Hyperglycemia and Hyperlipidemia Act Synergistically to Induce Renal Disease in LDL Receptor-Deficient BALB Mice

Diabetic nephropathy is the leading cause of end-stage renal disease in Western countries, but only a portion of diabetic patients develop diabetic nephropathy. Dyslipidemia represents an important aspect of the metabolic imbalance in diabetic patients. In this study, we addressed the impact of combined hyperlipidemia and hyperglycemia on renal pathology. Kidneys from wildtype (WT) or LDL receptor-deficient BALB/cBy mice (BALB. LDLR -/-) were examined at 22 weeks of age. Diabetes was induced by administration of streptozotocin and mice were randomly assigned to either standard chow or Western diet. Chow fed BALB. LDLR -/- mice did not demonstrate renal abnormalities, whereas BALB. LDLR -/- mice fed a Western diet showed occasional glomerular and tubulointerstitial foam cells. Diabetic WT mice had modestly increased glomerular cellularity and extracellular matrix. Hyperlipidemic and diabetic BALB. LDLR -/- mice exhibited an increase in glomerular cellularity and extracellular matrix, accumulation of glomerular and tubulointerstitial foam cells and mesangial lipid deposits. The tubular epithelium demonstrated pronounced lipid induced tubular degeneration with increased tubular epithelial cell turnover. Hyperlipidemia and hyperglycemia seem to act synergistically in inducing renal injury in the BALB. LDLR-/- mouse. This model of diabetic nephropathy is unique in its development of tubular lesions and may represent a good model for hyperlipidemia-exacerbated diabetic nephropathy. Copyright (C) 2004 S. Karger AG, Basel

Cytokine Profiles of Stimulated Blood Lymphocytes in Asthmatic and Healthy Adolescents Cross the School Year

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-γ (IFN-γ), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th 1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-γ:IL-4 and IFN-γ:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation

Pituitary Lesions, Obesity, and Mesenteric Lipomas in Insulin-Resistant Horses

The aim of the current study was to identify associations between pituitary lesions, body condition scores, and mesenteric lipomas in horses with insulin resistance. Necropsy examinations were performed following euthanasia in 30 adult horses designated as insulin resistant (n = 11) or insulin sensitive (n = 19). Insulin sensitivity was determined using the insulin-modified frequently sampled intravenous glucose tolerance test and resting insulin concentrations. At necropsy, mesenteric lipomas were measured. The pituitary and adrenal glands, pancreas, and liver were evaluated histologically; pituitary glands were scored based on published criteria. Insulin-resistant horses had significantly higher pituitary scores (p = 0.0035) and body condition scores (p = 0.0001), even when adjusting for age, and a greater frequency of mesenteric lipomas (p = 0.014) and greater lipoma area (p = 0.0332) than insulin-sensitive horses. Regardless of insulin status, horses with pituitary scores ≥3 (diffuse hyperplasia; n = 25) had higher body condition scores (p = 0.0313) and a greater frequency of mesenteric lipomas (p \u3c 0.0002) than those with lower pituitary scores. High body condition score was not correlated to an increased frequency of mesenteric lipomas. Detection of higher pituitary scores in insulin-resistant horses suggested an association between insulin resistance and pituitary morphology. Horses in the insulin-resistant group and those with high pituitary scores had higher body condition scores and a greater frequency of mesenteric lipomas. These horses might be at increased risk for lipoma-associated colic

El Precerámico medio de Huarmey: historia de un sitio (pv35-106)

PV35-106 es el único sitio correspondiente al Precerámico medio que se ha podido ubicar en el área de Huarmey. Presenta la característica de tener una industria lítica muy particular, compuesta fundamentalmente por piezas astilladas y guijarros con golpe bipolar. El fechado radiocarbónico calibrado nos da para este yacimiento un lapso de tiempo que oscila entre cal. 5750 y cal. 4950 años a.C. A juzgar por los restos recuperados en las excavaciones, se trata de un grupo humano sedentario cuya economía básica fueron los recursos marinos. Pero hay indicios que ya se estaba iniciando un proceso hortícola. Las características culturales del sitio tienen parecido con las de la cultura Mongoncillo del vecino valle de Casma. Por todas las evidencias, parece que PV35-106 representa la transición entre la cultura Paijanense (Complejo Chivateros) y el Precerámico final.PV35-106 est le seul site correspondant au Précéramique moyen qui a pu être localisé dans la région de Huarmey. Le site se caractérise pour avoir une industrie lithique très particulière, composée fondamentalement par des pièces esquillées et des galets avec taille bipolaire. La datation radiocarbone date le site entre environ cal. 5750 et cal. 4950 av. J.C. D’après les restes récupérés dans les fouilles, il s’agirait d’un groupe humain sédentaire ayant une économie basée sur les ressources marines. Mais il y a aussi des indices qui montrent qu’un processus d’horticulture était en train de se développer. Les caractéristiques culturelles du site ressemblent à celle de la culture Mongoncillo de la vallée voisine de Casma. En accord avec les évidences, on peut conclure que le site PV35-106 représente la transition entre la culture Paijanienne (Complexe Chivateros) et le Précéramique final.PV35-106 is the only site found in the area of Huarmey that belongs to the Middle Preceramic. The principal characteristic of this site is that it displays a very particular lithic industry, which consists mainly of splintered pieces of stone and pebbles with bipolar percussion. The radiocarbon date situates the site between cal. 5750 and cal. 4950 BC. According to the remains found in the excavations, the site would have been inhabited by a sedentary human group with a marine-based economy. But there are also indications that a horticultural process was developing. The cultural characteristics of the site are similar to the Mongoncillo culture of the neighbouring valley of Casma. All the evidence leads us to conclude that PV35-106 represents the transition between the Paijanense Culture (Chivateros Complex) and that of the Late Preceramic

