Cytokine-induced iNOS expression in C6 glial cells: transcriptional inhibition by ethanol.

The effect of cytokines, lipopolysaccharide, and ethanol on inducible nitric-oxide synthase (iNOS) expression was studied in C6 glial cells. Maximal induced activity, measured by the accumulation of nitrite in culture medium, occurred following treatment with lipopolysaccharide and interferon-gamma. Each cytokine alone was ineffective, whereas an optimal combination of interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma was near maximal, indicating synergistic interactions. Other combinations caused submaximal activity. Ethanol is known to suppress iNOS expression in C6 cells induced by a phorbol ester plus lipopolysaccharide. The current work shows ethanol also suppresses cytokine-induced iNOS expression and reduces interleukin-1beta and tumor necrosis factor-alpha potency without affecting interferon-gamma potency. Ethanol-mediated reductions in cytokine-induced iNOS mRNA and immunoreactive protein levels suggested an effect on gene transcription. Therefore, C6 cells stably expressing 1846 and 526 base fragments of the rat iNOS gene promoter fused to a luciferase reporter gene were prepared and characterized and used to study the effect of ethanol on iNOS promoter activity. Promoter activity in stable transfected C6 cells was inhibited by ethanol exposure with a similar concentration dependence as observed for inhibition of nitrite production, indicating that iNOS inhibition by ethanol is transcriptional. Furthermore, ethanol inhibition of the 526 base fragment activity, which lacks interferon-gamma enhancement of lipopolysaccharide-induced luciferase activity, confirmed that interferon-gamma-responsive elements do not participate in acute ethanol-induced inhibition of rat iNOS gene transcription.

Prognostic value of baseline serum oestradiol in controlled ovarian hyperstimulation of women with unexplained infertility.

This study aimed to evaluate the prognostic value of the baseline serum oestradiol E2 level on the cycle pregnancy rate (PR) in women with unexplained infertility (UI) undergoing controlled ovarian hyperstimulation (COH). This study is unique in that it evaluates the effect of cycle day 1 (rather than day 3) E2 levels on cycle PR in a COH setting (without IVF) in women with UI (rather than multiple causes of infertility). Structured as a retrospective cohort study, the setting was the Ovulation Induction Clinic at an academic tertiary care hospital. One hundred and forty-five patients with UI underwent 374 cycles of COH with either human menopausal gonadotrophin (hMG) alone or hMG and clomiphene citrate. Outcome was measured as cycle pregnancy rate (PR) according to the cycle day 1 level of E2. Patients with an E2 level > 150 pmol/l on cycle day 1 of COH achieved a significantly lower PR (4%) compared with those with E2 levels < or = 150 pmol/l (13%). Logistic regression analysis demonstrated that women with day 1 E2 levels below 150 pmol/l were 3.2 times more likely to conceive than those with day 1 E2 levels above 150 pmol/l. Also, the impact of day 1 E2 levels on the chance of pregnancy was independent of day 1 serum FSH levels. Women with UI undergoing COH in our unit with an elevated baseline serum E2 > 150 pmol/l have a significantly lower PR and should be counselled regarding the decreased likelihood of pregnancy.

A new look at nurse burnout: the effects of environmental uncertainty and social climate.

As healthcare organizations deal with changes in the external environment, uncertainty in the internal environment is created. The purpose of this study was to explore the relationships among environmental uncertainty, social climate, and burnout among staff nurses. Multiple regression analysis was used to explore relationships among study variables. Perceived environmental uncertainty predicted burnout among staff nurses, although there was no significant relationship between burnout and objective measures of unit activity. The social climate of the workplace was negatively associated with burnout. The authors concluded that social networks are important during times of change and uncertainty in the work environment; in other words, a supportive workplace can protect against burnout.

Stress tolerance in transgenic tobacco seedlings that overexpress glutathione S-transferase/glutathione peroxidase.

Overexpression of a tobacco glutathione S-transferase with glutathione peroxidase activity (GST/GPX) in transgenic tobacco (Nicotiana tabacum L.) enhanced seedling growth under a variety of stressful conditions. In addition to increased GST and GPX activity, transgenic GST/GPX-expressing (GST+) seedlings had elevated levels of monodehydroascorbate reductase activity. GST+ seedlings also contained higher levels of glutathione and ascorbate than wild-type seedlings and the glutathione pools were more oxidized. Thermal or salt-stress treatments that inhibited the growth of wild-type seedlings also caused increased levels of lipid peroxidation. These treatments had less effect on the growth of GST+ seedling growth and did not lead to increased lipid peroxidation. Stress-induced damage resulted in reduced metabolic activity in wild-type seedlings while GST+ seedlings maintained metabolic activity levels comparable to seedlings grown under control conditions. These results indicate that overexpression of GST/GPX in transgenic tobacco seedlings provides increased glutathione-dependent peroxide scavenging and alterations in glutathione and ascorbate metabolism that lead to reduced oxidative damage. We conclude that this protective effect is primarily responsible for the ability of GST+ seedlings to maintain growth under stressful conditions.

