Etude expérimentale d'un nouveau sulfamide hypoglycémiant particulièrement actif,le HB 419 ou glibenclamide

Résumé Les auteurs ont montré chez la souris que le HB 419 administré chroniquement, stimule le développement des îlots de Langerhans et des cellules bêta. Ce produit est donc doué de l'action bêtacytotrophe. Chez le chien normal, l'administration pendant 4 mois de HB 419 a pour effets d'abaisser la glycémie à jeun ainsi que l'ensemble de la courbe de la glycémie nycthémérale.- L'expérimentation effectuée montre que sous l'influence de l'administration prolongée de HB 419, la quantité d'insuline endogène synthétisée et sécrétée en plus de la sécrétion normale est considérable.

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Experimental study on glibenclamide (HB 419), a new particularly action hypoglycaemic sulphonamide

Summary The authors have demonstrated that HB 419 chronically administered in the mouse, stimulated the development of the islets of Langerhans and particularly that of the beta cells. This substance is thus endowed with a beta cytotrophic action. — In the normal dog, HB 419 administered over a four-month period resulted in a decreased fasting glycaemia, as well as a decrease of the entire nyctohemeral glycaemia curve. The experiments carried out showed that under the influence of prolonged HB 419 administration, the amount of endogenous insulin synthesized and secreted over and above the normal secretory level, was considerable.

Le HB 419 ou glibenclamide portait initialement le nom de glybenzcyclamide. La dénomination commune internationale qui vient d'être définitivement adoptée est glibenclamide.     

Hypoalbuminemia: Pathogenesis and Clinical Significance

Hypoalbuminemia is associated with inflammation. Despite being addressed repeatedly in the literature, there is still confusion regarding its pathogenesis and clinical significance. Inflammation increases capillary permeability and escape of serum albumin, leading to expansion of interstitial space and increasing the distribution volume of albumin. The half‐life of albumin has been shown to shorten, decreasing total albumin mass. These 2 factors lead to hypoalbuminemia despite increased fractional synthesis rates in plasma. Hypoalbuminemia, therefore, results from and reflects the inflammatory state, which interferes with adequate responses to events like surgery or chemotherapy, and is associated with poor quality of life and reduced longevity. Increasing or decreasing serum albumin levels are adequate indicators, respectively, of improvement or deterioration of the clinical state. In the interstitium, albumin acts as the main extracellular scavenger, antioxidative agent, and as supplier of amino acids for cell and matrix synthesis. Albumin infusion has not been shown to diminish fluid requirements, infection rates, and mortality in the intensive care unit, which may imply that there is no body deficit or that the quality of albumin “from the shelf” is unsuitable to play scavenging and antioxidative roles. Management of hypoalbuminaemia should be based on correcting the causes of ongoing inflammation rather than infusion of albumin. After the age of 30 years, muscle mass and function slowly decrease, but this loss is accelerated by comorbidity and associated with decreasing serum albumin levels. Nutrition support cannot fully prevent, but slows down, this chain of events, especially when combined with physical exercise.     

Automated alignment of perioperative MRI scans: A technical note and application in pediatric epilepsy surgery

Conventional image registration utilizing brain voxel information may be erroneous in a neurosurgical setting due to pathology and surgery‐related anatomical distortions. We report a novel application of an automated image registration procedure based on skull segmentation for magnetic resonance imaging (MRI) scans acquired before, during and after surgery (i.e., perioperative). The procedure was implemented to assist analysis of intraoperative brain shift in 11 pediatric epilepsy surgery cases, each of whom had up to five consecutive perioperative MRI scans. The procedure consisted of the following steps: (1) Skull segmentation using tissue classification tools. (2) Estimation of rigid body transformation between image pairs using registration driven by the skull segmentation. (3) Composition of transformations to provide transformations between each scan and a common space. The procedure was validated using locations of three types of reference structural landmarks: the skull pin sites, the eye positions, and the scalp skin surface, detected using the peak intensity gradient. The mean target registration error (TRE) scores by skull pin sites and scalp skin rendering were around 1 mm and <1 mm, respectively. Validation by eye position demonstrated >1 mm TRE scores, suggesting it is not a reliable reference landmark in surgical scenarios. Comparable registration accuracy was achieved between opened and closed skull scan pairs and closed and closed skull scan pairs. Our procedure offers a reliable registration framework for processing intrasubject time series perioperative MRI data, with potential of improving intraoperative MRI‐based image guidance in neurosurgical practice. Hum Brain Mapp 37:3530–3543, 2016. © 2016 Wiley Periodicals, Inc.     

