Exposure to antibiotics induces expression of the Mycobacterium tuberculosis sigF gene: implications for chemotherapy against mycobacterial persistors

BACKGROUND: Although many studies have investigated macromolecular uptake in the stomach and small intestine, little is known about macromolecular uptake in the colon. AIMS: To investigate the mechanisms involved in the transport of large antigenically intact macromolecules across the proximal and distal colonic epithelium in the rabbit. METHODS: The mucosal to serosal movement of bovine serum albumin (BSA) was examined in modified Ussing chambers under short circuited conditions. The mucosal surface was exposed to varying concentrations of BSA, and after a 50 minute equilibration period, the mucosal to serosal flux of immunologically intact BSA was determined by ELISA. Total BSA flux was determined by the transport of radiolabelled 125I-BSA. RESULTS: Intact BSA transport in proximal and distal colonic tissue showed saturable kinetics. Intact BSA transport in the proximal and distal segment was 7% and 2% of the total 125I-BSA flux respectively. Immunologically intact BSA transport in the distal segment was significantly less than that in the proximal segment. Intact BSA transport in the proximal colon was significantly reduced following treatment with sodium fluoride, colchicine, and tetrodotoxin. Cholinergic blockade had no effect on the uptake of intact BSA. Conclusion: The findings indicate that the transport of intact macromolecules across the proximal and distal large intestine is a saturable process. Further, intact BSA transport in the proximal colon is an energy dependent process that utilises microtubules and is regulated by the enteric nervous system.     

Effects of temperature and volatile anesthetics on GABA(A) receptors

BACKGROUND: Potentiation of the activity of the gamma-aminobutyric acid type A (GABA(A)) receptor channel by volatile anesthetic agents is usually studied in vitro at room temperature. Systematic variation of temperature can be used to assess the relevance of this receptor to general anesthesia and to characterize the modulation of its behavior by volatile agents at normal body temperature. METHODS: Potentiation of the GABA(A) receptor by halothane, sevoflurane, isoflurane, and methoxyflurane was studied at six temperatures in the range 10-37 degrees C using the whole-cell patch-clamp technique and mouse fibroblast cells stably transfected with defined GABA(A) receptor subunits. RESULTS: Control GABA concentration-response plots showed small and physically reasonable changes in the GABA concentration required for a half-maximal effect, the Hill coefficient, and maximal response over the range 10-30 degrees C. Potentiations of GABA (1 microM) responses by aqueous minimum alveolar concentrations of the volatile anesthetic agents decreased with increasing temperature from 10-37 degrees C in an agent-specific manner (methoxyflurane > isoflurane > sevoflurane > halothane) but tended to equalize at normal body temperature (37 degrees C). These findings are in line with published results on the temperature dependence of anesthetic potencies in animals. CONCLUSIONS: These results are consistent with direct binding of volatile anesthetic agents to the GABA(A) receptor channel playing an important role in general anesthesia. The finding that the degree of anesthetic potentiation was agent-specific at low temperatures but not at 37 degrees C emphasizes the importance of doing in vitro experiments at normal body temperature.     

N-methyl-D-aspartate-stimulated increases in intracellular calcium exhibit brain regional differences in sensitivity to inhibition by ethanol

To determine what effect ovariectomy and the accompanying sudden loss of circulating gonadal hormones has on spatial learning performance in the adult rat, two groups of rats were tested on the Lashley III simple alley maze following surgery. Ovariectomized animals were compared with a control group of animals that underwent laparotomy at the same time. The ovariectomized group evidenced superior performance on the maze task, as measured by latency to reach goal (running times) and error scores. It is suggested that this finding provides further evidence for the role of gonadal steroid hormones in the manipulation of functions related to learning and memory, especially in the hippocampus.     

Assessing user interfaces for diverse user groups: evaluation strategies and defining characteristics

User interface designers are challenged to design for diverse users, including those of different genders, cultures and abilities; however, little research has been directed at this problem. One factor which may inhibit such research is its cost. This paper presents an approach which offers a way to seek out important characteristics of designs in a cost-effective way and reports on the results. In a study reported here, subjects from different nationalities and of both genders evaluated three dialog boxes specifically designed for 'white American women'. 'European adult male intellectuals', and 'English-speaking-internationals'. The dialog boxes were evaluated with conjoint techniques of preference rankings, and factor-analysed adjective ratings. These results showed that female subjects had stronger and more consistent patterns of preferences than the male subjects. All subjects preferred interfaces rated high on an accessibility factor and disliked complex layouts; this effect was even stronger for women. Nationality did not effect ratings. Gender had a stronger effect on the outcome than nationality.