Differential fibronectin expression in activated C6 glial cells treated with ethanol.

The central nervous system is particularly susceptible to alcohol effects and toxicity. Glial cells constitute the most common cell type in the brain and play critical roles in normal brain function and during infection and injury. Astrocytes in particular seem to be important targets for alcohol neurotoxicity during both development and in adulthood. To gain more insight into alcohol-mediated effects on astrocytes at the molecular level, gene expression in rat C6 glial cells was studied in the presence or absence of ethanol. The differential display of mRNA technique was used to screen the expressed genes in ethanol-treated rat C6 cells before and after treatment with lipopolysaccharide (LPS) combined with phorbol-12-myristate-13-acetate (PMA), conditions that mimic an infectious inflammatory state and cause immunologic activation. The present data show that fibronectin appeared as a major gene whose expression is increased in C6 cells by LPS plus PMA stimulation and decreased by chronic ethanol exposure, both in mRNA and protein levels. Fibronectin is a dimeric glycoprotein found in the extracellular matrix of most tissues, in the blood, and on cell surfaces and is involved in many cellular processes. These results show that chronic exposure to ethanol is associated with changes in astrocyte properties during immunologic activation that reduce fibronectin expression. The discovery of astrocyte fibronectin expression as a potential regulated target for chronic alcohol abuse may be useful in understanding, preventing, and treating some brain disorders associated with alcohol abuse and alcoholism.

A spontaneous luteinizing hormone surge is beneficial in women with unexplained infertility undergoing controlled ovarian hyperstimulation without in vitro fertilization.

OBJECTIVE: To determine whether a spontaneous luteinizing hormone (LH) surge influences the pregnancy and miscarriage rate in women with unexplained infertility undergoing controlled ovarian hyperstimulation (COH) without in vitro fertilization. DESIGN: Retrospective cohort study. SETTING: Ovulation Induction Clinic, Royal Hospital for Women, Sydney, Australia. PATIENTS: 145 patients with unexplained infertility who underwent 374 cycles of COH. METHODS: Two types of ovarian stimulation protocols were used: human menopausal gonadotrophin (hMG) alone or hMG and clomiphene citrate (CC). A spontaneous LH surge occurred in 54% of the total cycles. All patients received human chorionic gonadotrophin, whether or not a spontaneous LH surge occurred. All cycles were covered by natural intercourse. MAIN OUTCOME MEASURES: Cycle pregnancy rate and miscarriage rate in cycles with or without a spontaneous LH surge. RESULTS: The cycle pregnancy rate of the LH surge group was significantly higher than that of the no LH surge group for CC/hMG cycles (16.4% and 4.3% respectively, p = 0.02) but not for hMG alone cycles (12.8% and 10% respectively, P > .05). The miscarriage rate was not significantly different between the LH surge group and no LH surge group in either the CC/hMG cycles (30% and 75% respectively, P > .05) or the hMG alone cycles (22% and 38% respectively, P > .05). CONCLUSIONS: In women with unexplained infertility undergoing COH with CC/hMG, the occurrence of a spontaneous LH surge is a favorable event associated with a significantly increased pregnancy rate. The data showed a lower miscarriage rate, but there was insufficient power to confirm or refute this result.

Mobile access: opening health care doors.

By combining traditional services and resources, the HealthQuest mobile van travels through six counties in northeast Indiana to reach those who have no easy access to health care. Existing programs that focus on meeting the needs of infants, children and adults living in rural communities via the use of mobile primary care vans are reviewed as well as this recently developed program.

Human menopausal gonadotrophins in the treatment of unexplained infertility.

Ninety one patients with unexplained infertility were treated with human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG). The overall pregnancy rates were 29% per patient and 11% per cycle. In patients under the age of 37, the rates were 40% per patient and 15% per cycle. Many cycles (15%) were cancelled because of poor response to stimulation and by definition these women had normal cycles prior to stimulation. Within 1 year of ceasing HMG treatment, 9 patients had conceived spontaneously and another 4 conceived by GIFT.