Efficacy of a 1-week, once-daily regimen of terbinafine 1% cream in the treatment of tinea cruris and tinea corporis.
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Administration, Cutaneous↗
Biomedical subjects
A Hernandez
Publications and source records attributed to A Hernandez.
Urinary porphyrinogens in normal subjects and in patients with porphyria cutanea tarda and acute intermittent porphyria.
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Humans↗
Cardiac desensitization to adenosine analogues after prolonged R-PIA infusion in vivo.
To determine the effects of chronic in vivo stimulation of adenosine receptors, R-(-)-N6-(2-phenylisopropyl)adenosine (R-PIA), a selective A1 receptor agonist, was administered to rats as a continuous 7-day infusion (200 nmol/h). Inotropic and chronotropic responses of isolated atria to adenosine receptor agonists were markedly desensitized compared with the responses of atria from age-matched control animals. Carbachol's negative chronotropic effect was also attenuated, indicating a heterologous mode of desensitization. Antagonist radioligand binding assays indicated a 52% reduction in A1 adenosine receptor maximum binding, and competition binding assays revealed a significant loss of G protein-coupled high-affinity A1 receptors in atria from R-PIA-treated rats. Inhibitory G proteins (Gi) were significantly reduced, as quantified by immunoblot analysis, with no change in the amount of stimulatory G proteins. Ventricular membranes from R-PIA rats showed loss of Gi and uncoupling of A1 receptors, without a significant change in A1 receptor density. Thus chronic R-PIA infusion desensitized rat atrial muscle to the effects of adenosine receptor agonists via several regulatory adaptations, including downregulation of A1 adenosine receptors, uncoupling of A1 receptors from their associated G proteins, and loss of Gi proteins.
2-Chloroadenosine↗
Multiple regulation of S14 gene expression during brown fat differentiation.
S14 is a gene known to be under thyroid hormone control. Its mRNA concentration is very high in lipogenic tissues, and although the precise function of the protein is still unknown, indirect data suggest its implication in triglyceride synthesis. S14 gene expression is up-regulated by thyroid hormone in liver, white adipose tissue, and lactating mammary gland. However, in brown fat, the level of this sequence is increased 3-fold in the hypothyroid animal. We have used primary cultures of brown preadipocytes differentiated to fully mature brown adipocytes to investigate the influence of cellular differentiation and hormonal stimulation on S14 gene expression. Steady state levels of S14 mRNA rose from nondetectable levels in preadipocytes to reach a maximum in fully mature adipocytes. Treatment of brown adipocytes cultures with T3 did induce S14 gene expression. This induction reflects in part a posttranscriptional stabilization of the messenger by T3. Insulin, insulin-like growth factor-I, and inositol phosphate-glycan also increase the level of S14 mRNA. Norepinephrine (NE) plays a major role in the regulation of S14 gene, and 24 h after its addition, NE elicited a 20-fold decrease in mRNA S14 concentrations. An elevated intracellular concentration of cAMP is a strong negative effector of S14 gene expression, and neither NE nor cAMP action is totally overcome by T3. As happens in vivo, glucose is a potent stimulator of S14 mRNA; however, there is a lag time of several hours before its effects can be detected. The increase in S14 gene expression with the maturation stage of the cell suggests an important role for S14 in adipocyte differentiation.
Adipose Tissue, Brown↗
High-performance liquid chromatographic determination of N-[2(S)-(mercaptomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-methionine, the active plasma metabolite of a prodrug atriopeptidase inhibitor (SCH 42495), using a thiol selective (Au/Hg) amperometric detector.
A high-performance liquid chromatographic assay for the determination of N-[2(S)-(mercaptomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-methionine (SCH 42354; II), the active metabolite of the atriopeptidase inhibitor prodrug, N-[2(S)-(acetylthiomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-methi onine ethyl ester (SCH 42495; I), in human plasma was validated for use in clinical pharmacokinetic studies. Plasma (200 microliters) was processed by protein precipitation with acetone containing the internal standard, N-[2(S)-(mercaptomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L- ethionine (III). Compound II was recovered (ca. 90%) in the supernatant after centrifugation and prepared for injection by the addition of 0.15 M monochloroacetic acid containing 0.2 mM EDTA. Separation of II and III was accomplished on commercially available reversed-phase C8 columns designed for the separation of basic compounds. Both compounds were detected using amperometric detection (+0.125 V versus Ag/AgCl) on a thin-layer Au/Hg amalgam electrode. The lower limit of quantitation was 10 ng/ml, where the inter-assay precision (coefficient of variation) was +/- 11.4% and the inter-assay accuracy (bias) was +1.0%. No endogenous interferences were observed in the extracts obtained from drug-free plasma. The detector response (using either peak area or height ratios of II to III) was linear from 0.01 to 1.0 micrograms/ml. Compound II was stable in plasma supplemented with EDTA and sodium hydrogensulfite for at least 3 months when stored frozen at -78 degrees C; no significant decomposition of II was observed following three freeze-thaw cycles. The feasibility of this liquid chromatographic assay with electrochemical detection was demonstrated with plasma samples from hypertensive subjects administered 100 mg of compound I.
