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Biomedical subjects

A Morales

Publications and source records attributed to A Morales.

At least 19 recordsLinked to original sources
PubMed1996

Surgical treatment of penile veno-occlusive dysfunction: is it justified?

OBJECTIVES: Veno-occlusive dysfunction is a commonly diagnosed cause of impotence. Surgical removal of the intermediate (deep dorsal vein and its tributaries) venous system of the penis has been advocated as an effective treatment but recurrence of the dysfunction is common after a few months. We studied prospectively the first 100 cases of veno-occlusive dysfunction undergoing surgical treatment at our institutions. METHODS: One hundred consecutive patients undergoing penile venous ligation surgery were evaluated. All patients had a comprehensive workup prior to therapy. Surgery involved excision of the intermediate venous drainage. Short-term results were investigated by personal interview, and long-term outcome was determined by separate telephone interview of patients and their partners when available. RESULTS: Short-term success (3 months) was 62%, and long-term success (45 months) was 31%. Historical factors, preoperative testing results, and histologic assessment of the surgical specimens were not found to be helpful in predicting outcome. CONCLUSIONS: Despite the mediocre long-term results of the surgical procedure and lack of preoperative predictive factors, we believe that venous leak surgery could be offered to well-selected patients in whom the only other available alternative would be a prosthetic device.

Adult↗
PubMed1995

Incorporation of reconstituted acetylcholine receptors from Torpedo into the Xenopus oocyte membrane.

Xenopus oocytes are a valuable aid for studying the molecular structure and function of ionic channels and neurotransmitter receptors. Their use has recently been extended by the demonstration that oocytes can incorporate foreign membranes carrying preassembled receptors and channels. Here we show that when reconstituted in an artificial lipid matrix and injected into Xenopus oocytes, purified nicotinic acetylcholine receptors are efficiently inserted into the plasma membrane, where they form "clusters" of receptors that retain their native properties. This constitutes an innovative approach that, besides allowing the analyses of membrane fusion processes, is also a powerful technique for studying the characteristics and regulation of many membrane proteins (with their native stoichiometry and configuration) upon reinsertion into the membrane of a very convenient host cell system.

Animals↗
PubMed1995

Differential effect of buspirone and diazepam on negative contrast in one-way avoidance learning.

The main aim of the present work was to investigate the effect of buspirone, a 5-HT1A receptor agonist, on successive negative contrast in one-way avoidance learning. Successive negative contrast was induced by shifting rats from a large reward (30 s spent in the safe compartment) to a small reward (1 s). Acute administration of buspirone (0.25, 0.5, 0.75 and 1.0 mg/kg i.p.) did not attenuate the contrast effect, as opposed to that observed for diazepam (1 mg/kg i.p.). The highest dose of buspirone used, however, did interfere with the learning of the avoidance response itself. Chronic buspirone (20 days, 0.5 and 0.75 mg/kg i.p.) did not have any effect on successive negative contrast either. Overall, these results could suggest that the 5-HT1A receptor is not involved in the negative contrast effect studied, quite different to that observed for the gamma-aminobutyric acid (GABA) system. The findings are compared to results obtained with animal models selectively sensitive to some anxiolytic drugs, as are the so-called 'conflict models'.

Animals↗
PubMed1995

Evidence that the rat hepatic mitochondrial carrier is distinct from the sinusoidal and canalicular transporters for reduced glutathione. Expression studies in Xenopus laevis oocytes.

