Intestinal Epithelial Stem/Progenitor Cells Are Controlled by Mucosal Afferent Nerves

Background: The maintenance of the intestinal epithelium is of great importance for the survival of the organism. A possible nervous control of epithelial cell renewal was studied in rats and mice. Methods: Mucosal afferent nerves were stimulated by exposing the intestinal mucosa to capsaicin (1.6 mM), which stimulates intestinal external axons. Epithelial cell renewal was investigated in the jejunum by measuring intestinal thymidine kinase (TK) activity, intestinal H-3-thymidine incorporation into DNA, and the number of crypt cells labeled with BrdU. The influence of the external gut innervation was minimized by severing the periarterial nerves. Principal Findings: Luminal capsaicin increased all the studied variables, an effect nervously mediated to judge from inhibitory effects on TK activity or H-3-thymidine incorporation into DNA by exposing the mucosa to lidocaine (a local anesthetic) or by giving four different neurotransmitter receptor antagonists i.v. (muscarinic, nicotinic, neurokinin1 (NK1) or calcitonin gene related peptide (CGRP) receptors). After degeneration of the intestinal external nerves capsaicin did not increase TK activity, suggesting the involvement of an axon reflex. Intra-arterial infusion of Substance P (SP) or CGRP increased intestinal TK activity, a response abolished by muscarinic receptor blockade. Immunohistochemistry suggested presence of M3 and M5 muscarinic receptors on the intestinal stem/progenitor cells. We propose that the stem/progenitor cells are controlled by cholinergic nerves, which, in turn, are influenced by mucosal afferent neuron(s) releasing acetylcholine and/or SP and/or CGRP. In mice lacking the capsaicin receptor, thymidine incorporation into DNA and number of crypt cells labeled with BrdU was lower than in wild type animals suggesting that nerves are important also in the absence of luminal capsaicin, a conclusion also supported by the observation that atropine lowered thymidine incorporation into DNA by 60% in control rat segments. Conclusion: Enteric nerves are of importance in maintaining the intestinal epithelial barrier.Original Publication:Ove Lundgren, Mats Jodal, Madeleine Jansson, Anders T Ryberg and Lennart Svensson, Intestinal Epithelial Stem/Progenitor Cells Are Controlled by Mucosal Afferent Nerves, 2011, PLOS ONE, (6), 2, 16295.http://dx.doi.org/10.1371/journal.pone.0016295Copyright: Public Library of Science (PLoS)http://www.plos.org

ON DESIGN VERIFICATION OF PIPING SUPPORTS UNDER COMBINED STRESSES

ABSTRACT In this paper design verification rules for piping supports under combined stresses according to ASME NF and its appendices are reviewed and examined in detail. A comprehensive study on these rules for piping supports constructed using austenitic steel will be conducted for service limit levels A, B, C and D. Ongoing projects in Sweden will be used to address the application of these rules and to discuss the design philosophy embedded in ASME III, and its rationality in practical design. We show that the rules specified for service limit level D enforce a stronger design requirement than those specified for service limit level C, which is irrational and inconsistent with the general principle upon which ASME III is built. Our suggestions for improving these rules will be given

Genetics of Schizophrenia: Overview of Methods, Findings and Limitations

Genetics constitute a crucial risk factor to schizophrenia. In the last decade, molecular genetic research has produced novel findings, infusing optimism about discovering the biological roots of schizophrenia. However, the complexity of the object of inquiry makes it almost impossible for non-specialists in genetics (e.g., many clinicians and researchers) to get a proper understanding and appreciation of the genetic findings and their limitations. This study aims at facilitating such an understanding by providing a brief overview of some of the central methods and findings in schizophrenia genetics, from its historical origins to its current status, and also by addressing some limitations and challenges that confront this field of research. In short, the genetic architecture of schizophrenia has proven to be highly complex, heterogeneous and polygenic. The disease risk is constituted by numerous common genetic variants of only very small individual effect and by rare, highly penetrant genetic variants of larger effects. In spite of recent advances in molecular genetics, our knowledge of the etiopathogenesis of schizophrenia and the genotype-environment interactions remain limited

