Hyperinsulinemia Induced Altered Insulin Signaling Pathway in Muscle of High Fat- and Carbohydrate-Fed Rats: Effect of Exercise

Insulin resistance is a state of impaired responsiveness to insulin action. This condition not only results in deficient glucose uptake but increases the risk for cardiovascular diseases (CVD), stroke, and obesity. The present work investigates the molecular mechanisms of high carbohydrate and fat diet in inducing prediabetic hyperinsulinemia and effect of exercise on InsR signaling events, muscular AChE, and lactate dehydrogenase activity. Adult male Wistar rats were divided into the control (C) diet group, high-carbohydrate diet (HCD) group, high-fat diet (HFD) group, and HCD and HFD groups with exercise (HCD Ex and HFD Ex, respectively). Acetyl choline esterase activity, lactate dehydrogenase activity, total lactate levels, IRS1 phosphorylations, and Glut4 expression patterns were studied in the muscle tissue among these groups. High carbohydrate and fat feeding led to hyperinsulinemic status with reduced acetylcholine esterase (AChE) activity and impaired phosphorylation of IRS1 along with increased lactate concentrations in the muscle. Exercise significantly upregulated phosphoinositide 3 kinase (PI3K) docking site phosphorylation and downregulated the negative IRS1 phosphorylations thereby increasing the glucose transporter (GLUT) expressions and reducing the lactate accumulation. Also, the levels of second messengers like IP3 and cAMP were increased with exercise. Increased second messenger levels induce calcium release thereby activating the downstream pathway promoting the translocation of GLUT4 to the plasma membrane. Our results showed that the metabolic and signaling pathway dysregulations seen during diet-induced hyperinsulinemia, a metabolic condition seen during the early stages in the development of prediabetes, were improved with vigorous physical exercise. Thus, exercise can be considered as an excellent management approach over drug therapy for diabetes and its complications

Multiple failed closure of bladder in children with vesical exstrophy: Safety and efficacy of temporary ileal patch augmentation in assisting bladder closure

Objective: The surgical approach to small bladder template in exstrophy bladder is difficult. Previously, many of these children underwent ureterosigmoidostomy and in recent times, the trend is to do a delayed primary closure. We have used ileal patch as a temporary cover for these small bladders with a view to encourage bladder growth and early results are encouraging. Materials and Methods: In five of the 45 children with bladder exstrophy managed by radical soft-tissue mobilization over 10 years, primary bladder closure was not possible due to repeated failed closures. A detubularized ileum was used to patch the bladder initially and after 4 months the patch was excised and bladder closure with sphincter repair was done in second stage. Results: In five children (three girls and two boys) the mean age at initial bladder closure was 14 months and mean age at ileal patch was 22 months. In four patients, the bladder grew facilitating closure and in one patient it failed. There were no complications with the use of gut in patch. Conclusion: A temporary ileal patch seems promising in managing failed bladder closure in exstrophy patients. Long-term studies are needed before such a technique can be used in all patients with failed primary bladder closures

Tiger moth habitats and cointegration of larval versus epidemic waves.

<p>(A) Geographical range of <i>A</i>. <i>caricae</i> (marked as red) includes Indo-Australian tropics to Queensland and Vanuatu (Ref. 18 & 48). (B) Abundance of tiger moth caterpillars infested on <i>F</i>. <i>hispida</i> in Kerala during the year 2009. (C). The mean larval abundance cointegrate with total number of fever cases in selected districts of Kerala (marked as A-D) from the year 2009 to 2012. All the regions from hilly terrains to low lying lands of Kerala are heavily distributed with host plants that have close proximity to houses with illuminated lights. The maps were created using ArcGIS 10 software.</p

Population Explosions of Tiger Moth Lead to Lepidopterism Mimicking Infectious Fever Outbreaks

<div><p>Lepidopterism is a disease caused by the urticating scales and toxic fluids of adult moths, butterflies or its caterpillars. The resulting cutaneous eruptions and systemic problems progress to clinical complications sometimes leading to death. High incidence of fever epidemics were associated with massive outbreaks of tiger moth <i>Asota caricae</i> adult populations during monsoon in Kerala, India. A significant number of monsoon related fever characteristic to lepidopterism was erroneously treated as infectious fevers due to lookalike symptoms. To diagnose tiger moth lepidopterism, we conducted immunoblots for tiger moth specific IgE in fever patients’ sera. We selected a cohort of patients (n = 155) with hallmark symptoms of infectious fevers but were tested negative to infectious fevers. In these cases, the total IgE was elevated and was detected positive (78.6%) for tiger moth specific IgE allergens. Chemical characterization of caterpillar and adult moth fluids was performed by HPLC and GC-MS analysis and structural identification of moth scales was performed by SEM analysis. The body fluids and chitinous scales were found to be highly toxic and inflammatory in nature. To replicate the disease in experimental model, wistar rats were exposed to live tiger moths in a dose dependant manner and observed similar clinico-pathological complications reported during the fever epidemics. Further, to link larval abundance and fever epidemics we conducted cointegration test for the period 2009 to 2012 and physical presence of the tiger moths were found to be cointegrated with fever epidemics. In conclusion, our experiments demonstrate that inhalation of aerosols containing tiger moth fluids, scales and hairs cause systemic reactions that can be fatal to human. All these evidences points to the possible involvement of tiger moth disease as a major cause to the massive and fatal fever epidemics observed in Kerala.</p></div

Tiger moth disease in experimental rats.

