicity, hatched chicks from AF-B1 treatment groups exhibited erythroid anemia when compared to the acetone controls. Cell count, hematocrit, and hemoglobin concentration were all significantly reduced in the 12-day AF-B1 treatment groups compared with controls. Both sexes were equally affected. While the number of peripheral erythrocytes was reduced following exposure to AF-B1, the differentiation status of erythrocytes was apparently unaltered. Mean cell volume, percentage of circulating reticulocytes, and incidence of an erythroid differentiation marker, chicken fetal antigen, were parameters in which no treatment effects were observed. An apparent maturation effect was noted since adult hematocrits were similar between control and treatment groups. Possible explanations for this age effect are discussed. The ability to detect significant posthatch erythroid toxicity following embryonic exposure to mutagenic levels of AF-B1 suggests the importance of this general approach to perinatal carcinogenic evaluation.     

Modulation of somatic embryogenesis in early and late-stage embryos of wheat (Triticum aestivum L.) under the influence of (±)-abscisic acid and its analogs

Zygotic embryos from ten spring wheat (Triticum aestivum L.) genotypes were tested for embryogenic callus induction in the presence or absence of externally supplied (±)-abscisic acid (ABA) and two of its analogs, methyl abscisate and methyl epoxy-beta-ionylideneacetate. (±)-ABA and its analogs suppressed precocious germination of cultured late-stage embryos and promoted embryogenic callus induction. A significantly greater number of plants was regenerated from calli induced in the presence of ABA and ABA analogs. Early-stage embryos when cultured in the presence of (±)-ABA showed a negative response. Possible roles of ABA with respect to the expression of somatic embryogenesis are discussed.Dedicated to Dr. Friedrich Constabel on the occasion of his 60th birthday     

A retrospective analysis of American football hyperthermia deaths in the United States

Over the period 1980–2009, there were 58 documented hyperthermia deaths of American-style football players in the United States. This study examines the geography, timing, and meteorological conditions present during the onset of hyperthermia, using the most complete dataset available. Deaths are concentrated in the eastern quadrant of the United States and are most common during August. Over half the deaths occurred during morning practices when high humidity levels were common. The athletes were typically large (79% with a body mass index >30) and mostly (86%) played linemen positions. Meteorological conditions were atypically hot and humid by local standards on most days with fatalities. Further, all deaths occurred under conditions defined as high or extreme by the American College of Sports Medicine using the wet bulb globe temperature (WBGT), but under lower threat levels using the heat index (HI). Football-specific thresholds based on clothing (full football uniform, practice uniform, or shorts) were also examined. The thresholds matched well with data from athletes wearing practice uniforms but poorly for those in shorts only. Too few cases of athletes in full pads were available to draw any broad conclusions. We recommend that coaches carefully monitor players, particularly large linemen, early in the pre-season on days with wet bulb globe temperatures that are categorized as high or extreme. Also, as most of the deaths were among young athletes, longer acclimatization periods may be needed.     

Prevalence of clinical malaria and household characteristics of patients in tribal districts of Pakistan

BackgroundMalaria, disproportionately affects poor people more than any other disease of public health concern in developing countries. In resource-constrained environments, monitoring the occurrence of malaria is essential for the success of national malaria control programs. Militancy and military conflicts have been a major challenge in monitoring the incidence and controlling malaria and other emerging infectious diseases. The conflicts and instability in Afghanistan have resulted in the migration of refugees into the war-torn tribal districts of Pakistan’s Khyber Pakhtunkhwa (KPK) province and the possible introduction of many contagious epidemics. Although malaria is very common in all tribal districts, molecular, clinical and epidemiological data are scarce in these high-burden districts. Therefore, for the proper surveillance, detection, and control of malaria, obtaining and analyzing reliable data in these districts is essential.Methodology/Principal findingsAll 1,127 malaria-suspected patients were sampled within the transmission season in the tribal districts of KPK province between March 2016 to December 2018. After a detailed demographic and clinical investigation of malaria-suspected patients, the data were recorded. The data of the control group was collected simultaneously at the same site. They were considered as uncomplicated cases for statistical analyses. Blood samples were collected from malaria-suspected patients for the detection of Plasmodium species using microscopy and nested PCR (nPCR). Microscopy and nPCR examination detected 78% (n = 882) and 38% (n = 429) Plasmodium-positive patients, respectively. Among1,127 of 429nPCR detected cases with both species of malaria, the frequency of complications was as follows: anemia (n = 71; 16.5%), decompensated shock (n = 40; 9%), hyperpyrexia (n = 117; 27%), hyperparasitaemia (n = 49; 11%) hypoglycemia (n = 45; 10.5%), jaundice (n = 54; 13%), multiple convulsions (n = 37; 9%), and petechia (n = 16; 4%). We observed that 37% (n = 157 out of 429) of those patients infected by both Plasmodium species were children between the ages of 1 and 15 years old. The results revealed that Bajaur (24%), Kurram (20%), and Khyber (18%) districtshada higher proportion of P. vivax than P. falciparum cases. Most of the malaria cases were males (74%). Patients infected by both Plasmodium species tended to less commonly have received formal education and ownership of wealth indicators (e.g., fridge, TV set) was lower.Conclusions/SignificanceMalaria in tribal districts of the KPK province largely affects young males. P. vivax is a major contributor to the spread of malaria in the area, including severe malaria. We observed a high prevalence of P. vivax in the Bajaur district. Children were the susceptible population to malaria infections whereas they were the least expected to use satisfactory prevention strategies. A higher level of education, a possession of TV sets, the use of bed nets, the use of repellent fluids, and fridges were all associated with protection from malaria. An increased investment in socio-economic development, a strong health infrastructure, and malaria education are key interventions to reduce malaria in the tribal districts.     

