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Biomedical subjects

M Macías

Publications and source records attributed to M Macías.

At least 19 recordsLinked to original sources
PubMed2006

[Hepatic stellate cells: it's role in normal and pathological conditions].

Hepatic fibrosis is a dynamic and sophisticatedly regulated wound healing response to chronic hepatocellular injury. This fibrotic process results from the accumulation of extracellular matrix (ECM) including collagen, proteoglycan, and adhesive glycoproteins which are principally produced by hepatic stellate cells (HSC), a mesenchymal cell type located between parenchymal cell plates and sinusoidal endothelial cells in the space of Disse. In physiological conditions, quiescent HSCs play important roles in the regulation of retinoid homeostasis and ECM remodeling by producing ECM components as well as metalloproteases and its inhibitor. However during hepatic fibrogenesis, HSCs are known to be activated or "transdifferentiated" to myofibroblast-like cells which play a pivotal role in ECM remodeling and hepatic blood flow regulation. Activation of HSC is now well established as the key process involved in the development of hepatic fibrosis. Both basic morphology and functions of HSCs in normal conditions and its role in pathological fibrosis will be discussed in this review.

Animals↗
PubMed2003

Calcium alginate gel as encapsulation matrix for coimmobilized enzyme systems.

Encapsulation within calcium alginate gel capsules was used to produce a coimmobilized enzyme system. Glucose oxidase (GOD) and catalase (CAT) were chosen as model enzymes. The same values of Vmax and Km app for the GOD encapsulated system and for the GOD-CAT coencapsulated system were calculated. When gel beads and capsules were compared, the same catalyst deactivation sequence for the two enzymes was observed. However, when capsules were employed as immobilization support, GOD efficiencies were higher than for the gel beads. These results were explained in terms of the structure of the capsules.

Alginates↗
PubMed2001

Phytotoxic naphthopyranone derivatives from the coprophilous fungus Guanomyces polythrix.

Reinvestigation of the fermentation broth and mycelium of the coprophilous fungus Guanomyces polythrix, grown in static conditions, led to the isolation of several phytotoxic compounds, including two new naphthopyranone derivatives, namely (2S, 3R)-5-hydroxy-6,8-dimethoxy-2,3-dimethyl-2,3-dihydro-4H-naphtho[2,3-b]-pyran-4-one and (2S, 3R)-5-hydroxy-6,8,10-trimethoxy-2,3-dimethyl-2,3-dihydro-4H-naphtho[2,3-b]-pyran-4-one. The structures of the new compounds were established by spectral and chiroptical methods. In addition, the structure of 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ester was unambiguously determined by X-ray analysis. The isolates caused significant inhibition of radicle growth of two weed seedlings (Amaranthus hypochondriacus and Echinochloa crusgalli) and interacted with both spinach and bovine brain calmodulins.

Amaranthus↗
PubMed2001

Melatonin, mitochondria, and cellular bioenergetics.

Aerobic cells use oxygen for the production of 90-95% of the total amount of ATP that they use. This amounts to about 40 kg ATP/day in an adult human. The synthesis of ATP via the mitochondrial respiratory chain is the result of electron transport across the electron transport chain coupled to oxidative phosphorylation. Although ideally all the oxygen should be reduced to water by a four-electron reduction reaction driven by the cytochrome oxidase, under normal conditions a small percentage of oxygen may be reduced by one, two, or three electrons only, yielding superoxide anion, hydrogen peroxide, and the hydroxyl radical, respectively. The main radical produced by mitochondria is superoxide anion and the intramitochondrial antioxidant systems should scavenge this radical to avoid oxidative damage, which leads to impaired ATP production. During aging and some neurodegenerative diseases, oxidatively damaged mitochondria are unable to maintain the energy demands of the cell leading to an increased production of free radicals. Both processes, i.e., defective ATP production and increased oxygen radicals, may induce mitochondrial-dependent apoptotic cell death. Melatonin has been reported to exert neuroprotective effects in several experimental and clinical situations involving neurotoxicity and/or excitotoxicity. Additionally, in a series of pathologies in which high production of free radicals is the primary cause of the disease, melatonin is also protective. A common feature in these diseases is the existence of mitochondrial damage due to oxidative stress. The discoveries of new actions of melatonin in mitochondria support a novel mechanism, which explains some of the protective effects of the indoleamine on cell survival.

Adenosine Triphosphate↗
PubMed2001

Effect of propranolol plus exercise on melatonin and growth hormone levels in children with growth delay.

