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Biomedical subjects

A Borges

Publications and source records attributed to A Borges.

At least 37 records · Page 2Linked to original sources

Inactivated state dependence of sodium channel modulation by beta-scorpion toxin.

We have examined the effects of a beta-scorpion toxin purified from the venom of the Venezuelan scorpion Tityus discrepans, TdVIII, on heterologously expressed rat skeletal muscle Na+ channels (rSkM1). TdVIII (100 nM) produced a leftward shift in the voltage dependence of activation and reduced the peak Na+ conductance of rSkM1 channels coexpressed with the rat brain beta1 subunit in Xenopus laevis oocytes, suggesting that TdVIII is a beta-scorpion toxin. These effects did not depend on the presence of the beta1 subunit. Modification of rSkM1 activation by TdVIII could be augmented by increasing the rate of stimulation (enhanced use-dependence). Shifts in channel activation were also enhanced by introducing conditioning pulses to -10 mV, and this enhancement increased with conditioning pulse duration. On the other hand, TdVIII did not affect the activation of fast-inactivation deficient mutant Na+ channels, I1303Q/ F1304Q/M1305Q. These results suggest that modulation of rSkM1 Na+ channel gating by TdVIII depends on the toxin interacting with the inactivated state of the alpha subunit.

Animals↗

Antibodies against Tityus discrepans venom do not abolish the effect of Tityus serrulatus venom on the rat sodium and potassium channels.

Anti-(Tityus serrulatus + Tityus bahiensis) and anti-Tityus discrepans venom polyclonal antisera were used to investigate whether antigenic differences exist between the venoms of the Brazilian T. serrulatus and the Venezuelan T. discrepans scorpions. Both antisera recognised the toxin-containing electrophoretic fractions of their cognate venoms and also those from Tityus zulianus and Tityus trinitatis venoms on Western blots. The anti-T. discrepans antiserum reacted only weakly with T. serrulatus toxic polypeptides. The effect of T. serrulatus alpha- or beta-toxins on rat skeletal muscle Na+ channels expressed in Xenopus laevis oocytes was abolished by pre-incubating the venom with anti-(T. serrulatus + T. bahiensis) serum but not with anti-T. discrepans serum. Nor did the Brazilian or the Venezuelan sera prevent the reduction in K+ currents by T. serrulatus venom in X. laevis oocytes expressing the rat brain delayed rectifying Shaker K+ channel (Kv1.2). These results indicate that toxins from T. serrulatus and T. discrepans venoms, which primarily target mammalian Na+ channels, are antigenically distinct, although they probably share common epitopes. Our results also suggest that Na+ channel-active toxins are the immunodominant antigens of the T. serrulatus venom.

Animals↗

Lateral thyrotomy for neurilemmoma of the larynx.

We present a rare case of neurilemmoma of the larynx, which was excised through a lateral thyrotomy approach with resulting restoration of laryngeal function. The advantage of the lateral thyrotomy approach for submucous tumours of the larynx is discussed.

Humans↗

Perceptions of tooth loss and periodontal problems in an independent elderly population: content-analysis of interview discourse.

Oral health/illness and surrounding socio-demographic and behavioral phenomena are poorly documented in the Mexican elderly. To establish the rationales explaining oral health/illness and tailor a Health Promotion intervention (1995-1997) accordingly, an interview nested in a questionnaire was done at baseline, with the recording of 228 interviews transcribed verbatim. Every transcript was subsequently assessed by content-analysis. Results showed that lack of oral hygiene, inadequate calcium intake and old age were the most common explanations of tooth-loss. Only a few factors were felt to be under control: the same state of relative adaptation that characterized people affected by gum problems. The themes that explained them were lack of oral hygiene, and (non-specific) infections. When interviewees evaluated the impact of good oral health on their lives, many made evaluations pertaining to quality of life, adequate function, and an attractive appearance generally.

Journal Article↗

Expression of genes encoding the E2 and E3 components of the Bacillus stearothermophilus pyruvate dehydrogenase complex and the stoichiometry of subunit interaction in assembly in vitro.

