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Biomedical subjects

A Salgado

Publications and source records attributed to A Salgado.

At least 19 recordsLinked to original sources
PubMed2005

Thapsigargin-sensitive cationic current leads to membrane depolarization, calcium entry, and insulin secretion in rat pancreatic beta-cells.

Glucose-induced insulin secretion by pancreatic beta-cells depends on membrane depolarization and [Ca2+]i increase. We correlated voltage- and current-clamp recordings, [Ca2+]i measurements, and insulin reverse hemolytic plaque assay to analyze the activity of a thapsigargin-sensitive cationic channel that can be important for membrane depolarization in single rat pancreatic beta-cells. We demonstrate the presence of a thapsigargin-sensitive cationic current, which is mainly carried by Na+. Moreover, in basal glucose concentration (5.6 mM), thapsigargin depolarizes the plasma membrane, producing electrical activity and increasing [Ca2+]i. The latter is prevented by nifedipine, indicating that Ca2+ enters the cell through L-type Ca2+ channels, which are activated by membrane depolarization. Thapsigargin also increased insulin secretion by increasing the percentage of cells secreting insulin and amplifying hormone secretion by individual beta-cells. Nifedipine blocked the increase completely in 5.6 mM glucose and partially in 15.6 mM glucose. We conclude that thapsigargin potentiates a cationic current that depolarizes the cell membrane. This, in turn, increases Ca2+ entry through L-type Ca2+ channels promoting insulin secretion.

Animals↗
PubMed2005

Epithelioid hemangioendothelioma and multiple thoraco-lumbar lateral meningoceles: two rare pathological entities in a patient with NF-1.

Epithelioid hemangioendothelioma (EHE) is a rare vascular soft-tissue tumour of intermediate malignancy. Neurofibromatosis type I (NF-1) is a genetic syndrome associated with soft tissue sarcoma and higher risk of developing neoplasia. Lateral meningoceles are uncommon entities, being mostly associated with NF-1. We report a case of a 31-year-old woman, with NF-1 and past history of right thalamic/peduncular astrocytoma WHO grade II, admitted to the Neurosurgery Department in December 2003 due to severe low back pain, irradiating to the left leg without a radicular pattern. Thoraco-lumbar magnetic resonance imaging (MRI) showed a large left posterior paravertebral expansive lesion, bilateral and multiple thoraco-lumbar lateral meningoceles and dural ectasias with scalloping of the vertebral bodies. Biopsy of the paravertebral mass lesion disclosed EHE. We present this case because of the novel association between NF-1 and EHE, and the unusual aggressiveness of the neoplasia. Additionally, we highlight the co-existence of bilateral and multiple lateral meningoceles.

Adult↗
PubMed2001

[Complete congenital atrioventricular block].

Congenital atrioventricular block is defined (Yater) as a documented conduction defect in a young subject with unquestionable bradycardia in the absence of a history of infection which might have caused the condition. This condition may be isolated or associated with structural cardiac disease. Isolated block is often observed in patients with mothers suffering from autoimmune disease, often clinically latent. Anti-Ro/SS-A and La/SS-B antibodies cross into the fetal circulation and cause inflammation of the fetal conduction system. The diagnosis of the conduction defect is sometimes made during fetal life by echocardiography. Echocardiography assesses fetal hemodynamic status and may detect signs of fetal deterioration. Long-term follow-up studies have revised the previously considered good prognosis of isolated congenital atrioventricular block but advances in cardiac pacing provide satisfactory treatment. Follow-up by Holter monitoring, exercise testing and echocardiography is justified in children and adolescents; the patients may become symptomatic at any age. Indications for permanent pacing in pediatric patients have been difficult to determine due to the lack of data from controlled studies and multicenter trials. Pacing is not always easy in children. Epicardial pacing is advocated in small patients (< 5 years of age or 30 kg in weight). A pacing mode which restores the normal atrioventricular sequence is theoretically superior to single ventricular pacing even with rate responsive frequency.

Adolescent↗
PubMed2000

[Angioplasty in aortic coarctation and recoarctation in children and adolescents].

