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PubMed2005

Update on the role of anticholinergic drug therapy in the management of overactive bladder.

OBJECTIVE: To review the published literature and describe the pathophysiology and management of overactive bladder (OAB), with emphasis on the comparative efficacy and adverse event profiles of anticholinergic agents approved for the management of OAB symptoms and evaluation of their place in therapy. DATA SOURCES: A MEDLINE search of English language literature that addresses the pathophysiology and management of OAB symptoms. The references in identified articles were evaluated for additional relevant articles. Drug Topics' Red Book was referenced for cost comparisons, and package inserts were used for specific drug and dosing information. STUDY SELECTION: Human studies that presented efficacy and safety data with respect to anticholinergic medications in the treatment of OAB were selected. DATA EXTRACTION: Studies were abstracted to identify key characteristics with respect to efficacy and safety in OAB, in particular anticholinergic side effects, with the greatest weight given to studies that compared two or more anticholinergic medications. DATA SYNTHESIS: Epidemiologic studies have shown that the unpredictable and bothersome symptoms associated with OAB occur in approximately 16% of the worldwide adult population. Conservative management of OAB should include a combination of pharmacologic and nonpharmacologic interventions that have been found to improve outcomes when used in appropriately selected patients. Although long recognized as the most effective pharmacotherapy for OAB, anticholinergic agents have been associated with poor tolerability attributable to anticholinergic adverse events. New medications, formulations, and drug delivery systems have been developed with the goal of achieving effective treatment with improved tolerability. CONCLUSIONS: Among these agents, extended-release and transdermal formulations have improved tolerability while retaining at least comparable efficacy. More research is needed regarding other routes of administration and new drug entities that specifically target the pathologic mechanisms involved in OAB.

Journal Article↗
PubMed1992

Carbohydrate-binding specificities of anti-erythrocyte lectins (haemagglutinins) in Anopheles gambiae gut extracts and haemolymph.

Lectins that agglutinate red blood cells (RBC) were demonstrated in Anopheles gambiae mosquito haemolymph and gut extracts. No apparent differences in haemagglutinin titres were detected between male and female mosquitoes and overall agglutinin levels were not increased following a bloodmeal. Titres were highest in the haemolymph and midgut extracts versus human AB, horse, chicken and goat RBCs and in hindgut against human AB, chicken and sheep; foregut extract gave relatively low titres. Adsorption of haemolymph and gut extracts with selected RBCs coupled with carbohydrate inhibition and the use of enzyme-treated RBCs revealed the presence of multiple (hetero-) agglutinins. An.gambiae lectins were specific for (1-1)-, (1-4)- or (1-6)-linked glucose based disaccharides, glucose and its (1-2) or (1-3) linkages with fructose and, to a lesser extent, aminated or N-acetylated glucose, or galactose and its deoxy derivatives. This study presents the first report of the occurrence of heterogenous anti-RBC agglutinins in haemolymph and gut extracts of the mosquito An.gambiae, together with the sugar-binding specificities of these lectins.

Adsorption↗
PubMed1990

Evaluation of Basidiomycete and Deuteromycete (Fungi Imperfecti) extracts for shared allergenic determinants.

Aqueous extracts of select members of the Basidiomycetes and Deuteromycetes (Fungi Imperfecti) were evaluated for the presence of shared allergenic determinants using skin prick and radio-allergosorbent test (RAST) inhibition. Twenty adults with perennial symptoms of rhinitis, with or without asthma, were skin-prick tested with six species of Deuteromycetes and seven species of Basidomycetes. Positive weal-and-flare reactivity to Pleurotus ostreatus was associated with Alternaria alternata, Fusarium solani and Epicoccum purpurescens. Positive skin reactivity to Calvatia cyathiformis was also associated with A. alternata and F. solani. Coprinus quadrifidus was associated only with F. solani, and Psilocybe cubensis was only associated with Aspergillus fumigatus. No other skin test associations were demonstrated. For every allergen tested by RAST inhibition, significant dose-dependent homologous inhibition was demonstrated. Although the ability of an individual heterologous extract to inhibit the direct RAST varied, inhibition was generally minimal. In the most extreme example, no heterologous allergen inhibited the A. alternata RAST. However, the Armillaria tabescens RAST was inhibited 52.6%, 38.1% and 25.1% by A. fumigatus, E. purpurescens, and Penicillium notatum, respectively, suggesting significant cross-reactivity. These results suggest that, although shared allergenic determinants exist between select species of Basidiomycetes and Deuteromycetes, crossreactivity is minimal and its clinical significance is not clear. These data confirm that for reliable diagnosis of fungal allergy, representatives of both major groups must be used.

