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Biomedical subjects

F J Alvarez

Publications and source records attributed to F J Alvarez.

At least 91 records · Page 5Linked to original sources

Patterns of smoking in Spain. Results from a regional general population survey.

Smoking patterns were examined in 2500 individuals, aged 14-70 years living in Castille and Leon (Spain) in the fall of 1992. Of these, 39.6% were regular smokers, 7.2% were occasional smokers, 14.8% were former smokers, and 30.4% were non-smokers. Sex differences were striking: there was a higher prevalence of regular smokers among males than females, males smoked much more, and were more frequently French-type cigarette smokers. A comparison of the present figures with data from an earlier survey carried out in 1989 suggests that smoking is decreasing in Spain.

Adolescent↗

Presence of calcitonin gene-related peptide in intraepithelial nerve fibers and motor end-plates of the cat esophagus: a light and electron microscopic study.

The morphology and distribution of the motor end-plates in the striated muscle and the terminal nerve fibers in the epithelium of the wall of the esophagus, which contain calcitonin gene-related peptide, were studied by light and electron microscopic immunocytochemistry, Varicose immunoreactive nerve fibers arising from the subepithelial plexus were seen to penetrate into the epithelium where they ended in terminal boutons. These nerve fibers lost their Schwann cells just at the point of penetration into the epithelium. Characteristically, the epithelial cells of the spinous layer showed prominent tonofilaments in the part of the cytoplasm in contact with the immunoreactive nerve varicosities, but membrane specializations between these structures were not observed. In the striated muscle of the esophageal wall there were small, elliptical, immunoreactive motor end-plates, which contained a small number of axonal clear vesicles and mitochondria. They were associated with relatively short and rarely branched junctional folds, reduced postjunctional surfaces and few organelles in the underlying sarcoplasm, features characteristic of the neuromuscular junctions of slow-fatiguing red muscle fibers. The two types of immunoreactive nerve endings, epithelial and muscular, presumably participate in afferent and efferent limbs respectively of the neural control of esophageal motility. The relationship between immunoreactive nerve terminals and epithelial cells in the spinous layer exhibiting prominent tonofilaments allowed us to speculate about the existence of two different patterns of reception to sensory stimuli. The intraepithelial fibers that end in the middle layer of the epithelium could be related to mechanoreceptor reflexes, while those that end in the upper layer may be related to thermoreceptor reflexes or facilitate information about the chemical and other characteristics of foods.

Animals↗

Gender differences in patterns of alcohol consumption in Spain.

Gender differences in alcohol consumption components, hazardous alcohol consumption, and drinking patterns among Spaniards were analyzed. The study was conducted in the fall of 1992 on 2,500 individuals, aged 14-70 years, who lived in the region of Castile and Leon (Spain). Males drank more frequently (with a high intake of alcohol), were more likely to be hazardous drinkers, and started drinking earlier than females. Both sexes drank beer in a similar way, but not wine and spirits. Males and females gave similar reasons for drinking and showed similar patterns of "family" drinking, although sex differences in other patterns of alcohol consumption were found. The relevance of results was discussed.

Adolescent↗

Screening for problem drinkers in a general population survey in Spain by use of the CAGE scale.

The CAGE scale has been used as a screening device for problem drinkers in a general population survey. The study was conducted in the fall of 1992 on 2,500 individuals, aged 14-70 years, who live in the region of Castile and Leon (Spain). Alcohol was consumed at least once a week by 51.3% of those surveyed. A total of 136 drinkers (10.6% of "weekly" drinkers, 5.4% of total sample) had positive CAGE scores, as determined by two or more affirmative answers, 120 men (14.3%) and 16 women (3.6%). Those with CAGE positive scores consumed a daily mean of 57.5 grams of pure alcohol per day. The utility of the CAGE scale in a general population survey and the difficulties in applying it are discussed.

Adolescent↗

Spinal epidural abscess caused by Brucella: case report.

