Protective efficacy of melatonin and insulin against LPS caused toxicity in diabetic mice.

Context: Deregulated glucose homeostasis leads to a life-threatening metabolic disorder known as diabetes. The insulin deficiency and hyperglycaemic condition related to diabetes cause dysregulation of the immune system.Objective: This study evaluated the combined efficacy of melatonin and insulin in attenuation of lipopolysaccharide (LPS) caused inflammation, macrophage functional impairment, and oxidative stress in the spleen of diabetic mice.Materials and Methods: Multiple low doses of streptozotocin (50mg/kg B. wt.) were administered intraperitoneally to induce diabetes. Diabetes mice were divided into two sets. Set-1 contained control, diabetes, diabetes insulin (2IU/100g B.wt.) treated, diabetes melatonin (100µg/100g. B.wt.) treated, and diabetes melatonin and insulin treated groups of mice. In set II, the same number of groups as those of set I were given a single dose of LPS (50µg/mice) 24 hours before euthanization.Results and Discussion: LPS caused a significant increase in oxidative stress, circulatory proinflammatory cytokines, significant suppression of antioxidant defense system, and phagocytic index in diabetic mice. Melatonin and insulin significantly improved the adverse effects caused by LPS treatment in diabetic mice. The present study noted that combined treatment of melatonin and insulin was more effective in attenuating LPS-induced devastating effects in laboratory mice.Conclusions: The present study may suggest a combinatorial approach in the therapeutic use of melatonin and insulin to improve such devastating conditions.

Melatonin attenuates diabetes-induced oxidative stress in spleen and suppression of splenocyte proliferation in laboratory mice.

Hyperglycaemic condition induced oxidative stress in diabetic individuals caused oxidative damages of internal organs, including immune organ spleen. We studied the effects of low doses of melatonin (25, 50, and 100 µg/100g. B.wt./day) on histoarchitecture, oxidative stress, and splenocyte proliferation in streptozotocin-induced diabetic mice. Melatonin significantly resisted the increase in blood glucose levels and showed a dose-dependent effect on circulatory melatonin, body weight, and relative spleen weight in diabetic mice. Exogenous melatonin suppressed the diabetes-induced lipid peroxidation and increased the activity of the antioxidant enzymes and antioxidant GSH in the spleen tissue of diabetic mice in a dose-dependent manner. Melatonin improved the reactivity of Nrf-2 and HO-1 in the spleen of diabetic mice. Melatonin treatment normalised the splenic cellularity and increased the splenocyte proliferation in a dose-dependent manner. The present study may suggest the dose-dependent effect of melatonin in attenuation of oxidative stress and suppression of splenocyte proliferation in diabetic mice.

A case of liver cirrhosis and Chilaiditi syndrome with atypical pneumonitis.

Respiratory distress is very uncommon as a presenting symptom of Chilaiditi syndrome. Furthermore, pneumonia is not documented with the syndrome, compromising further to the distress. We describe a middle-aged man, chronic alcoholic, recently diagnosed with liver cirrhosis, presented with a 1-year history of slowly progressive breathlessness. Recently, he developed mild-to-moderate hemoptysis and cough with aggravation of breathlessness. He did not have fever, chest pain, or orthopnea. He was cyanosed, requiring high-dose oxygen therapy. Later on, he stabilized with noninvasive ventilation. Chest imagings showed incidental Chilaiditi sign, liver cirrhosis, and atypical pneumonitis. With empirical antibiotics and high-dose steroid, he recovered completely but with baseline breathlessness. Here, we outline Chilaiditi syndrome as a rare association or manifestation of liver cirrhosis, and it can present with a respiratory compromise by both obstructive lung disease and atypical interstitial pneumonia. Early identification, vaccinations against common organisms, and possible early surgery may prevent morbidity and mortality of this type of patients.

Amlodipine (150 mg) Poisoning: A Case Study.

BACKGROUND: Treatments of patients with amlodipine (a calcium channel blocker, CCB) overdose/poisoning remain challenging and death is certain if not intervened timely. Furthermore, for the society, the availability and common use of this drug can drive more vulnerable groups, especially children, towards an accidental/suicidal poisoning. CASE REPORT: Herein, we describe the case of an 18 year-old-adolescent girl who took 150 mg of amlodipine with the suicidal intentions and was admitted in our hospital approximately 4-hours after the ingestion. She developed circulatory failure and tachypnea. Decontamination, calcium, glucagon, and dual vasopressors were started, however, persistent hypotension led to the initiation of hyperinsulinemiceuglycemia therapy. She recovered fully and discharged without any complications in few days. This case educates not only about the successful use of variant drugs in the management of CCB overdose/poisoning, but also calls for the attention of the society for a safe storage of often used drugs, especially away from the children/adolescents.

