Delayed eye and other consequences from exposure to methyl isocyanate: 93% follow up of exposed and unexposed cohorts in Bhopal

A follow up study three years after exposure to methyl isocyanate in 93% of exposed survivors and "control" residents in 10 Bhopali communities showed an excess of eye irritation, eyelid infection, cataract, and a decrease in visual acuity among the exposed people. Breathlessness was twice as common in the heavily exposed clusters as those with lower exposure, a trend that could not be explained by different age or smoking patterns (OR 2.05, 95% CI 1.36-3.08). Case referent analysis of outpatient attendances at Bhopal Eye Hospital, considering patients with severe refractive errors and astigmatism as "controls," showed a 40% increased risk of trachoma, 36% increased risk of other lid infections, and 45% increased risk of irritant symptoms among previously exposed people. "Bhopal eye syndrome" may thus include full resolution of the initial interpalpebral superficial erosion, a subsequent increased risk of eye infections, hyperresponsive phenomena (irritation, watering, and phlyctens), and possibly cataracts. It remains to be confirmed whether this reflects a more generalised disease as a consequence of previous exposure to methyl isocyanate or whether it is only the eye that is affected.     

Sequential clinico-histological studies in psoriasis following methotrexate therapy

Ten cases of psoriasis were studied to see the pattern of histological resolution and to evaluate clinico-histological correlation in psoriasis following weekly methotrexate therapy. Five sequential biopsies were taken in each patient. Scaling was first to regress followed by induration and erythema in 18, 26 and 35 days, respectively. Uniform granular layer appeared in 4 days, stratum corneum became orthokeratotic in 7 days, mitotic activity got restricted to basal layer in 7 days and rete ridges elongation was reduced to half in 11 days. Mild acanthosis, cellular infiltrate and vascular dilatation pesisted even after full clinical regression. Interestingly, 5 out of 10 biopsies revealed increase in cellular infiltrate and oedema after first methotrexate pulse.     

Desensitization of human breast-cancer cells by interferon-alpha

Continuous exposure of human breast cancer cells, MCF-7, to interferon-alpha (IFN) induces a state.of non-responsiveness termed as desensitization. mRNA 561 is transiently induced by IFN-alpha in MCF-7 cells, peak cytoplasmic levels are reached by six to twelve hours; the mRNA level declines steadily and is reduced to uninduced levels by forty eight hours. Induction of mRNA 561 was used as an index of responsiveness of cells to IFN-alpha and desensitization was characterized in MCF-7 cells and in MCF-7 cells transfected by the v-H-ras oncogene (MCF-7ras). The kinetics and degree of IFN-mediated induction of mRNA 561 was comparable in both the cell lines. Desensitization was observed in MCF-7 cells and not in MCF-7ras. It was a reversible event, requiring de novo protein synthesis as inclusion of cycloheximide inhibited desensitization. The cellular elements that mediate such a phenomena are elicited by IFNs during the initial phases of IFN action and may be polypeptides. The refractory period, the time after which MCF-7 cells become responsive, was determined to be five days. In conclusion, we demonstrate the use of mRNA 561 induction in evaluating desensitization. Inhibition of protein synthesis or transfection with ras blocks desensitization in MCF-7 cells.     

Study of lymphatic metastatic patterns in gastric carcinoma according to tumor location

A total of 226 cases of advanced gastric cancer which occupied only one third of the stomach were analyzed in order to clarify whether and how lymphatic spread differed according to the tumor location and gross type of tumor. Out of the 226 patients, 45 cases had tumor in the upper third, 74 cases had it in the middle third, and 107 cases had it in the lower third of the stomach. The incidence of lymph node metastasis was found to be much higher for the tumors located in the lesser curvature (51.6%), greater curvature and posterior wall (54.4%), as compared to the tumors located in the anterior wall (28.0%). The tumors located in the upper third of the stomach did not show any metastasis in the N3 node, while the tumors located in the lower third of the stomach did not show any metastasis in the left cardial nodes, short gastric nodes, and the nodes along the left gastroepiploic vessels. Similarly, the tumors from the middle third of the stomach did not invade the left cardial nodes.     

Identification of a novel pulmonary oedema producing toxin from Indian red scorpion (Mesobuthus tamulus) venom.

The experiments were conducted to identify the toxin that produces pulmonary oedema in Mesobuthus tamulus (BT) envenomed animals. Crude BT venom was subjected to Sephadex gel filtration (G-75) and the fractions were screened for optical density (OD), neurotoxicity (prolongation of compound action potential in frog sciatic nerve) and lethality. All these parameters exhibited a peak between 54-94 ml eluates. Fractions of this peak were pooled (SP) and loaded on to carboxymethyl cellulose column. The column was then eluted with increasing buffer concentrations at constant pH and temperature. Eluates were screened for neurotoxicity and OD. Four peaks of neurotoxic activity (T1-T4) were detected. T2 and T3 were lethal whereas T1 and T4 were non-lethal. T2 exhibited mainly neurotoxicity and failed to augment phenyldiguanide (PDG)-induced reflex response or to produce pulmonary oedema. T3 was having minimal neurotoxic actions but augmented PDG-reflex and produced pulmonary oedema. The effects of T3 persisted even after dialysis with 8 kDa cut-off filter but not those of T2. The T3 effects resembled toxic manifestations of BT venom and were blocked by aprotinin pre-treatment. T3 demonstrated a band at approximately 100 kDa in SDS-PAGE. The results demonstrate the presence of a lethal, high molecular weight, pulmonary oedema producing toxin in BT venom.     

