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Biomedical subjects

M Santos

Publications and source records attributed to M Santos.

At least 19 recordsLinked to original sources
PubMed2000

Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites.

Bacterial translocation appears to be an important mechanism in the pathogenesis of spontaneous infections in cirrhosis. Cirrhotic patients are commonly treated with beta-adrenoceptor blockers, but the impact of this treatment in the factors promoting bacterial translocation has not been investigated. This study was aimed at investigating in cirrhotic rats with ascites the effect of propranolol on intestinal bacterial load, transit, and permeability of the bowel and on the rate of bacterial translocation. Bacterial translocation to mesenteric lymph nodes and intestinal bacterial overgrowth, permeability (urinary excretion of (99m)Tc-diethylenetriaminepentaacetic acid [(99m)Tc-DTPA]), and transit (geometric center ratio of (51)Cr) were assessed in 29 rats with carbon tetrachloride (CCl(4)) cirrhosis and 20 controls. These variables were then measured in 12 placebo- and in 13 propranolol-treated ascitic cirrhotic rats. Bacterial translocation was present in 48% of the cirrhotic rats and in none of the controls. Cirrhotic rats with intestinal bacterial overgrowth had a significantly higher rate of translocation and slower intestinal transit than those without it. Among the 15 rats with overgrowth and a (99m)Tc-DTPA excretion greater than 10%, 15 had translocation and 2 had bacterial peritonitis. Only 1 of the 14 rats with either intestinal overgrowth or a (99m)Tc-DTPA excretion greater than 10% presented translocation. Compared with the placebo group, propranolol-treated animals had significantly lower portal pressure, faster intestinal transit, and lower rates of bacterial overgrowth and translocation. In ascitic cirrhotic rats, bacterial translocation results from intestinal overgrowth and severe damage to gut permeability. In this setting, intestinal overgrowth is associated with intestinal hypomotility. Propranolol accelerates the intestinal transit, decreasing the rates of bacterial overgrowth and translocation.

Animals↗
PubMed2000

Clinical and molecular studies in three Portuguese mtDNA T8993G families.

The T8993G mutation in the mitochondrial DNA adenosine triphosphatase 6 gene represents an important cause of maternally inherited Leigh's syndrome. Reported are the clinical findings and mutational loads in three Portuguese T8993G pedigrees. Polymerase chain reaction-restriction fragment length polymorphism analyses demonstrated the T8993G mutation in a high percentage of tissues from all patients (97% +/- 2.3%), but it was less abundant in the blood from 14 maternal relatives. The disease progressed severely in the probands but did not have the fatal course reported by others. To test whether this prolonged course was related to the presence of a specific, disease-associated haplogroup the origin of the mutational event in Portugal was traced. Haplotype investigation revealed an independent occurrence of the mutation in the three probands. These analyses represent the first molecular characterization of Portuguese patients with Leigh's syndrome.

Adenosine Triphosphatases↗
PubMed2000

Genetic polymorphism of alcohol dehydrogenase in europeans: the ADH2*2 allele decreases the risk for alcoholism and is associated with ADH3*1.

Polymorphism at the ADH2 and ADH3 loci of alcohol dehydrogenase (ADH) has been shown to have an effect on the predisposition to alcoholism in Asian individuals. However, the results are not conclusive for white individuals. We have analyzed the ADH genotype of 876 white individuals from Spain (n = 251), France (n = 160), Germany (n = 184), Sweden (n = 88), and Poland (n = 193). Peripheral blood samples from healthy controls and groups of patients with viral cirrhosis and alcohol-induced cirrhosis, as well as alcoholics with no liver disease, were collected on filter paper. Genotyping of the ADH2 and ADH3 loci was performed using polymerase chain reaction-restriction fragment length polymorphism methods on white cell DNA. In healthy controls, ADH2*2 frequencies ranged from 0% (France) to 5.4% (Spain), whereas ADH3*1 frequencies ranged from 47. 6% (Germany) to 62.5% (Sweden). Statistically significant differences were not found, however, between controls from different countries, nor between patients with alcoholism and/or liver disease. When all individuals were grouped in nonalcoholics (n = 451) and alcoholics (n = 425), ADH2*2 frequency was higher in nonalcoholics (3.8%) than in alcoholics (1.3%) (P =.0016), whereas the ADH3 alleles did not show differences. Linkage disequilibrium was found between ADH2 and ADH3, resulting in an association of the alleles ADH2*2 and ADH3*1, both coding for the most active enzymatic forms. In conclusion, the ADH2*2 allele decreases the risk for alcoholism, whereas the ADH2*2 and ADH3*1 alleles are found to be associated in the European population.