Genes encoding the dihydrolipoyl acetyltransferase (E2) and dihydrolipoyl dehydrogenase (E3) components of the pyruvate dehydrogenase (PDH) multienzyme complex from Bacillus stearothermophilus were overexpressed in Escherichia coli. The E2 component was purified as a large soluble aggregate (molecular mass > 1 x 10(6) Da) with the characteristic 532 symmetry of an icosahedral (60-mer) structure, and the E3 as a homodimer with a molecular mass of 110 kDa. The recombinant E2 component in vitro was capable of binding either 60 E3(alpha2) dimers or 60 heterotetramers (alpha2beta2) of the pyruvate decarboxylase (E1) component (also the product of B. stearothermophilus genes overexpressed in E. coli). Assembling the E2 polypeptide chain into the icosahedral E2 core did not impose any restriction on the binding of E1 or E3 to the peripheral subunit-binding domain in each E2 chain. This has important consequences for the stoichiometry of the assembled complex in vivo. The lipoyl domain of the recombinant E2 protein was found to be unlipoylated, but it could be correctly post-translationally modified in vitro using a recombinant lipoate protein ligase from E. coli. The lipoylated E2 component was able to bind recombinant E1 and E3 components in vitro to generate a PDH complex with a catalytic activity comparable with that of the wild-type enzyme. Reversible unfolding of the recombinant E2 and E3 components in 6 M guanidine hydrochloride was possible in the absence of chaperonins, with recoveries of enzymic activities of 95% and 85%, respectively. However, only 26% of the E1 enzyme activity was recovered under the same conditions as a result of irreversible denaturation of both E1alpha and E1beta. This represents the first complete post-translational modification and assembly of a fully active PDH complex from recombinant proteins in vitro.

Genes, Bacterial↗

Carbon dioxide emission from european estuaries

The partial pressure of carbon dioxide (pCO2) in surface waters and related atmospheric exchanges were measured in nine European estuaries. Averaged fluxes over the entire estuaries are usually in the range of 0.1 to 0.5 mole of CO2 per square meter per day. For wide estuaries, net daily fluxes to the atmosphere amount to several hundred tons of carbon (up to 790 tons of carbon per day in the Scheldt estuary). European estuaries emit between 30 and 60 million tons of carbon per year to the atmosphere, representing 5 to 10% of present anthropogenic CO2 emissions for Western Europe.

Journal Article↗

Knowledge and opinions about dental human health resources planning in Mexico.

Dental human health resource planning (DHHRP), or manpower planning in Mexico has been plagued by fundamental contradictions. In spite of having trained a great many dentists in the past two decades, the dental health status of the population has not significantly improved. Concurrently, the relative scarcity of patients in relation to the number of practising dentists seems to be more marked, a critical issue since most dental care is delivered under private schemes. In the present investigation, 196 practising dentists in Mexico City were interviewed to establish their knowledge and opinions about DHHRP, and their views about the introduction of innovative alternatives in transforming, evaluating and planning human health resources. Concerns were: a need to examine and re-define the aims, skill content and marketability of professional training in professional practice; a lack of consensus as to how this is to be achieved; and a degree of awareness that professional practice has a limited scope in meeting the challenge of providing adequate care because of maldistribution of dentists and of limited financial resources of patients.

Adult↗

Haemodynamic changes in patients undergoing high-risk PTCA under protection of transfemoral heart- lung machine support with centrifugal pumps.

Patients with a high risk for myocardial revascularization by cardiological or surgical means can be supported during high-risk PTCA with mechanical circulatory support (supp HR-PTCA). Between November 1994 and June 1997 we performed 28 supp HR-PTCA's under protection of a heart-lung machine (HLM) with femoro - femoral cannulation under regional anesthesia. We approached 2.8+/-1.5 stenoses and 1.7+/-0.6 vessels per patient. Primary success rate was 95 percent of the treated vessels. During unloading, pulmonary artery mean pressure fell to 42+/-29% of the starting value, and LVEDP was decreased to 36+/-42%. Mechanical unloading also resulted in a significant reduction of left ventricular volumes (unloaded LVEDVI and LVESVI represent 76.8% and 76.6% of pre-unloaded values, respectively, p<0.05). All patients except one survived the procedure and could be discharged from the hospital. Femoro-femoral cardio-pulmonary bypass under regional anesthesia provides sufficient protection for high risk PTCA procedures and enables high risk patients to benefit from coronary revascularization.

Adult↗

Combination of melatonin and tamoxifen as a chemoprophylaxis against N-nitroso-N-methylurea-induced rat mammary tumors.

The effect of melatonin (Mel) and or tamoxifen (Tam) was evaluated on a mammary tumor model induced in 50 day old female Sprague-Dawley rats by a single intraperitoneal (i.p.) injection of a direct carcinogen, N-nitroso-N-methylurea (NMU) (50 mg/kg b.wt./rat). These animals were treated with either Mel 200 microg/rat per day, orally in drinking water and/or Tam (s.c.) 60 microg/rat per week or 180 microg/rat per week. The total observation period was 300 days post-NMU administration in all the animals. The mean latency period of tumor appearance and tumor incidence was recorded. The mean latency period was significantly lengthened in all the treated groups as compared to that in the only NMU-administered rats (P < 0.001). Highly significant suppression of tumor incidence was observed in Mel + Tam180 group (P < 0.001). The other two groups i.e. Mel + Tam60, and Tam180 also showed significant suppression of tumor incidence (P < 0.01). Eight weeks after the initiation of treatment regimen, we observed marked reduction in [3H]thymidine incorporation into mammary gland DNA of Mel- and/or Tam-treated groups of animals as compared to the age-matched controls and NMU-administered rats, which correlated positively with the sparse mammary gland development seen in the whole mount preparations. The result of the combined therapy is highly promising and warrants clinical evaluation in the prophylaxis of breast carcinogenesis in humans.