We report a case of a patient with symptoms and signs of sciatica, due to spinal epidural abscess caused by Brucella, which was diagnosed by Magnetic Resonance Image. The literature is reviewed and the radiological features, particularly magnetic resonance image findings, are analyzed.

Abscess↗

Ultrastructural morphology, synaptic relationships, and CGRP immunoreactivity of physiologically identified C-fiber terminals in the monkey spinal cord.

The spinal cord terminations of two electrophysiologically identified single C-fibers (one identified as a C-nociceptor) were intra-axonally labeled with horseradish peroxidase and analyzed with both light and electron microscopy. Serial section ultrastructural analysis and postembedding immunocytochemical techniques for calcitonin gene-related peptide (CGRP), substance P (SP), and GABA were used to study the synaptology, and neuropeptide content. All C-terminal synapses were in laminae I and II. The terminals sampled (n = 73) from these two C-fibers rarely established glomerular synaptic complexes, but rather, simple terminals, usually measuring 1-4 microns in length and 1-3 microns in diameter. They most often established 1 or 2 (range 1 to 5) quite large asymmetric axodendritic synaptic contacts. Postsynaptic structures included dendritic spines and shafts with and without vesicles. C-terminals were filled with small round synaptic vesicles (45-60 nm) and also contained variable numbers of large dense-core vesicles (LDCVs, 80-110 nm). LDCVs inside identified C-terminals frequently displayed CGRP immunoreactivity. We were unable to detect SP immunoreactivity inside our sample of C-fiber LDCVs. C-terminals were never found postsynaptic to other profiles. Thus, the C-fiber terminals sampled in this study have simple synaptology, do not receive presynaptic control and contain CGRP immunoreactivity. They differ greatly from the terminals of A delta nociceptors studied previously by our group that had glomerular endings, often received presynaptic input and did not contain CGRP immunoreactivity. This suggests the existence of different processing mechanisms, at the level of the first synapse, for nociceptive inputs arriving to lamina I and II through different types of primary afferents.

Animals↗

Alcohol-related mortality in Spain.

Alcohol-related mortality and years of potential life lost in Spain in 1986 have been studied according to the official statistics with regard to the population mortality in our country. 6.1% of the deaths in Spain in 1986 were related to alcohol consumption, mainly caused by malignant neoplasm (26.0%), digestive diseases (23.6%), and unintentional injuries (21.1%). Mean potential years of life lost for alcohol-related deaths until 65 was 7.3. Unintentional injuries were responsible for the greater part (61.2%) of alcohol-related years of potential life lost. The present study shows the high mortality rate associated with alcohol consumption in our country, as well as its importance in premature death.

Aged↗

Patterns of alcohol consumption among the general population of Castile and Leon (Spain).

A total of 2500 individuals, aged 14-70, who live in Castile and Leon (Spain), were surveyed in the spring of 1989 with regard to their alcohol consumption and its patterns. Among those surveyed 26.2% were 'daily' drinkers and 66.0% 'weekly' drinkers. Differences of alcohol use (frequency) and intake were reviewed with regard to sociodemographic factors such as gender, age, and marital status. Beer (52.6%) was the favourite drink, with wine (20.6%) the second most commonly consumed alcohol beverage. Most of those surveyed (54.6%) were 'light' drinkers (1-39 g/day of pure alcohol), while 3.0% had an intake of over 80 g/day ('heavy' drinkers). The average age at which they started drinking was 16.2 years. The results allow a better understanding of the pattern of alcohol consumption in Spain.

Adolescent↗

Differential uptake of systemic fluorochrome Hoechst 33342 in lung and liver metastasis of B16 melanoma.