Adult↗
PubMed1999

Activation of mitogen-activated protein kinase regulates eotaxin-induced eosinophil migration.

Eotaxin is a potent eosinophil chemoattractant that plays an important role in regulating eosinophil tissue levels both in healthy individuals and in diseases associated with significant eosinophil infiltrates, such as the allergic inflammation observed in asthma. Here, we demonstrate that treatment of eosinophils with eotaxin induces the phosphorylation of the mitogen-activated protein kinases (MAPKs) p42 and p44, leading to kinase activation. Blockade of MAPK activation by the MAPK kinase inhibitor PD98059 leads to a dramatic decrease in eotaxin-induced eosinophil rolling in vivo and chemotaxis in vitro. This blockade in the leukocyte migration process is consistent with the observed inhibition of actin polymerization and rearrangement within the eosinophil following treatment with MAPK inhibitor. It is suggested, therefore, that the intrinsic mechanism of eotaxin-induced eosinophil rolling and migration involves activation of the p42/p44 MAPK, possibly through regulation of the cytoskeletal rearrangements necessary for chemotaxis.

Actins↗
PubMed1999

Immunohistochemical evidence of the presence of aromatase P450 in the rat hypophysis.

In order to analyze whether aromatase is present in the hypophysis of adult rats, we have performed an immunohistochemical study in young adult male and female rats. Our study has revealed that the hypophysis of adult rats contains aromatase, although marked differences are found between the sexes. The hypophyses of male rats have cells immunoreactive for the enzyme, 34.40% of these hypophyseal cells showing reaction. By contrast, cells from female rats show very little reaction, only 0.84% of them being reactive. No significant differences in the percentage of immunoreactive cells between one phase and another are observed during the estrous cycle. Our results point to the immunohistochemical expression of aromatase in the hypophysis of adult rats and at the same time suggest that its expression is sex-dependent. The enzyme may therefore be involved in the regulation of adenohypophyseal cytology by androgens.

Amino Acid Sequence↗
PubMed1999

Early diagnosis of subependymal giant cell astrocytoma in children with tuberous sclerosis.

OBJECTIVES: Intraventricular astrocytomas (subependymal giant cell astrocytomas) of tuberous sclerosis have a poor prognosis due to the obstruction of CSF flow. The aim of this study was to determine whether they could be differentiated during childhood and at an early preclinical stage, from subependymal nodules without any growing potential. METHODS: The first two MRIs of all children referred to this neuropaediatric centre between 1987 and 1996 were retrospectively blindly reviewed. RESULTS: Out of 60 patients, 24 disclosed subependymal nodules localised near the foramen of Monro, and eight of the 24 developed astrocytomas. Subependymal nodules were first detectable on MRI from 1 year of age in all cases and the first MRI evidence of growth occurred between 1 and 9 years (mean 4 years). At an early stage, subependymal nodules had different characteristics in patients who developed subependymal giant cell astrocytomas from those who did not. The nodules over 5 mm in diameter that were incompletely calcified and enhanced by gadolinium were at higher risk of growing, particularly in children with a familial history of tuberous sclerosis. To detect the subependymal giant cell astrocytomas earlier in tuberous sclerosis, it is advisible to systematically perform an MRI examination before 2 years of age and to repeat it every year if the patient has risk factors for developing astrocytomas.

Brain Neoplasms↗
PubMed1999

Seroprevalence of human cysticercosis in Maputo, Mozambique.

We carried out a serosurvey for cysticercosis among people visiting the Central Hospital of Maputo, the capital of Mozambique, between January and June 1993. A standardized questionnaire was designed to obtain information on demographic, socioeconomic, environmental, and behavioral characteristics related to the transmission of the infection. Four hundred eighty-nine individuals were tested for anti-cysticercosis antibodies: 222 blood donors and patients from the Department of Orthopedics, 148 patients from the Department of Neurology, and 119 patients from the Department of Psychiatry. The overall positivity rate was 12.1% (59 of 489). Anti-cysticercus antibodies was detected in 14.9% of the blood donors and patients from the Department of Orthopedics, 11.5% of the patients from the Department of Neurology, and 7.6% of the patients from the Department of Psychiatry. Living in poor sanitary conditions seems to be an important factor related to human cysticercosis in Maputo, Mozambique.

