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Biomedical subjects

M Macías

Publications and source records attributed to M Macías.

At least 37 records · Page 2Linked to original sources

Presence and effects of melatonin in Trypanosoma cruzi.

The unicellular organism Trypanosoma cruzi is an eukaryote whose cell cycle mainly occurs under darkness in the insect gut. The unique external phase corresponds to the metacyclic forms, the forms that are able to infect humans, which appear within the insect deyections. Thus, light may be a powerful stressor in this unicell. Epimastigote forms (the parasite forms that grow and transform to metacyclic forms in the insect gut) of Trypanosoma cruzi grow normally when cultured in a LD cycle of 0:24 hr, reaching exponential growth by the 7th day. A pulse of 2 hr of light (LD 2:22) was enough to block the growth of the epimastigotes, an effect that was correlated with the expression of heat-shock proteins during the first 120 min of light exposure. Thereafter, protein synthesis decreased. Light exposure of metacyclic forms also inhibits the parasitization ability. It is known that light regulates the production of melatonin in most animal species studied, including other unicells such as dinoflagellates. T. cruzi contains and synthesizes melatonin and, thus, light-mediated events on the parasite biological cycle could be mediated by light-induced changes in melatonin produced by this unicell. Epimastigotes cultured under continuous darkness produce melatonin over the 24 hr period in a biphasic manner. Coinciding with the melatonin peaks, there was high melatonin efflux from the parasite into the medium. Epimastigotes cultured for 7 days under a LD cycle of 2:22 hr showed a 55% reduction in melatonin content, although this reduction seems not to be related with the growth delay. In fact, incubation of epimastigotes with exogenous melatonin (1 pM) did not affect parasite growth, but significantly reduced their transformation into metacyclic forms by the 7-8th day of treatment. Thus, the light-dependent decrease in melatonin production by the unicell may be responsible, at least partially, for the light-induce parasitization inhibition. Moreover, melatonin production is highest in the metacyclic forms. These data support a link between light, melatonin production and parasitization ability of T. cruzi and suggest the participation of the indoleamine in its biological cycle.

Animals↗

Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents endotoxemia in lipopolysaccharide-induced multiple organ dysfunction syndrome in rats.

We evaluated the role of melatonin in endotoxemia caused by lipopolysaccharide (LPS) in unanesthetized rats. The expression of inducible isoform of nitric oxide synthase (iNOS) and the increase in the oxidative stress seem to be responsible for the failure of lungs, liver, and kidneys in endotoxemia. Bacterial LPS (10 mg/kg b. w) was i.v. injected 6 h before rats were killed and melatonin (10-60 mg/kg b.w.) was i.p. injected before and/or after LPS. Endotoxemia was associated with a significant rise in the serum levels of aspartate and alanine aminotransferases, gamma-glutamyl-transferase, alkaline phosphatase, creatinine, urea, and uric acid, and hence liver and renal dysfunction. LPS also increased serum levels of cholesterol and triglycerides and reduced glucose levels. Melatonin administration counteracted these organ and metabolic alterations at doses ranging between 20 and 60 mg/kg b. w. Melatonin significantly decreased lung lipid peroxidation and counteracted the LPS-induced NO levels in lungs and liver. Our results also show an inhibition of iNOS activity in rat lungs by melatonin in a dose-dependent manner. Expression of iNOS mRNA in lungs and liver was significantly decreased by melatonin (60 mg/kg b. w., 58-65%). We conclude that melatonin inhibits NO production mainly by inhibition of iNOS expression. The inhibition of NO levels may account for the protection of the indoleamine against LPS-induced endotoxemia in rats.

Animals↗

Comparison between tryptophan methoxyindole and kynurenine metabolic pathways in normal and preterm neonates and in neonates with acute fetal distress.