Acute coronary syndrome-related mortality audit in a teaching hospital at Port Blair, India.

BACKGROUND: India has a growing trend of acute myocardial infarction (AMI) due to shifting lifestyle. OBJECTIVE: To study the profile of patients died due to AMI and to find its risk correlates. METHODS: A study was conducted on consecutive AMI cases admitted in the teaching hospital at Port Blair from April 2011 to March 2016. During inpatients management, outcomes were followed up from admission till discharge or expiry. RESULTS: Of the total 491 cases, majority (75.99%) had ST-elevated myocardial infarction (STEMI); mean age of 73 deaths was 58.01 ± 13.60, mortality probability among females was less; in the age group 41-50 years the case fatality rate was the lowest (7.58%). Mean age of survival was 56.75 ± 10.47; great majorities were males across all age groups in cases and deaths; highest number of cases were in the age group 51-60 (34.21%); reportedly 83.10% had some physical activities; 6.52% were vegetarian; 34.22% were smokers; 10.39% had family history of AMI, majority (59.06%) were from white collar profession (teacher, clerical, etc.); 52.95% were diabetics; and 47.45% were hypertensives. Lifestyle-related risk factors, physical activity, and vegetarian diet were not protective; family history and addiction to smoking were significantly associated with AMI deaths. Thrombolytic intervention helped the survival of 73.68%, and the odds ratio of survival showed benefit. CONCLUSIONS: Acute STEMI had male and middle-age predominance with a common risk factor of family history, smoking, diabetes, and hypertension.

Synthesis of Octabromoperylene Dianhydride and Diimides: Evidence of Halogen Bonding and Semiconducting Properties.

A facile synthesis of octabromoperylene-3,4,9,10-tetracarboxylic dianhydride (Br8-PDA) (1), its diimides (Br8-PDIs) (2a-e), and bis-, tris-, and tetra-amino substituted diimides (5a-c) with six, five, and four remaining substitutable Br atoms, respectively, is reported. Octabromination results in facile chemical/electrochemical reduction, radical anion formation, and red-shifted optical properties. For the first time, diverse halogen-bonding interactions were identified in the PDA/PDI, which along with the attractive electronic features enhance the electron-transport characteristics compared to the di-/tetra-brominated PDIs (3/4).

Tsunami, post-tsunami malaria situation in Nancowry group of islands, Nicobar district, Andaman and Nicobar Islands.

BACKGROUND & OBJECTIVES: Due to tsunami in 2004 a large proportion of population in Nicobar group of Islands become homeless, and in 2006 large scale labour migration took place to construct the houses. In 2008, a significant increase in malaria incidence was observed in this area. Therefore, in March 2008, the situation of malaria was assessed in Nancowry Islands in Nicobar District to study the reasons for the observed upsurge in the number of cases, and to suggest public health measures to control the infection. METHODS: The methods included a retrospective analysis of long term trend in the behaviour of malaria over the years from 2001 to 2008, analysis of the acute malaria situation, and rapid fever and malaria parasitemia survey along with environmental component. Mass radical therapy (MRT) and post-intervention parasitemia survey were carried out. The malaria situation in the aftermath of MRT was analysed. RESULTS: During the post tsunami year (2005) there was a large increase in the incidence of malaria and this trend continued till 2008. The percentage of Plasmodium falciparum increased from 23 to 53 per cent from 2006 to 2007 that coincides with the labour influx from mainland. The study showed that Nancowry was highly endemic, with high transmission setting, and high risk area for malaria. Though, more number of migrant labourers suffered fever (75 vs 20%) and sought malaria treatment over past month but parasitemia survey showed higher point prevalence of malaria among native tribes (7.4 vs 6.5%). Post-MRT, there was a decline in the occurrence of malaria, though it did not last long. INTERPRETATION & CONCLUSIONS: The study findings suggest that the migrant workers hailing from non-endemic or moderately endemic settings became victims of malaria in epidemic proportion in high endemic and high transmission setting. To find out the reasons for deterioration of malaria situation at Nancowry in the aftermath of tsunami requires further research.

Clinical progression of chikungunya fever during acute and chronic arthritic stages and the changes in joint morphology as revealed by imaging.

This longitudinal follow-up study of 203 patients with serologically confirmed chikungunya (CHIK) virus infection describes the clinical features of CHIK fever during the first and tenth months of illness. During the acute stage CHIK fever presents with a wide array of symptoms. The foremost chronic symptoms at the end of a month were rheumatism (75%) and fatigue (30%). During the tenth month of follow-up the symptoms/signs observed were joint pain/swelling (46%), fatigue (13%) and neuritis (6%). The cure rate at the end of 9 months was 51%. Among the patients who had joint pain, 36% (34/94) met the American College of Rheumatology criteria to classify them as having rheumatoid arthritis. A subpopulation of the patients with joint pain (20/94) was tested for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody, and the joints were imaged by X-ray and magnetic resonance imaging (MRI). All tested negative for RF and one tested positive for anti-CCP. A radiolucent lesion in the X-ray was seen in the bones of five patients. The MRI findings were joint effusion, bony erosion, marrow oedema, synovial thickening, tendinitis and tenosynovitis. The study proves with relative certainty that CHIK arthritis is chronic inflammatory erosive arthritis, which has implications for management of the infection.

