Thomas R. Downs

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AIMS To investigate the distribution of beta-3 adrenergic receptors (β(3)ARs) in the rat bladder and to examine the contribution of urothelial β(3)ARs to agonist-induced suppression of bladder reflexes and relaxation of smooth muscle. METHODS Bladder tissue was collected from 8- to 10-month old female SD rats. In some samples, the urothelium was(More)
While the collection of genotoxicity data and insights into potential mechanisms of action for nano-sized particulate materials (NPs) are steadily increasing, there is great uncertainty whether current standard assays are suitable to appropriately characterize potential risks. We investigated the effects of NPs in an in vivo Comet/micronucleus (MN)(More)
BACKGROUND Cannabinoid (CB) receptors may be involved in the control of bladder function; the role of CB receptor subtypes in micturition has not been established. OBJECTIVES Our aim was to evaluate the effects of cannabinor, a novel CB2 receptor agonist, on rat bladder function. DESIGN, SETTING, AND PARTICIPANTS Sprague Dawley rats were used.(More)
OBJECTIVE To determine if a decrease in oestrogen (E) levels increases activity in bladder afferent nerves, by investigating the effects of E loss on afferent nerve activity in ovariectomized (OVX) rats, and making comparisons with findings in ageing female rats. MATERIALS AND METHODS Female Sprague-Dawley rats were divided into four groups: ageing; OVX+(More)
Reconstructed 3D human epidermal skin models are being used increasingly for safety testing of chemicals. Based on EpiDerm™ tissues, an assay was developed in which the tissues were topically exposed to test chemicals for 3h followed by cell isolation and assessment of DNA damage using the comet assay. Inter-laboratory reproducibility of the 3D skin comet(More)
Multiple organ dysfunction (MOD) is the leading cause of mortality in septic patients with circulatory shock. Recent evidence suggests that the overproduction of the cytokine, tumor necrosis factor-alpha(TNF), and oxygen free radical molecules may mediate the progression of sepsis to MOD and death. In this study, we have examined the ability of MDL 101,002,(More)
Angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), are two mechanistically similar enzymes involved in the metabolism of several vasoactive peptides. Selective inhibitors of ACE are effective antihypertensive agents in high-renin, renovascular rats and normal-renin, spontaneously hypertensive rats (SHR), but are not effective in the(More)
The molecular basis of insulin resistance, a major risk factor for development of Type II diabetes, involves defective insulin signaling. Insulin-mediated signal transduction is negatively regulated by the phosphotyrosine phosphatase, PTP1B, and numerous studies have demonstrated that organo-vanadium compounds, which are nonselective phosphotyrosine(More)
Evidence of a role for oxygen-derived free radicals in the pathophysiology of endotoxic shock has been found in animal models. However, the importance of free radicals in chronic models of bacterial infection has not been examined. In this study a novel nitrone radical spin trap is described and its activity in animal models of endotoxic shock and chronic(More)
PURPOSE We 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 METHODS A total of 24 female(More)