The growth and vascularization patterns of B16 melanoma colonies in the liver and lungs were measured and compared by histological techniques and dye diffusion patterns after injection of the fluorochrome Hoechst 33342. In the liver, the fluorescent pattern of dye diffusion revealed that uninodular tumours measuring up to 146 microns in diameter were not functionally vascularized. However, when the nodules fused to give rise to multinodular tumours measuring between 256 and 366 microns in diameter, a reticular dye diffusion pattern revealed functional tumour vascularization. In the lungs, subpleural, parenchymal and peritubular (i.e. surrounding blood vessels and airways) tumours were observed. The two former classes were vascularized down to thicknesses and diameters of 49 and 24 microns respectively. In contrast, dye diffusion was never seen in peritubular tumour cuffs up to 609 microns in thickness. The results indicate differences in vascularization patterns in B16 tumours in the liver and lungs, and differences between tumours growing in different sites within the lungs. If these results are applicable to metastases in these two organs, they indicate potential diffusion-mediated resistance to chemotherapy, and potential hypoxia-mediated resistance to radiotherapy of both metastases and micrometastases.

Animals↗

Mesostriatal and mesolimbic dopamine uptake binding sites are reduced in Parkinson's disease and progressive supranuclear palsy: a quantitative autoradiographic study using [3H]mazindol.

It has been suggested that not only mesostriatal but also mesolimbic pathways are involved in the degeneration of dopaminergic neurons in Parkinson's disease. Using quantitative ligand autoradiography we have investigated dopamine transporter sites in basal ganglia of patients affected by Huntington's chorea, Parkinson's disease and progressive supranuclear palsy. [3H]Mazindol, a ligand for catecholamine uptake, was used in the presence of desipramine to block the binding to norepinephrine uptake sites. Schizophrenic cases were entered in the study to take into account the effects of neuroleptics, commonly administered also to Huntington's disease patients, on dopamine uptake sites. In control cases high densities of [3H]mazindol binding sites were found in the caudate nucleus, putamen and nucleus accumbens, whereas very low densities were present in substantia nigra and ventral tegmental area. In Huntington's chorea the density of [3H]mazindol binding sites was slightly decreased in the caudate nucleus, an area severely affected by the neurodegenerative process. In schizophrenic patients the density of dopamine uptake sites in the basal ganglia was slightly reduced, mainly in the middle third of putamen. Both Parkinson's disease and progressive supranuclear palsy populations were characterized by a marked loss of [3H]mazindol binding sites in the neostriatum (about 75%) and in the nucleus accumbens (about 65%). These results suggest that in Parkinson's disease and progressive supranuclear palsy severe decreases of dopamine uptake sites occur not only in the mesostriatal pathway but also in the mesolimbic tract.

Aged↗

Kinetics and mechanism of degradation of Zileuton, a potent 5-lipoxygenase inhibitor.

Zileuton (N-(1-benzo[b]thien-2-ylethyl)N-hydroxyurea) is a powerful 5-lipoxygenase inhibitor. The chemical degradation of Zileuton and related hydroxyurea derivatives was studied in aqueous solutions as a function of pH and temperature. The pH profile for the degradation of Zileuton shows an acid-catalyzed region at pH values below 2, water hydrolysis of the protonated form at pH values from 3 to 8, and water hydrolysis of the unprotonated form at pH values greater than 9. Hydrolysis of the hydroxyurea moiety to give the hydroxylamine derivative represents the main degradation pathway for Zileuton. This product, however, is not stable and is present at low concentrations at pH values below 6 and not observed at pH values greater than 7. Further decomposition of the hydroxylamine derivative leads to the observed degradation products. Air oxidation to the isomeric oximes accounts for the observed products at pH values greater than 7. Hydrolysis of the oximes to the ketone derivative accounts for the observed products at pH values 2 to 6. Parallel decomposition pathways to the alcohol derivative were noted under strongly acidic conditions, pH 0 to 2.

Chromatography, High Pressure Liquid↗

The catalytic power of pyruvate decarboxylase. A stochastic model for the molecular evolution of enzymes.