Nasal mucociliary clearance in health and disease

“Standard saccharine test is used to detect nasal mucociliary clearance time in healthy individuals both adults and children. The length of the nose was measured radiologically and with the help of a soft malleable rubber catheter. For healthy individuals, mean nasal mucociliary clearance lime is 8.2 minutes in children and 9.5 minutes in adults. The mean nasal mucociliary clearance rates were 11.1 mm/min for children and 12.7 mm/min for adults. Deviated nasal septum, chronic sinusitis, allergic rhinitis, atrophic rhinitis, chronic smokers and patients with recent nasal packings were taken as diseased conditions in adults, whereas children with adenoid hyperplasia were taken for the study. In all of these, nasal mucociliary clearance was significantly prolonged.”     

Pure Sertoli cell tumor of the ovary: A case report

Pure Sertoli cell tumors are an uncommon variant of rare ovarian Sertoli‐Leydig cell tumors. Due to nonspecific clinical and imaging features, diagnosis is often made after histopathological examination. The prognosis is excellent as most are detected in the early stages and surgical resection is often curative in most cases.     

Mutations responsible for the carbapenemase activity of SME-1

SME-1 is a carbapenemase, produced by Serratia marcescens organism and causes nosocomial infections such as in bloodstream, wounds, urinary tract, or respiratory tract infections. Treatment of such infections becomes very complex due its resistance towards penicillins, cephalosporins, monobactams, and carbapenems. Resistance to such antibiotics is of great medical concern. The misuse and overuse of these antibiotics result in the clinical mutation and production of novel β-lactamase enzymes such as SME-1, which show resistance to carbapenems. Class A contains most of the clinically significant extended spectrum of β-lactamase enzymes and carbapenemases. In this study, class A β-lactamase SME-1 sequence, structure, and binding were compared with naturally mutated class A β-lactamase enzymes and a wild-type TEM-1. This study was performed for revealing mutations, which could be responsible for the carbapenemase activity of SME-1. The dynamic characteristics of SME-1 enzymes manifest a different degree of conservation and variability, which confers them to possess carbapenemase activities. Met69Cys, Glu104Tyr, Tyr105His, Ala237Ser, and Gly238Cys mutations occur in SME-1 as compared to wild-type TEM-1. These mutated residues are present close to active site residues such as Ser70, Lys73, Ser130, Asn132, Glu166, and Asn170, which participate in the hydrolytic reaction of β-lactam antibiotics. Furthermore, these mutated residues demonstrate altered interactions with the β-lactam antibiotics (results in altered binding) and within themselves (results in active site structure alterations), which results in expanding the spectrum of activity of these enzymes. This study provides important insights into the structure and activity relationship of SME-1 enzymes. This is evident from the Ω-loop structure modification, which forms the wall of the active site and repositioning of residues involved in hydrolytic reactions, when present in the complex with meropenem in a stable state of MD simulation at 50 ns. Hence, Met69Cys, Glu104Tyr, Tyr105His, Ala237Ser, and Gly238Cys mutations could result in an altered active site structure, binding, and activity of SME-1 with meropenem and thus become resistantant against meropenem, which is a carbapenem.

Sequencing, molecular docking and dynamics, analysis of naturally mutated class A β-lactamase SME-1 was done to compared with 13 naturally mutated class A β-lactamase including SHV-1 and wild class A β-lactamase TEM-1.     

Omega-3 Fatty Acids and Their Interaction with the Gut Microbiome in the Prevention and Amelioration of Type-2 Diabetes

Type-2 diabetes mellitus (T2DM) is often linked with hyperglycemia, disturbed lipid profiles, inflammation, and gut dysbiosis. Omega-3 fatty acid supplementation has a vital role in the management of T2DM. As a result, a better understanding of the potential role of omega-3 fatty acids in the development and progression of T2DM by influencing the intestinal microflora will help to improve the therapeutic intervention for T2DM and related complications. Focusing on the molecular mechanisms and signaling pathways induced by omega-3 fatty acids, this paper attempts to comprehensively review and discuss the putative associations between omega-3 fatty acids, gut dysbiosis, and the pathophysiology of T2DM and its related comorbidities. In addition, we contemplate the importance of gut microbiota in T2DM prevention and treatment and ponder the role of omega-3 fatty acids in T2DM by positively modulating gut microbiota, which may lead to discovery of novel targets and therapeutic strategies thereby paving way for further comprehensive, mechanistic, and clinical studies.