Intraoperative hyperglycemia augments ischemia reperfusion injury in renal transplantation: a prospective study.

Background. Diabetes is a risk factor for delayed graft function in kidney transplantation, and hyperglycemia increases ischemia reperfusion injury in animal models. Methods. To explore the role of perioperative hyperglycemia in ischemia reperfusion injury, we conducted a prospective study of 40 patients undergoing living donor renal transplantation. Blood glucose levels were monitored intraoperatively, and serum samples were obtained at the time anesthesia was induced and one hour after allograft reperfusion. The percentage change in neutrophil gelatinase-associated lipocalin (NGAL), a protein whose expression is increased with renal ischemia, was then used to determine the extent of injury. Results. In a multivariate model including recipient, donor, and transplant factors, recipient blood glucose >160 mg/dL at the time of allograft reperfusion (β 0.19, P-value < 0.01), warm ischemia time >30 minutes (β 0.11, P-value 0.13), and recipient age (β 0.05, P-value 0.05) were associated with percentage change in NGAL. These same predictors were associated with the percentage change in creatinine on postoperative day 2. Conclusions. Hyperglycemia is associated with increased ischemic injury in renal transplantation. Both creatinine and NGAL, a marker of ischemic injury and renal function, fall less rapidly in patients with elevated blood glucose

Exploring the functional domain and the target of the tetanus toxin light chain in neurohypophysial terminals

The tetanus toxin light chain blocks calcium induced vasopressin release from neurohypophysial nerve terminals. Here we show that histidine residue 233 within the putative zinc binding motif of the tetanus toxin light chain is essential for the inhibition of exocytosis, in the rat. The zinc chelating agent dipicolinic acid as well as captopril, an inhibitor of zinc-dependent peptidases, counteract the effect of the neurotoxin. Synthetic peptides, the sequences of which correspond to motifs present in the cytoplasmic domain of the synaptic vesicle membrane protein synaptobrevin 1 and 2, prevent the effect of the tetanus toxin light chain. Our results indicate that zinc bound to the zinc binding motif constitutes the active site of the tetanus toxin light chain. Moreover they suggest that cleavage of synaptobrevin by the neurotoxin causes the inhibition of exocytotic release of vasopressin from secretory granules

Charcot-Marie-Tooth disease-associated mutants of GDAP1 dissociate its roles in peroxisomal and mitochondrial fission

Journal ArticleCopyright © 2013 European Molecular Biology OrganizationMitochondria and peroxisomes can be fragmented by the process of fission. The fission machineries of both organelles share a set of proteins. GDAP1 is a tail-anchored protein of mitochondria and induces mitochondrial fragmentation. Mutations in GDAP1 lead to Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuropathy, and affect mitochondrial dynamics. Here, we show that GDAP1 is also targeted to peroxisomes mediated by the import receptor Pex19. Knockdown of GDAP1 leads to peroxisomal elongation that can be rescued by re-expressing GDAP1 and by missense mutated forms found in CMT patients. GDAP1-induced peroxisomal fission is dependent on the integrity of its hydrophobic domain 1, and on Drp1 and Mff, as is mitochondrial fission. Thus, GDAP1 regulates mitochondrial and peroxisomal fission by a similar mechanism. However, our results reveal also a more critical role of the amino-terminal GDAP1 domains, carrying most CMT-causing mutations, in the regulation of mitochondrial compared to peroxisomal fission. © 2013 European Molecular Biology Organization.Swiss National Science FoundationNational Center for Competence in Research (NCCR)BBSRCPortuguese Foundation for Science and Technology (FCT)Fundo Europeu De Desenvolvimento Regional (FEDER

Double infection with a resistant and a multidrug-resistant strain of Mycobacterium tuberculosis.