Pyruvate decarboxylase (PDC) catalyzes the decarboxylation of pyruvate anion by a factor of around 10(12), compared with the non-enzymic decarboxylation by thiamine, under standard state conditions of 1 mM pyruvate and thiamine diphosphate (TDP), pH 6.2. Free-energy diagrams constructed on the basis of earlier measurements for the enzymic and non-enzymic reactions give some information on catalysis by PDC. PDC stabilizes the reactant state preceding TDP addition to pyruvate by 76 kJ mol-1 and the transition state for the addition by 83 kJ mol-1. PDC stabilizes the reactant state preceding decarboxylation (presumably alpha-lactyl-TDP) by 27 kJ mol-1 and the transition state for decarboxylation by 68 kJ mol-1. In addition, the free-energy diagrams reveal a leveling of reactant-state free energies in the enzymic reaction compared with the non-enzymic reaction, in that the former are nearly equal to each other. The enzyme-bound transition-state energies are similarly leveled. The energetic leveling of reactant states has been noted by Albery, Knowles and their coworkers in many enzymic reactions and termed 'matched internal thermodynamics.' They showed that the result would arise naturally (and inevitably) in the 'evolution to perfection' of enzymes, when the evolutionary process was treated by a deterministic model. The critical assumption of this model was the validity of a Marcus-type or Brønsted-type linear free-energy relationship between rate and equilibrium constants for reactions occurring wholly within enzyme complexes. Here a completely stochastic simulation of molecular evolution, with no deterministic assumptions, is shown to reproduce both 'matched internal thermodynamics' and the 'matched internal kinetics' or leveling of transition-state energies noted here. The Albery-Knowles result is thus more general than might have been supposed.

Biological Evolution↗

[Pulmonary surfactant in experimental congenital diaphragmatic hernia].

This paper examines the amounts of tensoactive phospholipids in the lung tissue of rat fetuses treated with Nitrofen (TOK) and in control animals. The herbicide led to congenital diaphragmatic hernia (CDH) in some fetuses and to pulmonary hypoplasia (PH) in all. The amounts of phosphatidylcholine (PC), phosphatidylglycerol (PG), phosphatidylinositol (PI) and phosphatidylethanolamine (PE) per gram of fresh lung tissue were significantly increased in comparison with the control animals, those of phosphatidylserine (PS) and sphingomyelin (SM) were also increased, but not significantly. Fetuses with HP alone had intermediate values. These findings are in agreement with our previous demonstration of an excess of type II pneumocytes in this model, and point to the existence of some trouble of the secretion or release of surfactant in it; although they do no clarify whether the amount of alveolar surfactant is in fact decreased.

Animals↗

Synaptic interactions between GABA-immunoreactive profiles and the terminals of functionally defined myelinated nociceptors in the monkey and cat spinal cord.

This study analyzes the synaptic interactions between the central terminals of A delta high threshold mechanoreceptors (A delta HTMs) and GABA-immunoreactive profiles. A delta HTM primary afferents from three monkeys and one cat were electrophysiologically identified and intracellularly labeled with HRP, and their terminal arborizations in laminae I and II of the sacrocaudal spinal cord were studied at the ultrastructural level. GABA-immunoreactive profiles in relation to A delta HTM terminals were demonstrated using postembedding colloidal gold techniques. Monkey A delta HTM terminals (n = 131) usually constituted the central element of synaptic glomeruli; they established large asymmetric synaptic contacts with 1-13 dendrites (modal value 2-4) and were surrounded by 0-6 peripheral axon terminals (modal value 2-3). The large majority (around 85%) of the peripheral axon terminals were GABA immunoreactive. They were found presynaptic to the A delta HTM terminal and/or to dendrites postsynaptic to the primary afferent terminal. Furthermore, all peripheral axon terminals found presynaptic to the A delta HTM terminals showed GABA immunoreactivity. Within a single A delta HTM fiber, this synaptic arrangement was found in 20-60% of its boutons. In addition, 28% of the postsynaptic dendritic profiles displayed weak GABA immunoreactivity. Some of them contained vesicles; however, only in a few cases did we observe synapses between a GABA-immunoreactive vesicle-containing dendrite and a dendritic profile postsynaptic to an A delta HTM terminal. Similar synaptology and interactions with GABA-immunoreactive profiles were displayed by the terminals of the single cat A delta HTM fiber studied. Our data support the hypothesis that GABA-containing neurons use both presynaptic and/or postsynaptic mechanisms to exert a powerful control, presumably inhibitory, over the transmission of nociceptive information between A delta HTM afferents and second-order neurons in monkey and cat spinal cord. Our results also imply that GABA may be released within the synaptic glomeruli formed by A delta HTM terminals either by local dendrites or by axon terminals. We discuss the possibility that these GABAergic synapses can be driven by inputs from both primary afferents and/or descending systems to modulate the transmission of nociceptive sensory information.

