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Primary toxicity targets of alcohol and its metabolites in the pancreas are cellular energetics and endoplasmic reticulum (ER). Therefore, the role of AMP-Activated Protein Kinase (AMPKα) in amelioration of ethanol (EtOH)-induced pancreatic acinar cell injury including ER/oxidative stress, inflammatory responses, the formation of fatty acid ethyl esters (FAEEs) and mitochondrial bioenergetics were determined in human pancreatic acinar cells (hPACs) and AR42J cells incubated with/without AMPKα activator [5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)]. EtOH treated hPACs showed concentration and time-dependent increases for FAEEs and inactivation of AMPKα, along with the upregulation of ACC1 and FAS (key lipogenic proteins) and downregulation of CPT1A (involved β-oxidation of fatty acids). These cells also showed significant ER stress as evidenced by the increased expression for GRP78, IRE1α, and PERK/CHOP arm of unfolded protein response promoting apoptosis and activating p-JNK1/2 and p-ERK1/2 with increased secretion of cytokines. AR42J cells treated with EtOH showed increased oxidative stress, impaired mitochondrial biogenesis, and decreased ATP production rate. However, AMPKα activation by AICAR attenuated EtOH-induced ER/oxidative stress, lipogenesis, and inflammatory responses as well as the formation of FAEEs and restored mitochondrial function in *

Neonatal hyperbilirubinemia is a common problem with potentiality to cause irreversible brain damage. Reduction of serum bilirubin level is essential to minimize such damage. Compact fluorescent tubes, halogen bulbs, fiber optic blankets, and LEDs are commonly used light sources for phototherapy with varying efficacies. This study aimed at evaluating the effect of LED versus conventional phototherapy on (a) rate of reduction in total serum bilirubin levels, (b) effect on urinary lumirubin excretion, and (c) comparing side effects of phototherapies among neonates with hyperbilirubinemia. In this randomized control trial, 166 neonates ≥ 35 weeks of age requiring phototherapy were recruited and further divided into 2 groups [LED (83) and conventional (83)] by using computer generated random numbers. Serial total serum bilirubin levels and random urinary lumirubin levels were collected and side effects of phototherapy were noted. Rate of fall in total serum bilirubin levels (TSB, μmol/L/hour) and random urinary lumirubin levels were computed. Data were collected using a pretested proforma. Analysis was done with Statistical Package for Social Sciences (SPSS) version 11.5. Independent sample “t” test and Chi-square tests were used with p value of <0.05 being significant. Significant difference was documented in mean rate of decrease of TSB (μmol/L/hour) in LED group (5.3 ± 2.91) when compared to conventional group (3.76 ± 2.39) (p <0.001). A significant increase in mean random urinary lumirubin levels (arbitrary units) was observed in LED group (129.01 ± 33.18) when compared to conventional group (114.44 ± 44.84) (p = 0.021). Side effects were minimal and comparable in both groups. This study concludes the rates of decrease in total serum bilirubin levels and increase in urinary lumirubin levels were significant with LED when compared with conventional phototherapy, implying LED to be more efficacious.

Background: Chronic alcohol consumption impairs alveolar macrophage's (AM) function and increases risk for developing lung infection and pneumonia. However, the mechanism and metabolic basis of alcohol-induced AM dysfunction leading to lung infection are not well defined, but may include altered ethanol (EtOH) and reactive oxygen species metabolism and cellular energetics. Therefore, oxidative stress, endoplasmic reticulum (ER) stress, the formation of fatty acid ethyl esters [FAEEs, nonoxidative metabolites of EtOH], AMP-activated protein kinase (AMPK) signaling, and phagocytic function were examined in freshly isolated AM incubated with EtOH.Methods: AMs separated from bronchoalveolar lavage fluid samples obtained from normal volunteers were incubated with EtOH for 24 hours. AMPK signaling and ER stress were assessed using Western blotting, FAEEs by GC-MS, oxidative stress by immunofluorescence using antibodies to 4hydroxynonenal, and phagocytosis by latex beads. Oxidative stress was also measured in EtOH-treated AMs with/without AMPK activator [5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)] or inhibitor (Compound C), and in AMs incubated with FAEEs. mRNA expression for interleukins (IL-6 and IL-8), monocyte chemoattractant protein (MCP)-1, and transforming growth factor (TGF)-b was measured in AM treated with EtOH or FAEEs using RT-PCR.Results: EtOH exposure to AM increased oxidative stress, ER stress, and synthesis of FAEEs, decreased phosphorylated AMPK, and impaired phagocytosis. Attenuation or exacerbation of EtOHinduced oxidative stress by AICAR or Compound C, respectively, suggests a link between AMPK signaling, EtOH metabolism, and related oxidative stress. The formation of FAEEs may contribute to EtOH-induced oxidative stress as FAEEs also produced concentration-dependent oxidative stress. An increased mRNA expression of IL-6, IL-8, and MCP-1 by FAEEs is key finding to suggest a metabolic basis of EtOH-induced inflammatory response.Conclusions: EtOH-induced impaired phagocytosis, oxidative stress, ER stress, and dysregulated AMPK signaling are plausibly associated with the formation of FAEEs and may participate in the pathogenesis of nonspecific pulmonary inflammation.

Background:Insulin resistance (IR) has known to be associated with coronary artery disease (CAD), but the assessment of severity of the CAD based on IR in type 2 diabetes mellitus has not been established in detail.Aims:The aim of our study was to establish the correlation between IR and the severity of CAD in type 2 diabetes mellitus.Materials and Methods:In a cross-sectional study design, 61 consecutive patients with type 2 diabetes mellitus who underwent coronary angiogram for the evaluation of CAD were recruited. Fasting blood glucose, fasting insulin levels, systolic blood pressure and total cholesterol/high density lipoprotein-cholesterol ratio were determined. Homeostasis model assessment-IR (HOMA-IR) was correlated with severity of CAD, which was measured by modified Gensini Score.Results:There was a significant correlation between log HOMA-IR and severity of CAD (r = 0.303, P = 0.009) in diabetic patients. Correlation of the Gensini Score with other known risk factors was not significant.Conclusions:The results of our study indicate that we might able to predict the severity of CAD by measure of IR.