Role of Pre-Medicational Ondansetron and Ketamine to Prevent Shivering During Spinal Anaesthesia: A Comparative Study

Objective: Shivering is a common problem during anesthesia. Ketamine has been used for preventing shivering during anesthesia. Ondansetron (8 mg) has been recently evaluated for its peri-operative anti-shivering effect in patients undergoing spinal anesthesia. The objective of my study is to compare low dose Ondansetron with low dose Ketamine among patients undergoing spinal anesthesia in elective surgery in terms of frequency of shivering. Patients and Methods: Patients undergoing elective general surgical procedures at Department of Anesthesiology, Holy Family Hospital, Rawalpindi, were inducted in the study. The study design was a randomized control trial and conducted from Jan 2016 to June 2016. Patients were included through a consecutive non-probability sampling. After spinal anaesthesia, patients were randomly assigned to receive Ketamine 0.25 mg/kg (group A) or Ondansetron 4mg (group B) by lottery method. During surgery, shivering was recorded at 10 min interval and recorded in terms of frequency. Results: Out of the total 256 study participants, 128 patients in each group received the study drug (Ondansetron/ Ketamine) before surgery for prevention of shivering. Overall, there were 158 male and 98 female patients. The mean age of study population was 36 ± 11 yrs (range 21–40 yrs). Shivering occurred in 11 (4.3%) patients only. There was no significant difference between the gender distributions between the two groups (p=0.16). Patients pre-treated with Ketamine significantly experienced lesser shivering episodes than Ondansetron group (2 (1.6%) vs. 9 (7%), p=0.03). Conclusion: The findings of our study suggest that the prophylactic administration of low dose Ketamine (0.25 mg kg-1) and Ondansetron (4mg) produces anti-shivering effect in patients undergoing spinal anaesthesia. Ketamine (0.25 mg/kg) is significantly more effective than Ondansetron (4mg) during spinal anaesthesi

Use of Pregabalin as a Pre-Medication for Post-Operative pain in patients undergoing Laparoscopic Cholecystectomy

Background: Postoperative pain creates complications by increasing circulating level of catecholamines and systemic vascular resistance, thus putting the patients on increased risks of having stroke and myocardial infarction. In addition, it increases hospital stay, causing burden over economic as well as healthcare infrastructure. The aim of this study was to determine the frequency of pain in the postoperative period while using Pregabalin as pre-medication among patients undergoing laparoscopic cholecystectomy.Material and Methods: The randomized control trail was conducted at Department of Anesthesiology, Holy Family hospital, Rawalpindi from 1st Sept 2015 to 28th Feb 2016 over a period of 6 months. A total of 200 patients undergoing laparoscopic cholecystectomy were randomly divided in group A and B by consecutive non-probability lottery method. Group A received 100 mg oral Pregabalin 1 hour before surgery and Group B were not given Pregabalin and were taken as controls. Post-operative pain was measured by visual analog scale (VAS) in terms of pain scores at 4 hours postoperatively after the arrival of patient in the post-anesthesia care unit (PACU). SPSS version 17.0 was used to analyze the data.Results: A total of 200 patients were included in the study. There were 100 patients in each group. Based on the visual analog pain scores, 9 patients were pain free in group A compared with none in group B. Similarly, there were 55 patients in group A, who reported a pain score of 1 whereas no patient in group B had a VAS score of 1. There were 29 patients in group A and only 3 patients in group B with VAS score of 2 (90.6% vs. 9.4%). For VAS score of 3, there were 6 patients in group A and 34 patients from group B (15% vs. 85%). For a VAS score of 4, there were 1 patient in group A and 61 patients in group B (1.6% vs. 98.4%). Two patients in group B experienced a VAS score of 5. All this data was significant with chi square p value of 0.0001.Conclusion: Oral Pregabalin administered prior to laparoscopic cholecystectomy was effective in reducing postoperative pain in the patients. Further studies are needed for post-operative evaluation of side effects, different dosing schedules at different time intervals for both rest and dynamic pain

