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Biomedical subjects

H Moreno

Publications and source records attributed to H Moreno.

At least 73 records · Page 4Linked to original sources
PubMed1996

Bioequivalence study of two enalapril maleate tablet formulations in healthy male volunteers. Pharmacokinetic versus pharmacodynamic approach.

OBJECTIVE: Two different conventional release enalapril maleate tablet formulations were evaluated for their relative bioavailability (Eupressin tablets 10 mg, Biosintética as the test formulation vs Renitec tablets 10 mg Merck Sharp & Dhome, as the reference formulation). A single 20 mg oral dose of each preparation was administered to 18 healthy male adult volunteers and their bioequivalence was assessed by comparing the serum enalaprilat and total enalapril (enalaprilat plus enalapril maleate) concentration-time curves. Angiotensin converting enzyme (ACE) activity was also quantified in each serum sample. RESULTS: The pharmacokinetic parameters obtained for each formation were the area under the time-concentration curve from 0 to 24 h (AUC[0-24]), maximum concentration Cmax and the time at which it occurred (tmax). When serum enalaprilat concentration-time curves were employed to assess bioequivalence, the formulations were bioequivalent in the extent but not in the rate of absorption. However, no difference in either the extent or the rate of absorption were observed when serum total enalapril vs time curves were analysed. ACE activity-time curves were similar for both formulations and showed that ACE was 90% inhibited for 3-5 h after enalapril administration, and till approximately 50% after 24 h. At that time, circulating enalaprilat and total enalapril levels were less than the tenth of Cmax. CONCLUSION: The results show that complete bioequivalence of the two formulations can be concluded from serum total enalapril concentration data, and that serum ACE activity is not a suitable pharmacodynamic variable for assessing bioequivalence.

Adult↗
PubMed1996

Evaluation of two different oxygen inspiratory fractions on the hemodynamic effects of N omega-nitro-L-arginine methyl ester in anesthetized dogs.

The effect of two different oxygen inspiratory fractions (FiO2 = 21% and 100%) on the hemodynamic responses induced by N omega-nitro-L-arginine methyl ester (L-NAME) was investigated in anesthetized dogs. L-NAME (0.01-10.0 mg/kg), but not D-NAME, induced dose-dependent changes in the hemodynamic parameters of the animals. At the highest dose, L-NAME increased mean arterial blood pressure in both room air (from 86.2 +/- 3.2 to 125.1 +/- 7.8 mmHg) and pure oxygen (from 100.0 +/- 7.5 to 139.0 +/- 3.2 mmHg) ventilated animals. L-NAME also increased systemic and pulmonary vascular resistances. These effects were accompanied by a decrease in cardiac output and bradycardia (37% and 31% decreases for pure oxygen and room air, respectively). However, there were no significant differences in the responses to L-NAME between the dogs ventilated with FiO2 = 21% and those ventilated with FiO2 = 100%. L-NAME did not modify blood gas analyses, despite the expected difference in pO2 levels between the two experimental groups of animals (3 times higher in the animals ventilated with pure oxygen). These results indicate that nitric oxide release accounts for the maintenance of hemodynamic function in the anesthetized dog, and that L-NAME-induced effects are not affected by hyperoxemia.

Animals↗
PubMed1996

Influence of gastric acid secretion blockade and food intake on the bioavailability of a potassium diclofenac suspension in healthy male volunteers.

The bioavailability of a single dose of a potassium diclofenac (KDIC) suspension (Flogan, Merck, 7ml, 105 mg) was studied in 13 healthy male volunteers in the fasting state (placebo phase, PLA), after gastric acid secretion blockade (subacute pretreatment with omeprazole, OME phase) and after food intake (FOOD phase). A 14-day washout period between phases was adopted. Serum samples were obtained over a 24 hour interval and the diclofenac concentrations were determined by high pressure liquid chromatography with ultraviolet detection. From the serum diclofenac concentration vs time curves, the AUC[0-infinity] (area under the concentration vs time curves from 0 to infinity), Cmax (maximum achieved concentration), tmax (time to achieve Cmax), Ke (terminal first order elimination constant), half-life values (t1/2) and AUC[0-infinity]/t1/2 ratio as an index of diclofenac clearance, were obtained. All these variables were analyzed using both parametric and non-parametric statistics. In the presence of food, KDIC absorption was delayed (as shown by lower Cmax and greater tmax values) and decreased (as shown by lower AUC[0-infinity] values), and the serum diclofenac concentration vs time curves showed a biphasic pattern. Omeprazole pretreatment did not change the absorption parameters. Both of these treatments altered the diclofenac clearance, as assessed by the AUC[0-infinity]/t1/2, t1/2 and Ke values, although the changes were not considered to be clinically significant, because of the wide therapeutic range for diclofenac. The delay in the rate of diclofenac absorption produced by food intake was not due to an increase in the gastric pH, and could be of particular importance when rapid analgesia is desired.

