The renal pelvis

Mammals and birds are the only vertebrates known to produce a concentrated urine by means of renal medullary countercurrent systems. These two countercurrent systems, however, exhibit functional and anatomical differences which appear to be related to the fact that mammals are ureotelic while birds are uricotelic. In mammalian kidneys, urea accumulation in the medulla plays an important role in the concentrating mechanism. In bird kidneys, there is no accumulation of urea in the medulla. The mammalian renal medulla is surrounded by a muscular, funnel–shaped pelvic wall, leaving an elaborate urinary space between the renal medulla and the inside of the pelvic wall, while the bird renal medulla is surrounded by tight sheets of connective tissue leaving no space for the urine to contact the renal medulla. The mammalian renal pelvis makes it possible for urine to contact the epithelial covering of the inner and outer medulla, and the peristaltic contractions of the muscular pelvic wall exerts a rhythmic pumping action on the renal papilla. The functional significance of these two aspects of the renal pelvis have in recent years become the focus of attention by some renal physiologists

Patient profiling for success after weight loss surgery (GO Bypass study):An interdisciplinary study protocol

Despite substantial research efforts, the mechanisms proposed to explain weight loss after gastric bypass (RYGB) and sleeve gastrectomy (SL) do not explain the large individual variation seen after these treatments. A complex set of factors are involved in the onset and development of obesity and these may also be relevant for the understanding of why success with treatments vary considerably between individuals. This calls for explanatory models that take into account not only biological determinants but also behavioral, affective and contextual factors. In this prospective study, we recruited 47 women and 8 men, aged 25–56 years old, with a BMI of 45.8 ± 7.1 kg/m2 from the waiting list for RYGB and SL at Køge hospital, Denmark. Pre-surgery and 1.5, 6 and 18 months after surgery we assessed various endpoints spanning multiple domains. Endpoints were selected on basis of previous studies and include: physiological measures: anthropometrics, vital signs, biochemical measures and appetite hormones, genetics, gut microbiota, appetite sensation, food and taste preferences, neural sensitivity, sensory perception and movement behaviors; psychological measures: general psychiatric symptom-load, depression, eating disorders, ADHD, personality disorder, impulsivity, emotion regulation, attachment pattern, general self-efficacy, alexithymia, internalization of weight bias, addiction, quality of life and trauma; and sociological and anthropological measures: sociodemographic measures, eating behavior, weight control practices and psycho-social factors.Joining these many endpoints and methodologies from different scientific disciplines and creating a multi-dimensional predictive model has not previously been attempted. Data on the primary endpoint are expected to be published in 2018. Trial registration: Clinicaltrials. gov ID NCT02070081. Keywords: Gastric bypass (RYGB), Sleeve gastrectomy, Weight loss, Interdisciplinary, Study protoco

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Changes in fluid compartments in hamster renal papilla due to peristalsis in the pelvic wall

Changes in fluid compartments in hamster renal papilla due to peristalsis in the pelvic wall. The pelvic peristalsis “milks” the renal papilla in rodents. This study investigates the effect of the pelvic contractions upon the fluid in papillary loops of Henle (LH) and capillaries (cap) and on the volume of collecting duct (CD) cells, papillary epithelial (PE) cells and interstitium. In the anesthetized antidiuretic hamsters the urine was made green by an intravenous infusion of lissamine green. A snare was placed loosely around the papilla. The peristalsis was recorded on a Grass recorder using a fiberoptic light signal which changed intensity with the events in the pelvis and papilla. In one group of hamsters the snare was tightened during the contraction and in another group at the beginning of the relaxation. The papilla within the pelvis was then fixed immediately. It was epon-embedded for light and electron microscopy. In the group with contracted pelvis CD, LH, and cap were all closed and empty; the papilla was elongated. In the group with relaxed pelves these structures were full and open spaces were seen between the cells of CD and PE. Morphometric measurements showed that the intercollecting duct volume was larger in the papillae with relaxed pelvis, but that cell volume of PE was larger in the papillae with contracted pelvis. It is suggested that fluid moves into the cells during contraction when urine flows through the CD and into the interstitium during relaxation.Modifications des compartiments liquidiens dans la papille rénale de hamster par le péristaltisme de la paroi pelvienne. Le péristaltisme pelvien “trait” la papille rénale chez les rongeurs. Ce travail étudie l'effet de contractions pelviennes sur les liquides des anses de Henle papillaires (LH) et les capillaires (cap) et sur le volume des cellules du tube collecteur (CD), les cellules papillaires épithéliales (PE) et l'interstitium. Chez des hamsters anesthésiés en antidiurèse l'urine était rendue verte par une infusion i.v. de vert de lissamine. Un piège était étroitement mis en place autour de la papille. Le péristaltisme était enregistré sur un enregistreur de Grass utilisant un signal lumineux par fibre optique qui changeait d'intensité lors d'événements dans le pelvis ou la papille. Dans un groupe de hamsters, le piège était serré pendant la contraction, et dans un autre groupe pendant le début de la relaxation. La papille était alors fixée immédiatement dans le pelvis. Elle était inclue dans de l'épone pour microscopies optique et électronique. Dans le groupe avec le pelvis contracté, CD, LH, et cap étaient tous fermés et vides, alors que la papille était étirée. Dans le groupe au pelvis relaché, ces structures étaient pleines et des espaces ouverts étaient observés entre les cellules de CD et PE. Des mesures morphométriques ont montré que le volume des canaux intercollecteurs était plus large dans les papilles avec des pelvis relâchés, mais que les volumes cellulaires de PE étaient plus larges dans les papilles au pelvis contracté. Il est suggéré que le fluide se déplace dans les cellules pendant la contraction quand l'urine coule à travers le CD et vers l'interstitium pendant la relaxation