Adolescent↗
PubMed1999

[Comparison between penicillin and amoxicillin-clavulanic acid for the treatment of recurrent tonsillopharyngitis in childhood].

Fifty-one children aged 2-14 years with recurrent tonsillopharyngitis, presenting dysphagia, fever and lymphadenitis, with more than two similar episodes in the last three years and showing a beta-hemolytic group A streptococci in the pharyngeal smear, were studied. They underwent random treatment for ten days with phenoxymethylpenicillin (40-60 mg/kg/day) (n = 28) or amoxicillin-clavulanic acid (20-40 mg/kg/day) (n = 23) taken orally three times a day. Clinical and bacteriological tests were carried out at 10 days and 2, 6 and 12 months post-treatment. The clinical and bacteriological results showed the superiority of the amoxicillin-clavulanic acid treatment both in the short term (disappearance of symptoms) and in the long term (decrease in recurrence). These results support the idea that betalactamases produced by the pharyngeal flora play an important role in the failures of penicillin.

Adolescent↗
PubMed1998

Adaptive response of iron absorption to anemia, increased erythropoiesis, iron deficiency, and iron loading in beta2-microglobulin knockout mice.

Recently, a novel gene of the major histocompatibility complex (MHC) class I family, HFE (HLA-H), has been found to be mutated in a large proportion of hereditary hemochromatosis (HH) patients. Further support for a causative role of HFE in this disease comes from the observation that beta2-microglobulin knockout (beta2m-/-) mice, that fail to express MHC class I products, develop iron overload. We have now used this animal model of HH to examine the capacity to adapt iron absorption in response to altered iron metabolism in the absence of beta2m-dependent molecule(s). Mucosal uptake, mucosal transfer and retention of iron were measured in control and beta2m-/- mice with altered iron metabolism. Mucosal uptake of Fe(III), but not of Fe(II), by the mutant mice was significantly higher when compared with B6 control mice. Mucosal transfer in the beta2m-/- mice was higher, independent of the iron form tested. No significant differences were found in iron absorption between control and beta2m-/- mice when anemia was induced either by repetitive bleeding or by hemolysis through phenylhydrazine treatment. However, iron absorption in mice made anemic by dietary deprivation of iron was significantly higher in the mutant mice. Furthermore, the beta2m-/- mice manifested an impaired capacity to downmodulate iron absorption when dietary or parenterally iron-loaded. The expression of the defect in iron absorption in the beta2m-/- mice is quantitative, with iron absorption being excessively high for the size of body iron stores. The higher iron absorption capacity in the beta2m-/- mice may involve the initial step of ferric mucosal uptake and the subsequent step of mucosal transfer of iron to the plasma.

Adaptation, Physiological↗
PubMed1998

Nitric oxide synthase activity and L-arginine metabolism in the retinas from streptozotocin-induced diabetic rats.

1. Nitric oxide synthase (NOS) activity was studied in the retinas from normal rats and in the retinas from two groups of streptozotocin-induced (8 days and 4 months) diabetic rats. In each animal group, the NOS activity was correlated to the concentration of amino acids related to L-arginine metabolism and to L-arginine uptake. 2. Retinas from both groups of streptozotocin-induced diabetes (8 days and 4 months) showed an increased NOS activity compared with the NOS activity in retinas from normal rats. In retinas lysate from normal rats, the NOS activity was most potently inhibited by NO-Arg (1 mM), whereas, in both groups of streptozotocin-induced diabetes, the NOS activity was most potently inhibited by the NOS inhibitor aminoguanidine (0.5 mM). 3. The basal levels of the amino acids related to L-arginine metabolism-namely, L-arginine, L-citrulline, L-ornithine and L-glutamine-in retinas from both groups of rats with streptozotocin-induced diabetes were decreased compared with the amino acid levels in retinas from normal rats. 4. The uptake of L-[3H]arginine in retinas from both groups of rats with streptozotocin-induced diabetes was increased compared with the uptake of of L-[3H]arginine in retinas from normal rats.

Animals↗
PubMed1998

Performance characteristics of a new synthetic APTT reagent.

