Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base

The renal cortical interstitium: morphological and functional aspects

The renal interstitial compartment, situated between basement membranes of epithelia and vessels, contains two contiguous cellular networks. One network is formed by interstitial fibroblasts, the second one by dendritic cells. Both are in intimate contact with each other. Fibroblasts are interconnected by junctions and connected to basement membranes of vessels and tubules by focal adhesions. Fibroblasts constitute the “skeleton” of the kidney. In the renal cortex, fibroblasts produce erythropoietin and are distinguished from other interstitial cells by their prominent F-actin cytoskeleton, abundance of rough endoplasmic reticulum, and by ecto-5′-nucleotidase expression in their plasma membrane. The resident dendritic cells belong to the mononuclear phagocyte system and fulfil a sentinel function. They are characterized by their expression of MHC class II and CD11c. The central situation of fibroblasts suggests that signals from tubules, vessels, and inflammatory cells converge in fibroblasts and elicit an integrated response. Following tubular damage and inflammatory signals fibroblasts proliferate, change to the myofibroblast phenotype and increase their collagen production, potentially resulting in renal fibrosis. The acquisition of a profibrotic phenotype by fibroblasts in renal diseases is generally considered a main causal event in the progression of chronic renal failure. However, it might also be seen as a repair process

Postoperative analgesia with intramuscular morphine at fixed rate versus epidural morphine or sufentanil and bupivacaine in patients undergoing major abdominal surgery

We assessed the efficacy and side effects of postoperative analgesia with three different pain regimens in 90 patients undergoing major abdominal surgery. The patients were randomly assigned to one of three groups: epidural morphine (EM) or sufentanil (ES), both combined with bupivacaine, or IM morphine (IM) at fixed intervals. Before incision, patients in the epidural groups received sufentanil or morphine in bupivacaine via a thoracic catheter, followed by a continuous infusion 1 h later. General anesthesia consisted of N2O/O-2 and isoflurane for all groups. Patients in all groups received TV sufentanil as part of their anesthetic management. Patients in the IM group received TV sufentanil 1 mu g/kg before incision, and patients in all groups received sufentanil 10 mu g for inadequate analgesia. Postoperatively, the epidural or IM treatment was continued for greater than or equal to 5 days. Postoperative analgesia at rest and during coughing and movement was significantly better in the epidural groups than in the IM group during the 5 consecutive days. There were no significant differences between the epidural groups. The incidence of most side effects was similar in all groups. We conclude that epidural analgesia provided better pain relief than IM analgesia, even if the latter was optimized by fixed-dose administration at fixed intervals and included adjustments on demand. Epidural sufentanil and morphine, both combined with bupivacaine, seemed to be equally effective with similar side effects. Implications: Postoperative analgesia with epidural sufentanil or morphine and bupivacaine after major abdominal surgery seemed to be better than the conventional method of LM morphine treatment, despite optimal administration, i.e., fixed doses at fixed intervals with regular adjustments. Analgesic efficacy and side effects of epidural sufentanil and morphine were similar

The use of neuromuscular blocking agents in noncardiac surgery after dynamic cardiomyoplasty

Dynamic cardiomyoplasty is a surgical treatment to improve cardiac performance in patients with end-stage heart failure by wrapping the latissimus dorsi muscle around the heart. The use of skeletal muscle raises concerns about the safety of neuromuscular blocking agents used during general anaesthesia in noncardiac surgery in patients after cardiomyoplasty. We describe the administration of rocuronium to a patient undergoing carotid endarterectomy 18 months after cardiomyoplasty. No clinically relevant effects on haemodynamics were observed. We conclude that the use of nondepolarising neuromuscular blocking agents for noncardiac surgery in patients after cardiomyoplasty does not compromise cardiac performance in a clinically relevant way, although the time between the cardiomyoplasty procedure and the use of nondepolarising neuromuscular blocking agents remains a concern