Antitubercular activity of lomefloxacin in an experiment

The effect of lomefloxacin was studied on mice with experimental infection due to Mycobacterium tuberculosis. The antibiotic was administered in doses of 100 and 200 mg/kg. It was shown that the use of lomefloxacin for a month provided a lower death rate of the animals with progressing acute generalized tuberculosis, a lower level of the lesions in the internal organs and a lower number of the Mycobacterium isolates from them. The efficacy of the treatment depended on the drug dose. When lomefloxacin was used in a dose of 200 mg/kg, the survival rate was much higher and the number of the epithelial unicellular granulomas in the tissue of the lung and spleen was markedly decreased while with the lower dose the indices did not differ from those in the control.     

Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

Immunostimulatory DNA: sequence-dependent production of potentially harmful or useful cytokines

Certain bacterial immunostimulatory (i.s.) DNA sequences containing unmethylated CpG motifs stimulate antigen-presenting cells (APC) to express a full complement of costimulatory molecules and to produce cytokines including interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha. While IL-12 is key to their T helper cell (Th)1-promoting adjuvant activity, secretion of toxic levels of TNF-alpha is harmful in that it promotes toxic shock. Given the beneficial as well as harmful consequences of i.s. DNA, we investigated the possibility of identifying DNA sequences, i.e. CpG oligodeoxynucleotides (ODN) which differentially activate IL-12 versus TNF-alpha cytokine production in APC. Here, we describe an i.s. DNA sequence with these characteristics. While its potential to induce IL-12 is preserved, its ability to trigger TNF-alpha release is strongly curtailed both in vitro and in vivo. I.s. DNA could be segregated into lethal and non-lethal in a mouse toxic shock model. The non-toxic i.s. DNA was useful as an adjuvant, thus allowing cytotoxic T cell responses to the soluble protein ovalbumin and conferring a resistant Th 1 phenotype to BALB/c mice lethally infected with Leishmania major. This i.s. CpG motif may thus be prototypic for a useful immunostimulating DNA sequence that lacks harmful side effects.     

Significance of chloride channel activation in the gamma-aminobutyric acid induced growth hormone secretion in the neonatal rat pituitary

Growth hormone (GH) secretion of the neonatal pituitary is stimulated by tau-aminobutyric acid (GABA) (1,2). Since in most cases GABA is known to act by increasing postsynaptic membrane permeability to chloride ions we tested the importance of chloride channel activation in the GH stimulatory effect of GABA in the neonatal pituitary. In the absence of chloride in the superfusion medium GABA was without effect on GH secretion of the neonatal pituitaries and its effect was attenuated by chloride channel inhibitors. The effect of growth hormone releasing hormone (GHRH) on GH secretion was attenuated in the chloride-free media, but it was not affected by simultaneous administration of chloride channel blockers. The present study indicates that GH stimulatory effect of GABA in the neonatal pituitaries might involve chloride channel activation probably resulting in secondary activation of calcium channels.     

Metabolism-reproduction interactions in domestic animals

In farm animals as in human, reproduction is affected by changes in the level of energetic balance. The main factors that link metabolism and reproduction, like insulin, IGFs, glucose, FFA, leptin and NPY, act on hypothalamo-pituitary axis as well as on gonads by directly altering gametogenesis.     

Assessment of alcohol consumption and alcoholism in the elderly

This study evaluates characteristics associated with alcohol consumption or alcohol-related problems in an elderly population, as detected by CAGE questionnaire and self-reported alcohol intake respectively. Data were obtained from a multidimensional study carried out in a community-dwelling population aged 70-75 (n = 1205, 389 males and 816 females) living in the city center of Brescia, in northern Italy. All information was gathered by self-report. Male gender, better mood, daily function, somatic health, not living alone, and being married were significantly associated with self-reported alcohol consumption. Male gender, poorer cognitive function, and income dissatisfaction were significantly associated with alcohol problems as detected by CAGE. Data suggest that self-report of alcohol intake, though intrinsically loaded with imperfect internal consistency, does not necessarily indicate risk of alcoholism; on the contrary, it can reveal the positive psychological attitude of the drinking habit. CAGE questionnaire, which is sensitive to alcohol related problems, is associated with poor psychosocial conditions.     

Benefits of collecting local data on breast cancer and mammography practices in northwestern Pennsylvania

OBJECTIVES: A randomized trial was conducted to evaluate the effectiveness of a work-site health promotion program in reducing obesity and the prevalence of cigarette smoking. METHODS: Thirty-two work sites were randomized to treatment or no treatment for 2 years. Treatment consisted of health education classes combined with a payroll-based incentive system. Evaluation was based on cohort and cross-sectional surveys. RESULTS: Of 10,000 total employees in treatment work sites, 2041 and 270 participated in weight control and smoking cessation programs, respectively. Weight losses averaged 4.8 lbs, and 43% of smoking participants quit. Net 2-year reductions in smoking prevalence in treatment vs control work sites were 4.0% and 2.1% in cross-sectional and cohort surveys, respectively. No treatment effect was found for weight. Treatment effects for smoking prevalence and weight were both positively correlated with participation rates in the intervention programs (r = .45 for smoking and r = .55 for weight). CONCLUSIONS: This work-site health promotion program was effective in reducing smoking prevalence at a cost that is believed to make the investment worthwhile.     

The relationship between coffee consumption and serum cholesterol under consideration of smoking history

To provide insight into the stream of Medicare payments over time, a sixteen-year longitudinal study examines three age cohorts of beneficiaries, looking separately at beneficiaries who died during the study period and those who survived. The common wisdom that a small minority of the population accounts for a large majority of health care expenditures is tempered when health care use is examined over an extended period of time. By putting high average costs in the final years of life in the context of a cohort's total lifetime experience, the study shows a leveling of spending over time, resulting in a lower concentration of health care resources on a small fraction of the population.