STUDY OBJECTIVE: To determine the efficacy of percutaneous balloon angioplasty in children and adolescents with Coarctation and Recoarctation of the Aorta. DESIGN AND SETTING: We dilated native coarctation and recoarctation after a complete hemodynamic and angiographic assessment of the situation in a young population referred to a university hospital. PATIENTS AND INTERVENTION: In 22 patients with coarctation or recoarctation of the aorta, the systolic pressure gradient and the internal diameter of the stenotic area were measured before and after dilation, with a balloon catheter with an insufflation diameter no greater than the aortic diameter measured at the level of the diagram muscle. No infants were included nor patients with a rare aortic anatomy. RESULTS: A significant gradient reduction from 36.59 +/- 12.03 mm Hg to 10.45 +/- 7.52 mm Hg, as well an increase from 4.54 +/- 2.04 mm to 8.05 +/- 2.82 mm in aortic internal diameter, were achieved with no complications. CONCLUSIONS: Similar results were obtained both in native coarctation and recoarctation without significant complications. Age selection, aortic anatomy and balloon size were the major determinants of success.

Adolescent↗
PubMed1999

[Ductus closure in adults with the Rashkind device: comparative results].

INTRODUCTION: Catheter occlusion of the persistent ductus arteriosus with Rashkind device is an alternative to the surgical closure demonstrated in children, however a few results have been reported of occlusion in adults. METHOD: From 1990 to 1996 in 127 patients with persistent ductus arteriosus undergoing occlusion by Raskind device. Two groups according age: 105 children (< 14 years) and 22 adults (> 14 years), were studied retrospectively. The results were analysed by immediate aortogram and follow-up at 24 hours, 6 and 12 months by color-Doppler echocardiograms. RESULTS: The adults were frequently asymptomatic (86%) and with high incidence (59%) of silent ductus. Similar QP/QS (1.61 +/- 0.47 in adults vs 1.49 +/- 0.51) was calculated although pulmonary pressure was superior in children (12.50 +/- 2.97 vs 16.84 +/- 5.88 mmHg; p = 0.003). In group > 14 years the ductal anatomy favorable (Krichenko type A or B) was more frequent (91% vs 73%; p = 0.06) and ductal diameter significantly higher (3.03 +/- 1.50 vs 2.41 +/- 0.96 mm; p = 0.009). In adults 17 mm umbrella were used more frequently (91 vs 61%; p = 0.02). Absence complications (embolization, bacteremia, haemolysis, proximal stenosis of the left pulmonary artery) were found in adults against 4.72% in children. The occlusion were more effective in adults specially in early controls: 55% vs 34% (p = 0.09), 82% vs 69%, 91% vs 77% and 95% vs 83% (p > 0.10). Multivariate analysis identified age as an independent predictor of complete occlusion. CONCLUSION: Our experience in transcatheter occlusion of persistent ductus arteriosus with Rashkind device in adults support the efficacy, safety and excellent early results despite higher incidence of silent asymptomatic ductus.

Adolescent↗
PubMed1999

Antigens and antibodies in sera from human cases of epilepsy or taeniasis from an area of Mexico where Taenia solium cysticercosis is endemic.

Human neurocysticercosis is an important parasitic disease in developing countries. Most epidemiological studies on the disease have used antibody-based assays that allow the detection of transmission 'hot spots' and the identification of the main risk factors for transmission. However, such assays have low predictive value in the detection of active cases of neurocysticercosis. The screening potential of the most commonly used antibody-detection technique, the electroimmunotransfer blot assay (EITB), has now been compared with an antigen-capture assay, in an endemic region of Mexico. The subjects were 68 patients with late-onset epilepsy, 35 cases of taeniasis and a randomly selected, control group of 133 individuals from the same region. Parasite-specific antibodies and antigens were more common among the epileptics and taeniasis cases than among the controls. The antigens appeared to be associated with late-onset epilepsy and the antibodies with the presence of subcutaneous nodules. The sensitivities of both tests, to detect epilepsy or taeniasis, were low, but the specificity and the positive predictive value of the antigen-capture assay was high when used with the epileptics. As late-onset epilepsy and neurocysticercosis seem to be associated in endemic regions, antigen-capture assays are probably the most reliable method of detecting active cases of neurocysticercosis in epidemiological studies.