Chromatography, High Pressure Liquid↗
Isolated continuous rhythmic lingual myoclonus.
Isolated continuous lingual myoclonus is an exceptional entity, poorly documented and understood. A patient with a nonepileptic continuous rhythmical myoclonus, affecting the anterior portion of the tongue, as an independent involuntary disorder, is reported. Electromyography showed low frequency (2-4 Hz) bursts of genioglossus muscles activity. The EEG, visual, auditory and somatosensory evoked responses were normal. Imaging techniques like CT and MRI failed to reveal any brainstem or cerebellar lesion. Lingual myoclonus showed a very good response to sodium valproate.
Electroencephalography↗
Intestinal disaccharidases in five species of phyllostomoid bats.
1. Intestinal disaccharidases were studied in nectarivorous (Leptonycteris curasoae and Glossophaga soricina), frugivorous (Artibeus jamaicensis and Sturnira lilium), and insectivorous (Pteronotus personatus) adult bats. 2. Adult bats lacked measurable lactase activity. With the exception of trehalase activity, which was present only in P. personatus, nectar- and fruit-eating bats exhibited higher disaccharidase activities standardized by intestinal nominal area than insect-eating P. personatus. 3. Maltase and sucrase activities were significantly linearly correlated. 4. Apparent affinity of sucrase varied almost 5-fold among species. This variation may reflect unstirred layer effects resulting from sucrase being a membrane bound enzyme rather than differences in the "true" affinity of sucrase in solution. 5. Passerine birds showed higher maltase activity per unit of sucrase activity than bats and hummingbirds. Maximal sucrase and maltase activities standardized per intestinal nominal area are 1.5-2 times higher in hummingbirds than in nectar-feeding bats.
Animals↗
Nedocromil sodium prevents airway hyperreactivity induced by cigarette smoke in anaesthetized guinea-pigs.
Increased airway reactivity and influx of inflammatory cells into the airways have been demonstrated both in smokers and after smoke exposure in animal studies. We investigated the ability of nedocromil sodium and hydrocortisone to protect from the pathological alterations induced by direct cigarette smoke exposure in anaesthetized guinea-pigs. Active inhalation of cigarette smoke (15 s/min for 10 min) induced airway hyperreactivity, as shown by the enhanced bronchoconstrictor effect of histamine and was associated with an increase in total cells, macrophages and eosinophils in the BAL fluid. Nedocromil sodium given by aerosol (3 and 10 mg/ml for 30 s) completely prevented the ability of cigarette smoke to potentiate histamine induced bronchoconstriction. In parallel, nedocromil sodium inhibited the development of the inflammatory reaction triggered by smoke exposure. Hydrocortisone pretreatment (50 mg/kg s.c. twice) did not abolish the smoke induced airway hyperreactivity, nor did it inhibit the recruitment of proinflammatory cells within the airway lumen. Sensory neuropeptides have been demonstrated to be involved in the development of smoke induced airway hyperreactivity. The efficacy of nedocromil sodium in this model might depend on its ability to modulate the activation of the peptidergic system.
Animals↗
Grayanotoxin-I-modified eel electroplax sodium channels. Correlation with batrachotoxin and veratridine modifications.
To probe the structure-function relationships of voltage-dependent sodium channels, we have been examining the mechanisms of channel modification by batrachotoxin (BTX), veratridine (VTD), and grayanotoxin-I (GTX), investigating the unifying mechanisms that underlie the diverse modifications of this class of neurotoxins. In this paper, highly purified sodium channel polypeptides from the electric organ of the electric eel were incorporated into planar lipid bilayers in the presence of GTX for comparison with our previous studies of BTX (Recio-Pinto, E., D. S. Duch, S. R. Levinson, and B. W. Urban. 1987. J. Gen. Physiol. 90:375-395) and VTD (Duch, D. S., E. Recio-Pinto, C. Frenkel, S. R. Levinson, and B. W. Urban. 1989. J. Gen. Physiol. 94:813-831) modifications. GTX-modified channels had a single channel conductance of 16 pS. An additional large GTX-modified open state (40-55 pS) was found which occurred in bursts correlated with channel openings and closings. Two voltage-dependent processes controlling the open time of these modified channels were characterized: (a) a concentration-dependent removal of inactivation analogous to VTD-modified channels, and (b) activation gating similar to BTX-modified channels, but occurring at more hyperpolarized potentials. The voltage dependence of removal of inactivation correlated with parallel voltage-dependent changes in the estimated K1/2 of VTD and GTX modifications. Ranking either the single channel conductances or the depolarization required for 50% activation, the same sequence is obtained: unmodified > BTX > GTX > VTD. The efficacy of the toxins as activators follows the same ranking (Catterall, W. A. 1977. J. Biol. Chem. 252:8669-8676).