Mitochondrial GSH derives from a mitochondrial transport system (RmGshT), which translocates cytosol GSH into the mitochondrial matrix. Mitochondria of oocytes, isolated 3-4 days after microinjection of total liver mRNA, expressed a RmGshT compared with water-injected oocytes. The expressed RmGshT exhibited similar functional features as reported in isolated mitochondria of rat liver such as ATP stimulation, inhibition by glutamate, and insensitivity to inhibition by sulfobromophthalein-glutathione (BSP-GSH) and S-(2,4-dinitrophenyl)glutathione (DNP-GSH). The expressed RmGshT is localized in the inner mitochondrial membrane since expression is still observed in mitoplasts prepared from total liver mRNA-injected oocytes. Fractionation of poly(A)+ RNA identified a single mRNA species of approximately 3-3.5 kilobases encoding for the RmGshT, which was stimulated by ATP and inhibited by glutamate but not by BSP-GSH or DNP-GSH. Microinjection of this fraction did not lead to expression of plasma membrane GSH transport in intact oocytes, and conversely, oocytes microinjected with cRNA for rat liver sinusoidal GSH transporter (RsGshT) or rat liver canalicular GSH transporter (RcGshT) did not express mitochondrial GSH transport activity. Thus, our results show the successful expression of the rat hepatic mitochondrial GSH carrier, which is different from RsGshT and RcGshT, and provide the strategic basis for the cloning of this important carrier.

Animals↗
PubMed1995

Feeding S-adenosyl-L-methionine attenuates both ethanol-induced depletion of mitochondrial glutathione and mitochondrial dysfunction in periportal and perivenous rat hepatocytes.

Mitochondrial glutathione plays an important role in maintaining a functionally competent organelle. Previous studies have shown that ethanol feeding selectively depletes the mitochondrial glutathione pool, more predominantly in mitochondria from perivenous hepatocytes. Because S-adenosyl-L-methionine (SAM) is a glutathione precursor and maintains the structure and function of biological membranes, the purpose of the present study was to determine the effects of SAM on glutathione and function of perivenous (PV) and periportal (PP) mitochondria from chronic ethanol-fed rats. SAM administration resulted in a significant increase in the basal cytosol and mitochondrial glutathione in both PP and PV cells from both pair-fed or ethanol-fed groups. When hepatocytes from ethanol-fed rats supplemented with SAM were incubated with methionine plus serine or N-acetylcysteine, mitochondrial glutathione increased in parallel with cytosol, an effect not observed in cells from ethanol-fed rats without SAM. Feeding equimolar N-acetylcysteine raised cytosol glutathione but did not prevent the mitochondrial glutathione defect. In addition, SAM feeding resulted in significant preservation of cellular adenosine triphosphate (ATP) levels (23% to 43%), mitochondrial membrane potential (17% to 25%), and the uncoupler control ratio (UCR) of respiration (from 5.1 +/- 0.7 to 7.3 +/- 0.6 and 2.1 +/- 0.3 to 6.1 +/- 0.7) for PP and PV mitochondria, respectively. Thus, these effects of SAM suggest that it may be a useful agent to preserve the disturbed mitochondrial integrity in liver disease caused by alcoholism through maintenance of mitochondrial glutathione transport.

Administration, Oral↗
PubMed1995

Recovery of erectile function by the oral administration of apomorphine.

OBJECTIVES: Apomorphine has been reported to be effective in causing erections in animals and man when administered parenterally. The side effects, notably nausea, have seriously limited its clinical usefulness. We formulated apomorphine for controlled sublingual absorption and herein report on four preliminary studies evaluating efficacy and side effects in men with no documentable organic cause of erectile dysfunction. METHODS: Patients complaining of erectile dysfunction underwent a careful evaluation. Those with measurable organic dysfunction or known organic factors were excluded. Men with primarily psychogenic impotence were tested with one of four protocols of an apomorphine preparation (preliminary sublingual liquid, preliminary 5 mg tablet, aqueous nasal spray, and new 3 and 4 mg controlled absorption tablets). The erectile response of these men to the drug with visual erotic or sexually neutral stimulation was studied with the Rigiscan. RESULTS: Seven of 10 evaluable patients responded to the sublingual liquid preparation but the majority experienced significant nausea. The preliminary 5 mg tablet and aqueous forms did not produce useful responses free of side effects. The newly formulated controlled absorption 3 and 4 mg tablets were tested in 12 men. Eight of 12 (67%) developed erections in response to apomorphine. Erectile activity was seen during sexually neutral visual stimulation to a significantly greater extent than with placebo. Home trial use was found to be successful and sustained by 7 of 11 (64%) patients. CONCLUSIONS: We have shown that apomorphine will act as an erectogenic agent when absorbed through the oral mucosa. In a carefully selected group of impotent patients with no documentable organic causes of erectile dysfunction, but with proven erectile potential, 67% will experience significantly durable erections with a dose of 3 or 4 mg of apomorphine when formulated for controlled absorption. The results in these small groups appear to justify larger clinical studies of this proprietary formulation.

