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Biomedical subjects

R Pascual

Publications and source records attributed to R Pascual.

At least 37 records · Page 2Linked to original sources
PubMed1996

Nitrendipine and enalapril in the treatment of diabetic hypertensive patients with microalbuminuria.

A trial to study the efficacy, safety and tolerability of nitrendipine and enalapril in the treatment of diabetic hypertensive patients with microalbuminuria (MA) was performed to compare the effects of both drugs in the prevention of the renal impairment. Twenty-eight valid patients [13 with nitrendipine (N) and 15 with enalapril (E) with NIDDM, hypertension (diastolic blood pressure between 90 to 114 mm Hg) and MA (urinary albumin between 30 to 300 mg/24 hr) were recruited in a double blind, randomized trial. Following a placebo run-in period of two to four weeks, all eligible patients were randomly allocated to either N or E treatment. Treatment lasted six months, with two different visits at three and six months in which blood pressure (BP), heart rate (HR), renal function and MA were measured. No statistically significant differences on BP and metabolic parameters were found between both treatment groups. The geometric mean of final glomerular filtration rate (GFR) in the N group was 34.5% higher than in the E group, while the reduction on MA was most important in the E group. Eleven patients reported adverse events (AEs) and there were four dropouts, three of them due to AEs. We conclude that both treatments are a good choice for treating diabetic hypertensive patients with early altered renal function, as they reduce BP without altering metabolic parameters, increase GFR and reduce MA with a low frequency of AEs.

Adult↗
PubMed1996

[Diagnostic efficiency of biological markers of alcohol consumption for the detection of excessive drinkers].

The objective of our study was to test the usefulness of some biological markers of alcoholism to detect heavy drinkers, using a structured interview with a 7-day memory as this is currently considered the most reliable technique for determining alcohol consumption. A transversal, observational study was designed with a sample representative of the working population of the province of Alicante seen by the Ibermutua medical service. Participants were selected randomly and classified according to region and sex. The total sample include 1,033 subjects (644 men and 389 women, mean age 36 +/- 11.7 years). Of these 13.5 were heavy drinkers (> 40 g. of alcohol per day), 23.3 moderates drinkers (20-40 g. alcohol per day). Average consumption of alcohol was from 26 g/day + 29.9 grams. In order to quantify the random error, the confidence interval was set at 95. The methods used to test the biological markers were 2 x 2 tables and the calculation of indicators of sensitivity (S). specificity (E), positive predictive value (Vp+), negative predictive value (Vp-) and effectiveness. The highest S was obtained by associating various markers (65.5%), followed by GGT with 53.9%. The GGT/ALP quotient obtained an E of 95.9% and an AST of 92.2%. The GGT/ALP quotient achieved the best effectiveness (85%) and Vp+ (36.2%) and the association of markers the best Vp-at 92.9%, followed by GGT at 91.3%. In spite of the fact that the markers studied do not meet the conditions required to be considered acceptable as screening (S and E > 80%), their use seems appropriate if their limitations are kept in mind (many false negatives). As the GGT/ALP quotient has the highest E, there are few false positives. In order to decrease the number of false negatives, an evaluation of GGT or marker association can be done for those with negative values. In order to resolve the disadvantages of Vp+, the best solution is to order tests for groups of markers that are most prevalent in heavy drinkers.

Adult↗
PubMed1995

[The validity of the separate determination of total cholesterol in the primary prevention of coronary risk].

