Early alcoholic liver injury: Activation of lipocytes in acinar zone 3 and correlation to degree of collagen formation in the disse space

Acinar zone 3 areas in liver biopsy specimens from 23 alcoholics and 47 non-alcoholics were investigated by light microscopy and transmission electron microscopy to asses fibrosis in the perisinusoidal space and to evaluate the role of the lipocytes. Quantitative analysis by light microscopy on toluidine blue-stained sections showed a significant reduction in number of lipocytes--median values of 2.7 and 1.2 lipocytes per 100 hepatocytes in biopsies from chronic alcoholics showing no or varying degrees of zone 3 fibrosis, respectively, as compared to 3.6 lipocytes per 100 hepatocytes in non-alcoholic livers. By transmission electron microscopy, the reduction in number of lipocytes was related to a corresponding increase in number of cells rich in rough endoplasmic reticulum and microfilaments (activated lipocytes). The occurrence of activated cells was significantly correlated to fibrosis of the perisinusoidal space. Activation of lipocytes and collagenization of the perisinusoidal space appeared before light microscopic evidence of fibrosis and were topographically not related to Mallory bodies or alcoholic hepatitis.     

Analysis of Deaths Related to Anesthesia in the Period 1996-2004 from Closed Claims Registered by the Danish Patient Insurance Association

Background: Anesthesia is associated with complications, and some of them may be fatal. The authors investigated the circumstances under which deaths were associated with anesthesia. In Denmark, the specialty anesthesiology encompasses emergency medicine, chronic and acute pain medicine, anesthetic procedures, perioperative care medicine, and intensive care medicine.

Methods: The authors retrospectively investigated anesthesia related deaths registered by the Danish Patient Insurance Association.

Results: From 1996 to 2004, 27,971 claims were made by the Danish Patient Insurance Association covering all medical specialties, of which 1,256 files (4.5%) were related to anesthesia. In 24 cases, the patient's death was considered to result from the anesthetic procedure: 4 deaths were related to airway management, 2 to ventilation management, 4 to central venous catheter placement, 4 as a result of medication errors, 4 from infusion pump problems, and 4 after complications from regional blockades. Severe hemorrhage caused 1 death, and in 1 case the cause was uncertain.     

Rate and mechanism of enamel demineralization in situ.

In this paper, data are presented on the in situ demineralization of human enamel as a function of the demineralization period. To quantify the mineral loss parameters versus time, it is important to obtain information on the kinetics, and thus on the mechanism of dental caries. The results show that for in situ enamel demineralization, the lesion depth as well as the mineral loss parameter both vary linearly with the demineralization time. This is in contrast to in vitro lesion formation where the third power, or the square power of the lesion depth is linearly related to the demineralization time. In in situ demineralization, the rate-determining step of the demineralization process is the inhibitor-controlled dissolution process at the enamel crystallite surfaces, while the inhibitor content (F-, proteins etc.) in the lesion originating from the plaque, saliva and enamel is high. Furthermore, the study indicates that in in situ demineralization, interprismatic mineral loss is very important.     

Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions

CD16+ monocytes represent 5-10% of circulating monocytes in healthy individuals and are dramatically expanded in several pathological conditions including AIDS and HIV-1-associated dementia (HAD). CD16+ monocytes constitutively produce high levels of pro-inflammatory cytokines and neurotoxic factors that may contribute to the pathogenesis of these disorders. Monocyte recruitment into the central nervous system (CNS) and other peripheral tissues in response to locally produced chemokines is a critical event in immune surveillance and inflammation and involves monocyte arrest onto vascular beds and subsequent diapedesis. Here we investigate the ability of CD16+ monocytes to undergo transendothelial migration (TEM) under constitutive and inflammatory conditions. CD16+ monocytes underwent TEM across unstimulated human umbilical vascular (HUVEC) and brain microvascular endothelial (BMVEC) cell monolayers in response to soluble fractalkine (FKN/CX3CL1). Stimulation with tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) induced high and low expression of membrane-bound FKN on HUVEC and BMVEC, respectively, together with expression of VCAM-1 and intercellular adhesion molecule-1 (ICAM)-1. By contrast, only HUVEC expressed CD62E while BMVEC remained negative. Both CD16- and CD16+ monocyte subsets adhered to TNF/IFN-gamma-stimulated HUVEC with higher frequency than to unstimulated HUVEC. Monocyte chemoattractant protein-1 (MCP-1) triggered efficient TEM of CD16- monocytes across TNF/IFN-gamma-stimulated HUVEC, whereas soluble FKN failed to induce TEM of CD16+ monocytes across stimulated HUVEC. These results demonstrate that stimulation with TNF and IFN-gamma triggers expression of membrane-bound FKN on both HUVEC and BMVEC, but prevents TEM of CD16+ monocytes in response to soluble FKN. Thus, pro-inflammatory CD16+ monocytes may contribute to the pathogenesis of HAD and other inflammatory CNS diseases by affecting the integrity of the blood-brain barrier as a consequence of their massive accumulation onto inflamed brain vascular endothelial cells expressing FKN and other adhesion molecules.