<p>Tiger moth toxin exposed rats produced symptoms that resembled fever patients affected during the epidemic. (A) Hemorrhagic syndrome leading to fingernail breaks on both hands, a sign leading to melanonychia. (B) Erythematous rash was prominent on both hands. (C) Bleeding eyes observed as an early sign of the disease. (D) Eruption of erythematous rash on ears. (E) Removal of soft skin on the testes. (F) Edema was confined to the legs and this presentation was very common among fever patients.</p

Toxic responses in experimental rats.

<p>(A-B) Regeneration of megakaryocytes in response to platelet reduction was evident with larger megakaryocytes with irregular multilobulated nucleus and more prominent nucleoli in spleen and bone marrow respectively. (C-D) Mean megakaryocyte volume represented by Leishman-Giemsa positive cells (per field@400×) in spleen (<i>n</i> = 60) and bone marrow (<i>n</i> = 120) respectively. (E) Pneumonitis caused due to extensive proliferation of lymphocytes in the peribronchial region (br, bronchiole). (F) Hepatic tissue reports centrilobular necrosis characterized by prominent ballooning, swollen granular cytoplasm with fading nuclei and nuclear infiltration (cv, central vein). (G) Mild acute renal tubular necrosis illustrated by destroyed cells in proximal tubules (pr). (H) Toluidine blue-positive mast cells (inset red arrow) scattered in lung tissue. (I) Mean mast cell recruitment (per field@400×) in lung tissue of control and toxin groups (<i>n</i> = 120). Asterisks indicate significant difference, <i>t</i>-test, <i>P <</i> 0.05. Fig A,B = magnification 1000× and scale bar = 8 <i>μ</i>m. Fig E-G = 200× and 100 <i>μ</i>m. Fig H = 400× and 20 <i>μ</i>m.</p

Tiger moth and toxic components.

<p>(A) <i>A</i>. <i>caricae</i> showing its characteristic white discal-spotted forewings and black-spotted yellow hind wings. (B) Final instar forage on pioneer host leaves is active at night but elusive during day light. Larva is blackish with red prothorax and a central black stripe in which on each segment two black spots arranged longitudinally (Ref. 18). The photographs were originally taken by P J Wills (Fig A & B). (C) Lamellar type represents majority of the scales on the head, thorax, wings and abdomen (magnification 100×) (D) Scales on the female ovipositor were mostly of piliform type (magnification 500×). (E) Defensive fluids released from specific bleeding points. Broad arrow show hairy tufts or “<i>flechettes</i>” (piliform type) and narrow ones denote the toxic secretions from teguments. The photograph was originally taken by Anjana Mohan (Fig E).</p

Tiger moth specific IgE in human sera.

<p>(A) Immunoblot shows no specific IgE reaction of healthy control serum against tiger moth total protein extract. (B) Specific IgE reaction of patient’s serum against tiger moth total protein extract. The patient was a 40 year old male diagnosed negative for chikungunya, HbsAg and leptospirosis but his total IgE level was > 2,500 IU/mL. (C) Another patient positive to tiger moth specific IgE. A 39 year old male presented with complaints of high grade fever, headache and myalgia. Basic bloods showed thrombocytopenia (≈52000) with deranged liver enzymes and marginally elevated creatinine levels. (D) No bands were detected on moth extract against IgE hypersensitive serum to other allergens (IgE level was > 2,500 IU/mL). (E) No specific IgE reaction of fever control serum (IgE level was < 200 IU/mL) against tiger moth total protein extract. (F) Serum pre-incubated with tiger moth protein show no specific IgE reaction but the same serum (not pre-incubated) showed tiger moth specific IgE response. (G) Serum from patient shows no specific IgE reaction against cockroach total protein but that showed a previously positive IgE response against tiger moth protein. (H) Serum from patient shows no specific IgE reaction against <i>Hyblea</i> moth total protein but that showed a previously positive IgE response against tiger moth total protein. (I) β-actin loading control. (J) Tiger moth specific 42 and 40 kDa IgE bands were prominent when blotted with fever patient serum. (K) The above membrane (J) was further blotted against monoclonal anti-β-actin antibody followed by blotting with secondary anti-mouse IgG AP-linked antibody. No further binding of β-actin was observed at 42 kDa region.</p