Compared with beta-lactam antibiotics, rifampin releases smaller quantities of proinflammatory cell wall products from Streptococcus pneumoniae in vitro. Mice infected intracerebrally with S. pneumoniae were treated subcutaneously with 2-mg doses of rifampin or ceftriaxone (n=43 each) every 12 h for 3 days and then observed for another 3 days. Rifampin reduced overall mortality from 49% to 26% (P=.04). Kaplan-Meyer analysis revealed a substantial reduction of mortality during the first 24 h in mice receiving rifampin (difference in survival time: P=.007). Eight h after receiving a single 2-mg dose of rifampin or ceftriaxone, rifampin-treated mice had lower serum and cerebrospinal fluid concentrations of lipoteichoic and teichoic acids than did ceftriaxone-treated mice (median serum level: <0.5 vs. 27.0 ng/mL, P=.02; median cerebrospinal fluid level of pooled specimens: 97.5 vs. 206.0 ng/mL). Thus, the use of rifampin appears promising for reducing the release of proinflammatory bacterial components and decreasing early mortality in bacterial meningitis.
In 12 patients a moderate to marked improvement in all domains was observed upon treatment with 20-40 mg citalopram daily. Treatment for one year in the effective dose prevented recurrence of depressive symptomatology. P46.07 A rare case of neuroleptic malignant syndrome and the NMS spectrum concept It is concluded that citalopram is a well tolerated, safe, interaction-free and effective antidepressant in mentally retarded subjects with a depressive disorder.
Reduced 5-HT1A-receptor responsiveness has been reported in patients with panic disorder(PD) and/or agoraphobia (PDA). Although many of these patients are regular smokers, it has not been examined whether psychological or neurobiological effects induced by the selective 5-HT1A-receptor agonist, ipsapirone, are affected by the smoking status of the patients.In order to clarify this question neuroendocrine challenges with oral doses of ipsapirone (0.3 mg/kg) Neuropharmacological challenges with the selective 5-hydroxytryptamine-1A (5-HT1A) receptor agonist, ipsapirone, have been used in several studies to assess 5-HT1A-receptor related functions in patients suffering from various neuropsychiatric disorders (Broocks et al. 2000;Lesch et al. 1990a;Lesch et al. 1991;Lesch et al. 1990b;Lesch et al. 1992) and in healthy controls (Broocks et al. 1999;Kahn et al. 1994;Lesch et al. 1990c;Lesch et al. 1990d).Indices of abnormal serotonergic function have been reported in patients with panic disorder (PD) and/or agoraphobia (PDA). In particular, there is evidence for an increased sensitivity of the 5-HT 2C subsystem (Charney et al. 1987a;Charney et al. 1987b;Kahn et al. 1988a Kahn and Wetzler 1991;Kahn et al. 1988b). In contrast, stimulation of 5-HT 1A receptors by ipsapirone was followed by an attenuated hypothermic and ACTH/cortisol response in patients with PDA (Broocks et al. 2000;Lesch et al. 1992). In healthy controls, ipsapirone produces dose-dependent increases in plasma cortisol and ACTH as well as dose-dependent reductions in body temperature (Cowen 2001;Kahn et al. 1994;Lesch et al. 1989). Ipsapirone acts on specific serotonergic mechanisms in the brain through its high-affinity binding to the 5-HT 1A receptor subtype. The binding sites are predominantly located on serotonergic neurons in the raphe nuclei (presynaptic autoreceptors) and in limbic structures (postsynaptic receptors). Agonistic properties at presynaptic somatodendritic sites have been observed, resulting in decreased serotonergic neurotransmission (Peroutka 1985). Concerning the high selectivity of ipsapirone, it has to be considered that the metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) has been found to exert antagonistic effects at pre-and postsynaptic ␣ 2-adrenoceptors (Blier et al. 1991;Miller et al. 1992).Several lines of evidence suggest that serotonergic neurotransmission, including the regulation of 5-HT1A receptors, is affected by nicotine (Benwell et al. 1990;Kenny et al. 2001). Recent studies show that some of nicotine's psychotropic and endocrine effects are exerted by stimulation of 5-HT1A receptors on dorsal raphe neurons (Cheeta et al. 2001;Mihailescu et al. 2001).There is a high incidence of smoking in patients with anxiety and other psychiatric disorders (Breslau et al. 1993;Glassman 1993;Kendler et al. 1993;Marks et al. 1997;Miller and Gold 1998;Sellman et al. 1999). To our knowledge, no clinical studies have examined the question of whether psychological or neurobiological effects induced by serotonergic agents such as ipsapi...
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