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Biomedical subjects

Q M Zhu

Publications and source records attributed to Q M Zhu.

7 recordsLinked to original sources
PubMed2000

Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice.

Extracellular ATP is implicated in numerous sensory processes ranging from the response to pain to the regulation of motility in visceral organs. The ATP receptor P2X3 is selectively expressed on small diameter sensory neurons, supporting this hypothesis. Here we show that mice deficient in P2X3 lose the rapidly desensitizing ATP-induced currents in dorsal root ganglion neurons. P2X3 deficiency also causes a reduction in the sustained ATP-induced currents in nodose ganglion neurons. P2X3-null mice have reduced pain-related behaviour in response to injection of ATP and formalin. Significantly, P2X3-null mice exhibit a marked urinary bladder hyporeflexia, characterized by decreased voiding frequency and increased bladder capacity, but normal bladder pressures. Immunohistochemical studies localize P2X3 to nerve fibres innervating the urinary bladder of wild-type mice, and show that loss of P2X3 does not alter sensory neuron innervation density. Thus, P2X3 is critical for peripheral pain responses and afferent pathways controlling urinary bladder volume reflexes. Antagonists to P2X3 may therefore have therapeutic potential in the treatment of disorders of urine storage and voiding such as overactive bladder.

Adenosine Triphosphate↗
PubMed1999

Cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N alpha2A-adrenoceptor transgenic mice.

1. We investigated the cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N alpha2A-adrenoceptor mice. The in vitro pharmacology of these agonists was determined at recombinant (human) alpha2-adrenoceptors and at endogenous (dog) alpha2A-adrenoceptors. 2. In wild-type mice, rilmenidine, moxonidine (100, 300 and 1000 microg kg(-1), i.v.) and clonidine (30, 100 and 300 microg kg(-1), i.v.) dose-dependently decreased blood pressure and heart rate. 3. In D79N alpha2A-adrenoceptor mice, responses to rilmenidine and moxonidine did not differ from vehicle control. Clonidine-induced hypotension was absent, but dose-dependent hypertension and bradycardia were observed. 4. In wild-type mice, responses to moxonidine (1 mg kg(-1), i.v.) were antagonized by the non-selective, non-imidazoline alpha2-adrenoceptor antagonist, RS-79948-197 (1 mg kg(-1), i.v.). 5. Affinity estimates (pKi) at human alpha2A-, alpha2B- and alpha2C-adrenoceptors, respectively, were: rilmenidine (5.80, 5.76 and 5.33), moxonidine (5.37, <5 and <5) and clonidine (7.21, 7.16 and 6.87). In a [35S]-GTPgammaS incorporation assay, moxonidine and clonidine were alpha2A-adrenoceptor agonists (pEC50/intrinsic activity relative to noradrenaline): moxonidine (5.74/0.85) and clonidine (7.57/0.32). 6. In dog saphenous vein, concentration-dependent contractions were observed (pEC50/intrinsic activity relative to noradrenaline): rilmenidine (5.83/0.70), moxonidine (6.48/0.98) and clonidine (7.22/0.83). Agonist-independent affinities were obtained with RS-79948-197. 7. Thus, expression of alpha2A-adrenoceptors is a prerequisite for the cardiovascular effects of moxonidine and rilmenidine in conscious mice. There was no evidence of I1-imidazoline receptor-mediated effects. The ability of these compounds to act as alpha2A-adrenoceptor agonists in vitro supports this conclusion.

Adrenergic alpha-Antagonists↗
PubMed1997

N-arylpiperazinyl-N'-propylamino derivatives of heteroaryl amides as functional uroselective alpha 1-adrenoceptor antagonists.

Novel arylpiperazines were identified as alpha 1-adrenoceptor (AR) subtype-selective antagonists by functional in vitro screening. 3-[4-(ortho-Substituted phenyl)piperazin-1-yl]propylamines were derivatized with N,N-dimethyl anthranilamides, nicotinamides, as well as carboxamides of quinoline, 1,8-naphthyridine, pyrazolo[3,4-b]pyridine, isoxazolo[3,4-b]pyridine, imidazo[4,5-b]pyridine, and pyrazolo[1,5-a]pyrimidines. Strips of rabbit bladder neck were employed as a predictive assay for antagonism in the human lower tract. Rings of rat aorta were used as a "negative screen" for the test antagonists. Binding to alpha 1-ARs was relatively sensitive to size and electronic features of the arylpiperazine portion of the antagonists and permissive to these features on the heteroaryl carboxamide side. These structure-affinity findings were exploited to produce nicotinamides (e.g. 13ii and 25x) and pyrazolo[3,4-b]pyridines (e.g. 37f and 37y) ligands with nanomolar affinity at the alpha 1-AR subtype prevalent in the human lower urinary tract(pA2 values: 8.8, 10.7, 9.3, and 9.9, respectively) and displaying 2-3 orders of magnitude selectivity over the alpha 1D-AR.

