Smooth muscle of the bladder in the normal and the diseased state: pathophysiology, diagnosis and treatment

The smooth muscle of the normal bladder wall must have some specific properties. It must be very compliant and able to reorganise itself during filling and emptying to accommodate the change in volume without generating any intravesical pressure, but whilst maintaining the normal shape of the bladder. It must be capable of synchronous activation to generate intravesical pressure at any length to allow voiding. The cells achieve this through spontaneous electrical activity combined with poor electrical coupling between cells, and a dense excitatory innervation. In the diseased state, alterations of the smooth muscle may lead to failure to store or failure to empty properly. The diseased states discussed are bladder instability and diabetic neuropathy. Bladder instability is characterised urodynamically by uninhibitable rises in pressure during filling, and is seen idiopathically and in association with bladder outflow obstruction and neuropathy. In diabetic neuropathy, many of the smooth muscle changes are a consequence of diuresis, but there is evidence for alterations in the sensory arm of the micturition reflex. In the unstable bladder, additional alterations of the smooth muscle are seen, which are probably caused by the patchy denervation that occurs. The causes of this denervation are not fully established. Nonsurgical treatment of instability is not yet satisfactory; neuromodulation has some promise, but is expensive, and the mechanisms poorly understood. Pharmacological treatment is largely through muscarinic receptor blockade. Drugs to reduce the excitability of the smooth muscle are being sought, since they may represent a better pharmacological option.     

Two‐phase production of cyclohexene and cyclooctene oxides in water as an approach to pollution prevention

Liquid–liquid two‐phase epoxidation from cyclohexene and cyclooctene in aqueous potassium peroxymonosulfate (commercially available as Oxone^®) solution was studied as an application in pollution prevention. To avoid potential emissions of volatile organic compounds an aqueous solution was employed to replace the usual chlorinated solvents used in epoxide production. A droplet column reactor and stirred tank reactor were used to investigate two‐phase synthesis of epoxide. An aqueous Oxone^® solution was used to oxidize a dispersion of alkene droplets and form epoxide. The study of aqueous epoxidation in both reactors showed that the epoxidation of alkenes can be represented as a first order reaction with respect to alkene. The salting out effect of Oxone^® concentration was studied in both reactors and found to be very similar at optimal conditions. In comparing the two reactors, it was found that the droplet column reactor produces larger quantities of product per unit reactor volume for the same reaction time. The objective of this study is to provide an alternative reactor design and synthesis route that can meet pollution prevention goals. Copyright © 2004 Society of Chemical Industry     

Adaptive weighted outer-product learning associative memory

Associative-memory neural networks with adaptive weighted outer-product learning are proposed in this paper. For the correct recall of a fundamental memory (FM), a corresponding learning weight is attached and a parameter called signal-to-noise-ratio-gain (SNRG) is devised. The sufficient conditions for the learning weights and the SNRG's are derived. It is found both empirically and theoretically that the SNRG's have their own threshold values for correct recalls of the corresponding FM's. Based on the gradient-descent approach, several algorithms are constructed to adaptively find the optimal learning weights with reference to global- or local-error measure.     

Evidence for production and functional activity of nitric oxide in seminiferous tubules and blood vessels of the human testis

Previous studies have demonstrated that nitric oxide (NO) influences Leydig cell function. Here we provide evidence for NO production and activity in seminiferous tubules and blood vessels of the human testis. By immunohistochemistry, the soluble guanylyl cyclase (sGC), the intracellular NO receptor, and the second messenger, cyclic guanosine monophosphate (cGMP), were detected in myofibroblasts of the peritubular lamina propria in Sertoli cells, as well as in endothelial and smooth muscle cells of testicular blood vessels. Performed with isolated tubules and blood vessels, the biological activity of sGC could be proved by cGMP generation in response to treatments with the NO donor, sodium nitroprusside. The endothelial and neuronal subtypes of NO synthase (NOS) were localized immunohistochemically to the same cell types that express sGC and cGMP. In isolated tubules and vessels, the presence of endothelial NOS and neuronal NOS was confirmed by immunoblotting, and NOS activity was demonstrated by decreased cGMP production upon incubation with the NOS inhibitor L-nitro arginine methylester. These findings show that peritubular cells, Sertoli cells, and testicular blood vessels may be sites of NO production and activity, possibly involved in relaxation of seminiferous tubules and blood vessels to modulate sperm transport and testicular blood flow, respectively.     

Transformations for nonideal uniform circular arrays operating in correlated signal environments

The Davies transformation is a method to transform the steering vector of a uniform circular array (UCA) to one with Vandermonde form. As such, it allows techniques such as spatial smoothing for direction-of-arrival (DOA) estimation in a correlated signal environment, developed originally for uniform linear arrays, to be applied to UCAs. However, the Davies transformation can be highly sensitive to perturbations of the underlying array model. This paper presents a method for deriving a more robust transformation using optimization techniques. The effectiveness of the method is illustrated through a number of DOA estimation examples.     