Adult↗
PubMed2006

Interaction of Vimang (Mangifera indica L. extract) with Fe(III) improves its antioxidant and cytoprotecting activity.

A standard aqueous stem bark extract from selected species of Mangifera indica L. (Anacardiaceae)--Vimang, whose major polyphenolic component is mangiferin, displays potent in vitro and in vivo antioxidant activity. The present study provides evidence that the Vimang-Fe(III) mixture is more effective at scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals, as well as in protecting against t-butyl hydroperoxide-induced mitochondrial lipid peroxidation and hypoxia/reoxygenation-induced hepatocytes injury, compared to Vimang alone. Voltammetric assays demonstrated that Vimang, in line with the high mangiferin content of the extract, behaves electrochemically like mangiferin, as well as interacts with Fe(III) in close similarity with mangiferin's interaction with the cation. These results justify the high efficiency of Vimang as an agent protecting from iron-induced oxidative damage. We propose Vimang as a potential therapy against the deleterious action of reactive oxygen species generated during iron-overload, such as that occurring in diseases like beta-thalassemia, Friedreich's ataxia and haemochromatosis.

Animals↗
PubMed2003

Method for multiresidue determination of halogenated aromatics and PAHs in combustion-related samples.

Flue gas and fly ash samples have a complex composition. Thus, thorough extraction and selective cleanup prior to analysis are essential. This paper presents an evaluated method for determining halogenated dibenzo-p-dioxins (PXDD), halogenated dibenzofurans (PXDF), chlorinated biphenyls (PCB), chlorobenzenes (CBz), -phenols (CPh), dibenzo-p-dioxins (DD), dibenzofurans (DF), and polycyclic aromatic hydrocarbons (PAH) in a single sample. Since these combustion byproducts are ubiquitous, harmful environmental contaminants it is very important to obtain reliable assessments of them: especially specific PCDD/F and PCB congeners with Ah-receptor mediated toxicity. The reported method for this purpose includes techniques such as solid-phase extraction, Soxhlet-Dean-Stark extraction, cleanup using open liquid chromatographic columns, and finally GC/MS analysis/determination with quantification by the isotope dilution technique. The validation results presented here show good reproducibility for PXDD/F and PCB and are satisfactory for CPh, CBz, and PAH. An extraction efficiency test revealed that a nonpolar solvent did not completely extract a few analytes, i.e., diCPh and fluorene, which appear to require a more polar extraction agent. To pinpoint and minimize the loss of analytes, specific studies on reductions of their amounts during sample concentration were performed, showing that traditional rotary evaporation and nitrogen blow-down produce equally good results as a novel technique.

Chromatography, Liquid↗
PubMed1997

Applications of multimedia computers and video mixing to neuroethology.

Inexpensive multimedia computers offer new possibilities for mixing video and computer images, videotaping these mixed images, and extracting quantitative data from videotape. In this paper we describe methods for mixing images from a video camera and a Macintosh computer display using chroma keying, and we describe a simple circuit for analog video mixing and frame-counting. We present three applications of these video mixing methods to our neurophysiological and behavioral research with awake, behaving animals. These technologies enhance accuracy, speed, and flexibility during experiments, by allowing us to record an information-rich videotape of the subject and state of the experimental apparatus. After the experiment, these technologies facilitate selecting and extracting quantitative data from the videotape for further analysis. The videotape is especially useful in resolving minor inconsistencies or incomplete information in the notes and data files that often arise during analysis of complex experiments.

