Beta-endorphin modulation of lymphocyte proliferation: effects of ethanol

BACKGROUND: We have previously shown that alcohol suppresses the natural killer (NK) cell activity of splenic lymphocytes partly by reducing the secretion of opioid peptide beta-endorphin (beta-EP) and its positive influence on NK-cell cytolytic activity in rats. The inhibition of NK-cell cytolytic activity was also associated with a reduced number of NK cells after chronic ethanol administration. Hence, the possibility arises that chronic ethanol may alter NK cell proliferation, survival, or both. In this study, we investigated whether ethanol treatment for 1 to 4 weeks reduces the proliferation of other lymphocyte subsets and whether beta-EP regulates ethanol's effect on lymphocyte proliferation. METHODS: Male rats were ad libitum-fed rat chow, pair-fed with isocaloric liquid diet, or fed with ethanol-containing liquid diet for 1, 2, 3, or 4 weeks. Groups of these rats were infused with beta-EP with or without the delta-receptor antagonist naltrindol into the paraventricular nucleus of the hypothalamus. Splenocytes were isolated and used for flow cytometric analysis of the changes in the number of various lymphocyte subsets. Lymphocyte proliferation was determined by mitogen stimulation assays. RESULTS: Ethanol consumption resulted in a reduction of the number of CD161+ NK cells, CD3+ T lymphocytes, CD4+ T-helper cells, and CD8a+ cytotoxic T cells in a time-dependent fashion. Alcohol consumption also suppressed the proliferative response of lymphocyte subsets to concanavalin A, phytohemagglutinin, and lipopolysaccharide. Beta-EP promoted the lymphocytes' proliferative response to mitogens, whereas naltrindol blocked the effects of the opioid. Chronic alcohol consumption reduced the proliferative response of lymphocytes to beta-EP. CONCLUSIONS: These results suggest that chronic alcohol administration reduces immune function partly by decreasing the opioid-regulated mitogen-stimulated proliferation of lymphocyte subsets.     

A prospective-controlled study of pregnant veterinary staff exposed to inhaled anesthetics and x-rays

Most veterinary staff are women of reproductive age. They are exposed to "waste" anesthetic gas and ionizing radiation in their workplace, which may endanger fetal safety. Presently, exposure of female veterinary staff to these health hazards has not been adequately addressed in the medical literature. Our primary objective was to investigate the incidence of major malformations associated with occupational exposure to inhaled anesthetics and/or radiation among pregnant veterinary staff. The secondary objective was to determine the rates of other adverse outcomes. We prospectively collected data on and followed-up women occupationally exposed to inhaled anesthetics and/or radiation in veterinary practices in Ontario, and compared them to controls matched for maternal age and gestational age at the time of call to the Motherisk Program. A total of 95 women were prospectively enrolled and followed-up. Among the participants there were 87 (93.5%) and 88 (92.8%) livebirths in the study and control groups, respectively. There were 4 (4.8%) major birth defects in the study group and 3 (3.4%) in the control group. The rates of spontaneous abortion were also similar, 6 (6.4%) cases in the study group and 7 (7.4%) cases in the control group. These results suggest that Ontario female veterinary staff exposed to inhaled anesthetics and/or radiation do not seem to be at an increased risk for major malformations above baseline risk.     

Genistein-induced cell cycle arrest and apoptosis in a head and neck squamous cell carcinoma cell line.

Epidemiological studies have shown a lower incidence of breast, prostate, and colon cancers in Asian countries, particularly China and Japan, than in the United States. It is believed that genistein, a natural tyrosine kinase inhibitor and a metabolite of soy products, may be responsible for the protection from these cancers. Genistein was shown to inhibit cell proliferation and to induce cell cycle arrest at the G2-M phase in breast, prostate, and jurkat T cell leukemia cell lines. However, such studies have not been reported in squamous cell cancers of the head and neck. In this report, we show that genistein inhibits proliferation of a squamous cell carcinoma cell line HN4. Additionally, genistein caused cell cycle arrest at the S/G2-M phase and induced programmed cell death (apoptosis) in these cells. These effects appear to be dose and time dependent, irreversible, persisting when the cells were recultured in genistein-free medium for up to 72 hours, and specific for tumor cells, because genistein did not affect normal keratinocytes. These results suggest that if genistein shows similar results in clinical trials, it can be a potential chemopreventive/chemotherapeutic agent for cancers of the head and neck.     