Change of foot size with weightbearing. A study of 2829 children 3 to 18 years of age

The change of foot length and width with age has been reported in a few anthropometric studies in the literature. However, the relationship with body height rarely is reported, and the dynamic effect of weightbearing on foot size has not been documented. In this series, 2829 children 3 to 18 years of age of equal gender distribution were included in the study. The foot length and width on weightbearing and nonweightbearing were measured with a special precision electronic caliper. The foot length and width were found to increase linearly from the age of 3 years until 12 years in girls and 15 years in boys. This was followed by a phase during which the increase plateaued. The foot length and width increased significantly on weightbearing at all ages in both genders with a mean of 2.1 to 4.4 mm or 3.1% to 4.8%, respectively. The foot length and width also were found to correlate significantly with the body height in both genders, with a correlation coefficient of 0.96 to 0.98. No significant differences were found between the sizes of the dominant and nondominant foot in either gender.     

Chicken oviductal ecto-ATP-diphosphohydrolase. Purification and characterization

An ecto-ATP diphosphohydrolase (ATPDase) was purified to homogeneity from vesiculosomes shed from chicken oviduct. First, the ecto-ATPDase-enriched vesiculosomes were concentrated by filtration, differential centrifugation, and exclusion chromatography. Next, the nonionic detergent, Nonidet P-40, was used to extract the ecto-ATPDase from vesiculosomal membranes, and the solubilized enzyme was further purified by ion exchange (DEAE-Bio-Gel) and lentil-lectin-Sepharose 4B chromatography. In the final stage, immunoaffinity chromatography was utilized to obtain purified ecto-ATPDase. More than 25,000-fold purification was achieved. Specific activity of the purified enzyme was greater than 800 micronol/min/mg of protein with MgATP as the substrate, the highest ever reported for an ATPDase. The enzyme also hydrolyzed other nucleoside triphosphates in the presence of magnesium at similar rates and CaATP and MgADP at lower rates. The molecular mass of the purified glycoprotein was 80 kDa as determined by SDS-polyacrylamide gel electrophoresis and Western blot analysis. Based on its enzymatic properties, the relationship of the chicken oviduct ecto-ATPDase with other reported ATPDases and ecto-ATPases is discussed.     

Combination cytotoxic effects of cis-diamminedichloroplatinum(II) and 5-fluorouracil with and without leucovorin against human non-small cell lung cancer cell lines

Both cisplatin (CDDP) and leucovorin (LV) have been shown to enhance cytotoxicity of 5-fluorouracil (FUra) against murine and human neoplasms by increasing intracellular reduced folate concentrations. We were interested in their use in a combination to inhibit non-small cell lung cancer (NSCLC) cell growth and therefore conducted an in vitro study to investigate the cytotoxic activities of combinations of CDDP plus FUra, with and without LV (20 microM), against seven NSCLC cell lines. A tetrazolium assay with application of the classical isobole method was used to test drug combinations. We found that LV enhanced FUra but not CDDP cytotoxicity and that the degree of enhancement was negatively correlated with the effect of FUra. There was an overall additive combination effect of CDDP plus FUra, although there may be synergy at higher effect levels. There was synergy to a combination of CDDP, FUra, and LV, presumably primarily related to the synergistic effects of adding LV to FUra. In summary, LV and CDDP enhanced FUra cytotoxicity in a complementary fashion and there was clear synergy of a combination of CDDP, FUra, and LV against a panel of NSCLC cell lines. Our in vitro results provide a rationale for controlled clinical studies of this three-drug regimen in patients with NSCLC.     

Prospective study of carotid endarterectomy and contralateral carotid occlusion

A total of 700 patients who had carotid endarterectomy (CEA) in the UK and Ireland during a 6-month interval between March and August 1994 were studied prospectively. Some 108 patients (15.4 per cent) had a contralateral internal carotid artery occlusion. Previous reports have shown an associated stroke rate of about 10 per cent in these patients. This study assessed complications and outcome for patients undergoing CEA with contralateral internal carotid artery occlusion compared with those without. The indications for surgery were comparable between the two groups although the patients with occlusion had a slightly higher incidence of arrhythmia and stroke. Intraoperative shunts were used in a significantly higher proportion of those with occlusion (83.3 versus 64.7 per cent, P = 0.0001). The combined death and stroke rate for patients with occlusion was 5.6 per cent compared with 2.4 per cent for the remainder (P not significant). On the basis of the present data, CEA with a contralateral carotid artery occlusion carries only a slight increase in the rate of postoperative stroke and death. This increase was not statistically significant and is lower than that reported previously.