The pineal gland in humans is under both alpha- and beta-adrenergic control, although it seems that beta1-adrenoceptors are mainly implicated in melatonin secretion. In the present study, we evaluated the role of beta-adrenergic innervation on melatonin production and its relation with the production of growth hormone (GH). Thirty-four children (15 males and 19 females, mean age 10.5 +/- 0.8 years) from the University of Granada Hospital were studied. The children were included in a protocol for the evaluation of growth delay using the propranolol + exercise test. This standardized test allowed us to study simultaneously the role of an unspecific beta-adrenergic blocker such as propranolol and of an adrenergic stimulus such as exercise on the pineal production of melatonin. Changes in plasma levels of melatonin and GH were determined at basal, 120 and 140 min after the test was applied. Hormonal determinations were carried out by commercial radioimmunoassay kits previously standardized in our laboratory. The results show a significant decrease in plasma melatonin levels at 120 and 140 min after the test (P < 0.05), whereas GH levels increased significantly at 140 min (P < 0.001). The decrease of melatonin levels was a consequence of the test, since in a control group, the circadian decay of melatonin was significantly less pronounced (P < 0.05). These data suggest an inverse relationship between melatonin and GH after the propranolol + exercise test, and the reduction in melatonin may be related to its depletion by exercise-induced oxidative stress.

Adolescent↗
PubMed2001

Calcium-dependent effects of melatonin inhibition of glutamatergic response in rat striatum.

The effects of melatonin, amlodipine, diltiazem (L-type Ca2+ channel blockers) and omega-conotoxin (N-type Ca2+ channel blocker) on the glutamate-dependent excitatory response of striatal neurones to sensory-motor cortex stimulation was studied in a total of 111 neurones. Iontophoresis of melatonin produced a significant attenuation of the excitatory response in 85.2% of the neurones with a latency period of 2 min. Iontophoresis of either L- or N-type Ca2+ channel blocker also produced a significant attenuation of the excitatory response in more than 50% of the recorded neurones without significant latency. The simultaneous iontophoresis of melatonin + amlodipine or melatonin + diltiazem did not increase the attenuation produced by melatonin alone. However, the attenuation of the excitatory response was significantly higher after ejecting melatonin + omega-conotoxin than after ejecting melatonin alone. The melatonin-Ca2+ relationship was further supported by iontophoresis of the Ca2+ ionophore A-23187, which suppressed the inhibitory effect of either melatonin or Ca2+ antagonists. In addition, in synaptosomes prepared from rat striatum, melatonin produced a decrease in the Ca2+ influx measured by Fura-2AM fluorescence. Binding experiments with [3H]MK-801 in membrane preparations from rat striatum showed that melatonin did not compete with the MK-801 binding sites themselves although, in the presence of Mg2+, melatonin increased the affinity of MK-801. The results suggest that decreased Ca2+ influx is involved in the inhibitory effects of melatonin on the glutamatergic activity of rat striatum.

Amlodipine↗
PubMed2001

Melatonin and beta-endorphin changes in children sensitized to olive and grass pollen after treatment with specific immunotherapy.

BACKGROUND: Specific immunotherapy for respiratory allergy, a seasonal disease, significantly reduces the inflammatory process, attenuating the clinical symptoms. The mechanism for the clinical beneficial effect of immunotherapy has not yet been clarified. Melatonin shows a circadian and seasonal variation and together with the endogenous opioid system plays an immunomodulatory role acting on both specific and nonspecific immunity responses. Thus, the possibility that immunotherapy involved changes in the melatonin-opioid system was investigated. METHODS: Thirty-five children aged 3-15 years with rhinitis and asthma due to olive + grass pollen sensitization were studied. The patients were treated with depot extracts containing the identified allergens with increasing doses from 1 to 1,000 IU/ml during 3 months. Melatonin, beta-endorphin, total and specific IgE and IgG4 were determined before and after treatment. RESULTS: All children showed a significant improvement of their symptoms at the end of the treatment, coinciding with a significant drop of both melatonin and beta-endorphin levels. Total IgE decreased in most of the cases although the mean values did not show significant changes. Specific IgE and IgG4 were also unchanged. A significant correlation between melatonin and beta-endorphin and between beta-endorphin and IgG4 was found before immunotherapy, and these correlations disappeared when the treatment was finished. CONCLUSIONS: The decrease in the levels of melatonin and beta-endorphin suggests the disappearance of their stimulating influence on the immune system. Thus, hyposensitization after immunotherapy may involve, at least in part, the inhibition of the immunoenhancing properties of the melatonin-opioid system.

Adolescent↗
PubMed2001

Characterization of nocturnal ultradian rhythms of melatonin in children with growth hormone-dependent and independent growth delay.

