WSES Guidelines for the management of acute left sided colonic diverticulitis in the emergency setting

Acute left sided colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in acute setting. A World Society of Emergency Surgery (WSES) Consensus Conference on acute diverticulitis was held during the 3rd World Congress of the WSES in Jerusalem, Israel, on July 7th, 2015. During this consensus conference the guidelines for the management of acute left sided colonic diverticulitis in the emergency setting were presented and discussed. This document represents the executive summary of the final guidelines approved by the consensus conference.Peer reviewe

Effect of Lagenaria siceraria fruit powder on sodium oxalate induced urolithiasis in Wistar rats

Background: In spite of advances in the present practice of medicine, the formation and growth of calculi continues to trouble mankind, as there is no satisfactory drug to treat kidney stones. In India, many indigenous drugs are in use for the treatment of urinary calculus disease. Objective: The present study was intended to determine anti-urolithiatic effect of Lagenaria siceraria fruit powder (LSFP) against sodium oxalate (NaOx) induced urolithiasis in rats. Materials and Methods: Animals were grouped as Vehicle Group (received vehicle gum acacia 2% w/v 1 mL/kg/p.o.), NaOx Group(Sodium oxalate 70 mg/kg,i.p.), LSFP Group (500 mg/kg, p.o. LSFP suspended in gum acacia 2% + Sodium oxalate 70 mg/kg), Cystone Group (500 mg/kg, p.o. Cystone suspended in gum acacia 2% + Sodium oxalate 70 mg/kg). Result: The increased severity of microscopic calcium oxalate (CaOx) crystals deposition along with increased concentration in the kidney was seen after 7 days of NaOx (70 mg/kg, i.p.) pre-treatment. LSFP (500 mg/kg, p.o.) and standard marketed formulation Cystone (500 mg/kg, p.o.) caused a significant reversal of NaOx-induced changes in ion excretion and urinary CaOx concentration in 7 days treatment. Conclusion: From the results, it was concluded that LSFP showed beneficial effect against urolithiasis by decreasing CaOx excretion and preventing crystal deposition in the kidney tubules

Impaired ALDH2 activity decreases the mitochondrial respiration in H9C2 cardiomyocytes

Reactive oxygen species (ROS)-mediated reactive aldehydes induce cellular stress. In cardiovascular diseases such as ischemia-reperfusion injury, lipid-peroxidation derived reactive aldehydes such as 4-hydroxy-2-nonenal (4HNE) are known to contribute to the pathogenesis. 4HNE is involved in ROS formation, abnormal calcium handling and more importantly defective mitochondrial respiration. Aldehyde dehydrogenase (ALDH) superfamily contains NAD(P)(+)-dependent isozymes which can detoxify endogenous and exogenous aldehydes into non-toxic carboxylic acids. Therefore we hypothesize that 4HNE afflicts mitochondrial respiration and leads to cell death by impairing ALDH2 activity in cultured H9C2 cardiomyocyte cell lines. H9C2 cardiomyocytes were treated with 25, 50 and 75 μM 4HNE and its vehicle, ethanol as well as 25, 50 and 75 μM disulfiram (DSF), an inhibitor of ALDH2 and its vehicle (DMSO) for 4 h. 4HNE significantly decreased ALDH2 activity, ALDH2 protein levels, mitochondrial respiration and mitochondrial respiratory reserve capacity, and increased 4HNE adduct formation and cell death in cultured H9C2 cardiomyocytes. ALDH2 inhibition by DSF and ALDH2 siRNA attenuated ALDH2 activity besides reducing ALDH2 levels, mitochondrial respiration and mitochondrial respiratory reserve capacity and increased cell death. Our results indicate that ALDH2 impairment can lead to poor mitochondrial respiration and increased cell death in cultured H9C2 cardiomyocytes

Mitochondrial respiration indices.

