Efficacy of repeated cycles of combination therapy for the eradication of infecting organisms in chronic bacterial prostatitis

A total of 137 patients with a diagnosis of chronic bacterial prostatitis (CBP) were subjected to combination pharmacological therapy with antibacterial agents (ciprofloxacin/azithromycin), alpha-blockers (alfuzosin) and Serenoa repens extracts. Of those, 88 patients (64.2%) showed microbiological eradication at the completion of a 6-week cycle of therapy. Of the remaining 49 patients showing persistence of the causative organism(s) or reinfection at the end of treatment, 36 completed a second cycle of combination therapy for 6 weeks: 27 patients (75%) showed eradication of the causative organism, whereas in nine cases persistence or reinfection was observed. The cumulative eradication rate of the present study - calculated on a total of 137 enrolled patients - is 83.9%. Clinical examination showed a marked improvement of signs and symptoms linked to prostatitis. Remarkably, combination therapy could attenuate CBP symptoms prior to microbiological eradication, thus rapidly decreasing the impact of the disease on the quality of life of patients. Clinical remission was extended throughout a follow-up period of 30 months for 94% of patients, whereas seven patients showed relapse of the disease. In summary, our results indicate that about 20% of patients enrolled in this study, who were refractory to a protocol of 6-week combination therapy, could be 'rescued' by a second cycle of treatment. Clinical follow-up data show that combination therapy could ensure extended relief from CBP symptoms, and a general improvement in quality of life.     

Anticonvulsant, anxiolytic, and non-sedating actions of imidazenil and other imidazo-benzodiazepine carboxamide derivatives

Recent evidence suggests that α1-containing GABA_A receptors mediate the sedative, amnestic, and to some extent the anticonvulsant actions of non-selective benzodiazepine (BZ) receptor ligands, such as diazepam (DZ). Anxiolytic and in part, anticonvulsant actions of BZ ligands are mediated by α2-, α3-, and α5-containing GABA_A receptors. This has resulted in increasing interest in developing BZ ligands with selective actions at GABA_A receptors, including α2-, α3-, and α5-subunits, but devoid of efficacy at α1-containing receptors. To refine their spectrum of pharmacological actions, efforts are being made to minimize unwanted effects such as sedation, amnesia, and tolerance liabilities. A prototype for such BZ ligands is imidazenil (IMD), an imidazo-benzodiazepine carboxylic acid derivative that elicits potent anticonvulsant and anxiolytic actions at doses virtually devoid of sedative, cardio-respiratory depressant and amnestic effects, and anticonvulsant tolerance liability. To define the pharmacological profile of IMD and its derivatives, we compared the anticonflict (anxiolytic), anti-proconflict (antipanic), anti-bicuculline (BIC), and maximal electroshock seizure (MES) effects, and the suppression of locomotor activity by imidazo-benzodiazepine carboxylic acid derivatives to those of DZ and bretazenil (BTZ). We report here that IMD and one of its derivatives (RO 25-2775) possess dose-dependent anticonflict, anti-proconflict, and anti-BIC actions but failed to suppress locomotor activity. Like DZ, the other IMD derivatives (enazenil, RO 25-2776, and RO 25-2847) not only elicit dose-dependent anticonflict, anti-proconflict, anti-BIC, anti-MES effects but also suppress locomotor activity. In contrast, none of the IMD derivatives studied shows any similarity to BTZ, which elicits anticonflict, anti-proconflict actions and suppresses locomotor activity but is virtually inactive against BIC-induced tonic-clonic convulsions.     

Astringency Perception and Heritability Among Young Finnish Twins

The genetics of astringency perception and the contribution of astringency to the pleasantness and use frequency of phenol-rich foods and beverages were studied in a Finnish twin cohort of young adults (aged 22?C25 years). A total of 194 participants (96 males, 98 females) comprised of 81 full pairs (24 monozygotic, 57 dizygotic) and 32 twin individuals without the co-twin participating. Pleasantness and intensity of an apple juice with added tannic acid (TA juice; 1.5 g/L) relative to an untainted apple juice were recorded. Two saliva samples were collected, the first after 12 h of fasting and the second after the stimulation with TA juice. Saliva samples were characterized by determining the total protein, amylase, proline-rich protein, histatin, cystatin, and mucin contents. Participants filled in questionnaires comprising of pleasantness and use frequency of eight astringent items vs their less astringent counterparts. TA juice was perceived as less pleasant and more intense than the pure apple juice. The relationship between astringency, product pleasantness, and food use were found to be complex. Although astringency influenced significantly the sensory experience of the phenol-rich foods and beverages, the pleasantness and use frequency of the products were not primarily steered by their astringency level. In twin analyses, the first tentative evidence of the genetic variation underlying astringency perception was discovered.     

The regulation of hippocampal nicotinic acetylcholine receptors (nAChRs) after a protracted treatment with selective or nonselective nAChR agonists

In rats, 1 mg/kg twice daily for 10 d of nicotine, a nonselective agonist of nicotinic acetylcholine receptors (nAChRs), fails to change alpha4 and beta2 nAChR subunit mRNA but significantly decreased alpha7 nAChR subunit mRNA and protein expression, which is associated with a 35-40% decrease in the number of 125I-alpha-Bgtx binding sites in hippocampus. In addition, this schedule of nicotine treatment produced a 40% increase in the number of high- (K(D) 1 nM), but decreased by 25% the number of low-affinity (K(D) 30 nM) binding sites for 3H-epibatidine in hippocampus. In contrast, repeated treatment with lobeline (2.7 mg/kg twice daily for 10 d), which selectively binds to high-affinity binding nAChRs, fails to change the expression of high- or low-affinity nAChRs. These data suggest that a simultaneous upregulation of high-affinity nAChRs and downregulation of low-affinity nAChRs is elicited by ligands that can bind to both low- and high-affinity nAChRs, but not by selective agonists of high-affinity nAChRs. One might infer that in hippocampus, high- and low-affinity nAChRs may be located in the same cells. When these two receptor types are stimulated simultaneously by nonselective ligands for high- and low-affinity nAChRs, they interact, bringing about an increase in binding site density of the high-affinity nAChRs.