Administration, Oral↗
PubMed1996

Fimbria-fornix lesion impairs long-term potentiation in the dentate gyrus of the rat.

Bilateral aspiration lesions of the fimbria-fornix were performed in 10 male Sprague Dawley rats weighing 240-300 g under chloral hydrate narcose (420 mg/kg). Another 9 animals were operated in the same way, but no aspiration was carried out to constitute a control group. A week after surgery recording and stimulation electrodes were lowered to the dentate gyrus and the perforant path respectively, using the same narcose. After tetanic stimulation (10 trains at 400 Hz) a potentiation of the population spike develops in both groups, but the slope of the excitatory postsynaptic potential showed no potentiation in the lesioned group. Acetylcholinesterase histochemistry confirmed a severe reduction of the cholinergic innervation to the hippocampal formation, suggesting a causal relationship to the deficits seen in long-term potentiation. This impaired potentiation could be related to the memory deficits reported for fimbria-fornix lesioned rats. Such pattern of potentiation deviates from what has been described for aged, memory deficient rats, but closely corresponds to the changes described in infantile rats.

Acetylcholinesterase↗
PubMed1995

Enalapril does not prevent the myocardial ischemia caused by the chronic inhibition of nitric oxide synthesis.

In rats, chronic administration of the nitric oxide (NO) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) causes arterial hypertension, cardiac hypertrophy and myocardial ischemic alterations such as necrosis and fibrosis. In this study, we evaluated the effect of 8 weeks of treatment with enalapril maleate on cardiac weight and on the development of the histological alterations induced by L-NAME. Enalapril significantly inhibited the development of both arterial hypertension (117.2 +/- 5.8, 161.8 +/- 8.8 and 122.0 +/- 10.6 mm Hg, for control, L-NAME- and L-NAME + enalapril-treated animals, respectively) and left ventricular hypertrophy (1.36 +/- 0.13, 1.60 +/- 0.04 and 1.48 +/- 0.05 mg/g, for control, L-NAME- and L-NAME + enalapril-treated animals, respectively), but had no effect on the myocardial lesions. These findings demonstrate that although the renin-angiotensin system plays a major role in the development of arterial hypertension and cardiac hypertrophy, it does not modulate the ischemia-induced myocardial alterations observed in this model.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions.

The protein tyrosine kinase PYK2, which is highly expressed in the central nervous system, is rapidly phosphorylated on tyrosine residues in response to various stimuli that elevate the intracellular calcium concentration, as well as by protein kinase C activation. Activation of PYK2 leads to modulation of ion channel function and activation of the MAP kinase signalling pathway. PYK2 activation may provide a mechanism for a variety of short- and long-term calcium-dependent signalling events in the nervous system.

3T3 Cells↗
PubMed1995

Thalamocortical projections have a K+ channel that is phosphorylated and modulated by cAMP-dependent protein kinase.

The finding that some K+ channel mRNAs are restricted to certain populations of neurons in the CNS suggests that there are K+ channels tailored to certain neuronal circuits. One such example are the transcripts from the KV3.2 gene, the majority of which are expressed in thalamic relay neurons. To gain insights into the specific roles of KV3.2 subunits, site specific antibodies were raised to determine their localization in thalamic relay neurons. Immunohistochemical and focal lesioning studies demonstrate that KV3.2 proteins are localized to the terminal fields of thalamocortical projections. It is also shown that KV3.2 channels expressed in vitro are strongly inhibited through phosphorylation by cAMP-dependent protein kinase (PKA). Channels containing KV3.1 subunits, which otherwise exhibit nearly identical electrophysiological properties in heterologous expression systems but have a different and less restricted pattern of expression in the CNS, are not affected by PKA. Therefore, this modulation might be associated with the specific roles of KV3.2 subunits. Furthermore, we demonstrate that KV3.2 proteins can be phosphorylated in situ by intrinsic PKA. KV3.2 subunits display properties and have a localization consistent with a role in the regulation of the efficacy of the thalamocortical synapse, and could thereby participate in the neurotransmitter-mediated control of functional states of the thalamocortical system associated with global states of awareness.

Amino Acid Sequence↗
PubMed1994

Differential expression of Shaw-related K+ channels in the rat central nervous system.

