Evidence for the association of the SLC22A4 and SLC22A5 genes with Type 1 Diabetes: a case control study

BACKGROUND: Type 1 diabetes (T1D) is a chronic, autoimmune and multifactorial disease characterized by abnormal metabolism of carbohydrate and fat. Diminished carnitine plasma levels have been previously reported in T1D patients and carnitine increases the sensitivity of the cells to insulin. Polymorphisms in the carnitine transporters, encoded by the SLC22A4 and SLC22A5 genes, have been involved in susceptibility to two other autoimmune diseases, rheumatoid arthritis and Crohn's disease. For these reasons, we investigated for the first time the association with T1D of six single nucleotide polymorphisms (SNPs) mapping to these candidate genes: slc2F2, slc2F11, T306I, L503F, OCTN2-promoter and OCTN2-intron. METHODS: A case-control study was performed in the Spanish population with 295 T1D patients and 508 healthy control subjects. Maximum-likelihood haplotype frequencies were estimated by applying the Expectation-Maximization (EM) algorithm implemented by the Arlequin software. RESULTS: When independently analyzed, one of the tested polymorphisms in the SLC22A4 gene at 1672 showed significant association with T1D in our Spanish cohort. The overall comparison of the inferred haplotypes was significantly different between patients and controls (χ(2 )= 10.43; p = 0.034) with one of the haplotypes showing a protective effect for T1D (rs3792876/rs1050152/rs2631367/rs274559, CCGA: OR = 0.62 (0.41–0.93); p = 0.02). CONCLUSION: The haplotype distribution in the carnitine transporter locus seems to be significantly different between T1D patients and controls; however, additional studies in independent populations would allow to confirm the role of these genes in T1D risk

Hyperoxia-Induced Protein Alterations in Renal Rat Tissue: A Quantitative Proteomic Approach to Identify Hyperoxia-Induced Effects in Cellular Signaling Pathways

Introduction. In renal tissue as well as in other organs, supranormal oxygen pressure may lead to deleterious consequences on a cellular level. Additionally, hyperoxia-induced effect in cells and related free radicals may potentially contribute to renal failure. The aim of this study was to analyze time-dependent alterations of rat kidney protein expression after short-term normobaric hyperoxia using proteomics and bioinformatic approaches. Material and Methods. N = 36 Wistar rats were randomized into six different groups: three groups with normobaric hyperoxia (exposure to 100% oxygen for 3 h) and three groups with normobaric normoxia (NN; room air). After hyperoxia exposure, kidneys were removed immediately, after 3 days and after 7 days. Kidney lysates were analyzed by two-dimensional gel electrophoresis followed by peptide mass fingerprinting using tandem mass spectrometry. Statistical analysis was performed with DeCyder 2D software (p < 0.01). Biological functions of differential regulated proteins were studied using functional network analysis (Ingenuity Pathways Analysis and PathwayStudio). Results. Expression of 14 proteins was significantly altered (p < 0.01): eight proteins (MEP1A_RAT, RSSA_RAT, F16P1_RAT, STML2_RAT, BPNT1_RAT, LGMN_RAT, ATPA_RAT, and VDAC1_RAT) were downregulated and six proteins (MTUS1_RAT, F16P1_RAT, ACTG_RAT, ACTB_RAT, 2ABA_RAT, and RAB1A_RAT) were upregulated. Bioinformatic analyses revealed an association of regulated proteins with inflammation. Conclusions. Significant alterations in renal protein expression could be demonstrated for up to 7 days even after short-term hyperoxia. The identified proteins indicate an association with inflammation signaling cascades. MEP1A and VDAC1 could be promising candidates to identify hyperoxic injury in kidney cells

Depth of Neuromuscular Block Is Not Associated with Abdominal Wall Distention or Surgical Conditions during Gynecologic Laparoscopic Operations. A Prospective Trial

The influence of the degree of a neuromuscular block (NMB) on surgical operating conditions during laparoscopic surgery is debated controversially. The extent of abdominal distension during the time course of the NMB was assessed as a new measurement tool. In 60 patients scheduled for gynecologic laparoscopic surgery, the increase of the abdominal wall length induced by the capnoperitoneum was measured at 5 degrees of the NMB: intense NMB-post-tetanic count (PTC) = 0; deep NMB-train-of-four count (TOF) = 0 and PTC = 1-5; medium NMB-PTC > 5 and TOF = 0-1; shallow NMB-TOF > 1; full recovery-train-of-four ratio TOFR > 90%. Simultaneously, the quality of operating conditions was assessed with a standardized rating scale (SRS) reaching from 1 (extremely poor conditions) to 5 (excellent conditions). Fifty patients could be included in the analysis. The abdominal wall length increased by 10-13 mm induced by the capnoperitoneum. SRS was higher during intense NMB (4.7 +/- 0.5) vs. full recovery (4.5 +/- 0.5) (mean +/- SD; p = 0.025). Generally, an intense NMB did not increase abdominal wall length induced by capnoperitoneum. Additionally, its influence on the quality of surgical operating conditions seems to be of minor clinical relevance