To assess the existence of a possible nocturnal ultradian rhythm of melatonin in children, we analyzed 28 pediatric patients (mean age, 9.08 +/- 2.2 yr) with GH-dependent and GH-independent growth delay. Plasma melatonin was measured by RIA in children sampled every 30 min between 2100-0900 h. Statistical analysis consisted of cluster analysis to examine the presence of peaks and troughs. The pattern of melatonin levels was related to the cause of growth delay, although the means of the nocturnal concentrations of melatonin were similar in all children. Interestingly, children with a GH deficit showed a nearly normal melatonin profile, whereas children with normal GH values but abnormal growth displayed atypical profiles of melatonin. The results also prove the existence of an ultradian rhythm of melatonin in most of the patients studied. The ultradian rhythm of melatonin in children was characterized by irregular interburst intervals, thus differing from the rhythm previously described in adults that had an almost constant pulse frequency. Moreover, the existence of low and high melatonin producers was revealed in the study, a feature unrelated to the cause of growth delay. The group of children with a GH deficit showed the lowest values of integrated melatonin production and of the area of peaks and troughs. These results prove that children exhibit an ultradian rhythm of melatonin like that in adults. Whereas it is not clear whether the episodic production of melatonin is required for its biological actions, the existence of irregular pulses may reflect endocrine influences at this age and/or the immaturity of the intrinsic pulse generator.

Adult↗
PubMed2000

Glucose oxidase release from calcium alginate gel capsules.

Diffusion of glucose oxidase within calcium alginate gel capsules has been assayed and the experimental data fitted to a simple semi-empirical power equation, which is used to analyse the solute release from polymeric devices. It was found that an increase in the concentration of sodium alginate and calcium chloride gives rise to a reduction in the enzyme leakage. This was verified when glucose oxidase (GOD) diffusion percentages were compared in capsules with thicknesses of the same order of magnitude but obtained under different experimental conditions. So, the use of sodium alginate and calcium chloride solutions of concentrations 0.5% w/v and 2.6% w/v, respectively, lead to a diffusion percentage of 25 +/- 2. This percentage was reduced to 8 +/- 3 when sodium alginate and calcium chloride concentrations were fixed at 1% w/v and 4% w/v, respectively, even though the thicknesses of the capsules were of the same order of magnitude.

Journal Article↗
PubMed2000

A simplification of the protein assay method of Ramsay et al. for the quantification of Thiobacillus ferrooxidans in the presence of ferric precipitates.

A variation on Ramsay's method for microbial protein determination has been developed in order to quantify Thiobacillus ferrooxidans attached to ferric precipitates or in aqueous suspensions containing such precipitates. Some modifications have been introduced to provide a method that is more sensitive, simple and rapid. A linear standard curve is presented to permit a direct correlation between the protein concentration (mg/l) and the cell concentration (10(6) cells/ml). An application of this method has been demonstrated in the quantification of biomass immobilized on the surface of polyurethane foam particles in a packed bed reactor, several experiments having been conducted to establish the best conditions for the quantification studies.

Bacterial Proteins↗
PubMed2000

Phytotoxic compounds from the new coprophilous fungus guanomyces polythrix.

Bioactivity-directed fractionation of the fermentation broth and mycelium of the coprophilous fungus Guanomyces polythrix led to the isolation of several phytotoxic compounds, including five new naphthopyranone derivatives (1-5). In addition, rubrofusarin B, emodin, citrinin, and 4-hydroxybenzoic acid methyl ester were obtained. The structures of the new compounds were established by spectral and chiroptical methods. The isolates caused significant inhibition of radicle growth of two weed seedlings (Amaranthus hypochondriacus and Echinochloa crusgalli) and interacted with both spinach and bovine brain calmodulins.

Animals↗
PubMed2000

Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo.

Melatonin displays antioxidant and free radical scavenger properties. Due to its ability with which it enters cells, these protective effects are manifested in all subcellular compartments. Recent studies suggest a role for melatonin in mitochondrial metabolism. To study the effects of melatonin on this organelle we used ruthenium red to induce mitochondrial damage and oxidative stress. The results show that melatonin (10 mg/kg i.p.) can increase the activity of the mitochondrial respiratory complexes I and IV after its administration in vivo in a time-dependent manner; these changes correlate well with the half-life of the indole in plasma. Melatonin administration also prevented the decrease in the activity of complexes I and IV due to ruthenium red (60 microg/kg i.p.) administration. At this dose, ruthenium red did not induce lipid peroxidation but it significantly reduced the activity of the antioxidative enzyme glutathione peroxidase, an effect also counteracted by melatonin. These results suggest that melatonin modulates mitochondrial respiratory activity, an effect that may account for some of the protective properties of the indoleamine. The mitochondria-modulating role of melatonin may be of physiological significance since it seems that the indoleamine is concentrated into normal mitochondria. The data also support a pharmacological use of melatonin in drug-induced mitochondrial damage in vivo.