Administration, Sublingual↗
PubMed1995

A personal computer-based system for parallel line analysis of bioassay data.

A program is described for symmetric parallel line analysis of bioassay data with a logistic dose-response relationship. Dose-response relationship is transformed to semilog or log-log. A regression line can be calculated for the dose-response curve for standard and test samples, and produces potency estimate of test sample preparation relative to the standard preparation based on parallel-line bioassay statistical methods [3,4], together with detailed analysis of variance, estimates of slope, intercept and chi 2 test which permits a very sensitive test for linearity and parallelism of standard and test sample and facilitates detection of 'outliers', i.e. samples exhibiting non-parallelism. The general comparison of dose-response relationships produced by the program are a feature of particular interest.

Analysis of Variance↗
PubMed1995

Impotence.

Explore the source record for details and available documents.

Erectile Dysfunction↗
PubMed1995

Heparin neutralization by recombinant platelet factor 4 and protamine.

Protamine is the only available drug to reverse heparin-induced anticoagulation. Platelet factor 4 (PF4) is a basic polypeptide stored in platelets that reverses heparin. To investigate its potential as a reversal drug, we studied recombinant PF4 on anticoagulated blood obtained during cardiac surgery. Blood was obtained from 33 different venous reservoirs, and activated clotting time (ACT), heparin concentrations, and heparinase-ACT were determined. Anticoagulation was reversed by adding incremental PF4:heparin and protamine:heparin ratios to the heparinized blood, and the ACTs were determined (n = 21). Viscoelastic analysis of anticoagulation reversal was performed by adding protamine or PF4 at reversal ratios of 1.3:1 protamine:heparin, and 3.2:1 PF4:heparin using thromboelastography (n = 12). PF4 reversal ratios of 3:1 and 3.5:1 and protamine reversal ratios of 1:1, 1.5:1, 2:1 were not statistically different from heparinase-ACT values. There were no significant differences in viscoelastic measurements of clot formation between protamine and PF4. Recombinant PF4 at a 3.0:1 ratio reverses heparin-induced anticoagulation after cardiopulmonary bypass, and represents a potential alternative, especially for the protamine allergic patient.

Blood Coagulation↗
PubMed1995

Isolation and perfusion of the pudendal vasculature in male rats.

PURPOSE: The present study outlines a novel in situ technique to assess the regulation of vascular resistance in the penile vascular bed of the Wistar rat. MATERIALS AND METHODS: The isolation and perfusion of the pudendal artery were achieved by ligating all branches of the external iliac artery not directly connected to the internal pudendal artery. RESULTS: A linear flow-perfusion pressure curve was generated to ensure a viable preparation. A cumulative concentration-vascular response curve to the alpha 1-adrenoceptor agonist methoxamine (0.5-64 micrograms./ml.) was obtained. CONCLUSIONS: This novel methodology will allow reproducible and consistent quantitative assessments of the numerous factors (both neural and hormonal) that are proposed to govern the flow of blood in the penile vascular bed.

Animals↗
PubMed1995

Androgen receptor in the rat pancreas: genetic expression and steroid regulation.