Animals↗
PubMed1993

Biocompatibilities of organic solvents with Lactobacillus delbrueckii.

In the search for biocompatible extractants for extractive fermentation of lactic acid, the effect of twelve organic solvents on the activity of L. delbrueckii were studied at different concentration levels. On this basis, the compatibilities of twelve solvents with L. delbrueckii were summarized into four classes: completely compatible, compatible at molecular level, partially compatible and non-compatible. The characteristics were described qualitatively for each class in terms of relative values between the solubility of organic solvent in water (Cs) and the toxicity of organic solvent, which is indicated by a newly defined concentration parameter (Cm). The classification was helpful for the selection of extractant in extractive fermentation.

Fermentation↗
PubMed1975

Microsomal monooxygenation of the carcinostatic 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. Synthesis and identification of cis and trans monohydroxylated products.

Liver microsomal hydroxylation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was shown to occur on the cyclohexyl ring at positions 3 and 4. Four metabolites were isolated by selective solvent extraction and purifed by high-pressure liquid chromatography. cis-4-, trans-4-, cis-3-, and trans-3-OH derivatives of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea were synthesized and their chromatographic, mass spectral, and nuclear magnetic resonance characteristics matched those of the metabolites. The position of ring hydroxylation and the identity of each geometric isomer were established by nuclear magnetic resonance using a shift reagent in conjunction with spin decoupling techniques. Microsomes from rats pretreated with phenobarbital showed a sixfold increase in hydroxylation rate (19.5 vs. 3.3 nmol per mg per min). The induction was quite selective for cis-4 hydroxylation (19-fold); however, induction of trans-4 (threefold), cis-3 (threefold), and trans-3 (twofold) hydroxylation did occur. Quantitatively the cis-4-hydroxy metabolite was 67of the total product by phenobarbital-induced microsomes and 21% for normal microsomes. Microsomes from animals pretreated wit- 3-methyl-cholanthrene gave about the same rate and product distribution that normal microsomes gave. A mixture of 80% carbon monoxide-20% oxygen inhibited formation of all four hydroxy metabolites with the inhibition ranging from 55 to 78%.

Animals↗
PubMed2002

Changes in thiol reactivity and extractability of myofibril bound cardiac troponin C in porcine malignant hyperthermia.

We recently showed that a shift ( approximately 44%) in cardiac myosin isozyme from V3 to V1 occurs in the hearts of malignant hyperthermia (MH)-susceptible pigs and may be important in the disease. To follow up this finding, we investigated whether this myosin isozyme shift results in conformational changes in cardiac troponin C (cTnC). The two cysteine residues (Cys-35 and Cys-84) in the regulatory domain of cTnC make it possible to attach conformational probes to this region. Incorporation of a fluorescent probe, 7-diethylamino-3-(4'maleimidylphenyl)-4-methylcoumarin (CPM), into myofibril-bound cTnC was measured by alkaline urea gel electrophoresis, followed by quantification of the protein and the fluorescent label on the gels. The structural stability of cTnC incorporated into cardiac myofibrils was compared between normal and MH-susceptible pigs by selective cTnC extraction and re-incorporation. Changes were detected in both the reactivity of cTnC with CPM in rigor myofibrils and cTnC incorporation into myofibrils from the hearts of MH-susceptible pigs. These changes are very likely to be a consequence of the cardiac myosin isozyme shift in the hearts of MH-susceptible pigs, which may contribute to the changes in the myofilament response to Ca(2+) binding and to the modulation of cardiac contractility seen in this disease.

Actins↗
PubMed2002

Small-scale distribution of interstitial nitrite in freshwater sediment microcosms: the role of nitrate and oxygen availability, and sediment permeability.