The family of mammalian genes related to the Drosophila Shaker gene, consisting of four subfamilies, is thought to encode subunits of tetrameric voltage-gated K+ channels. There is compelling evidence that subunits of the same subfamily, but not of different subfamilies, form heteromultimeric channels in vitro, and thus, each gene subfamily is postulated to encode components of an independent channel system. In order to identify cells with native channels containing subunits of one of these subfamilies (Shaw-related or ShIII), the cellular distribution of ShIII transcripts was examined by Northern blot analysis and in situ hybridization. Three of four ShIII genes (KV3.1, KV3.2, and KV3.3) are expressed mainly in the CNS. KV3.4 transcripts are also present in the CNS but are more abundant in skeletal muscle. In situ hybridization studies in the CNS reveal discrete and specific neuronal populations that prominently express ShIII mRNAs, both in projecting and in local circuit neurons. In the cerebral cortex, hippocampus, and caudate-putamen, subsets of neurons can be distinguished by the expression of specific ShIII mRNAs. Each ShIII gene exhibits a unique pattern of expression; however, many neuronal populations expressing KV3.1 transcripts also express KV3.3 mRNAs. Furthermore, KV3.4 transcripts are present, albeit at lower levels, in several of the neuronal populations that also express KV3.1 and/or KV3.3 mRNAs, revealing a high potential for heteromultimer formation between the products of three of the four genes. Expression of ShIII cRNAs in Xenopus oocytes was used to explore the functional consequences of heteromultimer formation between ShIII subunits. Small amounts of KV3.4 cRNA, which expresses small, fast-inactivating currents when injected alone, produced fast-inactivating currents that are severalfold larger when coinjected with an excess of KV3.1 or KV3.3 cRNA. This amplification is due to both an increase in single-channel conductance in the heteromultimeric channels and the observation that less than four, perhaps even a single KV3.4 subunit is sufficient to impart fast-inactivating properties to the channel. The oocyte experiments indicate that the apparently limited, low-level expression of KV3.4 in the CNS is potentially significant. The anatomical studies suggest that heteromultimer formation between ShIII proteins might be a common feature in the CNS. Moreover, the possibility that the subunit composition of heteromultimers varies in different neurons should be considered, since the ratios of overlapping signals change from one neuronal population to another. In order to proceed with functional analysis of native ShIII channels, it is important to known which subunit compositions might occur in vivo. The studies presented here provide important clues for the identification of native homo- and heteromultimeric ShIII channels in neurons.

Animals↗
PubMed1993

Evaluation of an attenuated Trypanosoma cruzi strain in rats. Analysis of survival, parasitemia and tissue damage.

Infection and tissue damage induced by parasites of an attenuated Trypanosoma cruzi culture strain (TCC) were studied in "I" line of inbred rats. Suckling rats (S), 3-5 day old were inoculated i.p. with 10(6) TCC (S1), 10(7) TCC (S2) and 10(8) TCC (S3). Weaned rats (W), 21-25 day old were inoculated s.c. with 10(6) TCC (W1), 10(7) TCC (W2) and 10(8) TCC (W3). The cultures yielded up to 2% of trypomastigotes. Controls inoculated either i.p. or s.c. with 10(6) blood form trypomastigotes (SC and WC) as well as normal controls (NC) were included. Survival was 100% in S1, S2 and S3, and 0% in SC on day 13 post-infection (p.i.). The latter animals died with acute Chagas disease signs. Survival was 100% in the W groups. In the first 30 days p.i. parasites were detected in S1, S2 and S3 and W1, W2, W3 groups after exhaustive examination. Parasites were easily found in WC and SC until day 13. Xeno-diagnoses were positive (5/5) at 2 months p.i. and negative at 6 months p.i. (W1, W2, W3, 0/23; WC, 0/5). Only cardiac lesions were slightly increased. The frequency of focal chronic myocarditis seemed to be increased in a dose-independent manner (S1, S2, S3, 26%; W1, W2, W3, 46%) but was not significant in comparison with NC, and even was lower than usually found in WC (61.3%). The reduced virulence and pathogenicity suggest that the TCC strain suffered a remarkable attenuation after long term in vitro culture.

Animals↗
PubMed1992

Cloning of ShIII (Shaw-like) cDNAs encoding a novel high-voltage-activating, TEA-sensitive, type-A K+ channel.

Transient voltage-dependent potassium (K+) currents, also known as A currents, have been of great interest to neurophysiologists due to their special roles in neuronal excitability. Several cDNAs encoding transcripts expressing A currents have been characterized. Recently, a cDNA (KShIIIC or Raw3) was isolated which expresses an unusual A current that is highly sensitive to TEA, and activates at potentials more positive than -20 mV. Channels containing this protein may have specialized roles in modulating the electrical behaviour of neurons. Here we report the isolation and characterization of two rat cDNAs corresponding to two alternatively spliced transcripts (KShIIID.1 and KShIIID.2) from another gene (KShIIID) of the same subfamily as KShIIIC, the ShIII or Shaw-related gene subfamily. KShIIID.1 also expresses an unusual high-voltage-activating, TEA-sensitive A-type channel. There are, however, significant differences between KShIIIC and KShIIID channels which may have interesting functional consequences. The two most important differences are: (i) KShIIID channels conduct in the steady-state over a much broader window of potentials than KShIIIC; this reflects differences between the kinetic schemes of the two channels; and (ii) KShIIID inactivates with significantly slower kinetics than KShIIIC. The identification of KShIIID transcripts contributes to our knowledge of the molecular components that may determine the functional diversity of A currents and provides exciting opportunities to increase our understanding of the structure and function of K+ channels.