OBJECTIVE: To analyze the kynurenine and methoxyindole metabolic pathways of tryptophan in order to identify changes in premature neonates and in neonates suffering from fetal distress. METHODS: One hundred and twelve neonates were assigned to three groups: normal neonates (control group), preterm neonates (neonates born before the 37th gestational week) and neonates suffering from fetal distress. Each of these groups was then divided in two subgroups according to the time of birth corresponding with the time of blood sampling: a diurnal subgroup, comprising neonates whose blood was sampled between 0900 and 2100 h, and a nocturnal subgroup, comprising neonates whose blood was sampled between 2100 and 0900 h. Blood samples from the umbilical artery and vein were taken in the delivery room at birth from each neonate for measurement of melatonin, the main methoxyindole pathway metabolite. Urine samples were collected from 0900 to 2100 h (diurnal groups) and from 2100 to 0900 h (nocturnal groups), and the presence of kynurenic acid, xanturenic acid, 3-hydroxyantranilic acid, L-kynurenine and 3-hydroxykynurenine determined. RESULTS: The results show the existence of diurnal/nocturnal differences in the concentration of melatonin in cord blood and in the urinary excretion of kynurenines. In normal neonates, the production of methoxyindoles (determined as melatonin) is decreased during the day and increases at night, whereas production of kynurenines is high during the day, decreasing at night. In the fetal distress group, a significant increase in the umbilical artery concentration of melatonin was found. This group also showed a reduction in L-kynurenine concentrations in the diurnal and nocturnal groups, and an increase in xanturenic acid and 3-hydroxyantranilic acid during the day. Correlation and regression studies confirmed that the differences in the day/night pattern of the tryptophan metabolic pathways were greater in normal neonates than in the preterm and fetal distress groups. CONCLUSIONS: The results indicate the existence of an imbalance in tryptophan metabolites in preterm infants and those with fetal distress, blunting the normal diurnal/nocturnal rhythm of both melatonin and kynurenines.

Acute Disease↗

[Kikuchi's disease. A clinicopathological study of 3 cases].

We had reviewed all the patients with Histiocytic Necrotizing Lymphadenitis (Kikuchi's disease) seen in a General Hospital during two years. Three of the six cases were young females who showed the same clinical symptoms: Fever and unilateral painful, lymphadenopathy, usually at the latero-cervical region. All patients have mild neutropenia and high levels of serum transaminases. The lymph node biopsy yielded the proper diagnostic in all cases. The course of disease was good, and all patients healed without treatment one to two month after the symptom started. To date, we have not recorded any relapse. Our finding are quite similar to the other cases published in the medical literature. The benign course of this disease, and the need for biopsy to get a correct diagnosis, can explain why this disease may be unrecognized in clinical practice.

Adolescent↗

[Ulegyria and epilepsy].

Ulegyria is a derangement of the architecture of the cerebral cortex characterised by the presence of multiple small cerebral convolutions. It is caused by hypoxic-ischaemic damage of these convolutions in the perinatal period. This differentiates it from polimcrogyria which is due to damage during the period of late neuronal migration or early postmigration. The clinical findings vary from cases with hardly any symptoms to more severe forms which show psychomotor retardation, convulsive crises and/or motor defects. We describe the case of a 21-year-old patient who suffered anoxia during delivery, with a very low Apgar score, who presented with epileptic crises in childhood (motor foci which became generalized) with good anticonvulsant control. On examination, there was a slight mental handicap. On magnetic resonance an uligyric area was seen in the occipital cortex. High resolution magnetic resonance allows the diagnosis of this type of change in the cerebral cortex in the living patient since the differences between grey and white matter can be distinguished better than with computerized tomography.

Adult↗

Cell protective role of melatonin in the brain.