BACKGROUND: The aim of this study was to validate total cholesterol (TC) determination in the primary prevention of coronary risk and evaluate the prevalence of low HDL cholesterol (HDL-C) levels at the different TC cut-off points to thereby determine the TC level at which HDL-C determination is of interest. METHODS: The atherogenic index was used as the reference method in TC evaluation with the values of low HDL-C levels being evaluated at the following TC cut-off points: 160, 180, 200, 220, 240, 250, and 300 mg/dl (4.44; 4.66; 5.18; 5.70; 6.22; 6.48; 7.77 mmol/l). According to the results of the Framingham study the atherogenic index or the existence of low HDL-C levels were considered as abnormal. The sample included 4,162 workers from the province of Alicante (Spain) selected by consecutive sampling and opportunistic search in January and February, 1993. Validity was calculated with confidence interval of 95%. RESULTS: The atherogenic index was high in 43.7% of the sample, ranging from 6% in the population with TC lower than 160 mg/dl (4.14 mmol/l) to 76.4% in those oscillating between 250-299 mg/dl (6.48-7.76 mmol/l). Low HDL-C levels were detected in 20.1% with a prevalence ranging from 38.8% in those with a TC of less than 160 mg/dl (4.14 mmol/l) to 11.9% in those with TC > or = 250 mg/dl (> or = 6.48 mmol/l). The cut-off points for low TC had high sensitivity (S) and low specificity (SP) (160 mg/dl [4.14 mmol/l]: S = 91.1%, SP = 11.5%; 180 mg/dl [4.66 mmol/l]: S = 95.2%, SP = 30.2%). The highest TC points presented very low S and very high SP (250 mg/dl [6.48 mmol/l]: S = 46.3%, SP = 87.7%; 300 mg/dl [6.48 mmol/l]: S = 7.4%, SP = 97%). CONCLUSIONS: The HDL-cholesterol should be determined in people with a total cholesterol of less than 200 mg/dl (5.18 mmol/l) since, in this group there is an important percentage of individuals with an altered atherogenic index and low HDL-C levels.

Adult↗
PubMed1993

Effects of sensitization on vasoactive intestinal polypeptide-induced relaxation and its concentration and binding in guinea-pig airways.

We investigated the relaxant effect of vasoactive intestinal polypeptide (VIP) in trachea and lung parenchyma from normal and sensitized guinea-pigs. A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings was used. In intact trachea, concentration-response curves for VIP entering from the mucosal surface (pD2 = 6.61 +/- 0.06) were displaced to the right compared with those for adventitial entry (pD2 = 6.78 +/- 0.04). Epithelium removal produced a leftward shift (approximately 2.8-fold) in the mucosal VIP concentration-response curve. Sensitization did not alter the responsiveness (maximal effect) or sensitivity (pD2 values) of tracheal rings to VIP irrespective of the surface of drug entry and of the absence or presence of epithelium. VIP-induced relaxation of normal and sensitized lung strips was also similar. Sensitization resulted in a significant decrease in tracheal VIP content (from 2.16 +/- 0.07 in normal to 0.60 +/- 0.08 nmol/mg protein in sensitized trachea; P < 0.05; n = 7) whereas the affinity of both high- and low-affinity binding sites for VIP increased as compared to that of normal trachea. Differences were not found in the binding capacities of normal and sensitized trachea. VIP content and binding did not differ in normal and sensitized lung. In conclusion, immunological sensitization produced changes in VIP tracheal content and binding but neither VIP-induced relaxation of isolated airways nor the influence of epithelium in this response was altered.

Animals↗
PubMed1993

Environmental deprivation delays the maturation of motor pyramids during the early postnatal period.

The effects of environmental deterioration upon the development of motor cortex was studied in 30 Sprague-Dawley albino rats during lactation (1st-18th postnatal days). The use of Golgi-Cox-Sholl methodology allowed qualitative and particularly quantitative evaluations since impregnation of neurons take place at random without any selectivity. Morphometric studies were assessed by measuring layers II-III pyramidal neurons, basal dendritic branching, under camera lucida. Early environmental impoverishment results in a highly significant decrease in the number and length of peripherical branches and terminal dendrites. These results extend previous observations made predominantly in non-motor cortices which indicate that during early postnatal life restrictions or enrichments of the environment may be associated with quantitative changes in the differentiation of cerebrocortical neurons. It is of upmost importance to consider that the potential effects of different types of epigenetic cues are highly selective since pyramids of pups subjected to mild nutritional manipulation during the same developmental period remained unaffected.

Animals↗
PubMed1993

Role of endothelium in the responses to noradrenaline in normal and sensitized guinea-pig aorta.