<p>Mitochondrial oxygen consumption rate (OCR) of control and DM rats: A) Mitochondrial basal OCR (Δ OCR from basal minus of Antimycin-A). B) ADP OCR (ADP minus Oligomycin). C) Maximum OCR (FCCP minus Antimycin-A). D) FCCP-induced mitochondrial respiratory reserve capacity. (Area under curve of FCCP minus area under curve oligomycin) was plotted as a graph. E) The ratio between state 3 and 4 respirations was depicted as the respiratory control rate (RCR). The data expressed are mean ± SEM. N = 6–11. ** <i>p</i> < 0.01 <i>vs</i> control;.***P<0.0001 <i>vs</i> control.</p

Cardiac Mitochondrial Respiratory Dysfunction and Tissue Damage in Chronic Hyperglycemia Correlate with Reduced Aldehyde Dehydrogenase-2 Activity

<div><p>Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial isozyme of the heart involved in the metabolism of toxic aldehydes produced from oxidative stress. We hypothesized that hyperglycemia-mediated decrease in ALDH2 activity may impair mitochondrial respiration and ultimately result in cardiac damage. A single dose (65 mg/kg; i.p.) streptozotocin injection to rats resulted in hyperglycemia with blood glucose levels of 443 ± 9 mg/dl <i>versus</i> 121 ± 7 mg/dl in control animals, p<0.0001, N = 7–11. After 6 months of diabetes mellitus (DM) induction, the rats were sacrificed after recording the functionality of their hearts. Increase in the cardiomyocyte cross sectional area (446 ± 32 μm² <i>Vs</i> 221 ± 10 μm²; p<0.0001) indicated cardiac hypertrophy in DM rats. Both diastolic and systolic dysfunctions were observed with DM rats compared to controls. Most importantly, myocardial ALDH2 activity and levels were reduced, and immunostaining for 4HNE protein adducts was increased in DM hearts compared to controls. The mitochondrial oxygen consumption rate (OCR), an index of mitochondrial respiration, was decreased in mitochondria isolated from DM hearts compared to controls (p<0.0001). Furthermore, the rate of mitochondrial respiration and the increase in carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)-induced maximal respiration were also decreased with chronic hyperglycemia. Chronic hyperglycemia reduced mitochondrial OXPHOS proteins. Reduced ALDH2 activity was correlated with mitochondrial dysfunction, pathological remodeling and cardiac dysfunction, respectively. Our results suggest that chronic hyperglycemia reduces ALDH2 activity, leading to mitochondrial respiratory dysfunction and consequently cardiac damage and dysfunction.</p></div

Mitochondrial respiration indices.

<p>Mitochondrial oxygen consumption rate (OCR) of control and DM rats: A) Mitochondrial basal OCR (Δ OCR from basal minus of Antimycin-A). B) ADP OCR (ADP minus Oligomycin). C) Maximum OCR (FCCP minus Antimycin-A). D) FCCP-induced mitochondrial respiratory reserve capacity. (Area under curve of FCCP minus area under curve oligomycin) was plotted as a graph. E) The ratio between state 3 and 4 respirations was depicted as the respiratory control rate (RCR). The data expressed are mean ± SEM. N = 6–11. ** <i>p</i> < 0.01 <i>vs</i> control;.***P<0.0001 <i>vs</i> control.</p

Levels of mitochondrial complex proteins.

<p>A). Western blot images of mitochondrial OXPHOS respiratory complex protein levels and VDAC (Porin) were shown in DM compared to control. A cocktail antibody comprising the following subunits of respiratory complex proteins are used: NADH dehydrogenase (ubiquinone) 1 beta subcomplex 8 (NDUFB8; complex I), succinate dehydrogenase complex, subunit B, iron sulfur (SDHB/Ip; complex II), ubiquinol-cytochrome c reductase core protein II (UQCR2; complex III), cytochrome c oxidase subunit 2 (COXII; complex IV) and ATP synthase 5A (ATP 5A, Complex V). B, C, D, E and F). Quantification of the levels of each of the above mentioned subunits were shown, respectively. The data was presented as % of proteins normalized to porin levels.</p

Correlation between ALDH2 activity and mitochondrial respiratory dysfunction, cardiac pathological remodeling and cardiac dysfunction.

<p>Graphs showing direct correlation between ALDH2 activity with A) Respiratory reserve capacity, B) Maximum OCR and inverse correlation with C) Hypertrophy, D) Fibrosis, E) Systolic dysfunction and F) diastolic dysfunction. Data were analyzed by linear regression (*<i>** < 0</i>.<i>001</i>, <i>** < 0</i>.<i>01</i>, <i>* p < 0</i>.<i>05)</i>. N = 4 per group. Open and closed circles denote control and DM respectively.</p