The spatial distribution of interstitial NO2(-) concentrations was studied in NO3(-)-exposed freshwater sediment microcosms, using pore water extractions as well as ion-selective microsensors. Porewater extractions revealed ecotoxicologically critical NO2(-) concentrations in hypoxic and anoxic sediment layers in which significant NO3(-) consumption took place. In contrast, the use of ion-selective microsensors demonstrated the high capacity of the thin oxic surface layer of the sediments to consume NO2(-) and to produce NO3(-). Two modes of NO3(-) supply to the sediments were compared: In treatments with NO3(-) supply to the overlying water, a subsurface maximum of NO2(-) concentration was observed, coinciding with the site of maximum NO3(-) consumption. When NO3(-) was perfused up through the sediment cores, however, NO2(-) accumulated throughout the entire sediment column. Such spatially extensive NO2(-) accumulations were only observed in sediments poor in organic matter with a relatively high permeability. By manipulating the O2 content of the overlying water, the release of NO2(-) from the sediments could be influenced: In treatments with air-saturated overlying water, the sediments did not release detectable amounts of NO2(-) into the water phase. When kept hypoxic (25% air saturation) instead, significant NO2(-) accumulations were recorded in the overlying water. These findings suggest that in treatments with air-saturated overlying water, NO2(-) that was produced in deeper sediment layers (denitrifying conditions) was completely consumed at the oxic sediment surface (nitrifying conditions) before it could reach the overlying water.

Biological Availability↗
PubMed1985

Isolation of an actin-binding protein from membranes of Dictyostelium discoideum.

We prepared a probe of radiolabeled, glutaraldehyde cross-linked filamentous actin (F-actin) to study binding of actin to membranes of Dictyostelium discoideum. The probe bound to membranes or detergent extracts of membranes with a high affinity and in a saturable manner. The binding could be reduced by boiling of either the actin probe or the membranes, or by addition of excess native F-actin, but not by addition of an equivalent amount of bovine serum albumin, to the assay. The probe labeled several proteins when used to overlay sodium dodecyl sulfate gels of Dictyostelium membranes. One of these labeled proteins was a 24,000-mol-wt protein (p24), which was soluble only in the presence of a high concentration of sodium deoxycholate (5%, wt/vol) at room temperature or above. The p24 was purified by selective detergent extraction and column chromatography. When tested in a novel two-phase binding assay, p24 bound both native monomeric actin (G-actin) and F-actin in a specific manner. In this assay, G-actin bound p24 with a submicromolar affinity.

Actins↗
PubMed2006

Fractionation and extractability of sulfur, iron and trace elements in sulfidic sediments.

This study describes iron and sulfur fractionation, and the related extractability of selected trace elements (As, Cd, Cr, Cu, Ni, Pb and Zn) in estuarine sediments. The sediments were sulfidic, with moderately high concentrations of pore-water sulfide (200-600 micromol l(-1)) and acid-volatile sulfide (AVS; 9.9-129 micromol g(-1)). Pyrite-S concentrations increased with depth, with 63-251 micromol g(-1) at site W1 and 312-669 micromol g(-1) at site W2. The degree of sulfidisation was generally high (>80%), indicating that Fe may be limiting pyrite accumulation. The ratios of AVS to pyrite-S increased with sediment depth, as expected for the pyritisation of solid-phase AVS. Cadmium, Pb and Zn extractability in 1M HCl indicated that these elements are not significantly sequestered during pyritisation, whereas sequestration may be important for As, Cu and possibly Ni. Extractability trends for Cr suggest that diagenesis in sulfidic sediments may enhance Cr reactivity. Overall, replacement of AVS by pyrite during diagenesis may enhance the reactivity of Cd, Cr, Pb and Zn, whereas As, Cu and possibly Ni may be rendered less reactive.

Australia↗
PubMed1975

Bronchoprovocation: effect on priming and desensitization phenomenon in the lung.

