Quantitative Histomorphometry of the Healthy Peritoneum

The peritoneum plays an essential role in preventing abdominal frictions and adhesions and can be utilized as a dialysis membrane. Its physiological ultrastructure, however, has not yet been studied systematically. 106 standardized peritoneal and 69 omental specimens were obtained from 107 patients (0.1–60 years) undergoing surgery for disease not affecting the peritoneum for automated quantitative histomorphometry and immunohistochemistry. The mesothelial cell layer morphology and protein expression pattern is similar across all age groups. Infants below one year have a thinner submesothelium; inflammation, profibrotic activity and mesothelial cell translocation is largely absent in all age groups. Peritoneal blood capillaries, lymphatics and nerve fibers locate in three distinct submesothelial layers. Blood vessel density and endothelial surface area follow a U-shaped curve with highest values in infants below one year and lowest values in children aged 7–12 years. Lymphatic vessel density is much lower, and again highest in infants. Omental blood capillary density correlates with parietal peritoneal findings, whereas only few lymphatic vessels are present. The healthy peritoneum exhibits major thus far unknown particularities, pertaining to functionally relevant structures, and subject to substantial changes with age. The reference ranges established here provide a framework for future histomorphometric analyses and peritoneal transport modeling approaches

Reduced microvascular density in omental biopsies of children with chronic kidney disease

Endothelial dysfunction is an early manifestation of cardiovascular disease (CVD) and consistently observed in patients with chronic kidney disease (CKD). We hypothesized that CKD is associated with systemic damage to the microcirculation, preceding macrovascular pathology. To assess the degree of "uremic microangiopathy", we have measured microvascular density in biopsies of the omentum of children with CKD.Omental tissue was collected from 32 healthy children (0-18 years) undergoing elective abdominal surgery and from 23 age-matched cases with stage 5 CKD at the time of catheter insertion for initiation of peritoneal dialysis. Biopsies were analyzed by independent observers using either a manual or an automated imaging system for the assessment of microvascular density. Quantitative immunohistochemistry was performed for markers of autophagy and apoptosis, and for the abundance of the angiogenesis-regulating proteins VEGF-A, VEGF-R2, Angpt1 and Angpt2.Microvascular density was significantly reduced in uremic children compared to healthy controls, both by manual imaging with a digital microscope (median surface area 0.61% vs. 0.95%, p<0.0021 and by automated quantification (total microvascular surface area 0.89% vs. 1.17% p = 0.01). Density measured by manual imaging was significantly associated with age, height, weight and body surface area in CKD patients and healthy controls. In multivariate analysis, age and serum creatinine level were the only independent, significant predictors of microvascular density (r2 = 0.73). There was no immunohistochemical evidence for apoptosis or autophagy. Quantitative staining showed similar expression levels of the angiogenesis regulators VEGF-A, VEGF-receptor 2 and Angpt1 (p = 0.11), but Angpt2 was significantly lower in CKD children (p = 0.01).Microvascular density is profoundly reduced in omental biopsies of children with stage 5 CKD and associated with diminished Angpt2 signaling. Microvascular rarefaction could be an early systemic manifestation of CKD-induced cardiovascular disease

Reduced microvascular density in omental biopsies of children with chronic kidney disease