Delineating WWOX protein interactome by tandem affinity purification-mass spectrometry : Identification of top interactors and key metabolic pathways involved

It has become clear from multiple studies that WWOX (WW domain-containing oxidoreductase) operates as a “non-classical” tumor suppressor of significant relevance in cancer progression. Additionally, WWOX has been recognized for its role in a much wider array of human pathologies including metabolic conditions and central nervous system related syndromes. A myriad of putative functional roles has been attributed to WWOX mostly through the identification of various binding proteins. However, the reality is that much remains to be learned on the key relevant functions of WWOX in the normal cell. Here we employed a Tandem Affinity Purification-Mass Spectrometry (TAP-MS) approach in order to better define direct WWOX protein interactors and by extension interaction with multiprotein complexes under physiological conditions on a proteomic scale. This work led to the identification of both well-known, but more importantly novel high confidence WWOX interactors, suggesting the involvement of WWOX in specific biological and molecular processes while delineating a comprehensive portrait of WWOX protein interactome. Of particular relevance is WWOX interaction with key proteins from the endoplasmic reticulum (ER), Golgi, late endosomes, protein transport, and lysosomes networks such as SEC23IP, SCAMP3, and VOPP1. These binding partners harbor specific PPXY motifs which directly interact with the amino-terminal WW1 domain of WWOX. Pathway analysis of WWOX interactors identified a significant enrichment of metabolic pathways associated with proteins, carbohydrates, and lipids breakdown. Thus, suggesting that WWOX likely plays relevant roles in glycolysis, fatty acid degradation and other pathways that converge primarily in Acetyl-CoA generation, a fundamental molecule not only as the entry point to the tricarboxylic acid (TCA) cycle for energy production, but also as the key building block for de novo synthesis of lipids and amino acids. Our results provide a significant lead on subsets of protein partners and enzymatic complexes with which full-length WWOX protein interacts with in order to carry out its metabolic and other biological functions while also becoming a valuable resource for further mechanistic studies.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y Aplicada

Wwox deletion leads to reduced GABA-ergic inhibitory interneuron numbers and activation of microglia and astrocytes in mouse hippocampus

The association of WW domain-containing oxidoreductase WWOX gene loss of function with central nervous system (CNS) related pathologies is well documented. These include spinocerebellar ataxia, epilepsy and mental retardation (SCAR12, OMIM: 614322) and early infantile epileptic encephalopathy (EIEE28, OMIM: 616211) syndromes. However, there is complete lack of understanding of the pathophysiological mechanisms at play. In this study, using a Wwox knockout (Wwox KO) mouse model (2 weeks old, both sexes) and stereological studies we observe that Wwox deletion leads to a significant reduction in the number of hippocampal GABA-ergic (γ-aminobutyric acid) interneurons. Wwox KO mice displayed significantly reduced numbers of calcium-binding protein parvalbumin (PV) and neuropeptide Y (NPY) expressing interneurons in different subfields of the hippocampus in comparison to Wwox wild-type (WT) mice. We also detected decreased levels of Glutamic Acid Decarboxylase protein isoforms GAD65/67 expression in Wwox null hippocampi suggesting lower levels of GABA synthesis. In addition, Wwox deficiency was associated with signs of neuroinflammation such as evidence of activated microglia, astrogliosis, and overexpression of inflammatory cytokines Tnf-a and Il6. We also performed comparative transcriptome-wide expression analyses of neural stem cells grown as neurospheres from hippocampi of Wwox KO and WT mice thus identifying 283 genes significantly dysregulated in their expression. Functional annotation of transcriptome profiling differences identified ?neurological disease? and ?CNS development related functions? to be significantly enriched. Several epilepsy-related genes were found differentially expressed in Wwox KO neurospheres. This study provides the first genotype-phenotype observations as well as potential mechanistic clues associated with Wwox loss of function in the brain.Fil: Hussain, Tabish. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados UnidosFil: Kil, Hyunsuk. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados UnidosFil: Hattiangady, Bharathi. Texas A&M Health Science Center College of Medicine; Estados UnidosFil: Lee, Jaeho. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados UnidosFil: Kodali, Maheedhar. Texas A&M Health Science Center College of Medicine; Estados UnidosFil: Shuai, Bing. Texas A&M Health Science Center College of Medicine; Estados UnidosFil: Attaluri, Sahithi. Texas A&M Health Science Center College of Medicine; Estados UnidosFil: Takata, Yoko. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados UnidosFil: Shen, Jianjun. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Shetty, Ashok K.. Texas A&M Health Science Center College of Medicine; Estados UnidosFil: Aldaz, Claudio Marcelo. University of Texas Health Science Center at Houston. University of Texas Md Anderson Cancer Center; Estados Unido