Animals↗
Release of contracting autacoids by aortae of normal and atherosclerotic rabbits.
The aim of our study was to examine the release of various lipid and peptide contracting autacoids by aortae of normal and atherosclerotic rabbits. Leukotriene (LT) E4, an enzymatic derivative of LTC4, thromboxane (Tx) B2, and endothelin-1 (ET-1) were measured by radioimmunoassay techniques in aortic preparations of normal and cholesterol-fed rabbits. Intact aortae of normal rabbits incubated with the calcium ionophore A23187 for 1 h at 37 degrees C released LTE4 and TxB2 (22 +/- 3.5 and 14.8 +/- 2 pg/mg of tissue, respectively, mean +/- SEM, n = 33). Removal of aortic endothelium was associated with a significant reduction in LTE4 (44%) and TxB2 (58%) release. In aortic preparations from cholesterol-fed rabbits, the release of LTE4 was significantly enhanced (41 +/- 8 pg/mg of tissue, mean +/- SEM, n = 27) whereas TxB2 was not significantly altered. No detectable amounts of ET-1 were measured after 1 h of incubation. However, at 4 h, an endothelium-dependent release of ET-1 from normal aortae was demonstrated. In atherosclerotic aortae, ET-1 release was significantly higher than in controls (10 +/- 1.3 vs. 5 +/- 0.5 pg/cm2, mean +/- SEM, n = 16). We conclude that enhanced formation of vasoconstrictor autacoids may contribute to altered vasomotion of atherosclerotic blood vessels.
Animals↗
Preparation of right-side-out plasma membrane vesicles from Penicillium cyclopium: a critical assessment of markers.
A plasma membrane fraction was obtained by the combined use of differential centrifugation and aqueous polymer two-phase partitioning techniques. Vanadate-inhibited ATPase and glucan synthase activities were highly enriched in this fraction, although the presence of ATPase activity which was not inhibited by vanadate, nitrate, molybdate, anyimycin A or azide was also detected. Other intracellular membrane marker activities were present at very low or undetectable levels. A further separation step using Percoll density gradient centrifugation resulted in the separation of a fraction which exclusively contained vanadate-inhibited ATPase activity, and was enriched with silicotungstic-acid-staining membrane material. Latency tests performed on the plasma membrane markers showed that the membrane vesicles were in the right-side-out orientation.
5'-Nucleotidase↗
Functional and structural damage in Leishmania mexicana exposed to the cationic peptide dermaseptin.
The effect of dermaseptin (DS), a 34 amino acid residue cationic peptide isolated from Phyllomedusa sauvagii skin, has been studied on promastigotes of Leishmania mexicana growing in vitro. Within 5 min of incubation in the presence of DS, the flagellated parasites lost their motility. DS inhibited promastigote growth by 50% at a concentration of 3 microM and by 100% at 10 microM. Immunocytochemical, freeze fracture, label fracture and electron microscopic observations have shown that the amphipathic peptide generates perturbations of the lipid bilayer leading to altered permeability of the surface membrane and death of the parasite.
Amphibian Proteins↗
Inactivation of endothelin by polymorphonuclear leukocyte-derived lytic enzymes.
Cultured bovine aortic endothelial cells (BAEC) released endothelin-1 (ET-1) in the culture medium in a time-dependent fashion. Coincubation of fMLP-activated human polymorphonuclear leukocytes (PMN) with BAEC caused a fast (maximal activity was reached within 15 minutes) and cell number-dependent disappearance of ET-1 from the medium. This effect was direct to ET-1, because it was also present when PMN were incubated with the synthetic peptide in the absence of BAEC. PMN-dependent disappearance of ET-1 was associated with loss of constrictor activity on isolated rabbit aorta. PMN-released products were responsible for ET-1 degrading activity, because supernatants of activated PMN were equally effective as the intact cells. Resting PMN, in the same time frame, were uneffective. Eglin C, a potent blocker of PMN-derived elastase and cathepsin G, reversed the ET-1 inhibitory activity of fMLP-stimulated PMN and of their supernatant. Direct addition of elastase and cathepsin G to synthetic ET-1 destroyed its immunoreactivity and this effect was blocked by eglin C. High-performance liquid chromatography (HPLC) analysis supported the hypothesis that ET-1 degradation by PMN was due to enzymatic proteolysis. These data provide evidence that activated PMN are able to degrade ET-1 through the release of proteases. Because physiologic concentrations of PMN can destroy high amounts (up to 100 nmol/L) of ET-1 within a few minutes, we propose that this mechanism of ET-1 inactivation has biologic relevance.