Pain Medication Requirements After Sacropexy and Combination Interventions

Background and Objectives: Laparoscopic surgery is associated with reduced morbidity, and postoperative pain is reduced. The aim of this study was to assess postoperative pain intensity, analgesic requirements, and the influence of cofactors after laparoscopic sacral colpopexy. Methods: The study assessed 287 patients treated with laparoscopic sacropexy for genital prolapse with a Pelvic Organ Prolapse Quantification grade >1. Patients were asked to evaluate their pain postoperatively using a 4-point verbal pain rating scale. In addition, medical records were analyzed regarding the requirement for analgesic medication. Results: Patients distinguished between abdominal pain and shoulder pain after laparoscopy. Abdominal pain reached maximum severity on day 1 and showed a good response to nonsteroidal antiphlogistics, whereas shoulder pain was rarely found (6.27%). Of the patients, 38% required no pain treatment or required 1 dose at most. The need for pain medication reached its climax on day 1 and decreased during the 5 following days. Non-opioid analgesics provided a sufficient therapeutic effect. Conclusion: Laparoscopic sacropexy is associated with a moderate degree of postoperative pain. Non-opioid analgesics should be preferred as first-line therapy. The typical shoulder-tip pain showed only a low prevalence in our study group. From our point of view, the low rate of shoulder-tip pain corresponded with the low intra-abdominal carbon dioxide pressure

Dexamethasone decreases the duration of rocuronium-induced neuromuscular block A randomised controlled study

BACKGROUND Several drugs influence the time course of neuromuscular block during general anaesthesia. OBJECTIVE To evaluate the effect of a single dose of dexamethasone 8 mg on the time course of a rocuronium-induced neuromuscular block. DESIGN A randomised controlled, unblinded, monocentre trial. SETTING Kreiskrankenhaus Dormagen, Dormagen, Germany. PATIENTS One hundred and eight adult patients scheduled for elective gynaecological laparoscopic surgery allocated to three groups. INTERVENTIONS Patients received dexamethasone 8 mg intravenously 2 to 3 h prior to surgery (Group A), during induction of anaesthesia (Group B) or after recovery of the neuromuscular block (Group C, control). MAIN OUTCOME MEASURES The time course of the neuromuscular block of rocuronium 0.3 mg kg(-1) was assessed using acceleromyography. The primary end point was the time from start of injection of rocuronium until recovery to a train-pof-pfour ratio of 0.9. RESULTS The clinical duration was decreased in Group A (15.8 +/- 4.5 min) compared with Group B (18.7 +/- 5.8 min; P = 0.031). The recovery index was reduced in Group A (6.8 +/- 1.8 min) compared with Group B (8.1 +/- 2.6 min; P = 0.018) and Group C (8.3 +/- 2.8 min; P = 0.01). The recovery to a train-pof-pfour ratio of 0.9 was shorter in Group A (30.4 +/- 6.9 min) than in Groups B (36.3 +/- 10.7 min; P 0.031) and C (36.8 +/- 11.3 min; P = 0.02). CONCLUSION A single dose of dexamethasone 8 mg attenuated rocuronium-pinduced block by 15 to 20% if administered 2 to 3 h prior to induction of anaesthesia. However, the administration of dexamethasone during induction of anaesthesia did not influence the time course of the neuromuscular block

Value of Clinical and Laboratory Inflammation Factors in the Postoperative Period after Laparoscopic Urogynecological Surgery

Background/Aims: Leukocytes and C-reactive protein (CRP) levels are often used to detect infections. The aim of this study was to evaluate the diagnostic and screening validity of leukocytes and CRP levels as well as body temperature >38 degrees C to predict infections after laparoscopic sacrocolpopexy. Methods: The study included 287 patients suffering from genital prolapse higher than POP-Q I. In addition to the sacrocolpopexy, a laparoscopic supracervical hysterectomy was performed in cases of preexisting uterus (n = 171). Leukocytes and CRP levels were analyzed preoperatively and 4 days after surgery. Early and late onset of infections was documented. Results: Urinary tract infection was identified as the most frequent early postoperative complication (11.4%). Early wound infections were found in 2.8% of the patients (8/287). Late onset of infections was found in 1% of patients (3/287). Areas under ROC curves were low for both leukocytes (0.52, 95% CI: 0.37-0.66) and CRP levels (0.60, 95% CI: 0.44-0.77). Conclusion: Our findings question the benefit of routine determination of leukocytes and CRP levels 4 days after surgery. The sensitivity and specificity of leukocytes and CRP levels are probably more significant after normalization of the initial tissue response (days 8-10). (C) 2014 S. Karger AG, Base

Interictal spikes, fast ripples and seizures in partial epilepsies - combining multi-level computational models with experimental data.: computational and experimental models of epilepsy

International audienceEpileptic seizures, epileptic spikes and high-frequency oscillations (HFOs) are recognized as three electrophysiological markers of epileptogenic neuronal systems. It can be reasonably hypothesized that distinct (hyper)excitability mechanisms underlie these electrophysiological signatures. The question is 'What are these mechanisms?'. Solving this difficult question would considerably help our understanding of epileptogenic processes and would also advance our interpretation of electrophysiological signals. In this paper, we show how computational models of brain epileptic activity can be used to address this issue. With a special emphasis on the hippocampal activity recorded in various experimental models (in vivo and in vitro) as well as in epileptic patients, we confront results and insights we can get from computational models lying at two different levels of description, namely macroscopic (neural mass) and microscopic (detailed network of neurons). At each level, we show how spikes, seizures and HFOs can (or cannot) be generated depending on the model features. The replication of observed signals, the prediction of possible mechanisms as well as their experimental validation are described and discussed; as are the advantages and limitations of the two modelling approaches