1. The pharmacological reactivity of sensitized blood vessels has been less studied than that of the airways. Aorta rings were obtained from normal (non-sensitized) and actively sensitized guinea-pigs, and prepared for isometric recording of tension changes. 2. Noradrenaline (10 nM-0.1 mM), histamine (0.1 microM-0.1 mM) and KCl (10-100 mM) produced concentration-related contractions of normal tissues. Removal of endothelium resulted in a marked leftward and upward shift of the concentration-response curve for noradrenaline but it did not alter histamine- or KCl-induced responses. Pretreatment with L-NG-nitroarginine (L-NOARG, 30 microM), haemoglobin (5 microM) or ibuprofen (10 microM) enhanced noradrenaline-induced responses without affecting those to histamine or KCl. 3. Removal of endothelium or pretreatment with L-NOARG or ibuprofen did not alter agonist-induced responses in sensitized tissues. Acetylcholine (1 microM)-induced relaxation of the contraction produced by noradrenaline (1 microM) in intact rings was diminished in sensitized compared to normal tissues. 4. Neuronal uptake and release of [3H]-noradrenaline did not differ in normal and sensitized tissues. 5. Loss of the modulatory role of endothelium and other mechanisms may be involved in the hyperreactivity of sensitized guinea-pig aorta.

Animals↗
PubMed1993

Relaxation by calcium antagonists of potassium-contracted trachea from normal and sensitized guinea-pigs: influence of epithelium and the surface of drug entry.

A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings, isolated from normal (unsensitized) or sensitized guinea-pigs, was used to study the role of the epithelium in the relaxation produced by calcium antagonists (verapamil, nifedipine, cinnarizine and flunarizine) of K(+)-induced contraction. In trachea from normal guinea-pigs, the relaxation to verapamil for unrestricted or mucosal drug entry was reduced in the absence of epithelium, whereas the relaxation produced by nifedipine, cinnarizine or flunarizine was unchanged. In sensitized trachea, the relaxation elicited by the calcium antagonists tested was similar in intact and epithelium-denuded tracheal rings irrespective of the surface of drug entry. These results confirm that the epithelium influences the relaxation to verapamil. This modulatory effect is absent in sensitized trachea and is not shared by other calcium antagonists.

Animals↗
PubMed1993

Early life environmental deterioration, nutrition and ontogenesis of the motor cortex in the rat: a Golgi study.

Sprague-Dawley albino rats were subjected to an experimental paradigm in which environmental and nutritional variables were studied from birth to day 18. The use of Golgi-Cox-Sholl methodology allowed quantitative evaluations of neurons which were randomly impregnated with metallic mercury after fixation in a mercury salt. The nutritional treatment employed did not significantly influence the cytoplasmatic differentiation of cortical neurons although it was able to induce gross morphological modifications in body weight and size. By contrast, an impoverished surrounding during a limited period of time had a profound effect on the basal dendritic tree. The evidence presented here suggests the importance of the preweaning environment on the development of neural appendages. Motor pyramids of pups housed in deteriorated conditions underwent a progressive decrement in the length and number of peripheral branches and terminal dendrites. A decreased rate of cortical differentiation was also observed in overnourished pups as a result of reducing the litter size. This regressive event, can probably be attributed to social and sensory-motor limitations of the experimental group. However, to confirm this possibility, further research is required.

Animal Nutritional Physiological Phenomena↗
PubMed1992

cDNA cloning and sequence analysis of human pancreatic procarboxypeptidase A1.

Using polyclonal antibodies raised against human pancreatic procarboxypeptidases, a full-length cDNA coding for an A-type proenzyme was isolated from a lambda gt11 human pancreatic library. This cDNA contains standard 3' and 5' flanking regions, a poly(A)+ tail and a central region of 1260 nucleotides coding for a protein of 419 amino acids. On the basis of sequence comparisons, the human protein was classified as a procarboxypeptidase A1 which is very similar to the previously described A1 forms from rat and bovine pancreatic glands. The presence of the amino acid sequences assumed to be of importance for the zymogen inhibition by its activation segment, primarily on the basis of the recently reported crystal structure of the B form, further supports the proposed classification.

Amino Acid Sequence↗
PubMed1992

Frequency domain models of the EEG.

