1-乙基-6-氟-1,4-二氢-4-氧代-7-(4-芳酰硫代氨甲酰基-1-哌嗪基)-3-喹啉羧酸的合成及抗菌作用

Thirteen new 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-aroyl-thiocarbamoyl- 1 piperazinyl)-3-quinoline carboxylic acids were prepared, Their structures were characterized by elemental analysis, IR, HNMR and MS spectra.Preliminary pharmacological tests indicated that some of compounds Ia～m possess strong inhibiting activity against Escherichia coli, Bacillus subtilis and Proteus at concentration of 100 μg/ml.     

Adrenal function under long-term raloxifene administration.

The aim of the present study was to evaluate the effect of long-term (12 months) administration of raloxifene hydrochloride (60 mg/day) on the steroid production of the adrenal cortex and on the hypothalamic-pituitary-adrenal axis in postmenopausal women. We performed a basal evaluation, a corticotropin releasing factor (CRF) (100 microg i.v. bolus) test and a dexamethasone (DXM) (0.25 mg) suppression-adrenocorticotropic hormone (ACTH) (10 microg i.v. bolus) stimulation test in 11 postmenopausal women, before and after 3, 6 and 12 months of raloxifene treatment. Raloxifene administration significantly modified circulating levels of adrenal steroids, decreasing cortisol (-24%), dehydroepiandrosterone (DHEA) (-36%), and its sulfate (DHEAS) (-41%), and androstenedione (-29%), and increasing circulating allopregnanolone (+39%) levels. Progesterone and 17OH-progesterone levels remained unmodified, while estradiol and estrone levels showed a significant decrease (-51% for estradiol and -61% for estrone). We also observed an increase in circulating ACTH (+58%) and beta-endorphin (+120%). No modifications in the hormonal responses to CRF were observed during the treatment. DXM significantly suppressed circulating steroids at any time with a lower suppression of cortisol from the third month and a higher suppression of DHEA at 12 months. ACTH administration was associated with a significantly blunted cortisol response from the sixth month and a significantly increased response of allopregnanolone from the third month. The present data exclude a raloxifene effect on pituitary sensitivity to CRF and demonstrate a reduced adrenal sensitivity to ACTH, sustained by the opposite changes in basal cortisol and Delta5 androgens, which were reduced, and in ACTH and beta-endorphin, which were increased, as well by the reduced response of cortisol to the direct ACTH stimulus. The reduction of circulating cortisol levels and cortisol response to the ACTH challenge suggests that raloxifene protects against the neurotoxic effects of endogenous glucocorticoids. Furthermore, the progressive increase in basal allopregnanolone and its increased response to ACTH indicate that chronic raloxifene administration exerts direct effects on the pattern of adrenal enzymes, leading to specific changes in the circulating levels of this anxiolytic progesterone metabolite. The important reduction in the circulating levels of estradiol and estrone under long-term raloxifene administration may represent a further mechanism by which this molecule may exert a protective effect against breast and endometrial malignancies.     

Pursuit eye movement dysfunction in obsessive-compulsive disorder.

Disturbances in neural circuitry including the basal ganglia and prefrontal cortex have been hypothesized to be a cause of obsessive-compulsive disorder (OCD). Because eye movements are often impaired in neurologic diseases affecting these brain areas, oculomotor functioning was assessed in 17 unmedicated patients with OCD and in 25 normal controls. As compared with control subjects, patients with OCD demonstrated low-gain (slow) pursuit eye movements and an increased frequency of square wave jerk intrusions, but no increase in anticipatory saccades. In addition, several OCD patients showed an unusual pattern of intrusive, brief epochs of high-gain (fast) pursuit lasting on the order of 50 to 130 msec. These epochs of fast pursuit moved the eyes ahead of the target being tracked, and were terminated by corrective reversal saccades. Studies of eye movement abnormalities may provide an informative neurophysiologic approach for studying disturbances in basal ganglia and frontal cortical function that have been observed in functional neuroimaging and neuropsychological studies of OCD.     

Stimulus effects of ibogaine in rats trained with yohimbine, DOM, or LSD.

The stimulus effects of ibogaine were compared with those of yohimbine, an alpha 2-adrenoceptor antagonist, 2,5-dimethoxy-4-methylamphetamine (DOM), a 5-hydroxytryptamine2 (5-HT2) agonist, and lysergic acid diethylamide (LSD), a nonspecific 5-HT agonist. Rats were trained with either yohimbine (6 mg/kg), DOM (0.6 mg/kg), or LSD (0.1 mg/kg) vs. no treatment in a two-lever discrimination task. Tests of generalization were then conducted with ibogaine. In yohimbine-trained animals, 39.7% of responses following ibogaine (15 mg/kg) were on the drug-appropriate lever, but this response level was not significantly different from no treatment-appropriate responding. A response distribution that was significantly different from responding under both drug and no treatment training conditions was observed in DOM-trained rats after administration of 15 mg/kg ibogaine. Pizotyline (BC-105) blocked all DOM-appropriate responding produced by ibogaine. In LSD-trained animals, 20 mg/kg ibogaine mimicked LSD. Pizotyline blocked LSD-appropriate responding produced by ibogaine in five of six animals. The present data suggest the involvement of 5-HT2 receptor activity, and the possibility of a 5-HT1A contribution, in the stimulus properties of ibogaine.     

Criteria for evaluating the clinical and practical utility of models used by nurses

Arguably, nursing, like all health care disciplines, is an applied science. Essentially, this refers to the application of theory in order to understand and respond to the health problems of clients. These theories may be drawn (borrowed) from any applied science, or generated inductively from clinical nursing practice. Alternatively, nurses may attempt to apply deductive theory (global theoretical frameworks) known as nursing models. In this paper, all theoretical approaches, irrespective of origin, are referred to as models used by nurses. Thirteen criteria by which clinicians, and others, can evaluate the clinical and practical utility of models used by nurses which are expressed in the form of questions are identified and discussed. The criteria are an extension, both in detail and in number, of those developed by Reynolds and Cormack and subsequently applied by those writers to the Johnson Behavioural System Model of Nursing. The value, or otherwise, of individual models, or of models in general, will not be discussed in this paper. However, the authors propose that if the evaluation criteria described here are applied to existing models, serious deficits will be identified in relation to their clinical and practical utility.     

Expression of c-fos, fos B, and egr-1 in the medial preoptic area and bed nucleus of the stria terminalis during maternal behavior in rats

The spatial and temporal pattern of expression of the protein products of immediate early genes (IEGs) c-fos, fos B, and egr-1 were mapped in medial preoptic area (MPOA) and ventral bed nucleus of stria terminalis (VBST) during maternal behavior in rats. Immunocytochemical analysis indicated significant increases in the number of cells expressing c-Fos after 2 h of pup exposure, while Fos B levels showed a delayed response, reaching maximal levels after 6 h.