In recent years an increasing amount of data has been published involving melatonin in the control of brain function. The pineal gland exerts a depressive influence on CNS excitability. This activity is linked to melatonin, since pharmacological doses of the hormone prevent seizures in several animal models. In addition, melatonin also has analgesic properties in these species. However, the sites and mechanism of melatonin action are not known. A role for the pineal gland and its hormone melatonin as a homeostatic system controlling brain excitability has been proposed, and GABA-containing neurons may be involved in some central action of melatonin. There is evidence supporting a role of melatonin in the regulation of the GABA-benzodiazepine receptor complex, and it appears that melatonin potentiates this inhibitory neurotransmitter system in brain. Melatonin does not bind to GABA or benzodiazepine binding sites themselves, because in vitro binding data showed that melatonin is a weak competitor of benzodiazepine binding in brain membranes at concentrations greater than 10(-5) M. The effect of melatonin on brain activity also involves the participation of corticotropic and opioid peptides, and the existence of an opioid-antiopioid homeostatic system is proposed, with the GABA-benzodiazepine receptor complex as an effector. Moreover, the interaction of melatonin with corticotropic peptides and mitochondrial benzodiazepine receptors may result in a participation of neurosteroids in the control of GABA activity and function. The most recently available data from biochemical and electrophysiological studies support the possibility that the anticonvulsant and depressive effects of melatonin on neuron activity may depend on its antioxidant and antiexcitotoxic roles, acting as a free radical scavenger and regulating brain glutamate receptors. The full characterization of the nuclear melatonin receptor explains the genomic effects of melatonin, opening a new perspective regarding actions and roles of melatonin as a cellular protector.

Animals↗

[Experimental osteoarthritis and its course when treated with S-adenosyl-L-methionine].

Degenerative arthropathy was experimentally induced in the right knee of 24 rabbits. The animals were randomly divided in 3 groups of 8 rabbits each. S-Adenosyl-L-Methionine (SAMe) was administered intramuscularly to 2 groups. One group received 30 and 60 mg/kg/day i.m. The remaining group was a control and received only a diluent. After 12 weeks of therapy rabbits were sacrificed and tibial and femoral cartilage specimens of both knees were taken. The latter was stained with hematoxylin -eosine, Masson's trichromic and Safranine 0 stains and was microscopically studied. The thickness and cell density of the lesioned cartilages were significantly greater in both groups treated with SAMe than the group control (p less than 0.001). Statistical differences (p less than 0.05) were found within 60 and 30 mg/kg/day of SAMe. A greater concentration of proteoglycans in the cartilage matrix was found in animals treated were as, a severe reduction was found in controls. The severity of the lesions, based on the histologic-histochemical analysis, was significantly lower in rabbits receiving SAMe (p less than 0.0005). These differences were correlated with the administration of SAMe and the possible mechanisms of action are discussed.

Animals↗

Molecular diagnosis of the fragile X and FRAXE syndromes in patients with mental retardation of unknown cause in Mexico.

The fragile X syndrome (Fra-X) is the most common cause of inherited mental retardation with X-linked semi-dominant inheritance. The prevalence of Fra-X in the Mexican population is unknown. The aim of this population screening study was to determine if Fra-X or FRAXE mutations are the cause of a number of cases of mental retardation in a sample of Mexican children with mental retardation of unknown cause (MRUC) and to stress the importance of performing molecular analysis of the FMR-1 gene in all patients with MRUC. We report here the direct analysis of CGG and GCC repeats within the FMR-1 and FMR-2 genes, respectively, in 62 unrelated patients with MRUC. Two male index cases had the CGG expansion, although they did not express the Xq27.3 fragile site cytogenetically. Fra-X diagnosis was highly suspected on a clinical basis in one of the patients, but not in the other. Both mothers were found to be premutation carriers. The molecular studies of FMR-1 showed that the proportion of MRUC patients with Fra-X is 3.2%. This frequency was not significantly different to that reported in most populations. As reported in other series, no patients with FRAXE were found in our sample. Our findings confirm that the molecular analysis of the FMR-1 gene is necessary in MRUC patients to achieve unequivocal diagnosis of fragile X syndrome, carrier premutation detection and for accurate genetic counseling.

Child↗

Mathematical model of the oxidation of ferrous iron by a biofilm of Thiobacillus ferrooxidans.

Microbial oxidation of ferrous iron may be a viable alternative method of producing ferric sulfate, which is a reagent used for removal of H(2)S from biogas. The paper introduces a kinetic study of the biological oxidation of ferrous iron by Thiobacillus ferrooxidans immobilized on biomass support particles (BSP) composed of polyurethane foam. On the basis of the data obtained, a mathematical model for the bioreactor was subsequently developed. In the model described here, the microorganisms adhere by reversible physical adsorption to the ferric precipitates that are formed on the BSP. The model can also be considered as an expression for the erosion of microorganisms immobilized due to the agitation of the medium by aeration.