Priming, or increased sensitivity to antigen, has not been demonstrated in the lung and could play a role in asthmatic symptomatology during seasonal pollen exposure. It is also an important consideration in the design of any experimental protocol requiring serial bronchoprovocations with antigen. Thirteen patients with a history of asthma symptoms during the pollen season and a positive skin test to ragweed extract were selected. Patients were given bronchial challenge out of season on 4 successive days with stepwise inhalations of antigen, and airways conductance was monitored in the body plethysmograph. Antigen dose-response curves were drawn, and the cumulative dose required for a 35% reduction in specific airway conductance was calculated and designated Provocation Dose (PD35). No regular trend toward either priming or desensitization was noted. The daily changes in antigen sensitivity did not correlate with daily variation of baseline pulmonary function. To determine if there was any priming due to natural exposure to pollen, 9 patients were brought back and rechallenged during the pollen season with no significant increase in bronchial sensitivity to ragweed extract. The PD35 method provides figures useful for comparing dose-response curves and shows a one-log variation from day to day. Any evaluation by bronchial challenge of antigen sensitivity or drug efficacy must take into account such variation.

Aerosols↗
PubMed1991

Sensitivity to common allergens: relation to respiratory symptoms and bronchial hyper-responsiveness in children from three different climatic areas of Australia.

In order to examine further the relation between atopy, as defined by skin-prick tests, and respiratory illness, we studied three populations of schoolchildren aged 8-11 years and living in different climatic areas of New South Wales, Australia. Skin-prick tests were performed using 13 commercial allergen extracts. Respiratory and allergic symptoms were assessed using a self-administered questionnaire to parents and bronchial hyper-responsiveness (BHR) was measured by histamine inhalation test. We defined current asthma as BHR together with symptoms of wheeze in the 12 months prior to study. Children with one or more positive skin weals of greater than or equal to 3 mm had significantly more recent wheeze, hayfever, eczema and BHR than children with smaller weals (P less than 0.001). In each area, 95-97% of all atopic children were sensitized to one of the following seven allergens: house dust, Dermatophagoides farinae, D. pteronyssinus, cat dander, plantain, rye grass, and Alternaria tenuis. Thus, these seven selected allergen extracts and a skin weal of 3 mm could be used to detect clinically relevant atopy in these populations of children. Sensitivity to house dust mite had the strongest independent association with current asthma in all three areas. The associations of other allergen sensitivities with BHR or current asthma were area dependent, indicating the influence of local allergen levels on respiratory illness in children. The potency of house dust mite sensitivity in increasing the risk of children having BHR and current asthma is confirmed.

Allergens↗
PubMed1991

An in vivo study of dentin sensitivity: the relation of dentin sensitivity and the patency of dentin tubules.

Dentin hypersensitivity can be a major problem for periodontal patients. The relationship between dentin hypersensitivity and the patency of dentin tubules in vivo has been established. Thirteen adult patients with teeth scheduled for extraction were selected and a stent fabricated to confirm location of the root surface being examined. Response to a constant air blast was recorded on a numeric pain rating scale (from 0 to 4) during the course of treatment. The tooth surface was initially treated with 0.5 molar EDTA (pH = 7.4), to remove the smear layer and expose tubules. The region was then treated with either a 3% monopotassium-monohydrogen oxalate solution or a 3% sodium chloride solution, both at pH = 2.4. Solutions were prepared to be indistinguishable to the examiner. Response to air was evaluated before and after EDTA treatment and after treatment with a desensitizing agent. The patient was anesthetized and the treated tooth extracted. Specimens were sectioned, critical point dried, sputter coated with gold, and examined under the scanning electron microscope. Photomicrographs were analyzed by computer assisted digital analysis to evaluate the degree of tubule occlusion. Statistical analysis by repeated measures ANOVA for univariate tests of hypothesis for within subject effects showed the sodium chloride solution was more effective in reducing dentin sensitivity than the potassium oxalate solution. Scanning electron micrographic analysis revealed a mean dentin tubule aperture size of 1.720 square microns following EDTA treatment alone, 0.564 square micron following potassium oxalate treatment, and 0.386 square micron following sodium chloride treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Second-order features extraction in the cat visual cortex: selective and invariant sensitivity of neurons to the shape and orientation of crosses and corners.