Androgens influence the incidence and prevalence of pancreatic cancer in humans and animal models. To our knowledge there has been molecular demonstration of the presence of neither the androgen receptor (AR) nor transcripts of the AR gene. Reverse-transcription polymerase chain reaction (RT-PCR)-Southern blotting was employed for molecular detection and measurement of the androgen receptor messenger ribonucleic acid (AR mRNA) in pancreas. Total RNA obtained from pancreas, prostate, seminal vesicles, and testes of neonatal and adult male and female rats, as well as castrated males substituted with testosterone cyclopentylate, was analyzed by Northern blot technique. Positive hybridization to AR cDNA was obtained in all tissues assayed but not in the pancreas. However, a clear AR 32P cDNA hybridization signal was obtained in pancreatic tissues after cDNA synthesis using RT-PCR-Southern blotting. The levels of the AR transcripts obtained by RT-PCR in the various pancreatic samples were as follows: adult females and neonatal animals > castrated adult males > adult males > castrated adult males substituted with testosterone. These results indicated that the pancreatic tissue possessed transcriptional activity of the AR gene, although to a lesser extent than the typical androgen responsive tissues (prostate and seminal vesicles). In conclusion, transcriptional activity of the AR gene in the pancreas seemed to be modulated by the androgenic milieu in the tissue similar to that reported for the classical androgen-responsive organs.

Androgens↗
PubMed1995

Serum prolactin levels and neonatal seizures.

To assess the effects of neonatal seizures on the hypothalamus and to test clinical use of prolactin as a neonatal seizure marker, we studied postictal and recovery baseline serum prolactin levels in 19 neonates whose seizures were classified according to their clinical and EEG features. Postictal prolactin levels were obtained 30 min after the seizure, and recovery levels were ascertained 2-4 days later. The ratio of postictal prolactin level to recovery baseline level (prolactin ratio) was used as an indicator of postictal prolactin increase. The specificity and sensitivity of a prolactin ratio of > 2 was compared with the current standard of diagnosis (seizure discharges recorded by ictal EEG). Infants with electroclinical seizures had significantly higher prolactin ratios than control infants or infants with seizures without EEG correlation. Marked prolactin increases were noted only in infants with focal tonic seizures and temporal electrode involvement. A prolactin ratio of > 2 had a specificity of 100% and a sensitivity of 40%. We conclude that neonatal seizures have variable effects on the hypothalamus and that the low sensitivity and the need to await recovery levels limit the clinical value of prolactin ratio as a neonatal seizure marker.

Biomarkers↗
PubMed1995

Role of oxidative stress generated from the mitochondrial electron transport chain and mitochondrial glutathione status in loss of mitochondrial function and activation of transcription factor nuclear factor-kappa B: studies with isolated mitochondria and rat hepatocytes.

Mitochondria are an important source of reactive oxygen intermediates because they are the major consumers of molecular oxygen in cells. Respiration is associated with toxicity, which is related to the activation of oxygen to reactive intermediates. The purpose of the present study was to examine the role of reduced glutathione (GSH) in the maintenance of mitochondrial functions during oxidative stress induced through selective inhibition of the complex III segment of the electron transport chain. Hydrogen peroxide monitored by the fluorescence of dichlorofluorescein increased in a time- and dose-dependent manner on incubation of mitochondria with antimycin A (AA), an inhibitor of complex III. However, blockade of complex I or II with rotenone or thenoyltrifluoroacetone, respectively, did not result in accumulation of hydrogen peroxide. Depletion of mitochondrial GSH to 10-20% of control by preincubation with diethylmaleate (0.8 mM) or ethacrynic acid (250 microM) also increased dichlorofluorescein and malondialdehyde levels and resulted in an additional (2-3-fold) increase after AA. Similar results were obtained when mitochondrial GSH depletion was produced by treatment with buthionine L-sulfoximine before mirochondria isolation. The endogenous oxidative stress induced by AA was accompanied by a moderate loss of activity of ATPase complex (77% of control) and complex IV of respiration (75% of control), which was accentuated after depletion of mitochondrial GSH (51% and 45% of control, respectively). Similar results were observed in isolated hepatocytes in which depletion of mitochondrial GSH and AA led to peroxidation and mitochondrial dysfunction. In addition, with electrophoretic mobility shift assay of the transcription factor nuclear factor-kappa B (NF-kappa B), we detected its activation in response to AA (2-3-fold). Depletion of mitochondrial GSH in hepatocytes (20% of control) led to further enhancement of NF-kappa B activation (2-4-fold), which correlated with generation of hydrogen peroxide. Thus, our results suggest that GSH protects mitochondria against the endogenous oxidative stress produced at the ubiquinone site of the electron transport chain. Mitochondrial GSH depletion potentiates oxidant-induced loss of mitochondrial functions. Oxidant stress in mitochondria can promote extramitochondrial activation of NF-kappa B and therefore may affect nuclear gene expression.