Adolescent↗
PubMed1991

Edge extraction by active defocusing.

A novel edge extraction method that employs an active defocusing technique is presented. The method is based on the principle that a Laplacian-of-Gaussian (LOG) operation can be approximated by a Difference-of-Gaussian (DOG) operation. While such an operation is usually done in digital image processing, it can also be very effective conducted in a combination of optical techniques and digital processing. In this edge extraction method, a focused image of an object in a scene is first acquired. The image of the scene is then slightly defocused by changing the focal length of the camera. A real time subtraction operation is applied to subtract the defocused image from the previously acquired image. It produces a residual image that emphasizes abrupt intensity variations. An objective evaluation, called an edge index, is performed on the resulting image. The amount of defocusing is carefully adjusted according to this measurement so that a desired edge image is generated. Boundaries of objects can then be obtained by further enhancement of the edge image. Since this edge detection method is an optical-based process aided by digital processing, it is fast and relatively inexpensive.

Artificial Intelligence↗
PubMed1989

Tissue selectivity of propranolol derivatives in vivo. A confirmation of in vitro findings.

The beta-adrenergic antagonist activities of a p-toluidide and a p-trifluoromethylanilide derivative of propranolol were tested in intact rats to determine whether the unusual in vitro profiles on myocardium and adipose tissue were found in vivo. The relative potencies of p-toluidide derivatives studied in pithed rats were 1.3 for the rate of change in left ventricular pressure with respect to time (dP/dt) and 4.6 for heart rate (HR) compared to propranolol. The values for p-trifluoromethylanilide were 2.5 (dP/dt) and 4.6 (HR). The SR-isomer of the p-toluidide derivative was 81 times more potent than propranolol in inhibiting effects on dP/dt and 27 times more effective than propranolol on HR, whereas the SS-isomer was 0.17 times (dP/dt) and 0.16 times (HR) as potent as the parent compound. In fasted rats, infusion of isoproterenol resulted in an increase of 10.6 +/- 3.1 mg/dl in plasma non-esterified fatty acid (NEFA) and an increase of 46 +/- 9 mg/dl in glucose. Unlike propranolol, neither the p-toluidide nor the p-trifluoromethylanilide derivative blocked the increase in plasma NEFA, although they both blocked the increase in plasma glucose. It appeared that the p-toluidide and p-trifluoromethylanilide derivatives of propranolol were more selective for the beta 1-adrenergic receptors on the heart as opposed to the beta 1-like adrenoceptors on adipose tissue. These findings were qualitatively and generally quantitatively in agreement with our previous findings in vitro. Therefore, the in vitro data may be useful in predicting atypical and tissue selective in vivo effects of these types of compounds.

Adipose Tissue↗
PubMedDate not supplied

Fluconazole is a potent inhibitor of antipyrine metabolism in vivo in mice.

Fluconazole, a bis-triazole antifungal, is distinguished from imidazole antifungals (e.g. ketoconazole) by its potency and pharmacokinetic characteristics. Imidazole-containing compounds are well documented to inhibit the hepatic cytochrome P-450-dependent enzyme system; whether this effect occurs with a bis-triazole agent is unknown. The [14C]antipyrine breath test was employed to investigate the effects of fluconazole on this enzyme system in CD-1 male mice. Control, ketoconazole (100 mg/kg), and fluconazole (1 and 10 mg/kg) were studied in single- and multiple-dose experiments. Fluconazole had potent inhibitory effects on the total (mean = -73% +/- 2%), demethylase (mean = -90% +/- 2%), and nondemethylase (mean = -60% +/- 4%) elimination rate constants (all p less than 0.001). The fraction of the administered radioactivity excreted as 14CO2 was decreased by 50-80% in the fluconazole groups (p less than 0.001). These effects were seen after single- and multiple-dose studies; however, return to baseline occurred more quickly in the multiple-dose group. These effects were significantly more pronounced than those observed with equipotent doses of ketoconazole. These results provide evidence that fluconazole is a potent, partially selective, and reversible inhibitor of the cytochrome P-450-dependent enzyme system in mice. Future studies will be required to assess this property and possible interactions with drugs metabolized by this enzyme system in humans.

Animals↗