Effects of carbenoxolone on syncytial electrical properties and junction potentials of guinea-pig vas deferens

The effects of the putative gap junction blocker carbenoxolone on smooth muscle syncytial properties and junction potentials were studied in guinea pig vas deferens (GPVD). Treatment with 50 μM carbenoxolone reversibly and significantly increased input resistance (R _in) (by 682.5 ± 326.0 %, P < 0.05) and abolished cable potentials within 6–7 mins of incubation, without disturbing resting membrane potential. Carbenoxolone reversibly and significantly increased the amplitude of spontaneous excitatory junction potentials (sEJPs) by 96.9 ± 35.45% (P < 0.05), shifted their amplitude distribution rightwards, and reduced their frequency of occurrence by 58.17 ± 17.7% (P < 0.05), without altering their time courses. Similarly, carbenoxolone increased the amplitude of evoked excitatory junction potentials (eEJPs) by 17.7 ± 5.88% and τ _decay by 19.43 ± 8.29% (P < 0.05). Our results indicate that carbenoxolone alters the electrical properties and junctional potentials of the GPVD by a mechanism consistent with a relatively specific block of gap junctions. These results suggest that gap junction mediated cell-to-cell communication may significantly modulate the electrical properties and junctional potentials of the GPVD and consequently the physiological functioning of this tissue.     

An indicator device for monitoring of room illuminance level in the radiological image viewing environment

Illuminance level in the softcopy image viewing room is a very important factor to optimize productivity in radiological diagnosis. In today's radiological environment, the illuminance measurements are normally done during the quality control procedure and performed annually. Although the room is equipped with dimmer switches, radiologists are not able to decide the level of illuminance according to the standards. The aim of this study is to develop a simple real-time illuminance detector system to assist the radiologists in deciding an adequate illuminance level during radiological image viewing. The system indicates illuminance in a very simple visual form by using light emitting diodes. By employing the device in the viewing room, illuminance level can be monitored and adjusted effectively.     

Biaryl ureas as potent and orally efficacious melanin concentrating hormone receptor 1 antagonists for the treatment of obesity

Herein, we report a small molecule MCH-R1 antagonist which demonstrates oral efficacy in chronic rodent models. Substituted phenyl biaryl urea derivatives were synthesized and evaluated as MCH-R1 antagonists for the treatment of obesity. The structure-activity relationship studies in this series resulted in identification of urea 1 as a potent and selective MCH-R1 antagonist. Compound 1 exhibited oral efficacy in chronic (28 d) rodent models at 3-30 mpk showing significant reduction in food intake and weight gain relative to controls.     

Protective effect of taurine on myocardial antioxidant status in isoprenaline-induced myocardial infarction in rats

We have examined the protective effect of taurine on the myocardial antioxidant defense system in isoprenaline (isoproterenol)-induced myocardial infarction in rats, an animal model of myocardial infarction in man. Levels of diagnostic marker enzymes in plasma, lipid peroxides and reduced glutathione, and the activity of glutathione-dependent antioxidant enzymes and anti-peroxidative enzymes in the heart tissue were determined. Intraperitoneal administration of taurine significantly prevented the isoprenaline-induced increases in the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine phosphokinase in the plasma of rats. Taurine exerted an antioxidant effect against isoprenaline-induced myocardial infarction by preventing the accumulation of lipid peroxides and by maintaining the level of reduced glutathione and the activity of glutathione peroxidase, glutathione-S-transferase, catalase and superoxide dismutase at near normality. The results indicated that the cardioprotective potential of taurine was probably due to the increase of the activity of the free radical enzymes, or to a counteraction of free radicals by its antioxidant nature, or to a strengthening of myocardial membrane by its membrane stabilizing property.     

Coats-type retinal telangiectasia in case of Kabuki make-up syndrome (Niikawa-Kuroki syndrome)

PURPOSE: To report a case of Kabuki make-up syndrome (KMS) or Niikawa-Kuroki syndrome with Coats-type retinal telangiectasia, which has not been previously reported. METHODS: Observational case report. CONCLUSIONS: There have been only two reports of retinal pigmentation abnormalities and a single case of bilateral macular deposits in KMS, but this is the first report of a Coats type retinal telangiectasia. This case highlights the importance of thorough posterior segment examination in cases of KMS.     

Discovery of 4-[(Z)-(4-bromophenyl)- (ethoxyimino)methyl]-1'-[(2,4-dimethyl-3- pyridinyl)carbonyl]-4'-methyl-1,4'- bipiperidine N-oxide (SCH 351125): an orally bioavailable human CCR5 antagonist for the treatment of HIV infection

Structure-activity studies on piperidino-piperidine 3 led to the discovery of SCH 351125 (1), a selective CCR5 antagonist with potent activity against RANTES binding (K(i) = 2 nM), which possesses subnanomolar activity in blocking viral entry and has excellent antiviral potency versus a panel of primary HIV-1 viral isolates. Compound 1, which has good oral bioavailability in rats, dogs, and monkeys, is proposed as a potential therapeutic agent for the treatment of HIV-1 and has entered human clinical trials.     

Specific investigations in chronic urinary bilharziasis.

Seventy-two patients with histologically confirmed chronic urinary bilharziasis were studied for the reliability of some specific investigative tools in diagnosing this disease, namely urinalysis, serology, urography, and cystoscopy. Of the 72 patients 36 (50%) had hematuria and only 3 (4%) had ova of Schistosoma haematobium on urinalysis. Sixty-two patients (86%) had features of bilharziasis on intravenous urography (IVU). Of the remaining 10 patients with negative urography 6 underwent serology and all had positive results. Of the total patients 52 underwent serology and 49 had significant bilharzial antibody titer (94.2%). At cystoscopy all patients (100%) had features of bilharziasis. It is concluded that the most reliable diagnostic tools in chronic urinary bilharziasis are cystoscopy, serology, and to a lesser extent urography. Unlike early bilharziasis, chronic bilharziasis can be missed if total reliance is placed on urinalysis for screening a population at risk.