Electrochemical Insight into the Use of Microbial Fuel Cells for Bioelectricity Generation and Wastewater Treatment

Microbial fuel cell (MFC) technology is anticipated to be a practical alternative to the activated sludge technique for treating domestic and industrial effluents. The relevant literature mainly focuses on developing the systems and materials for maximum power output, whereas understanding the fundamental electrochemical characteristics is inadequate. This experimental study uses a double-chamber MFC having graphite electrodes and an anion-exchange membrane to investigate the electrochemical process limitations and the potential of bioelectricity generation and dairy effluent treatment. The results revealed an 81% reduction in the chemical oxygen demand (COD) in 10 days of cell operation, with an initial COD loading of 4520 mg/L. The third day recorded the highest open circuit voltage of 396 mV, and the maximum power density of 36.39 mW/m2 was achieved at a current density of 0.30 A/m2. The electrochemical impedance spectroscopy analysis disclosed that the activation polarization of the aerated cathode was the primary factor causing the cell’s resistance, followed by the ohmic and anodic activation overpotentials

Delineating WWOX Protein Interactome by Tandem Affinity Purification-Mass Spectrometry: Identification of Top Interactors and Key Metabolic Pathways Involved

It has become clear from multiple studies that WWOX (WW domain-containing oxidoreductase) operates as a “non-classical” tumor suppressor of significant relevance in cancer progression. Additionally, WWOX has been recognized for its role in a much wider array of human pathologies including metabolic conditions and central nervous system related syndromes. A myriad of putative functional roles has been attributed to WWOX mostly through the identification of various binding proteins. However, the reality is that much remains to be learned on the key relevant functions of WWOX in the normal cell. Here we employed a Tandem Affinity Purification-Mass Spectrometry (TAP-MS) approach in order to better define direct WWOX protein interactors and by extension interaction with multiprotein complexes under physiological conditions on a proteomic scale. This work led to the identification of both well-known, but more importantly novel high confidence WWOX interactors, suggesting the involvement of WWOX in specific biological and molecular processes while delineating a comprehensive portrait of WWOX protein interactome. Of particular relevance is WWOX interaction with key proteins from the endoplasmic reticulum (ER), Golgi, late endosomes, protein transport, and lysosomes networks such as SEC23IP, SCAMP3, and VOPP1. These binding partners harbor specific PPXY motifs which directly interact with the amino-terminal WW1 domain of WWOX. Pathway analysis of WWOX interactors identified a significant enrichment of metabolic pathways associated with proteins, carbohydrates, and lipids breakdown. Thus, suggesting that WWOX likely plays relevant roles in glycolysis, fatty acid degradation and other pathways that converge primarily in Acetyl-CoA generation, a fundamental molecule not only as the entry point to the tricarboxylic acid (TCA) cycle for energy production, but also as the key building block for de novo synthesis of lipids and amino acids. Our results provide a significant lead on subsets of protein partners and enzymatic complexes with which full-length WWOX protein interacts with in order to carry out its metabolic and other biological functions while also becoming a valuable resource for further mechanistic studies