The structure of the normal resting EEG crosspectrum SVV(omega) is analyzed using complex multivariate statistics. Exploratory data analysis with Principal Component Analysis (PCA) is followed by hypothesis testing and computer simulations related to possible neural generators. The SVV(omega) of 211 normal individuals (ages 5 to 97) may be decomposed into two types of processes: the xi process with spatial isotropicity reflecting diffuse, correlated cortical generators with radial symmetry, and processes that seem to be generated by more spatially concentrated, correlated sources. The latter are reflected as spectral peaks such as the process. The eigenvectors of the xi process are the Spherical Harmonic Functions which explains the recurring pattern of maps characteristic of the spatial PCA of qEEG data. A new method for estimating sources in the frequency domain which fits dipoles to the whole crosspectrum is applied to explain the characteristics of the localized sources.

Age Factors↗
PubMed1991

Conservation of the sequence of the Alzheimer's disease amyloid peptide in dog, polar bear and five other mammals by cross-species polymerase chain reaction analysis.

Neuritic plaque and cerebrovascular amyloid deposits have been detected in the aged monkey, dog, and polar bear and have rarely been found in aged rodents (Biochem. Biophy. Res. Commun., 12 (1984) 885-890; Proc. Natl. Acad. Sci. U.S.A., 82 (1985) 4245-4249). To determine if the primary structure of the 42-43 residue amyloid peptide is conserved in species that accumulate plaques, the region of the amyloid precursor protein (APP) cDNA that encodes the peptide region was amplified by the polymerase chain reaction and sequenced. The deduced amino acid sequence was compared to those species where amyloid accumulation has not been detected. The DNA sequences of dog, polar bear, rabbit, cow, sheep, pig and guinea pig were compared and a phylogenetic tree was generated. We conclude that the amino acid sequence of dog and polar bear and other mammals which may form amyloid plaques is conserved and the species where amyloid has not been detected (mouse, rat) may be evolutionarily a distinct group. In addition, the predicted secondary structure of mouse and rat amyloid that differs from that of amyloid bearing species is its lack of propensity to form a beta sheeted structure. Thus, a cross-species examination of the amyloid peptide may suggest what is essential for amyloid deposition.

Alzheimer Disease↗
PubMed1991

Epithelium modulates the reactivity of sensitized guinea-pig trachea: influence of the surface of drug entry.

A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings isolated from sensitized guinea-pigs was applied to study the role of the epithelium in modulating responses to KCl, acetylcholine, histamine and antigen (bovine serum albumin, BSA). Epithelium removal did not alter the responsiveness or sensitivity of tracheal rings to KCl. In contrast, a leftward shift occurred for concentration-response curves to acetylcholine (concentration ratio (CR) = 4.1), histamine (CR = 2.9) and BSA (CR = 33.9) entering from the mucosal surface of de-epithelialized trachea. This shift was not associated with changes in the maximal effect of the spasmogens. Response to the adventitial entry of these spasmogens was not altered by epithelial stripping. These results confirm that the epithelium modulates tracheal responses to certain spasmogens including antigen challenge. This role was exclusively exerted for mucosal drug entry. The mechanism underlying this protective effect of epithelium remains to be determined.

Acetylcholine↗
PubMed1991

Response to noradrenaline and histamine in normal and sensitized guinea pig aorta and its relation to endothelium.

Pharmacological reactivity of sensitized blood vessels has been less studied than that of airways. Aorta rings were obtained from normal and actively sensitized guinea pigs and prepared for isometric recording of tension changes. Noradrenaline (10 nM-10 microM), histamine (0.1 microM-0.1 mM) and KCl (10-100 mM) produced concentration-related contractions of normal tissues. Removal of endothelium resulted in a marked left upward shift of the concentration-response curve to noradrenaline but it did not alter histamine- or KCl-induced responses. Pretreatment with ibuprofen (10 microM) or L-NG-nitroarginine (L-NOARG, 3.3 microM) enhanced noradrenaline-induced responses without affecting those to histamine or KCl. Removal of endothelium or pretreatment with ibuprofen or L-NOARG did not alter agonist-induced responses in sensitized tissues. Neuronal uptake and release of [3H]-noradrenaline did not differ in normal and sensitized tissues. Loss of the modulatory role of endothelium and other mechanisms may be involved in the hyperreactivity of sensitized guinea pig aorta.