Metabolismo miocárdico após cardioplegia sangüínea hipotérmica retrógrada contínua Myocardial metabolism after hypothermic retrograde continuous blood cardioplegia

CASUÍSTICA E MÉTODOS: Realizamos uma análise metabólica da cardioplegia sangüínea hipotérmica retrógrada contínua em um estudo prospectivo de 15 pacientes consecutivos encaminhados para operação eletiva de revascularização miocárdica. Os critérios de inclusão foram doença coronária bi ou triarterial e função ventricular preservada (FE > 40%). Os critérios de exclusão foram angina instável, diabéticos insulino-dependentes e operações associadas. Três pacientes foram excluídos do trabalho (operação associada e deslocamento do cateter de cardioplegia retrógrada). Amostras de sangue arterial e do seio coronário foram simultaneamente colhidas: antes do início da CEC, na abertura da aorta e com 10, 30 e 60 minutos de reperfusão, para análise do conteúdo de oxigênio e da concentração de lactato. Quatro biópsias miocárdicas foram obtidas do ápice do ventrículo esquerdo: (1) após instalação da CEC (mas antes do pinçamento aórtico), (2) imediatamente após o término da indução cardioplégica, (3) antes do despinçamento aórtico e (4) com 30 minutos de reperfusão, para análise dos níveis de ATP, ADP, AMP e lactato no miocárdio. A isoenzima CK-MB foi analisada no sangue venoso. RESULTADOS: Não houve mortalidade no grupo. Houve uma diminuição da extração artério-venosa do lactato e do oxigênio pelo coração durante a reperfusão, somente havendo uma recuperação parcial ao final de 60 minutos de reperfusão. O ATP e os outros nucleotídeos tiveram os seus níveis mantidos no miocárdio durante o pinçamento aórtico, mas estes caíram nos primeiros 30 minutos de reperfusão. O lactato acumulou-se no músculo cardíaco durante o pinçamento aórtico e diminuiu durante a reperfusão. Houve um aumento da enzima CK-MB, principalmente entre a terceira e sexta horas de pós-operatório. CONCLUSÕES: Do ponto de vista metabólico, o método não evitou o metabolismo anaeróbico durante o período de pinçamento aórtico e que somente com 60 minutos de reperfusão houve uma recuperação metabólica parcial. Essas alterações são, provavelmente, o reflexo da injúria isquêmica celular ocorrida durante o pinçamento aórtico e são de efeito transitório.<br>MATERIAL AND METHODS: An metabolic analyse of hypothermic retrograde continuous blood cardioplegia was done in a prospective study of 15 patients scheduled for elective CABG. Inclusions criteria were double or triple vessel coronary artery disease and preserved left ventricular function (ejection fraction > 40%). Exclusions criteria were unstable angina, insulin-treated diabetes mellitus and associated peroperative procedures. Three patients were excluded of the study (associated procedure and coronary sinus catether dislocation). Arterial and coronary sinus blood samples were simultaneouslly taken: before ECC (extracorporeal circulation), when the aortic clamp was takem off and 10, 30 and 60 minutes after reperfusion for analysing of oxygen content and lactate concentration. Four transmural left ventricular biopsies samples were obtained: before aortic clamping, immediately after the inicial cardioplegia bolus, immediately before aortic declamping and 30 minutes after reperfusion for analysing of the levels of ATP, ADP, AMP and lactate in the myocardial. The CK-MB isoenzyme was analysed in venous blood samples. RESULTS: There was no mortality in the group. There was a decrease in the arterial-venous extraction of oxygen and lactate in the heart during reperfusion, occurring a parcial recuperation only at 60 minutes of reperfusion. The ATP and the others nucleotides had their levels in the myocardium maintened during aortic clamping, but these levels decreased during the first 30 minutes of reperfusion. The lactate was accumulated in the heart muscle during aortic clamping and his levels also decreased during reperfusion. The CK-MB levels were elevated specially between the third and sixth post-operative hour. CONCLUSIONS: In the metabolic point of view the method could not avoid an anaerobic metabolism during cross-clamping and only after 60 minutes of reperfusion there was a parcial metabolic recuperation. These alterations were probably a reflexion of cellular ischemic injury occurred during cross-clamping and they were of transitory effect