Adult↗
PubMed1999

Factors predictive of outcome on admission to an acute geriatric ward.

AIM: To investigate which factors predict outcome of elderly patients on discharge and at 6 months. METHODS: A prospective study in an acute geriatric ward. Within 48 h of admission, patients were assessed for social factors, geriatric problems, admission diagnoses, medication, function and mental ability. Outcome measures were mortality, length of stay, institutionalization, readmissions and attendance at accident and emergency within 6 months. RESULTS: 353 patients were studied, with a mean age of 81.8 years. Logistic regression analyses showed that variables predicting hospital mortality were Barthel index on admission, pre-morbid disability and polypharmacy. The only variable independently predictive of prolonged stay in hospital was a Barthel score of <45 on admission. Functional disability on admission was predictive of institutionalization on discharge. Variables predicting mortality within 6 months of discharge were Barthel index on admission <65, presence of pressure sores, malnutrition and polypharmacy. Variables independently predictive of institutionalization were mental state and a low pension. Those who took more than five drugs on admission were more likely to attend accident and emergency and be readmitted. CONCLUSION: Limited activities of daily living and geriatric problems on admission are the strongest predictive factors of outcome, independent of diagnoses.

Aged↗
PubMed1999

Characterization of the activation pathway of phosphoramidate triester prodrugs of stavudine and zidovudine.

The phosphoramidate triester prodrugs of anti-human HIV 2', 3'-dideoxynucleoside analogs (ddN) represent a convenient approach to bypass the first phosphorylation to ddN 5'-monophosphate (ddNMP), resulting in an improved formation of ddN 5'-triphosphate and, hence, higher antiviral efficacy. Although phosphoramidate derivatization markedly increases the anti-HIV activity of 2',3'-didehydro-2', 3'-dideoxythymidine (d4T) in both wild-type and thymidine kinase-deficient CEM cells, the concept is far less successful for the 3'-azido-2',3'-dideoxythymidine (AZT) triesters. We now investigated the metabolism of triester prodrugs of d4T and AZT using pure enzymes or different biological media. The efficiency of the first activation step, mediated by carboxylesterases, consists of the formation of the amino acyl ddNMP metabolite. The efficiency of this step was shown to be dependent on the amino acid, alkyl ester, and ddN moiety. Triesters that showed no conversion to the amino acyl ddNMP accumulated as the phenyl-containing intermediate and had poor, if any, anti-HIV activity. In contrast to the relative stability of the triesters in human serum, carboxylesterase-mediated cleavage of the prodrugs was found to be remarkably high in mouse serum. The subsequent conversion of the amino acyl ddNMP metabolite to ddNMP or ddN was highest in rat liver cytosolic enzyme preparations. Although L-alaninyl-d4TMP was efficiently converted to d4TMP, the main metabolite formed from L-alaninyl-AZTMP was the free nucleoside (AZT), thus explaining why d4T prodrugs, but not AZT prodrugs, retain anti-HIV activity in HIV-infected thymidine kinase-deficient cell cultures. The rat liver phosphoramidase responsible for the formation of ddNMP was shown to be distinct from creatine kinase, alkaline phosphatase, and phosphodiesterase.

Amino Acids↗
PubMed1998

Marked inhibitory activity of masked aryloxy aminoacyl phosphoramidate derivatives of dideoxynucleoside analogues against visna virus infection.

