Stefan Beckert

Lactate stimulates endothelial cell migration

The significance of the high lactate levels that characterize healing wounds is not fully understood. Lactate has been shown to enhance collagen synthesis by fibroblasts and vascular endothelial growth factor (VEGF) production by macrophages and endothelial cells. VEGF has been shown to induce endothelial cell migration. However, it has not been shown whether accumulated lactate correlates with the biological activity of VEGF. Therefore, we investigated the effect of lactate on migration of endothelial cells. Human umbilical vein endothelial cells and human microvascular endothelial cells were cultured to subconfluent monolayers in standard six‐well tissue culture plates. Following a 24‐hour serum starvation, cells were treated with the indicated concentrations of l‐lactate. Cell migration was assessed using a modified Boyden chamber. VEGF protein in the cell culture supernatant was measured by enzyme‐linked immunoassay. Lactate‐enhanced VEGF protein synthesis in a time‐ and dose‐dependent manner. Lactate added into the bottom well did not stimulate cellular migration from the upper well. However, lactate when added together with endothelial cells to the bottom well of the Boyden chamber increased cellular migration in a dose‐dependent manner. This effect was blocked by anti‐VEGF and by cycloheximide. Lactate enhances VEGF production in endothelial cells, although lactate, itself, is not a chemoattractant. We conclude that the lactate‐mediated increase in cellular migration is regulated by VEGF.

Functional vascular anatomy of the peritoneum in health and disease

Abstract The peritoneum consists of a layer of mesothelial cells on a connective tissue base which is perfused with circulatory and lymphatic vessels. Total effective blood flow to the human peritoneum is estimated between 60 and 100 mL/min, representing 1–2 % of the cardiac outflow. The parietal peritoneum accounts for about 30 % of the peritoneal surface (anterior abdominal wall 4 %) and is vascularized from the circumflex, iliac, lumbar, intercostal, and epigastric arteries, giving rise to a quadrangular network of large, parallel blood vessels and their perpendicular offshoots. Parietal vessels drain into the inferior vena cava. The visceral peritoneum accounts for 70 % of the peritoneal surface and derives its blood supply from the three major arteries that supply the splanchnic organs, celiac and superior and inferior mesenteric. These vessels give rise to smaller arteries that anastomose extensively. The visceral peritoneum drains into the portal vein. Drugs absorbed are subject to first-pass hepatic metabolism. Peritoneal inflammation and cancer invasion induce neoangiogenesis, leading to the development of an important microvascular network. Anatomy of neovessels is abnormal and characterized by large size, varying diameter, convolution and blood extravasation. Neovessels have a defective ultrastructure: formation of large “mother vessels” requires degradation of venular and capillary basement membranes. Mother vessels give birth to numerous “daughter vessels”. Diffuse neoangiogenesis can be observed before appearance of macroscopic peritoneal metastasis. Multiplication of the peritoneal capillary surface by neoangiogenesis surface increases the part of cardiac outflow directed to the peritoneum.

Peritoneal innervation: embryology and functional anatomy

Abstract The parietal peritoneum (PP) is innervated by somatic and visceral afferent nerves. PP receives sensitive branches from the lower intercostal nerves and from the upper lumbar nerves. Microscopically, a dense network of unmyelinated and myelinated nerve fibers can be found all over the PP. The unmyelinated fibers are thin and are ending just underneath the PP. The myelinated fibers can penetrate the PP to reach the peritoneal cavity, where they lose their myelin sheath and are exposed to somatic and nociceptive stimuli. PP is sensitive to pain, pressure, touch, friction, cutting and temperature. Noxious stimuli are perceived as a localized, sharp pain. The visceral peritoneum (VP) itself is not innervated, but the sub-mesothelial tissue is innervated by the autonomous nerve system. In contrast to the PP, the visceral submesothelium also receives fibers from the vagal nerve, in addition to the spinal nerves. VP responds primarily to traction and pressure; not to cutting, burning or electrostimulation. Painful stimuli of the VP are poorly localized and dull. Pain in a foregut structure (stomach, duodenum or biliary tract) is referred to the epigastric region, pain in a midgut structure (appendix, jejunum, or ileum) to the periumbilical area and pain from a hindgut source (distal colon or rectum) is referred to the lower abdomen or suprapubic region. Peritoneal adhesions can contain nerve endings. Neurotransmitters are acetylcholine, VIP, serotonin, NO, encephalins, CGRP and substance P. Chronic peritoneal pain can be exacerbated by neurogenic inflammation, e.g. by endometriosis.

Diagnostik und Therapie der pAVK – So gehen Sie vor

Patienten mit einer peripheren arteriellen Verschlusskrankheit sind meist kritische Kranke und weisen aufgrund der zugrundeliegenden Pathogenese kardiale-, pulmonale und renale Begleiterkrankungen mit entsprechend hoher Mobiditat und Mortalitat auf. Ein langjahriger Nikotinabusus sowie ein Diabetes mellitus verschlechtern die Prognose zusatzlich. Deshalb gilt es, diese Patienten einer interdisziplinaren Therapie zukommen zu lassen. Ein klarer Algorithmus aus Anamnese, klinischer Untersuchung sowie entsprechender Diagnostik mittels Duplex-Sonografie und digitaler Subtraktionsangiografie spielt hierbei eine zentrale Rolle, um die Patienten stadiengerecht einer adaquaten Therapie zukommen zu lassen und das Voranschreiten der Erkrankung mit der Gefahr eines Extremitatenverlustes zu verhindern.

Peritonealkarzinose – Aktuelle Therapieansätze

Ein metastatischer Befall des Bauchfells (Peritonealkarzinose), wurde bis vor wenigen Jahren als terminales Krankheitsstadium angesehen. Durch das Konzept der maximalen Zytoreduktion (Peritonektomie) und hyperthermen intraperitonealen Chemotherapie (HIPEC) konnte das Uberleben ausgewahlter Patienten bei gleichzeitig stabiler Lebensqualitat verbessert werden. Entscheidendes Selektionskriterium scheint das intraabdominelle Tumorvolumen zu sein, das anhand des Peritoneal Cancer Index (PCI) bereits praoperativ abgeschatzt werden kann. Obligat ist jedoch vor Einleitung einer derartigen Therapie die Vorstellung eines jeden Patienten in einer interdisziplinaren Tumorkonferenz.