Animals↗

Telomerase activity during cardiac development.

Telomerase is a ribonucleoprotein involved in maintaining telomere length in stem cells and immortal and actively dividing cells. We report here for the first time that telomerase is developmentally regulated in the normal rat heart. When we compared rat hearts at different developmental stages, we found that telomerase activity decreased to 20% of the fetal level by 5 days after birth, and was undetectable by 20 days after birth. These results indicate that the rate of cardiomyocyte proliferation decreases dramatically soon after birth in the rat. Of several non-cardiac tissues examined, telomerase activity was highest in fetal and adult rat liver, suggesting that there is an active mechanism for maintaining long telomeres in liver tissue at all stages. The disappearance of telomerase activity in the rat heart at the time that cardiomyocytes become terminally differentiated suggests that telomerase downregulation is important in the permanent withdrawal of cardiomyocytes from the cell cycle.

Animals↗

Role of stress echocardiography in risk stratification early after an acute myocardial infarction. EPIC (Echo Persantin International Cooperative) and EDIC (Echo Dobutamine International Cooperative) Study Groups.

Resting and stress echocardiography is a 'one-stop shop', which enables a wide range of information to be collected on resting function, myocardial viability, and induced ischaemia, all of which are useful for prognostic stratification. Large scale, multicentre, prospectively collected data show the prognostic failure of resting function and inducible ischaemia, both independently and combined, which are especially effective in predicting cardiac death. The GISSI data show that the increment of risk as a result of reduction in ventricular function has a hyperbolic trend, with a relatively moderate increase in mortality for ejection fraction values between 50 and 30%, but with marked increases below 30%. The EPIC data show that the 1-year risk of cardiac death is as low as 2% in patients with negative dipyridamole stress echocardiography: it doubles if the test is positive at a high dose, and is almost four times higher if it is positive at a low dose. In the field of prognostic stratification, in the absence of carefully controlled studies, the choice between coronary angiography as the only essential study, or use of a non-invasive test to discriminate access to catheterization currently reflect alternate philosophical approaches rather than scientifically based decisions. In the invasive approach, stress echocardiography offers relief from the vicious circle of chest pain-coronary angiography revascularization. In the non-invasive and physiological approach, stress echo is capable of offering, in one sitting, an insight into the main determinants of survival: function, viability, and ischaemia.

Echocardiography↗

Barbiturate anticonvulsants: a neuropsychological and quantitative electroencephalographic study.

We studied 11 epileptic children aged 7 to 14 years with quantitative electroencephalographic (EEG) and neuropsychological tests, both on and off the barbiturate anticonvulsants phenobarbital and mephobarbital, comparing them to 13 controls matched for age and IQ who received testing at similar intervals. Neuropsychological tests employed were the Wechsler Intelligence Scale for Children-Revised (WISC-R), Bender-Gestalt, controlled oral word association test (COWAT), selected subtests of the Wechsler Memory Scale-Revised, Purdue Peg Board, Stroop Test, Trail Making Test, Wide Range Achievement Test-Revised, and Achenbach Behavior Rating Scale. There was no difference between on- and off-drug quantitative EEG in percentage power of any frequency band between 0.6 and 32 Hz. Neuropsychological data from all 11 subjects were analyzed with a two-factor analysis of variance with repeated measures on the time factor. The only difference from controls was on the Stroop Test. Parents reported clear behavioral changes in 6 of 11 subjects, but in 4 of these children the behavioral changes were sufficiently mild that parents chose to continue the barbiturate anticonvulsants: irritability, oppositional attitude, and overactivity were described. Mephobarbital was reported by parents to cause less severe problems than phenobarbital in subjects who had taken both barbiturate anticonvulsants. Barbiturate anticonvulsants have no effect on quantitative EEG and limited effects on neuropsychological tests in school-aged children.

Adolescent↗

[Cerebral toxoplasmosis in AIDS patients, CT and MRI images and differential diagnostic problems].