Type I collagen markers in cord serum of appropriate vs. small for gestational age infants born during the second half of pregnancy

BACKGROUND: The serum concentration of the N-terminal propeptide of type I procollagen (PINP) reflects the synthesis rate of type I collagen, whereas the corresponding C-terminal telopeptide (ICTP) mirrors its degradation. DESIGN: PINP and ICTP were measured in a total of 690 cord serum samples from 592 appropriate-for-gestational-age (AGA) infants and 98 smal-for-gestational-age (SGA) infants. These markers were compared between AGA and SGA infants of different gestational ages, ranging from 23 to 41 weeks, and birth weights, from 620 to 4555 g. RESULTS: Both PINP and ICTP levels were very high in the preterm AGA infants and declined significantly with advancing gestational age, paralleling the shape of the fetal growth velocity curve. Regardless of the quite large interindividual variations observed in these markers, PINP was significantly lower in both the preterm and term AGA infants than in the SGA infants. This was also the case for ICTP in the preterm infants of gestational age less than 36 weeks. In stepwise multiple regression analyses, gestational age, being either AGA or SGA and head circumference were significant factors to explain the levels of PINP and ICTP. The levels of PINP and ICTP were correlated with each other highly significantly in both the AGA and SGA infants (rs = 0.700 and 0.692, respectively; P < 0.001 in both). CONCLUSIONS: The levels of type I collagen markers seem to follow closely the shape of the fetal growth velocity curve during different stages of gestation. However, because of the large interindividual variations observed, further studies are needed before the significance of these markers for the assessment of normal and abnormal fetal growth can be established.     

Attitudes of Law Enforcement Officers Regarding Automated External Defibrillators

OBJECTIVE: To assess the knowledge and attitudes of law enforcement officers regarding treating out-of-hospital cardiac arrest (OHCA) and using automated external defibrillators (AEDs). METHODS: This was a survey conducted among officers serving Marion County, Indiana. RESULTS: Of 1,130 surveys distributed, 929 (82.2%) were returned. Among these officers, 603 (66.4%) were certified in cardiopulmonary resuscitation (CPR) and 103 (11.3%) had received AED training. Most officers had limited knowledge regarding OHCA. A 100-point knowledge score (mean +/- SD: 31.9 +/- 14.3) was higher in officers who had performed CPR while on duty [35.0, 95% confidence interval (95% CI) = 32.9 to 37.2, p = 0.005] and who were AED-trained (40.8, 95% CI = 38.0 to 43.6, p < 0.001). Of the respondents, 367 (40.1%) believed that AED usage by local law enforcement was needed, and 323 (35.6%) stated that they would feel comfortable using an AED if trained. A 100-point attitude score (mean +/- SD: 32.1 +/- 21.0) was higher in officers who had CPR certification (38.2, 95% CI = 35.6 to 40.8), who had performed CPR while on duty (40.6, 95% CI = 37.7 to 43.5), who were AED-trained (39.5, 95% CI = 35.6 to 43.4), and who had improved OHCA knowledge (+3.8 per 10 points knowledge score, 95% CI = 3.0 to 4.7), p < 0.001, all significant factors. CONCLUSIONS: Limited knowledge and negative attitudes of law enforcement officers regarding their involvement in treating OHCA and using AEDs are commonly present. These factors could result in barriers that negatively impact law enforcement AED programs.     