Hintergrund: Eine chronische Niereninsuffizienz geht mit einer exzessiven Zunahme an Morbidität und Mortalität einher. Insbesondere bei Kindern und jungen Erwachsenen mit einer Niereninsuffizienz seit dem Kindesalter ist die Lebenserwartung im Vergleich zu gesunden Gleichaltrigen deutlich eingeschränkt. Dies ist vor allem der Zunahme an kardiovaskulären Erkrankungen geschuldet. Zu einer frühen Manifestation kardiovaskulärer Erkrankungen zählt eine endotheliale Dysfunktion. Die Rolle der Mikrozirkulation als strukturelle Basis der endothelialen Funktion ist bisher in diesem Zusammenhang nur wenig untersucht worden. In dieser Arbeit wurde die Kapillardichte im omentalen Gewebe terminal niereninsuffizienter Kinder untersucht, um die Bedeutung struktureller Veränderungen der Mikrozirkulation im Rahmen der chronischen Niereninsuffizienz im Kindesalter näher zu beleuchten. Patienten und Methoden: Omentales Gewebe wurde von 32 gesunden Kindern im Alter von 0-18 Jahren während elektiver abdomineller Operationen entnommen, sowie von 23 gleichaltrigen terminal niereninsuffizienten Kinder zum Zeitpunkt der initialen Katheteranlage vor Beginn einer Peritonealdialysetherapie. Die Kapillaren wurden mit Hilfe der CD 31-Immunhistochemie dargestellt und mit einem Digitalmikroskop und einer Analyse-Software ausgewertet. Zur Identifizierung von Pathomechanismen möglicher Veränderungen der Kapillardichte bei chronischer Niereninsuffizienz wurden Apoptose- und Autophagie-Marker sowie der interne und externe Anteil des Vascular endothelial growth factor (VEGF)-Rezeptors 2 mit immunhistochemischen Methoden quantifiziert. Ergebnisse: Es zeigte sich eine signifikant reduzierte Kapillardichte bei chronisch niereninsuffizienten Kindern im Vergleich zu gesunden gleichaltrigen Kindern. (mediane Kapillardichte bei den Kontrollen 0,95 % der Gesamtfläche vs. 0,61 % bei den niereninsuffizienten Kindern, p= 0,0021). Bei den niereninsuffizienten Kindern war die Kapillardichte invers mit den Kreatinin- und Harnstoffwerten korreliert (Kreatinin: r= -0,57, p= 0,0286; Harnstoff: r= -0,54, p= 0,0479). In der multivariaten Analyse waren die Größe und das Vorhandensein einer Niereninsuffizienz die einzigen signifikanten unabhängigen Prädiktoren der Kapillardichte und erklärten 42% der Varianz. Bei den niereninsuffizienten Kindern war die Körpergröße der einzige signifikante unabhängige Prädiktor und konnte 66% der Varianz der Kapillardichte erklären. Es zeigten sich weder Hinweise für Autophagie oder Apoptose bei den niereninsuffizienten Kindern, noch ließen sich Unterschiede des intra-oder extrazellulären Anteils des VEGF-Rezeptors 2 zwischen den beiden Gruppen erkennen. Schlussfolgerung: In dieser Arbeit konnte eine signifikante Rarefizierung der Mikrovaskulatur im omentalen Gewebe chronisch terminal niereninsuffizienter Kinder nachgewiesen werden. Dies ist wahrscheinlich Ausdruck einer generalisierten mikrovaskulären Erkrankung und ein frühes Zeichen kardiovaskulärer Veränderungen bei chronischer Niereninsuffizienz. Eine Stimulierung der Angiogenese könnte einen zukünftigen therapeutischen Ansatz zur Verbesserung der Prognose bei Patienten mit chronischer Niereninsuffizienz bieten.Background: Chronic kidney disease (CKD) is associated with a high cardiovascular morbidity and mortality. Especially children with end stage renal disease (ESDR) have a significantly diminished life expectancy compared to an aged-matched general population. One of the leading causes for death is cardiovascular disease. Endothelial dysfunction is an early manifestation of cardiovascular disease and can be seen even at early stages of CKD. However, only few studies have analyzed the morphology of the microcirculation, which provides the structural basis of the endothelial function. To investigate the role of structural alterations of the microcirculation in pediatric ESRD, this study examined capillary density in omental biopsies. Patients and Methods: Omental tissue was obtained from 32 healthy children (0-18 years) undergoing elective abdominal surgery and 23 age-matched cases with stage 5 CKD at the time of catheter insertion for initiation of peritoneal dialysis. To examine capillary density, omental biopsies were stained with CD 31-antibody and evaluated manually by a digital microscope and analyzer software. To assess potential mechanism of structural changes of the microcirculation, quantitative immunohistochemistry was performed for markers of autophagy and apoptosis, and for abundance of the intra-and extracellular domains of the receptor for the vascular endothelial growth factor (VEGF), VEGFR2. Results: Microvascular density in omental biopsies was significantly reduced in uremic children compared to healthy age-matched children. Median capillary surface area was 36% lower in CKD 5 (median surface area in controls 95% of total surface area vs. 0,61% in CKD, p= 0,0021. In CKD, capillary density was also inversely correlated with serum creatinine and urea levels (creatinine r= -0,57, p= 0,0286; urea r= -0,54, p= 0,0479). In multivariate analysis, the presence of CKD and height were the only independent significant predictors of capillary density and explained 42% of the variability. For the CKD group, the only significant independent predictor was height and this variable explained 66% of the capillary density. There was no evidence for autophagy or apoptosis in omental biopsies of CKD patients and no significant differences for the intra- or extracellular domain of the VEGF receptor 2 between both groups. Conclusions: We found profound capillary rarefaction in omental biopsies of children with stage 5 CKD. Rarefaction of the microvasculature of the omentum could indicate generalized microvascular disease as an early systemic manifestation of CKD-induced cardiovascular disease. Stimulation of angiogenesis might be a future therapeutic target to improve the long-term outcome of children with CKD

