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PRS-211092

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项与 Pharmos Ltd. 相关的文献（医药）

2011-02-01·Journal of Urology1区 · 医学

Cannabinor, a Selective Cannabinoid-2 Receptor Agonist, Improves Bladder Emptying in Rats With Partial Urethral Obstruction

1区 · 医学

Article

作者: Stief, Christian G. ; Rosenbaum, Jan S. ; Alroy, Iris ; Gratzke, Christian ; Hedlund, Petter ; Downs, Thomas R. ; Streng, Tomi ; Andersson, Karl-Erik ; Limberg, Brian J.

PURPOSEWe studied the effects of chronic treatment with the novel selective cannabinoid 2 receptor agonist cannabinor (Procter & Gamble Pharmaceuticals, Cincinnati, Ohio) on bladder function in conscious rats with partial urethral obstruction and on the functional properties of isolated detrusor muscle.MATERIALS AND METHODSA total of 24 female Sprague-Dawley® rats with surgically created partial urethral obstruction received daily intraperitoneal injections of 3 mg/kg cannabinor (12) or saline as controls (12) for 2 weeks. Cystometry was done, the rats were sacrificed and the bladders were prepared for in vitro studies.RESULTSMean ± SEM bladder weight was 0.97 ± 0.15 gm in controls and 0.53 ± 0.08 gm in cannabinor treated rats (p <0.05). There was no difference between the groups in the mean micturition interval, or mean baseline, threshold, flow or maximum pressure. In controls and cannabinor treated rats mean post-void residual volume was 0.28 ± 0.07 and 0.06 ± 0.02 ml, mean micturition compliance was 0.032 ± 0.006 and 0.069 ± 0.016 ml/cm H(2)O, and mean bladder wall force at the start of flow was 950 ± 280 and 1,647 ± 325 mN/gm, respectively (each p <0.05). Nonvoiding contractions were significantly less frequent in cannabinor treated rats than in controls. We noted no difference in carbachol (Sigma®) half maximum concentration between the groups but the carbachol maximum response in detrusor strips from cannabinor treated rats was significantly higher than that in control strips.CONCLUSIONSIn rats with partial urethral obstruction treated daily for 14 days with cannabinor bladder weight was lower, the ability to empty the bladder was preserved and nonvoiding contraction frequency was low compared to those in controls. Detrusor preparations from cannabinor treated rats showed a higher response to nerve stimulation than those from controls. Selective cannabinoid 2 receptor activation may be a novel principle to enable improved bladder function after partial urethral obstruction.

2010-01-08·Journal of Pharmacy and Pharmacology3区 · 医学

The role of molecular physicochemical properties and apolipoproteins in association of drugs with triglyceride-rich lipoproteins: in-silico prediction of uptake by chylomicrons

3区 · 医学

作者: Amselem, Shimon ; Hoffman, Amnon ; Fanous, Joseph ; Yacovan, Avihai ; Qadri, Bashir ; Gershkovich, Pavel

AbstractObjectivesThe uptake of drugs by chylomicrons is a key element in both intestinal lymphatic transport and postprandial alterations in the disposition profile of lipophilic drugs. The aim of this article was to elucidate the factors that affect this phenomenon.MethodsThe degree of association of 22 model lipophilic molecules with rat chylomicrons was assessed and correlated in silico with calculated physicochemical properties. The in-silico model was then validated using an external set of molecules. The uptake by chylomicrons was also compared to the association with a marketed artificial emulsion.Key findingsThe most important physicochemical property that affects the affinity to chylomicrons was found to be LogD7.4; however, a multiparameter model was required to describe properly the uptake process. The in-silico model (R2Y = 0.91, R2X = 0.91 and Q2 = 0.82) that was created using a combination of eight molecular descriptors enabled successful prediction of the affinity of the external set of molecules to chylomicrons. The association with the artificial emulsion was statistically different from the uptake by chylomicrons for four (out of nine) molecules.ConclusionsThe association of drugs with chylomicrons is a complex process, which involves the lipophilic core as well as surface apoproteins. The in-silico model based on multiple physicochemical properties of the drugs is able to predict successfully the degree of association with chylomicrons.

2008-04-01·Neurosurgical Review3区 · 医学

Dexanabinol prevents development of vasospasm in the rat femoral artery model

3区 · 医学

Article

作者: Kısmet Çivi ; Varol Sahintürk ; Hilmi Özden ; Ramazan Durmaz ; Amselem Shimon ; Ahmet Ozsandik ; Cengiz Bayçu

We postulated that a multi-potential agent such as dexanabinol may prevent the development of vasospasm after subarachnoid hemorrhage. We tested the effect of dexanabinol (10 mg/kg) on established vasospasm in a rat femoral artery model. Dexanabinol was given as single or repeated doses. On the 7th day after blood application, vessels were prepared for transmission electron microscopy studies, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling staining, and studying vessel morphology including luminal area and wall thickness. Application of blood to femoral artery caused a significant narrowing of luminal area (p<0.001) and a marked increase of radial wall thickness (p<0.001) when compared to controls. Similar to its single injection, repeated doses of dexanabinol markedly widened luminal area (p<0.001) near to control values (p>0.05) and decreased radial wall thickness significantly compared to hemorrhage (p<0.05) and vehicle-treated groups (for single p<0.05 and repetitive injections p<0.01). Both single and multiple dexanabinol injections also lowered apoptotic index (p<0.001). In conclusion, dexanabinol seems to prevent established vasospasm and endothelial cell apoptosis.

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