Evaluation of cellular immune responses in rhesus monkeys subjected to adenovirus-mediated gene transfer into the cervix.

We reported previously that direct injection of a recombinant adenovirus (rAd), Ad5CMV-beta-gal, into the cervix of the rhesus monkey resulted in efficient beta-galactosidase expression in the cervix within 3 days. In these studies, we also observed the induction of anti-adenovirus (Ad)-specific immunoglobulin G responses after 22 days. In the continuation of evaluating the anti-Ad-specific immune responses resulting from this approach of gene targeting to the cervix, we measured the cellular immune responses. The introduction of Ad5CMV-beta-gal into the cervix by direct injection, but not by the abrasion technique, resulted in the induction of strong proliferative responses against extracts of cells infected with Ad5CMV-beta-gal but not against control uninfected cells. These responses were initially detected at 22 days postinjection and coincided with the abrogation of transgene expression. Significant levels of proliferative responses were maintained for < or =83 days. Multiple injections of rAds had no significant enhancing effect on either the level or longevity of the proliferative responses. At 3 days after the injection of Ad5CMV-beta-gal, when the transgene expression in the cervix was clearly evident, proliferative responses against the rAd were not detectable. However, the production of low but significant amounts of interleukin-10, a cytokine characteristic of T helper type 2 responses that promote humoral immune responses, was observed at the 3-day point in these animals. These results suggest that significant differences exist between the kinetics of transgene expression and the priming of specific host immune responses, and that these differences may be important for devising alternate strategies to improve techniques for Ad-mediated gene therapy of cervical cancer.     

Strategies for eradication of poliomyelitis--the Indian experience.

Substantial progress has been made towards achieving global eradication of poliomyelitis by the end of the year 2000; the goal set by the World Health Assembly in May 1988. The basic strategies to eradicate polio are: attaining high routine coverage with at least three doses of OPV; conducting national immunization days (NIDs) in polio endemic countries; establishing a sensitive system of acute flaccid paralysis (AFP) surveillance to track wild poliovirus circulation; and conducting "mopping-up" immunization when polio is reduced to focal transmission. By the end of 2000. India was in the midst of the sixth National Immunization Days (NIDs). Surveillance system for Acute Flaccid Paralysis (AFP) continued to achieve the recommended non-polio AFP rate of at least 1 per 100,000 population < 15 years per year (1.88 for week 51 ending 23rd December 2000), the adequate stool specimen collection rate was 83% that met the target of > 80%. Some States in the south and west have started to implement mopping-up immunization campaigns as the end-stage strategy to eliminate the last remaining foci of transmission. While most of India appears to be well placed to eradicate polio by the end of 2000 or shortly thereafter, concerns remain about low coverage in parts of the densely populated northern States of Uttar Pradesh and Bihar where high intensity transmission persists. The Government of India has embarked upon an intensified strategy that relies on extra rounds of NIDs; house-to-house immunization to reach previously missed children; and aggressive mopping-up campaigns including pre-emptive mopping-up in the known reservoirs in Uttar Pradesh and Bihar. Extensive microplanning and supervision of the supplementary immunization activities is critical to achieve the target of polio eradication.     

Revolutions in ophthalmology

Cataract is the major cause of blindness worldwide. The transition of couching of cataract to most modem phaco-emulsification gained popularity with more scientific capsulorhexis. Ongoing research is taking place with laser technologies for removal of cataract. Surgery has an important role in advanced corneal diseases. Corneal transplantation is the most successful form. The refractive errors can be corrected by laser-assisted in-situ keratomileusis, intrastromal corneal rings and phacic intra-ocular lenses. Current research is going on to identify the gene responsible for glaucoma and once this is identified, medical therapy can be developed to control the disease. Thermocautery or photocoagulation and indenting the globe so as to bring the choroid nearer the break by scleral buckling forms the basis of modern surgery of retinal detachment. Vitreoretinal diseases, macular degeneration, diabetic retinopathy are no longer considered problematic. We are optimistic that more clinical breakthroughs are expected in the 21st century with new advances of ophthalmic researches.