What to do before it starts? FRITZ - The early intervention and therapy centre in Berlin

First episode psychosis frequently manifest in young adulthood and can impact severely on the lives of the affected individuals and their relatives. In most cases, a first episode psychosis is preceded by a long-term prodromal phase with heterogeneous symptomatology and considerable functional impairment. The early identification of individuals at high risk of psychosis enables a timely implementation of preventive strategies, and an early diagnosis and the start of an adequate therapy, including pharmacological, psychotherapeutic and socio-therapeutic approaches, are essential for the prognosis of the disease. These aims are best achieved in specialised early intervention centres for young people experiencing first-episode psychosis. While in many countries such centres form part of standard care provisions, in German-speaking areas they remain the exception. The Early Intervention and Therapy Centre FRITZ am Urban offers in-and out-patient care for persons at risk of psychosis as well as for individuals in an early phase of the disease. Low-threshold counselling, an open and supportive attitude on the part of the multidisciplinary team, the availability of regular contact persons, the preservation of patient autonomy, the strengthening of a patient's self-esteem and peer consultation and peer support are designed to create a positive first contact experience with the psychiatric care system. The treatment on offer is of a pronounced psychotherapeutic orientation, and an early application of Individual Placement and Support (IPS) strategies not only seeks to reduce symptoms but also to contribute to functional recovery

Service Use of an Early Intervention Centre, Clinical and Socio-demographic Characteristics of Young Adults with Early Psychosis with and without Migration Background

Background The present study evaluated service use of our newly established Early Intervention and Treatment Centre (FRITZ) in Berlin for young adults with first or early psychosis with and without migration background. Methods We conducted a retrospective chart review of inpatients with early psychosis who were admitted to FRITZ between May 2014 and May 2015. We investigated the proportion of patients with migration background, socio-demographic and clinical characteristics of patients. Results Corresponding to the proportion of migrants in the catchment area, 35% of our service users from the catchment area (n = 60) had a migration background. Migrants had a better social adaption, but showed lower insight into illness, less substance induced psychoses and less inpatient admissions. The majority of all patients were admitted to FRITZ via the emergency department. Conclusions The findings indicate that FRITZ was almost equally well received by patients with and without migration background. Patients with migration background showed distinct socio-demographic and clinical characteristics that could be relevant for treatment. Implications for future clinical practice are discussed

Retrotransposons and siRNA have a role in the evolutionof desiccation tolerance leading to resurrection of the plantCraterostigma plantagineumTobias

\u2022 Craterostigma plantagineum can lose up to 96% of its water content but fully recover within hours after rehydration. The callus tissue of the plant becomes desiccation tolerant upon pre-incubation with abscisic acid (ABA). In callus and vegetative organs, ABA addition and water depletion induce a set of dehydrationresponsive genes. \u2022 Previously, activation tagging led to the isolation of Craterostigma desiccation tolerant (CDT-1), a dehydration-related ABA-inducible gene which renders callus desiccation tolerant without ABA pre-treatment. This gene belongs to a family of retroelements, members of which are inducible by dehydration. \u2022 Craterostigma plantagineum transformation with mutated versions of CDT-1 indicated that protein is not required for the induction of callus desiccation tolerance. Northern analysis and protoplast transfection indicated that CDT-1 directs the synthesis of a double-stranded 21-bp short interfering RNA (siRNA), which opens the metabolic pathway for desiccation tolerance. \u2022 Via transposition, these retroelements have progressively increased the capacity of the species to synthesize siRNA and thus recover after dehydration. This may be a case of evolution towards the acquisition of a new trait, stimulated by the environment acting directly on intra-genomic DNA replication