PubMed · 13613942
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W G SPECTOR. 1958. Substances which affect capillary permeability.. https://pubmed.ncbi.nlm.nih.gov/13613942/
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Sepsis remains the most common cause of death in intensive care units of the developed world. Accurate models of this disease syndrome are crucial for to the understanding of the complex pathophysiology of this disorder. The administration of a small dose of lipopolysaccharide to healthy volunteers is one such model of spontaneous human sepsis. Although this human endotoxemia model appears to be reasonably effective in mimicking early biochemical, metabolic, hematologic and cardiovascular septic responses in septic shock, the ability to mimic other aspects of human sepsis is open to question. The current study demonstrates that human experimental endotoxemia fails to generate evidence of increased vascular permeability within the relatively short time frame of the study.
Gap junction intercellular communication (GJIC) plays a significant role in the vascular system. Regulation of GJIC is a dynamic process, with alterations in connexin (Cx) protein expression and post-translational modification as contributing mechanisms. We hypothesized that the endothelial autacoid nitric oxide (NO) would reduce dye coupling in human umbilical vein endothelial cells (HUVECs). In our subsequent experiments, we sought to isolate the specific Cx isoform(s) targeted by NO or NO-activated signaling pathways. Since HUVEC cells variably express three Cx (Cx37, Cx40, and Cx43), this latter aim required the use of transfected HeLa cells (HeLaCx37, HeLaCx43), which do not express Cx proteins in their wild type form. Dye coupling was measured by injecting fluorescent dye (e.g., Alexa Fluor 488) into a single cell and determining the number of stained adjacent cells. Application of the NO donor SNAP (2 microM, 20 min) reduced dye coupling in HUVEC by 30%. In HeLa cells, SNAP did not reduce dye transfer of cells expressing Cx43, but decreased the dye transfer from Cx37-expressing cells to Cx43-expressing cells by 76%. The effect of SNAP on dye coupling was not mediated via cGMP. In contrast to its effect on dye coupling, SNAP had no effect on electrical coupling, measured by a double patch clamp in whole cell mode. Our results demonstrate that NO inhibits the intercellular transfer of small molecules by a specific influence on Cx37, suggesting a potential role of NO in controlling certain aspects of vascular GJIC.
PURPOSE: To report a case of type I Gaucher's disease with rare presentation of fundus abnormalities in long-term observation. DESIGN: Observational case report. METHODS: This 53-year-old Taiwanese woman suffered from type I Gaucher's disease for 12 years, with initial presentation of hepatoslpenomegaly in 1992. RESULTS: At that time, poor vision with unusual macular change and peripheral retinal vessel leakage was also noted. She received a complete ophthalmic examination at the initial visit and again 12 years later in 2003. She was treated with imiglucerase injection during the last 4 years. However, her visual acuity was 10/200 in both eyes. The macular and peripheral retinal degenerative change progressed after 12 years. CONCLUSIONS: Fundus changes associated with Gaucher's disease are uncommon. We should not neglect the possibility of retinal involvement and progression in these patients.