Animals↗

Morpho-functional study of vascular fluorochrome delivery to lung and liver metastases of Lewis lung carcinoma (3LL).

The growth of 3LL liver and lung metastases related to its vascular organization was studied by morphological and functional methods, using the Hoechst 33342 fluorescent DNA staining technique. Experimental liver and lung metastases were produced in syngeneic C57BL/6 mice by injection of 3LL tumor cells into a lateral tail vein or into the spleen, respectively. The resulting neoplasms were composed of large cells arranged in sheets with a thin irregularly distributed stroma. Scattered blood vessels with an open or closed lumen were observed within the tumor. Functional study of H33342 diffusion showed a single and reticular fluorescent pattern in liver metastases. In contrast, in lung metastases the fluorochrome diffusion revealed two different fluorescent patterns related to the location of the metastasis. Thus, parenchymal and subpleural metastasis presented a fluorescent pattern similar to that observed in the liver whereas metastases located around blood vessels and conducting airways never displayed fluorescence. In summary, our results suggest that the target metastatic organ and/or intra-organ location modulates the characteristics of metabolic exchange of the tumor cells in relation to the vascular organization of the metastatic focus.

Animals↗

Sub-populations of smaller diameter trigeminal primary afferent neurons defined by expression of calcitonin gene-related peptide and the cell surface oligosaccharide recognized by monoclonal antibody LA4.

Immunocytochemistry has been used to examine the trigeminal ganglion cell populations in the rat which expresses calcitonin gene-related peptide (CGRP) and the oligosaccharide antigen recognized by the monoclonal antibody LA4. Calcitonin gene-related peptide and LA4 identify two large but mainly separate populations of trigeminal ganglion cells. Depending on the method of assessment used, CGRP-immunoreactive cells represent 29-37% of trigeminal ganglion cells while LA4 labels 26-40% of the cells, but with only 8% overlap between the two populations. Both CGRP and LA4 label predominantly small diameter cells (mean diameters 23 microns and 25 microns respectively) but with CGRP cells exhibiting a greater range of diameters than LA4 cells. The cell sizes indicate that small diameter CGRP-immunoreactive cells and most LA4-immunoreactive cells are likely to have unmyelinated axons, and together the two populations can account for the great majority of unmyelinated trigeminal primary afferent neurons. Centrally, CGRP and LA4 show distinct patterns of staining. Thus although both antigens are found in lamina II of subnucleus caudalis of the spinal trigeminal nucleus, CGRP is most abundant in lamina I and lamina II outer while LA4 immunoreactivity is most dense in lamina II inner. In addition CGRP-, but not LA4-, immunoreactive fibres occur in the magnocellular portion of caudalis. Previous studies have show that in rat dorsal root ganglion cells CGRP coexists with most other known neuropeptides and can therefore be used as a general marker for peptide-containing primary afferents. In contrast LA4 labels a cell population which is probably largely identical to that identified by the presence of fluoride resistant acid phosphatase or by the binding of lectins such as Griffonia simplicifolia isolectin B4 and this population does not contain neuropeptides. Our results thus provide further evidence that unmyelinated primary afferents can be divided into peptide and non-peptide containing subpopulations and that these populations innervate distinct regions of laminae I and II.

Animals↗