Adsorption↗

[Management of difficult cases of biliary lithiasis].

UNLABELLED: To assess that insertion of a biliary endoprosthesis is a safe and effective treatment in patients with retained common bile duct stones (CBDS). BACKGROUND: Before 1974, surgical exploration including cholecystectomy with choledochotomy was the only effective treatment for CBDS. However, morbi-mortality increases rapidly in the elderly and is over 10% in patients over 65, particularly if other serious medical conditions are present. Endoscopic sphincterectomy is now an established procedure, with a success rate of about 90%, complications are relatively rare, and mortality is about 1%. However, the size and number of the stones, the appearance of the terminal bile duct and presence of peripapillary diverticulum influence the outcome. At the present time technique of fragmenting the stones using intracorporeal electrohydraulic, extracorporeal shock waves or laser lithotripsy would be seen to be an attractive alternative approach. Endoprosthesis insertion is a safe, effective and cheap treatment in CBDS. PATIENTS, METHODS AND RESULTS: 40 patients with unextractable CBDS were studied and treated with endoscopic stenting. Four patients were lost for follow-up. The remaining patients comprised 29 females and 7 males, with a mean age of 67 years. Four patients underwent surgical treatment for post-sphincterotomy haemorrhage (1 patient), internal endoprosthesis migration (1 patient) and peripapillary diverticulum (2 patients). In 7 high-risk patients with large CBDS, recurrent obstructive jaundice was successfully treated by replacing the endoprosthesis. In 6 of them we added medical treatment with ursodeoxycholic acid and after 24 months follow-up, the stones disappeared. In 13 patients the endoprosthesis were inserted temporally, and in a second approach we removed the CBDS by mechanical lithotripsy. The remaining 12 patients were still alive without symptoms after a follow-up of 24 months. CONCLUSIONS: On the basis of these findings we therefore concluded that endoscopic insertion of a biliary endoprosthesis is a safe and effective treatment for CBDS in patients in whom endoscopic sphincterotomy and attemps to remove the stones are not successful.

Adult↗

[The endoscopic treatment of carcinoma of Vater's ampulla].

UNLABELLED: The ampullary carcinoma is a rare tumor. Its early and accurate diagnosis will lead to early treatment and subsequent better prognosis. Endoscopic retrograde cholangiopancreatography (ERCP) has been shown to be one of the best diagnostic tools. Furthermore an endoscopic biliary drainage procedure: endoscopic sphincterotomy or endoprosthesis placement, can be performed immediately following the diagnostic procedure. PATIENTS AND METHODS: Endoscopic drainage was attempted in 20 patients with a success rate of 90 percent. There were 8 females and 12 males, with a mean age of 71 years (range 43-92), and were admitted to the hospital with obstructive jaundice. Endoscopic insertion of a biliary endoprosthesis (9 cms long 3.2 mm [10 Fr] diameter), was successful in 18 patients whom made uneventful recovery and their jaundice resolved completely. RESULTS: In 18 of them an endoscopic sphincterotomy was carried out. Two patients developed cholangitis, the endoprosthesis were removed and a new one inserted. The survival rate of these patients was 3 and 18 months respectively. Failure of endoscopic sphincterotomy or endoprosthesis insertion in 2 remaining patients, was ascribed to an inability to cannulate the papilla due to infiltrating tumor. The median survival time in 15 remaining patients was 4 months (1-18 months) and died by metastatic disease. Five patients underwent Whipple's procedure, and all survived the operation. Two died, by metastatic disease, with a median survival time of 16 months and 3 still alive at 46, 25 and 18 months post-operatively. Carcinoma of the ampulla of Vater is not resectable in 25-50% of the patients because of metastatic disease, deep extension of the tumor or general contraindications for major surgery. CONCLUSIONS: Endoscopic sphincterotomy or endoprosthesis insertion as a definitive treatment modality should be reserved for poor surgical candidates and those patients with limited life expectancy due to metastatic disease.

Adult↗