Molecular docking analysis of an isoflavone derivative with the protein phosphatase 1 from Leishmania donovani

Leishmaniasis is one of the most neglected diseases with high morbidity and mortality rate. Severe side effects with existing drug and lack of proper vaccine encouraged us to design alternative models to combat the disease. We showed that PP1 of Leishmania donovani mediates immunomodulation in host macrophages needed for parasite survival. Therefore, it is of interest to report the molecular docking analysis of 512 isoflavone derivatives with the phosphatase 1 protein from Leishmania donovani to highlight compound 362 (5-hydroxy-5-{9-[2-methoxy-2-(2-methylfuran-3-yl) ethyl]-1H, 3H, 4H, 10bH-pyrano[4,3-c]chromen-3-yl}pentanoic acid) having good binding features and acceptable ADMET properties for further consideration.     

Temporal and spatial distribution of meiotin-1 in anthers of Lilium longiflorum

Meiotin-1 is a chromatin associated, conserved protein found in meiocytes immediately preceding and during meiosis and is thought to have a role in determining the higher order structure of meiotic chromosomes [Riggs and Hasenkampf: Chromosoma 101:92–98, 1991]. In the studies reported here we utilized immunoblotting and immunocytochemical techniques to examine the temporal and spatial distribution of meiotin-1 in the anthers of Lilium longiflorum. The results with the anti-meiotin-1 immune serum were compared with those obtained using an anti-his-tone Hl immune serum. The anti-histone Hl immune serum gave constant immunostaining in all cell types of the anther at all of the stages tested. In contrast, the anti-meiotin-1 immune serum only gave immunostaining with the microsporocytes and to a lesser extent with the nutritive layer, the tapetum. It did not react with the cells of the anther wall. Meiotin-1 immunostaining was first present in significant quantities in the microsporocytes as they accumulated in the G1 phase before the onset of premeiotic S phase and reached peak levels in the time interval between leptotene and pachytene—the same interval when chromosome synapsis occurs and when reciprocal genetic exchange is thought to occur. Immunostaining for both meiotin-1 and histone H1 uniformly decorates the longitudinal axes of the chromosomes. Our data are consistent with the idea that the role of meiotin-1 may be to tag certain sequences or to limit the degree of chromosome condensation that occurs during meiotic prophase. © 1993 Wiley-Liss, Inc.     

MYP2 locus genes: Sequence variations,genetic association studies and haplotypic association in patients with High Myopia

High Myopia (HM) is a common complex-trait eye disorder. There is essential evidence that genetic factors play a significant role in the development of nonsyndromic high myopia. Identification of susceptibility genes of high myopia will shed light on the pathophysiological mechanism underlying their genesis. This was a case control study examining the prospect of association of DLGAP1, EMILIN2 & MYOM1 genes on MYP2 locus in purely ethnic (Kashmiri) population representing a homogeneous cohort. Genomic DNA was extracted using phenol chloroform and salting out method. Extracted DNA was genotyped for polymorphic variations in MYOM1, EMILIN2 and DLGAP1 genes involving Sanger di-deoxy method. Allele frequencies were tested for Hardy-Weinberg disequilibrium in 224 cases and compared with 220 emmetropic controls. In DLGAP1, documented single nucleotide polymorphism (SNP); Pro517Pro was observed. A previously reported Asn451Asn SNP was observed in EMILIN2. MYOM1 showed five polymorphic variations; two in coding region (Gly333Gly & Gly341Ala) and three intronic (c.1022+23, G>A; c.3418+44 G>T & c.3418+65; C>G). All of the elucidated SNPs were having statistical significant role in increasing or decreasing the risk of disease. Although not statistically significant, a novel Glu507Lys SNP was observed in DLGAP1 (P>0.05). In silico predictions showed MYOM1 Gly341Ala to be benign & tolerated substitution while as DLGAP1 Glu507Lys to be possibly damaging substitution. The studied SNPs followed Over-Dominant, Recessive and Co-Dominant mode of inheritance with specific haplotypes associated with the disease. Our study reveals the involvement of MYP2 locus candidate gene polymorphism in the pathogenesis of HM.