Amino Acid Sequence↗
PubMed1992

[Clinical heterogeneity of the autistic syndrome: a study of 60 families].

Sixty families ascertained through a single proband, has helped to better define infantile autism as a heterogeneous group of disorders. Forty four patients showed a characteristic facio- auricular dysplasia. Twenty four of these, showed increased pyruvate and lactate and laboratory findings of metabolic acidosis i.e., anion gap above 18 mEq/L or serum bicarbonate below 21 mEq/L but only nine of these probands demonstrated reduction of plasma bicarbonate below 18 mEq/lt. Plasma amino acids in 17 probands and matched controls showed increased taurine with the rest of amino acids significantly (p less than 0.05) below the control level. Glutamate and aspartate were also significantly elevated (p less than 0.05; Student t-test). Segregation analysis in thirty four of these families which linked through at least one ancestral family name, suggested autosomal recessive inheritance (p = 0.20). Three out of eight probands who received megadoses of pyridoxine (Vitamin B6), subjectively gained in language abilities, affectivity and response to behavior modification therapy. Five autistic patients proved to have clinically defined syndromes: two with the Martin-Bell syndrome, and three girls affected respectively with the Rett syndrome, phenylketonuria and dicarboxylic aciduria.

Acidosis↗
PubMed1992

Depressed adjuvant arthritis in chronically Trypanosoma cruzi infected rats: reversal by cyclophosphamide.

Chronically Trypanosoma cruzi infected "I" rats and syngeneic naive recipients, transferred with a T cell enriched spleen cell population from infected donors, develop an attenuated arthritis when challenged with complete Freund's adjuvant. We report that cyclophosphamide, 40 mg/kg body weight, given 48 h before induction, was able to reestablish or exacerbate adjuvant arthritis in infected and control rats, respectively. Although the T cell enriched spleen cells from infected donors continued to down regulate adjuvant arthritis in syngeneic recipients given cyclophosphamide 48 h before cell transfer, treatment of infected donors with cyclophosphamide, 48 h before cell collection, prevented these cells from exerting such effect when transferred to healthy recipients receiving no cyclophosphamide. It is suggested that cyclophosphamide may primarily affect a suppressor cell population, present in the infected host, with regulatory activity on adjuvant arthritis.

Animals↗
PubMed1990

Clinical experience in Mexico with a new oral rehydration solution with lower osmolality.

A clinical trial was conducted to compare the safety and efficacy of a new oral rehydration solution (ORS) with that of the ORS recommended by the World Health Organization (WHO). One hundred thirty infants with dehydration due to acute diarrhea were randomized into two groups: 68 infants received the WHO ORS containing sodium and glucose in a concentration of 90 and 111 mmol/L, respectively, and an osmolality of 311 mosm/kg (ORS-90); 62 infants received an ORS containing sodium and glucose in a concentration of 60 and 90 mmol/L, respectively, with an osmolality of 240 mosm/kg (ORS-60). Treatment failure was noted in seven infants (10.3%) in the ORS-90 group; the causes of failure were high stool output (three cases), persistent vomiting (three cases), and ileus (one case). Only one patient in the ORS-60 group (1.6%) was considered a failure because of high stool output. No significant differences were noted in the serum sodium levels in either group of patients, both in relation to the natremia seen on admittance or that seen after rehydration. A trend was observed toward correction of hypernatremia or hyponatremia with both types of ORS. A similar situation was observed with respect to the variations seen in serum potassium levels. The results from this study suggest that there may be clinical advantages of using an ORS with concentrations of sodium and glucose and a total osmolality lower than that of ORS-90, because of the lower incidence of treatment failures.

Diarrhea↗
PubMed1986

Huntington's disease in Venezuela: neurologic features and functional decline.

We studied 65 Huntington's disease patients and 225 at-risk individuals over the past 4 years. The rate of decline of these untreated patients from Venezuela was similar to that seen in US patients who had received neuroleptic drugs. Chorea, oculomotor dysfunction, and dysdiadochokinesis were early symptoms; parkinsonian features and dystonia came later. Juvenile patients declined nearly twice as fast as adult-onset patients. No distinctive neurologic phenotypes were seen in children of two affected parents.

Adult↗