An immunocompetent patient was dually infected with a resistant and a multidrug-resistant strain of Mycobacterium tuberculosis (TB). The multidrug-resistant strain, which belongs to the W- strain/Beijing family, was first isolated after 3 months of therapy. Inappropriate treatment led to further drug resistance and unsuccessful therapy. Thus, additional infections with resistant M. tuberculosis strains should be considered when tuberculosis therapy fails

1 The Prosodic Marking of Phrase Boundaries: Expectations and Results

ABSTRACT Using sentence templates and a stochastic context-free grammar a large corpus (10,000 sentences) has been created, where prosodic phrase boundaries are labeled in the sentences automatically during sentence generation. With perception experiments on a subset of 500 utterances we verified that 92 % of the automatically marked boundaries were perceived as prosodically marked. In initial automatic classification experiments for three levels of boundaries recognition rates up to 81 % could be achieved. 1.1 Introduction and Material A successful automatic detection of phrase boundaries can be of great help for parsing a word hypotheses graph in an automatic speech understanding (ASU) system. Our recognition paradigm lies within the statistical approach; we therefore need a large training database, i.e. a corpus with reference labels for prosodically marked phrase boundaries. In this paper we wil

Acute Hyperglycemia Worsens Hepatic Ischemia/Reperfusion Injury in Rats

Acute hyperglycemia is known to worsen ischemia/reperfusion (I/R) injury following myocardial infarction and stroke. We investigated whether acute hyperglycemia worsens injury and amplifies the inflammatory response evoked by hepatic I/R. Rats were pretreated with an intraperitoneal injection of 25% glucose or 0.9% sodium chloride (10 ml/kg BW). Subsequently, rats underwent partial (70%) hepatic ischemia for 45 min. After 4 h of reperfusion, hepatic injury, oxidative stress, inflammation, and heat shock protein expression were assessed. Liver injury was increased in the hyperglycemic group with alanine aminotransferase (ALT) and aspartate aminotransferease (AST) serum concentrations of 7,832 ± 3,374 and 10,677 ± 4,110 U/L compared to 3,245 ± 2,009 and 5,386 ± 3,393 U/L (p < 0.05 vs. control). Hyperglycemic I/R was associated with increased liver nitrotyrosine concentrations and increased neutrophil infiltration. I/R upregulated the protective heat shock proteins HSP32 and HSP70 in control animals, but this protective mechanism was inhibited by hyperglycemia: HSP32 expression decreased from 1.97 ± 0.89 (control) to 0.46 ± 0.13 (hyperglycemia), HSP70 expression decreased from 18.99 ± 11.55 (control) to 3.22 ± 0.56 (hyperglycemia), (expression normalized to sham, both p < 0.05 vs. control I/R). Acute hyperglycemia worsens hepatic I/R injury by amplifying oxidative stress and the inflammatory response to I/R. The increase in injury is associated with a downregulation of the protective heat shock proteins HSP32 and HSP70

Automatic classification of prosodically marked phrase boundaries in German

A large corpus has been created automatically and read by speakers. Phrase boundaries were labeled in the sentences automatically during sentence generation. Perception experiments on a subset of 500 utterances showed a high agreement between the automatically generated boundary markers and the ones perceived by listeners. Gaussian distribution and polynomial classifiers were trained on a set of prosodic features computed from the speech signal using the automatically generated boundary markers. Comparing the classification results with the judgments of the listeners yielded in a recognition rate of 87%. A combination with stochastic language models improved the recognition rate to 90%. We found that the pause and the durational features are most important for the classification, but that the influence of F0 is not neglectable

Protecting the Kidney in Liver Transplant Recipients: Practice‐Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134132/1/ajt13765_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134132/2/ajt13765.pd

Improving parsing of spontaneous speech with the help of prosodic boundaries

Parsing can be improved in automatic speech understanding if prosodic boundary marking is taken into account, because syntactic boundaries are often marked by prosodic means. Because large databases are needed for the training of statistical models for prosodic boundaries, we developed a labeling scheme for syntactic-prosodic boundaries within the German VERBMOBIL project (automatic speech-to-speech translation). We compare the results of classifiers (multi-layer perceptrons and language models) trained on these syntactic-prosodic boundary labels with classifiers trained on perceptual-prosodic and purely syntactic labels. Recognition rates of up to 96% were achieved. The turns that we need to parse consist of 20 words on the average and frequently contain sequences of partial sentence equivalents due to restarts, ellipsis, etc. For this material, the boundary scores computed by our classifiers can successfully be integrated into the syntactic parsing of word graphs; currently, they improve the parse time by 92% and reduce the number of parse trees by 96%. This is achieved by introducing a special Prosodic Syntactic Clause Boundary symbol (PSCB) into our grammar and guiding the search for the best word chain with the prosodic boundary scores