About 1/3 of neurons (52/174) studied in the cat striate cortex (area 17 or V1) gave a larger (by 3.2 times on average) response to a flashed cross or corner centered in the receptive field (RF) than to a single bar of optimal orientation. Most such neurons (71.4%) were found to be highly selective both to shape (angle between the lines) and to orientation of these figures. In the studied neuronal selection we also found all possible types of invariance of sensitivity to orientation and/or shape of these figures. We found neurons with selectivity to form of the figure and invariance to its orientation and vice versa. Some cells were found invariant both to form and orientation of the cross or corner but highly sensitive to flashing of any such figure in the RF. The role of RF center and surrounding area in sensitivity to cross figures was also studied in 44 additional units. Separated and combined stimulation of these zones revealed in different units summation, antagonism and absence of interaction of these zones by the selectivity index (figure/bar response ratio). Possible mechanisms of the described effects are discussed as well as their functional implication for second-order feature extraction in the visual cortex: selective or invariant sensitivity of neurons to the shape and orientation of the line-crossings.

Animals↗
PubMed1996

Hepatitis C.

OBJECTIVES: To review the virology, epidemiology, pathogenesis, natural history, clinical manifestations, and current treatment of hepatitis C virus (HCV) infection. DATA SOURCES: The MEDLINE database (1966 to 1996) was searched for English-language articles and abstracts on HCV and non-A, non-B hepatitis. Papers cited in relevant primary articles were also reviewed. STUDY SELECTION: More than 500 original and review articles were evaluated, and the most relevant were selected. DATA EXTRACTION: Data were extracted and reviewed by all authors. DATA SYNTHESIS: In most patients, HCV infection results in chronic hepatitis. The disease is insidious and subclinical but may progress over decades into end-stage liver disease and hepatocellular carcinoma, which makes HCV cirrhosis a leading indication for orthotopic liver transplantation. Current diagnostic methods are highly sensitive and specific, and quantitative assessment of viral load may help to predict and monitor response to treatment. The only available therapeutic option is interferon, and this agent is effective in only a small subset of patients. CONCLUSIONS: Infection with HCV is a significant public health problem that has important clinical and financial consequences. The tailoring of specific therapy according to viral load or genotype, better patient selection, and use of combination drug regimens may improve the chance of viral clearance and sustained biochemical and histologic response. Further understanding of the basic virology of HCV and the exact mechanisms of viral persistence and tissue injury is needed to help define future therapeutic and preventive strategies.

Carcinoma, Hepatocellular↗
PubMed2006

Selective Th1 up-regulating activity of Withania somnifera aqueous extract in an experimental system using flow cytometry.

Withania somnifera (Ashwagandha) is reported to be immunoprotective and immunoadjuvant. We studied its roots aqueous extract on T helper (Th) immunity using flow cytometry. This extract was standardized with six withanolides as marker compounds using HPLC. Once daily dose ranging from 25 to 400 mg/kg/p.o. was used to study effect on Th1: IFN-gamma, IL-2 and Th2: IL-4 cytokine modulation. We also studied effect on CD4 and CD8 in normal and immunesuppressed mice. The results indicate that extract at 100 mg/kg resulted significant selective up-regulation of Th1 response. Treatment with extract showed significant increase in CD4 and CD8 counts as compared to control and cyclopsorin A, with a faster recovery of CD4+ T cells in immunesuppressed animals. Under immunesuppressed conditions, potentiation of cellular and humoral immune responses of extract was comparable to levamisole. This study indicates the selective Th1 up-regulating effect of extract and suggests its use for selective Th1/Th2 modulation.

Animals↗