No abstract

Although the negative effect of excessive alcohol consumption on later stressful events has long been recognized, pathophysiological mechanisms are incompletely understood. We examined possible roles of oxygen radicals and glutathione content in mesenteric venules of chronically ethanol-fed rats exposed to ischemia-reperfusion. Changes in microvascular hemodynamics, such as red blood cell (RBC) velocity, leukocyte adherence, and albumin extravasation, were monitored in postcapillary venules by intravital fluorescence microscopy. Chronic ethanol feeding significantly exaggerated the magnitude of the decrease in RBC velocity, the increased number of adherent leukocytes, and increased albumin leakage elicited by 10 min of ischemia followed by 30 min of reperfusion. Oxidative stress in the endothelium of venules monitored by dihydrorhodamine 123 (DHR) fluorescence was more severe in rats fed ethanol chronically. Both superoxide dismutase and N-acetyl-L-cysteine, which is known to increase glutathione content, reduced the ischemia-reperfusion-induced decrease in RBC velocity, the number of adherent leukocytes, and the increase in albumin leakage, as well as oxidative activation of DHR. This suggests that the increased reperfusion-induced microvascular disturbances in the mesenteric venules of rats fed ethanol chronically are significantly correlated with excessive production of oxygen-derived free radicals and decreased glutathione synthesis.

These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-alpha production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.

The major objective of this study was to investigate whether endothelin-1 (ET-1) plays a significant role in endotoxin-induced microcirculatory disturbances of the intestinal mucosa. Submucosal microvessels of the rat ileum were observed by intravital microscopy with a high-speed video camera system. Preceding the apparent intestinal mucosal damage, red blood cell (RBC) velocity was significantly decreased 30 min after endotoxin treatment in both arterioles and venules. The number of leukocytes sticking to submucosal venules was significantly increased at 30 min. BQ-123, an ETA-receptor antagonist, significantly attenuated the decrease in RBC velocity and also prevented an increase in leukocyte sticking as well as the subsequent mucosal damage induced by endotoxin. The ET-1 concentrations began to be elevated in plasma at 15 min and in the mucosa at 30 min and subsequently further increased in a time-dependent manner. A significant decrease in calcium-dependent nitric oxide synthase activity and significant increases in the concentration of platelet-activating factor (PAF) were demonstrated in the intestinal mucosa after endotoxin treatment. BQ-123 also significantly attenuated these changes. We concluded that the increased ET-1 production in intestinal mucosa induced by endotoxin stimulation could lead to leukocyte sticking and decreased RBC velocity in the intestinal microcirculatory beds via ETA receptors, which are closely related to increased production of PAF and decreased synthesis of constitutive nitric oxide.

Objective A prospective study was performed to observe the effects of nonsteroidal anti-inflammatory drug (NSAID) eyedrops on intraocular pressure (IOP) and the ocular surface in primary open-angle glaucoma (POAG) patients treated with 0.005% latanoprost eyedrops. Methods Forty-eight subjects were randomized into two study groups (NSAID and control). Latanoprost was continued for 10 weeks in all subjects. At the end of week 4, pranoprofen was added in the NSAID group, and treatment lasted for 4 weeks, whereas patients in the control group were treated with latanoprost alone. IOP was measured in both groups every 2 weeks, and the changes in the ocular surface in the NSAID group were evaluated once a month. Results Pranoprofen addition resulted in a decrease in IOP in the NSAID group compared to the control group (p < 0.01). After pranoprofen was discontinued, IOP significantly increased in the NSAID group (p < 0.01), remaining approximately at the same IOP as when they were being treated with latanoprost alone. During the same examination, no significant variations in IOP were found in the control group. Patients who were treated with latanoprost alone showed gradual improvements in ocular surface symptom scores and conjunctival hyperemia scores during the first four weeks of treatment (p < 0.01). When pranoprofen eyedrops were added, ocular surface symptom scores decreased (p < 0.01), but conjunctival hyperemia scores did not change significantly. Conclusions For POAG patients treated with latanoprost, the combination of pranoprofen can not only significantly enhance the latanoprost-induced IOP-lowering effect but also relieve the uncomfortable ocular symptoms caused by latanoprost.