Animals↗
PubMed1995

Oral and topical treatment of erectile dysfunction. Present and future.

A great deal of progress has been made in the pharmacological treatment of erectile dysfunction. At present, however, the most effective therapies require intracavernosal injections with a number of associated drawbacks. An increasing number of oral and transdermal agents have been introduced clinically or are at various phases in their development. It is evident that severe end-organ disease probably will not result in successful systemic therapy. Nevertheless, in men with intact or mildly dysfunctional erectile mechanisms, noninvasive treatments can offer some measure of success. Further study of individual and synergistic activity of available compounds is underway.

Administration, Oral↗
PubMed1995

Immunotherapy of an experimental adenocarcinoma of the prostate.

We have developed and tested a fractionated, purified and deproteinized emulsion of a mycobacterial cell wall (MCW) and report on a controlled study of this compound in the treatment of the experimental R3327-H adenocarcinoma of the prostate. The intraperitoneal route of administration was found ineffective at the weekly dose of 500 micrograms. The intratumoral administration of 1000 micrograms of MCW exhibited significant antitumor activity. Tumors larger than 2.2 cm.3 in volume showed evidence of temporary regression, but no cures were recorded in these animals. Complete tumor regression was found in 50% of the rats with tumor volumes less than 2.2 cm.3 at the onset of treatment. The animals in this group not responding initially were treated with a second 3-week course of MCW which resulted in complete tumor regression in one-half of the animals, for a total cure rate, in the smaller tumor cohort, of 75%. Mycobacterial cell wall is an effective biological response modifier in the Dunning R3327-H adenocarcinoma of the prostate in Copenhagen rats. Additional studies to elucidate the effect of the compound in relation to dose and tumor volume are underway.

Adenocarcinoma↗
PubMed1994

Electrophysiological properties of newborn and adult rat spinal cord glycine receptors expressed in Xenopus oocytes.

The properties of glycine receptors (GlyRs) from newborn and adult rat spinal cord were studied in Xenopus oocytes injected with whole mRNA or the heavy (H) or light (L) mRNA fractions encoding their respective GlyRs. Mean open times and conductances of channels gated by H- or L-GlyRs were determined by noise analysis or voltage jumps. We found that adult H- and L-GlyRs opened channels that differed in their mean open time but had the same channel conductance. Both H- and L-GlyRs gated Cl- currents that displayed a similarly strong outward rectification. Nevertheless, single channels of adult H- and L-GlyRs did not rectify and their mean open times were only slightly altered by voltage. It follows that the outward rectification of adult GlyRs is due mainly to a reduction in the number of open channels. In contrast to H-GlyRs, whose characteristics seem to remain essentially unchanged with age, L-GlyRs from newborn and adult rats have different properties. Channels of newborn L-GlyRs have a higher conductance, longer open time, and greater voltage dependency than those from the adult. Interestingly, properties of newborn GlyRs expressed by whole mRNA were markedly different from those encoded by newborn or adult L or H mRNA. These results demonstrate that the functional heterogeneity of GlyRs is developmentally regulated.

Age Factors↗