Animals↗
PubMed2000

Effect of clonidine on plasma ACTH, cortisol and melatonin in children.

An interaction between melatonin and adrenocorticotropin (ACTH) seems to occur in humans and both hormones respond to beta-adrenergic stimulation. As in lower animal species, human pineal gland also contains alpha2-adrenergic receptors as does the hypothalamus-pituitary axis. In this study the response of the pineal gland and of the hypothalamus-pituitary-adrenal axis to alpha2-adrenergic stimulation was assessed. Twenty-nine children (21 males, mean age 11.2 +/- 0.6 yr and eight females, mean age 9.1 +/- 1.1 yr) from the University of Granada Hospital were studied. The children were diagnosed as having growth problems but with a normal response of growth hormone (GH) to clonidine test. Changes in plasma levels of ACTH, cortisol and melatonin were evaluated in these children after oral administration of the alpha2-adrenoceptor agonist clonidine (100 microg/m2) or a placebo. Plasma ACTH, cortisol and melatonin were measured before (basal) and at 30, 60 and 90 min after oral clonidine or placebo administration. Hormonal determinations were carried out by commercial radioimmunoassay kits, previously standardised in our laboratory. The results show a significant decrease in plasma ACTH, cortisol and melatonin 30 min after clonidine administration (P < 0.001), reaching lowest values at 90 min after the drug was administered. The reduction in the levels of these hormones is independent of their normal circadian decay since the control group showed a significantly different pattern of behaviour. These data support the existence of an inhibitory alpha2-adrenergic influence on both the pineal gland and the hypothalamus-pituitary-adrenal in children and further support the presence of alpha2-adrenoceptors in the human pineal gland.

Adrenergic alpha-Agonists↗
PubMed2000

Structure-related inhibition of calmodulin-dependent neuronal nitric-oxide synthase activity by melatonin and synthetic kynurenines.

We recently described that melatonin and some kynurenines modulate the N-methyl-D-aspartate-dependent excitatory response in rat striatal neurons, an effect that could be related to their inhibition of nNOS. In this report, we studied the effect of melatonin and these kynurenines on nNOS activity in both rat striatal homogenate and purified rat brain nNOS. In homogenates of rat striatum, melatonin inhibits nNOS activity, whereas synthetic kynurenines act in a structure-related manner. Kynurenines carrying an NH(2) group in their benzenic ring (NH(2)-kynurenines) inhibit nNOS activity more strongly than melatonin itself. However, kynurenines lacking the NH(2) group or with this group blocked do not affect enzyme activity. Kinetic analysis shows that melatonin and NH(2)-kynurenines behave as noncompetitive inhibitors of nNOS. Using purified rat brain nNOS, we show that the inhibitory effect of melatonin and NH(2)-kynurenines on the enzyme activity diminishes with increasing amounts of calmodulin in the incubation medium. However, changes in other nNOS cofactors such as FAD or H(4)-biopterin, do not modify the drugs' response. These data suggest that calmodulin may be involved in the nNOS inhibition by these compounds. Studies with urea-polyacrylamide gel electrophoresis further support an interaction between melatonin and NH(2)-kynurenines, but not kynurenines lacking the NH(2) group, with Ca(2+)-calmodulin yielding Ca(2+)-calmodulin-drug complexes that prevent nNOS activation. The results show that calmodulin is a target involved in the intracellular effects of melatonin and some melatonin-related kynurenines that may account, at least in part, for the neuroprotective properties of these compounds.

Animals↗
PubMed1999

High frequency of de novo deletions in Mexican Duchenne and Becker muscular dystrophy patients. Implications for genetic counseling.

Duchenne muscular dystrophy (DMD) is the most common lethal hereditary neuromuscular disease. As there is no effective treatment, accurate carrier detection is essential for genetic counseling and prevention. Although linkage analysis has been widely used for this purpose, being an indirect analysis it has several limitations. Using linkage analysis for carrier detection, we found serious limitations, mainly because 82.9% of all proposita were isolated cases. We used quantitative polymerase chain reaction for direct carrier detection in families with exon deletions and found a higher than expected frequency of de novo deletions (62.2%). Furthermore, only 20.7% of the mothers of isolated deletion DMD/Becker muscular dystrophy (BMD) patients were found to be carriers. This result suggests that the Mexican population has a high frequency of de novo DMD mutations.

Creatine Kinase↗