Cranial computed-tomographies (CT) and magnetic resonance imaging (MRI) of 14 patients with AIDS and central nervous system toxoplasmosis (CNST) were reviewed. In spite of the low specificity of CT and MRI findings in CNS mass lesions of AIDS patients, there are some features which have been observed as more typical of CNST, namely: 94.9% of the lesions were round shaped and 94.5% had ring or nodular enhancement; 81.3% of the cases presented multiple lesions; 60.2% of the lesions were localized at the cerebral cortical or corticomedullary junction (100% of the cases showed at least 1 lesion in this localization); 34.6% of the lesions had less than 1cm in diameter.; on nonenhanced CT, 91.3% of the lesions were hypodense.; On T2-weighted MR images, 53.4% of the lesions had at least one hypointense zone on T2-weighted images. The existence of target-shaped lesions with hypointense centre on T2-weighted MR images (29.3% the observed lesions) is also suggestive of CNST, which, to our belief, had not been previously reported and will need confirmation with larger series. The visualization of iso/hyperdense lesions on nonenhanced CT or irregular shape lesions is uncommon in CNST. The finding of a solitary lesion, on CT or MR, it is not, by itself, a good criterion of differential diagnosis.

AIDS-Related Opportunistic Infections↗

Glutathionylspermidine metabolism in Escherichia coli.

Intracellular levels of glutathione and glutathionylspermidine conjugates have been measured throughout the growth phases of Escherichia coli. Glutathionylspermidine was present in mid-log-phase cells, and under stationary and anaerobic growth conditions accounted for 80% of the total glutathione content. N1,N8-bis(glutathionyl)spermidine (trypanothione) was undetectable under all growth conditions. The catalytic constant kcat/Km of recombinant E. coli glutathione reductase for glutathionylspermidine disulphide was approx. 11,000-fold lower than that for glutathione disulphide. The much higher catalytic constant for the mixed disulphide of glutathione and glutathionylspermidine (11% that of GSSG), suggests a possible explanation for the low turnover of trypanothione disulphide by E. coli glutathione reductase, given the apparent lack of a specific glutathionylspermidine disulphide reductase in E. coli.

Amino Acid Sequence↗

Site-directed mutagenesis of the redox-active cysteines of Trypanosoma cruzi trypanothione reductase.

The gene for trypanothione reductase from the Silvio strain of Trypanosoma cruzi has been cloned, sequenced and overexpressed in Escherichia coli using the constitutive lpp promoter on the expression plasmid pBSTNAV. Up to 13% of the total soluble protein is enzymically active trypanothione reductase with kinetic properties similar to the enzyme purified from T. cruzi. In order to assess the catalytic role of the putative active-site cysteine residues (C53 and C58), three mutant proteins have been constructed by site-directed mutagenesis substituting alanine or serine residues for cysteine; [C53A]trypanothione reductase, [C53S]trypanothione reductase and [C58S]trypanothione reductase. Although the purified, recombinant mutant proteins were catalytically inactive with NADPH and trypanothione disulphide as substrates, all showed comparable levels of transhydrogenase activity between NADPH and thio-NADP+, suggesting that the mutant proteins had correctly folded in vivo. All three mutants showed substantially different catalytic parameters for thio-NADP+ than the wild-type enzyme, presumably as a consequence of modifying the environment of the enzyme-bound flavin, thereby altering its chemical reactivity. The purified [C58S]trypanothione reductase showed spectral properties similar to the oxidised wild-type enzyme but, unlike the wild-type enzyme, did not acquire the characteristic charge-transfer complex of the EH2 form on addition of NADPH. In contrast, in the absence of NADPH both [C53A]trypanothione reductase and [C53S]trypanothione reductase showed spectral properties similar to the EH2 form of the wild-type enzyme. These data indicate that both C53 and C58 are essential for overall catalysis, with the thiolate anion of C58 interacting with the enzyme-bound FAD and C53 interacting with the disulphide substrate. These mutants should be useful in crystallographic studies of reaction intermediates which cannot be obtained with the catalytically active native enzyme.

Animals↗

A preliminary study of the neuropsychological heterogeneity of familial schizophrenia.

This exploratory study describes the heterogeneity of the neuropsychological deficits that characterize familial schizophrenia. Forty-six familial schizophrenics showed significantly more variability in abstraction and problem-solving and motor control than 39 non-familial schizophrenics. Cluster analyses of these two neuropsychological parameters indicate that while the non-familial schizophrenics fall into one homogeneous cluster, the familial schizophrenics fall into three relatively distinct clusters which differ significantly in their morbid risk for schizophrenic-spectrum disorder. These preliminary data suggest that frontal lobe deficits are associated with an increased familial risk for schizophrenia.

Adolescent↗