Performance characteristics of a totally synthetic activated partial thromboplastin time (APTT) reagent, recently available commercially, were evaluated and compared with a rabbit-brain extracted reagent. We found that the synthetic reagent, Synthasil, returned significantly higher normal APTT values than the brain-extracted reagent, Thrombosil. APTT ratios (APTT patients/normal mean APTT), yielded by Synthasil were higher in the majority of patients receiving heparin therapy. Synthasil also returned longer APTT values than did Thrombosil on normal plasma spiked with heparin. On patients with lupus anticoagulants, APTTs assayed with Synthasil were generally longer than with Thrombosil. However, the differences disappeared when APTT values were converted to ratios. Factors XII-, XI-, IX- and VIII-deficient plasmas supplemented with normal plasma to yield activities of 2-50%, generally gave longer APTTs with Synthasil than with Thrombosil. However, this was not always the case on plasmas from haemophilias A and B patients. No reduction in Synthasil activity was noted after the reagent had been left at 24 degrees C for 28 days.

Coagulation Protein Disorders↗
PubMed1998

Aspirin synergistically potentiates isoflurane minimum alveolar concentration reduction produced by morphine in the rat.

BACKGROUND: The combination of opioids and nonsteroidal antiinflammatory drugs is more analgesic than the summed effect of each drug administered separately. This synergism has been used to obtain analgesia in the postoperative period at doses at which side effects are minimal. The aim of this study is to evaluate the analgesic interaction between aspirin and morphine in the rat during isoflurane anesthesia. The reduction in minimum alveolar concentration of isoflurane (MAC(ISO)) was used as an objective measure of the analgesic potency of individual drugs and their use in combination. METHODS: Thirty-seven male Wistar rats were anesthetized with isoflurane in oxygen, and the MAC(ISO) was determined before and after the intravenous administration of aspirin and morphine. Rats were administered morphine alone (1, 3, and 10 mg/kg) or morphine (1 and 3 mg/kg) and aspirin (30 mg/kg). The MAC(ISO) was determined from alveolar gas samples at the time of tail clamp. The duration of MAC(ISO) reduction was recorded. RESULTS: Aspirin did not have an effect on MAC(ISO), (average, 1.35+/-0.1%), whereas the combination of morphine (1 and 3 mg/kg) and aspirin (30 mg/kg) produced a reduction in the dose of morphine needed to produce the same degree of MAC(ISO) reduction. Actual MAC(ISO+drug) data were as follows: 1 mg/kg morphine, 1.17+/-0.14%; 3 mg/kg morphine, 0.98+/-0.15%; 1 mg/kg morphine plus aspirin, 0.90+/-0.04%; 10 mg/kg morphine, 0.63+/-0.13%; and 3 mg/kg morphine plus aspirin, 0.64+/-0.06%. CONCLUSIONS: The synergistic effects of aspirin and morphine allow a clinically significant reduction in the requirements of isoflurane and isoflurane plus morphine, and these drug combinations may decrease the side effects associated with the use of single higher, equianalgesic doses of these drugs.

Analgesics, Opioid↗
PubMed1998

Costello syndrome in two Brazilian children.

The increasing number of children with Costello syndrome described world wide has helped in delineating further the characteristic features of this condition. We report here two children, seen in the Genetic Division of the Brasilia University Hospital, showing the main features of the syndrome: "coarse" face, redundant skin on the feet and hands, hyperextensible hand and finger joints, curly hair, growth and psychomotor retardation, and feeding problems. In addition, one of the patients developed hydrocephalus during the evolution of the disease, making the third published patient with this complication. We discuss the appropriateness of serial brain imaging studies in Costello syndrome in light of the relative frequency of central nervous system malformations.

Brazil↗
PubMed1998

Repeated pulmonary infection by Nocardia asteroides complex in a patient with bronchiectasis.

A rare case of pulmonary nocardiosis was presented in a nonimmunocompromised patient who had chronic airway obstruction and bronchiectasis without corticoid treatment. The microbial diagnosis was established after isolating Nocardia in bronchial aspirate and sputum samples. An in vitro study showed sensitivity only to imipenem, netilmicine, amikacin and ofloxacin. The evolution was chronic, with multiple clinical recurrences in spite of prolonged antibiotic treatment. Finally, the eradication of Nocardia was achieved with the combination of imipenem and amikacin.

Amikacin↗