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.     

Treatment of perianal fistulas with ND:YAG laser--results in twenty cases

Excision of perianal fistulas using a 1.064 micron wavelength neodymium:yttrium aluminum garnet (ND:YAG) contact tipped laser with primary wound closure was used to treat 20 dogs with perianal fistulas. Overall, 19 of 20 (95%) dogs had resolution of fistulas after one or more ND:YAG treatments. The period of resolution ranged from 10 to 42 months with a mean of 22.9 months. Sixteen of 20 (80%) dogs had resolved fistulas after one laser excision. Three of the four recurrences underwent additional laser treatments with successful results. The total number of laser procedures ranged from one to three with a mean of 1.2 procedures. Postoperatively, anal tone as judged by digital rectal examination was reduced in about 60% of the cases, but clinical evidence of fecal incontinence only occurred in four of 20 cases. This was managed effectively with diet modification. The tendency toward loss of anal tone or fecal incontinence depended on the severity of preexisting anal stenosis. On a client survey, 19 of 20 owners believed that their animals experienced less pain during defecation after surgery and rated the results as excellent or good. The overall success rate using ND:YAG laser excision compared very favorably with previously reported studies of other methods of treatment for perianal fistulas in dogs.     

Managing Impressions Online: Self-Presentation Processes in the Online Dating Environment

This study investigates self-presentation strategies among online dating participants, exploring how participants manage their online presentation of self in order to accomplish the goal of finding a romantic partner. Thirty-four individuals active on a large online dating site participated in telephone interviews about their online dating experiences and perceptions. Qualitative data analysis suggests that participants attended to small cues online, mediated the tension between impression management pressures and the desire to present an authentic sense of self through tactics such as creating a profile that reflected their "ideal self," and attempted to establish the veracity of their identity claims. This study provides empirical support for Social Information Processing theory in a naturalistic context while offering insight into the complicated way in which "honesty" is enacted online.     

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.