Communication Predicts Medication Self-Efficacy in Glaucoma Patients

Medication self-efficacy, or patients’ confidence that they can perform medication-related behaviors, is associated with better glaucoma medication adherence. Little is known about how to enhance glaucoma patients’ medication self-efficacy. Our purpose is to examine whether patient-provider communication increases glaucoma patients’ medication self-efficacy

Archvillin, a muscle-specific isoform of supervillin, is an early expressed component of the costameric membrane skeleton

The membrane skeleton protein supervillin binds tightly to both F-actin and membranes and can potentiate androgen receptor activity in non-muscle cells. We report that muscle, which constitutes the principal tissue source for supervillin sequences, contains a approximately 250 kDa isoform of supervillin that localizes within nuclei and with dystrophin at costameres, regions of F-actin membrane attachment in skeletal muscle. The gene encoding this protein, \u27archvillin\u27 (Latin, archi; Greek, archos; \u27principal\u27 or \u27chief\u27), contains an evolutionarily conserved, muscle-specific 5\u27 leader sequence. Archvillin cDNAs also contain four exons that encode approximately 47 kDa of additional muscle-specific protein sequence in the form of two inserts within the function-rich N-terminus of supervillin. The first of these muscle-specific inserts contains two conserved nuclear targeting signals in addition to those found in sequences shared with supervillin. Archvillin, like supervillin, binds directly to radiolabeled F-actin and co-fractionates with plasma membranes. Colocalization of archvillin with membrane-associated actin filaments, non-muscle myosin II, and--to a lesser extent--vinculin was observed in myoblasts. Striking localizations of archvillin protein and mRNA were observed at the tips of differentiating myotubes. Transfected protein chimeras containing archvillin insert sequences inhibited myotube formation, consistent with a dominant-negative effect during early myogenesis. These data suggest that archvillin is among the first costameric proteins to assemble during myogenesis and that it contributes to myogenic membrane structure and differentiation

Craniux: A LabVIEW-Based Modular Software Framework for Brain-Machine Interface Research

This paper presents “Craniux,” an open-access, open-source software framework for brain-machine interface (BMI) research. Developed in LabVIEW, a high-level graphical programming environment, Craniux offers both out-of-the-box functionality and a modular BMI software framework that is easily extendable. Specifically, it allows researchers to take advantage of multiple features inherent to the LabVIEW environment for on-the-fly data visualization, parallel processing, multithreading, and data saving. This paper introduces the basic features and system architecture of Craniux and describes the validation of the system under real-time BMI operation using simulated and real electrocorticographic (ECoG) signals. Our results indicate that Craniux is able to operate consistently in real time, enabling a seamless work flow to achieve brain control of cursor movement. The Craniux software framework is made available to the scientific research community to provide a LabVIEW-based BMI software platform for future BMI research and development

How valid are assessments of conception probability in ovulatory cycle research? Evaluations, recommendations, and theoretical implications

Over the past two decades, a large literature examining psychological changes across women's ovulatory cycles has accumulated, emphasizing comparisons between fertile and non-fertile phases of the cycle. While some studies have verified ovulation using luteinizing hormone (LH) tests, counting methods – assessments of conception probability based on counting forward from actual or retrospectively recalled onset of last menses, or backward from actual or anticipated onset of next menses – are more common. The validity of these methods remains largely unexplored. Based on published data on the distributions of the lengths of follicular and luteal phases, we created a sample of 58,000+ simulated cycles. We used the sample to assess the validity of counting methods. Aside from methods that count backward from a confirmed onset of next menses, validities are modest, generally ranging from about .40–.55. We offer power estimates and make recommendations for future work. We also discuss implications for interpreting past research