Animals↗
PubMed1991

Bioavailability of fluoride from dietary sepiolite in the lamb.

Nine weeks after weaning, 12 lambs were randomised to 2 groups, each consisting of 6 animals. One group received a diet containing 213.9 mg/kg of fluor (F) in the form of sodium fluoride (NaF) and the other group received a diet containing 212.3 mg/kg of fluor in the form of sepiolite. The 24 h time courses of plasma fluoride concentrations showed that after feeding the average peak plasma concentration of the NaF-fed group was 0.75 microgram F/ml; that of the sepiolite-fed group was 0.35 microgram F/ml. The 12-h area under the plasma concentration curve (AUC) values in the NaF-fed group were higher with statistical significance (P less than 0.001) at each time point. Compared with fluoride from NaF, the relative bioavailability of fluoride from sepiolite was found to be very weak.

Animal Feed↗
PubMed1990

Autolysis of proproteinase E in bovine procarboxypeptidase A ternary complex gives rise to subunit III.

Extracts of bovine pancreatic tissue are shown by HPLC to contain two distinct ternary complexes of procarboxypeptidase A (subunit I), chymotrypsinogen C (subunit II) and either proproteinase E or subunit III. It is shown that proproteinase E in the complex generates subunit III by removal of 13 N-terminal residues when the former is allowed to autolyze in solution or when catalytic amounts of isolated active proteinase E are added to it. Autolysis of proproteinase E was accompanied by the loss of potential activity towards specific synthetic substrates and occurred at a higher rate in pancreatic juice than in pancreatic tissue extracts, even when both were processed in the presence of serine protease inhibitors. We conclude that subunit III (also called truncated protease E) is an autolytic product of proproteinase E and not an ab initio component of the native ternary complex.

Amino Acid Sequence↗
PubMed1990

Role of epithelium in agonist-induced contractile responses of guinea-pig trachealis: influence of the surface through which drug enters the tissue.

1. A method has been used in guinea-pig isolated tracheal rings to achieve selective drug entry from the adventitial or mucosal surface. A study has been made of the effects of epithelium removal on responses to spasmogens entering the tissue solely from the adventitial or the mucosal surface. 2. Cumulative concentration-response curves for KCl (1 to 100 mM), acetylcholine (0.1 microM to 10 mM) and histamine (1 microM to 1 mM) were constructed in intact and epithelium-denuded tracheal rings in circumstances where drug entry was unrestricted or restricted to the adventitial or mucosal surface. 3. Epithelium removal did not alter the responsiveness or sensitivity of tracheal rings to KCl either when drug entry was unrestricted or when drug entry was restricted to the adventitial or mucosal surface. 4. When acetylcholine entered from the mucosal or adventitial surfaces of intact tracheal rings its concentration-response curve was displaced to the right with respect to that obtained for unrestricted drug entry. A greater rightward shift was observed for mucosal drug entry than for adventitial drug entry. Epithelium removal potentiated acetylcholine entering from the mucosal surface to a greater extent (27.5 fold) than it potentiated acetylcholine entering from both surfaces (4 fold). Epithelium removal did not potentiate effects of acetylcholine entering from the adventitial surface alone. 5. In intact tracheal segments, concentration-response curves for histamine entering from the mucosal surface were displaced to the right compared with those for histamine entering in an unrestricted fashion or from the adventitial surface alone. This displacement was absent in epithelium-denuded preparations. Epithelium removal potentiated (2-3 fold) histamine entering from the mucosal surface or entering in an unrestricted way. It did not potentiate histamine entering from the adventitial surface alone. 6. Our findings suggest that the epithelium does not modulate tracheal responses to KC1. Its ability to modulate responses to acetylcholine and histamine is observed when these spasmogens enter the tissue from the mucosal surface but not when they enter from the adventitial surface. The mechanism by which epithelium removal preferentially potentiates acetylcholine and histamine entering from the mucosal rather than the adventitial surface remains to be determined.

Acetylcholine↗