Peripheral melatonin modulates seasonal immunity and reproduction of Indian tropical male bird Perdicula asiatica.

Seasonal changes in pineal function are well coordinated with seasonal reproductive activity of tropical birds. Further, immunomodulatory property of melatonin is well documented in seasonally breeding animals. Present study elucidates the interaction of peripheral melatonin with seasonal pattern of immunity and reproduction in Indian tropical male bird Perdicula asiatica. Significant seasonal changes were noted in pineal, testicular and immune function(s) of this avian species. Maximum pineal activity along with high immune status was noted during winter month while maximum testicular activity with low immune status was noted in summer. During summer month's long photoperiod suppressed pineal activity and high circulating testosterone suppressed immune parameters, while in winter short photoperiod elevated pineal activity and high circulating melatonin maintained high immune status and suppressed gonadal activity. Therefore, seasonal levels of melatonin act like a major temporal synchronizer to maintain not only the seasonal reproduction but also immune adaptability of this avian species.

Melatonin and differential effect of L-thyroxine on immune system of Indian tropical bird Perdicula asiatica.

Interaction of thyroxine and melatonin on immune status was noted in vivo and in vitro when peripheral melatonin was high and thyroxine low in plasma of male Perdicula asiatica during reproductively inactive phase. During this phase exogenous thyroxine (4 microg/100g. Bwt./day) and melatonin (25 microg/100g. Bwt./day) increased immune parameters (spleen weight, total leukocyte count, lymphocyte count, percent stimulation ratio) and increased splenocyte density in spleen. In vitro l-thyroxine (10(-6)M/ml) supplementation decreased the splenocyte proliferation which was reversed by melatonin (500 pg/ml) supplementation. In vivo l-thyroxine showed immunoenhancing effect while in vitro it decreased the splenocyte proliferation presenting a differential effect. In the absence of internal physiological conditions of the birds, T(4) showed a negative effect on splenocytes proliferation in vitro when treated alone. However, melatonin maintained its lymphoproliferative effect under both conditions. Thus, avian splenocyte exposed to different hormonal conditions in vitro might have produced different signal peptides other than in vivo, thereby making the result different.

Melatonin prevents testosterone-induced suppression of immune parameters and splenocyte proliferation in Indian tropical jungle bush quail, Perdicula asiatica.

During reproductive inactive phase (winter months) peripheral high melatonin and low testosterone was noted in male Indian tropical bird, Perdicula asiatica. During this phase exogenous testosterone (1 mg/100 g Bwt./day) suppressed the immune parameters [spleen weight, total leukocyte count (TLC), lymphocyte count (LC), and percent stimulation ratio (% SR)] and depleted splenic cellular density, while melatonin (25 microg/100g Bwt./day) restored the immune parameters and splenic cellular density to the level of control birds. In vitro suppression of splenocyte proliferation by testosterone (3 ng/ml) was also reversed by melatonin (500 pg/ml) supplementation. Therefore, high melatonin in circulation during the reproductive inactive phase acts as immunostimulator and is of high adaptive significance to this bird for survival during the adverse conditions of season and reproductive phase.

Trade-off between L-thyroxin and melatonin in immune regulation of the Indian palm squirrel, Funambulus pennanti during the reproductively inactive phase.

The thyroid gland and its hormones have been reported to influence reproduction and metabolism in a positive manner. However, research to date provides strong evidence for a reciprocal relationship between the immune system and hormones of the hypothalamus-pituitary-thyroid axis. The present study has been taken to elucidate the effect of L-thyroxin (T(4)) on immune parameters such as total leukocyte count, percent lymphocyte count, blastogenic response and percent stimulation ratio of thymocytes and splenocytes of a seasonally breeding rodent, Funambulus pennanti, during its reproductively inactive phase when peripheral T(4) is low. Treatment with L-thyroxin at a near-physiological dose of 35 microg/100 g body weight during evening hours showed a significant elevation of all immune parameters. However, combined treatment of L-thyroxin and melatonin (25 microg/100 g body weight) had no additive effect. On the other hand, in vitro supplementation of T(4) (10(-6) M) either alone or in combination with melatonin (0.5 microM) did not induce any significant change on thymocyte and splenocyte proliferation. Therefore, a trade-off effect of L-thyroxin and melatonin on the immune system (T- and B-cell differentiation) is suggested for this rodent.