Effects of combined treatment with pravastatin and ursodeoxycholic acid on hepatic cholesterol metabolism

BACKGROUND: Treatment with ursodeoxycholic acid and also, to some degree, statins reduces cholesterol saturation of bile. The present study aimed [1] to study the effects of combined treatment with ursodeoxycholic acid and pravastatin on hepatic cholesterol metabolism and [2] to evaluate if the addition of pravastatin to ursodeoxycholic acid treatment has beneficial effects on the lipid composition of gallbladder bile in gallstone patients. MATERIALS AND METHODS: Nineteen patients with cholesterol gallstones were subjected to combined treatment with ursodeoxycholic acid (500 mg bid) and pravastatin (20 mg bid) for three weeks before cholecystectomy. Eleven patients received ursodeoxycholic acid only and 20 untreated gallstone patients served as controls. Gallbladder bile was collected, and for both the patients receiving combined treatment and the controls a liver biopsy was also obtained peroperatively. RESULTS: The cholesterol saturation of bile averaged 59% in the patients on combined treatment, 60% in the ursodeoxycholic acid-treated patients, and 130% in the untreated controls. In the patients receiving ursodeoxycholic acid, this bile salt constituted approximately 60% of all bile salts. The patients receiving combined treatment had reduced cholesterol synthesis, as reflected by a 45% reduction in serum lathosterol. The activity and the mRNA levels of cholesterol 7 alpha-hydroxylase and the mRNA levels for the low density lipoprotein-receptor were not significantly affected. CONCLUSIONS: Pravastatin does not further reduce the cholesterol saturation of bile in gallstone patients treated with ursodeoxycholic acid, although hepatic cholesterol synthesis is inhibited. The study supports the important concept that de novo synthesized cholesterol is not particularly important for biliary cholesterol secretion in humans.     

Basic metabolism: proteins

Proteins serve a range of physiological functions in health and in disease. Their overall structure is determined predominantly by the sequence of amino acids when they are synthesized, which in turn is a derivative of the sequence of nucleotides in the corresponding segment of DNA. There is a constant turnover of body protein, the rate of which exceeds dietary protein intake and therefore suggests a degree of recycling. Some amino acids that enter the body protein pool can be synthesized (‘non-essential’ amino acids) while others can only be obtained through dietary means (‘essential’ amino acids). During critical illness and significant trauma there appears to be dysregulation such that synthesis of some non-essential amino acids is limited, while there is an increase in amino acid oxidation. Modification of dietary intake to address the potential imbalance in illness is probably insufficient in isolation to prevent muscle wasting.     

iQ200全自动尿液显微镜分析仪筛检尿路感染

目的探讨iQ200全自动尿液显微镜分析仪(简称iQ200)用于筛检尿路感染的可行性。方法214例中段尿标本在作病原体分离培养后立即用iQ200检测细菌(BACT)、小颗粒(ASP)和酵母菌(YST)等3项参数,用UF100全自动尿沉渣分析仪(简称UF100)检测细菌(BACT)和酵母菌(YLC)等2项参数。以培养结果作为金标准,应用受试者工作特征(ROC)曲线确定iQ200和UF100各项参数的最佳临床判断界值,评价各项参数的灵敏度、特异度、假阳性率、假阴性率和ROC曲线下面积。结果iQ200的BACT、ASP和YST的最佳临床判断界值分别为4.5/μl、2 404.5/μl和8.5/μl,灵敏度分别为73.3%、90.0%和90.5%,特异度为96.2%、46.9%和90.2%,假阳性率为3.3%、48.4%和8.4%,假阴性率为2.8%、0.9%和0.9%,ROC曲线下面积为0.862、0.698和0.946。UF100的BACT和YLC的最佳临床判断界值为4 657.6/μl、41.6/μl,灵敏度为76.0%、61.9%,特异度为76.8%、97.4%,假阳性率为17.8%、1.4%,假阴性率为5.6%、3.3%,ROC曲线下面积为0.821和0.795。结论iQ200用于筛检尿路真菌感染和革兰阴性杆菌感染具有一定的价值,但不能代替病原体的培养鉴定。