Alcohol's contribution to compromised immunity

Alcoholics frequently suffer from infectious diseases and have increased rates of some cancers, indicating that alcohol impairs the immune system, which protects the body against this type of damage. Alcohol interferes with the functions of many of the cells and molecules that are part of the immune system. For example, alcohol inhibits the functions of the cells that ingest and destroy invading microorganisms (i.e., neutrophils, monocytes, and macrophages). Both acute and chronic alcohol exposure also alter the production of signaling molecules that help coordinate the immune response (i.e., cytokines). Finally, alcohol adversely affects the functions of the cells that mediate the immune response against specific microorganisms and long-term immunity (i.e., T cells and B cells). As a result, alcoholics have an increased susceptibility to diseases caused by bacterial infections, such as tuberculosis and pneumonia. Alcoholics also may be more susceptible to infections from the virus that causes AIDS. In addition, alcohol intoxication can exacerbate the immune suppression that occurs after traumatic injuries.     

Altered bladder function in transgenic mice expressing rat elastin

The elasticity of tissues subjected to repeated deformation is provided by the presence of elastic fibers in the extracellular matrix (ECM). The most abundant component of elastic fibers is elastin, whose soluble precursor is tropoelastin. To establish the role elastin plays in the bladder, this study describes the biosynthetic, histologic, and physiologic consequences of expression of an isoform of rat tropoelastin in transgenic mouse bladder. The polymerase chain reaction (PCR) was used to determine expression of a rat tropoelastin minigene in transgenic mice. Histochemical methods were used to demonstrate changes in elastic fibers in frozen sections of bladder. Cystometric analysis was carried out in transgenic and non-transgenic mice, prior to and after 3 weeks of partial outlet obstruction. The PCR assay demonstrated that bladder tissue of transgenic mice expressed rat tropoelastin mRNA, whereas non-transgenes did not. Increased deposition of elastic fibers was demonstrated with the Verhoeff-van Gieson stain. Bladders of transgenic animals were more compliant than bladders of their non-transgenic littermates. Partial outlet obstruction resulted in increased bladder volume and more compliant bladders in non-transgenic mice. In contrast, the bladder volume and compliance in transgenes was almost unchanged by obstruction. This study demonstrates that normal elastic fiber assembly is prerequisite for the compliant properties of the bladder wall. Moreover, the response of the bladder to obstruction is critically influenced by elastin synthesis.     

Ischemia and reperfusion-induced histologic changes in the rat retina. Demonstration of a free radical-mediated mechanism

Histologic alterations of ischemia- and reperfusion-induced retinal damage are critically dependent on the duration of the period of ischemia. Male Sprague Dawley rats were anesthetized, and a suture was placed behind the globe including the central retinal artery. Because it was desirable that untreated eyes show a great histologic change due to reperfusion-induced damage (in order that maximum scope would exist for demonstration of any protective effect of a drug treatment), a preliminary series of studies established the time-induced characteristics for the retina with transient regional ischemia. Eyes (n = 6-12 in each group) were subjected to 30, 60, or 90 min of ischemia followed by 0.5, 1, 2, 4, and 24 hr of reperfusion, respectively. The 30-min ischemia followed by reperfusion did not result in any histologic changes; 60-min ischemia followed by reperfusion induced a moderate retinal edema which returned to the preischemic value after 24 hr of reperfusion. The 90-min ischemia followed by reperfusion further aggravated retinal edema and increased the migration of neutrophil leukocytes. Even after 24 hr of reperfusion, the retinal edema had not disappeared although an attenuation was observed. In this study, the rats were treated with superoxide dismutase (SOD-PEG, 15 x 10(3) U/kg) or EGB 761 (100 mg/kg) for 10 days (chronic treatment). The SOD and EGB 761 significantly reduced the development of reperfusion-induced retinal edema and significantly prevented the neutrophil leukocyte infiltration. Both also had a protective effect against reperfusion-induced injury when these agents were administered just before reperfusion ("late" administration).(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of invasion markers CD44v6/v3, NM23 and MMP2 in laryngeal and hypopharyngeal carcinoma

Twelve laryngeal squamous cell carcinoma cases (7 laryngeal and 5 hypopharyngeal cancer; 15 samples) were analysed by immunohistochemistry for the expression of invasion markers CD44v6/v3, NM23 and matrix metalloproteinase, MMP2. The laryngeal epithelium showed CD44v6⁺v3⁺NM23^- /MMP2^- phenotype. When tumors were grouped into TNM categories the phenotype of the T2 and T3 tumors was similar, characterised by decreased CD44v3⁺ and lack of MMP2 expressions. Meanwhile the NM23 expression was more frequent in T3 tumors. In T4 stage the frequency of NM23 and MMP2 positive cases increased (5/6 and 4/6, respectively) but there was no correlation with the appearence of lymph node metastasis. Comparison of the phenotype of laryngeal and hypopharyngeal tumors, irrespective of the TNM stages, revealed characteristic differences: T2 stage laryngeal tumors showed decreased CD44v3 and occasional NM23 and MMP2 positivity, while in T3 stage these tumors were characterised by increased frequency of NM23 positivity. The phenotype of the hypopharyngeal tumors was significantly different with a high frequency of MMP2 positive cases (5/6) and NM23⁺1ow CD44v3⁺ phenotype. The sharp differences in the phenotypes of laryngeal and hypopharyngeal carcinomas were connected to the differences in their invasive capacity unlike to the size of the tumors, since the T4 stage hypopharyngeal tumors had a significantly smaller size than laryngeal ones, even at lower stages. This work was supported by the Hungarian Ministry of Welfare: ETT No: T-11-100/93