Animals↗
Adrenaline-induced tracheal relaxation ex vivo is depressed following aerosol antigen challenge of sensitized guinea-pigs.
We investigated the changes in beta-adrenoceptor responses induced in guinea-pig tracheal and cardiac tissues by the anaphylactic reaction. Antigen aerosol challenge in sensitized guinea-pigs resulted in a marked reduction in adrenaline relaxation in isolated trachea ex vivo. The isoprenaline effect was also slightly decreased by antigen exposure, suggesting a possible impairment of tracheal beta-adrenoceptor function. On the other hand, the chronotropic and inotropic activity of adrenaline in isolated atria was not modified by the anaphylactic shock, suggesting a specific involvement of lung beta-adrenoceptors in the allergic reaction.
Aerosols↗
Fibrinolytic parameters and lipoprotein (a) levels in plasma of patients with coronary artery disease.
Fibrinolysis and lipid disturbances have been considered as independent risk factors for coronary artery disease. Besides this, lipoprotein(a), which is characterized by its homology with plasminogen may interfere with the fibrinolytic function. To evaluate the eventual correlation between fibrinolytic parameters, lipoprotein (a) and other risk factors, 46 patients with coronary artery disease (34 with chronic angina pectoris and 12 with myocardial infarction) were studied. Increased basal values of t-PA antigen (8.2 and 6.6 vs. 4.2 ng/ml) but decreased response after stimulus (2.2 and 1.8 vs. 3.8 ng/ml) and increased levels of lipoprotein(a) (24.7 and 35.9 vs. 10.5 mg/dl) were the most relevant differences between coronary artery disease patients and controls. No correlation between lipoprotein(a) and fibrinolytic parameters was found. Therefore plasma concentration of the main plasma fibrinolytic parameters and lipoprotein(a) seem to be unrelated though the relevance of this interaction at a local level needs to be studied.
Aged↗
Patients treated with a monoclonal antibody (ab1) to the colorectal carcinoma antigen 17-1A develop a cellular response (DTH) to the "internal image of the antigen" (ab2).
The anti-tumor effector functions of unconjugated MAb in cancer therapy are not fully understood. Direct cytotoxic mechanisms have been demonstrated as well as induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies. If such a humoral response is induced, then an idiotypic cellular response would also be anticipated. Human monoclonal ab2s which mimic a tumor-associated antigen (TAA) (CO17-1A) of colorectal carcinoma (CRC) cells ("the internal image of the antigen") were produced. These ab2s were injected intradermally to patients with metastatic CRC who had been treated with the anti-colon carcinoma MAb 17-1A (ab1). Five out of 12 patients had a specific DTH (delayed-type hypersensitivity) reaction of the tuberculin type, which was proven by immunohistochemical analysis of skin biopsies. Serum ab3 was demonstrated in 4/4 tested DTH+ patients and also in 4 DTH patients. Control patients did not show any skin reactivity. Generation of an idiotypic response induced by the infused antibody (ab1) might be regarded as an active anti-tumor "vaccination". Induction of an idiotypic cellular and humoral cascade might be an important anti-tumor effector function of MAb and should be considered in future strategies for such therapy in cancer patients.
Antibodies, Anti-Idiotypic↗
Further evidence for the molecular heterogeneity of chronic myeloid leukemia.
Cytogenetic and molecular techniques were performed on samples obtained from 29 patients with chronic myelocytic leukemia (CML); 27 were in the chronic phase and two were in blast crisis. A further five cases were also analyzed, two with atypical CML (aCML), one with chronic neutrophilic leukemia (CNL), and two with juvenile CML (JCML). Most of the cases with typical CML were Philadelphia chromosome (Ph) positive and had a rearrangement within the major breakpoint cluster region (M-bcr). One of these cases was shown to be Ph positive but showed no rearrangement within the M-bcr. Two cases with clinical features typical of CML were Ph negative. One of these showed a rearrangement within the M-bcr, but no rearrangement was demonstrated in the other. Both patients in blast crisis were Ph positive and M-bcr positive. One showed a second Ph. Patients with aCML were Ph negative and had no M-bcr rearrangement. A polymorphism within the M-bcr was found with BglII in one case. No Ph chromosome or M-bcr rearrangement was found in CNL or JCML. These data support the molecular heterogeneity reported in CML.
Blast Crisis↗