Lipophilic masked aryloxyaminoacylphosphoramidate derivatives of 2',3'-dideoxynucleoside (ddN) analogues with potent anti-HIV activity (i.e., stavudine [d4T], azidothymidine [AZT], dideoxycytidine [ddC], 3'thio-2',3'-dideoxy cytidine [3TC], dideoxyadenosine [ddA], and 2',3'-didehydro-2',3'-dideoxyadenosine [d4A]) activity were evaluated for their activity against visna virus (VV) in sheep choroid plexus (SCP) cells. The activity of several prodrug derivatives against VV proved markedly superior to that of the corresponding free ddN analogues. In particular, the d4A and ddA prodrug derivatives were exquisitely inhibitory in this model system (50% effective concentration [EC50], < or = 0.003 microM), and their anti-VV potency exceeded by at least 200-fold the antiviral potency of the corresponding free nucleosides. Marked differences were noted in the anti-VV potencies of several of the test compounds depending on the nature of the amino acid linked to the 5'-phosphate moiety, the nature of the nucleoside, or both. In view of the stability of the prodrugs in lamb serum, the VV infection model in lambs may be considered highly useful for investigating the in vivo antiretroviral efficacy of these type of drugs, particularly the d4T, ddA, and d4A prodrug derivatives.

Animals↗
PubMed1998

Metabolism and anti-HIV activity of phosphoramidate derivatives of D4T-MP with variations in the amino acid moiety.

The metabolism of different phosphoramidate prodrugs of d4T-MP, in which the phosphate group is linked to a phenyl group and the alkyl ester of an amino acid was studied in crude CEM cell extracts. Significant (80-100%) conversion to the amino acyl d4T-MP metabolite was obtained with derivatives containing L-alanine or methyl-L-aspartic acid. A lower degree of conversion was seen with derivatives containing L-phenylalanine, L-methionine, methyl-L-glutamic acid or L-leucine. Derivatives containing D-alanine, beta-alanine, glycine, L-valine or L-lactate showed no conversion to the amino acyl d4T-MP metabolite. Overall, there was a close correlation between the anti-HIV activity of these prodrugs and their conversion rate to the amino acyl d4T-MP metabolite. Our data suggest that the enzymes involved in the formation of the amino acyl d4T-MP metabolite have a rather stringent specificity for L-alanine as the amino acid moiety. In addition, these enzymes were found to be markedly species-dependent, their activities being highest in mouse serum, followed by guinea pig serum, but only minimal in human serum. Mouse serum therefore appears to be the medium of choice to isolate and identify the enzymes that are involved in the metabolism of these phosphoramidate prodrugs.

Amino Acids↗
PubMed1998

Angiocentric cutaneous T-cell lymphoma of childhood (hydroa-like lymphoma): a distinctive type of cutaneous T-cell lymphoma.

BACKGROUND: Angiocentric cutaneous T-cell lymphomas of childhood (ACTCLC) are an unusual type of T-cell lymphomas that present with a vesiculopapular eruption mimicking hydroa vacciniforme. Most patients have been children from Asia and Latin America. OBJECTIVE: The purpose of this study was to describe four cases of ACTCLC; to discuss its clinical, histopathologic, and immunohistochemical features; to consider its possible relationship to the Epstein-Barr virus (EBV); and to clarify its classification within the spectrum of angiocentric lymphomas. METHODS: The clinical, histopathologic, and immunohistochemical features of four cases of ACTCLC were identified and analyzed. In addition in situ hybridization for EBV was performed in all cases. RESULTS: The clinical features were similar to previous cases reported under different names, such as hydroa-like lymphomas, edematous, scarring vasculitic panniculitis. Histologically, all showed angiocentric infiltrates composed mainly of T cells. In all cases there were variable numbers of CD30+ cells. The EBV was present in three of the cases. CONCLUSION: ACTCLC is a distinct type of T-cell lymphoma. It affects mainly children, and the EBV appears to play a role in the pathogenesis of this disease.

Child↗
PubMed1997

Phosphoramidate derivatives of d4T as inhibitors of HIV: the effect of amino acid variation.

Phosphoramidate derivatives of the nucleoside analogue, 2',3'-dideoxy-2',3'-didehydro thymidine (d4T) have been prepared as potential membrane-soluble pro-drugs of the big-active free phosphate forms. In particular phenyl phosphates, linked via nitrogen to methyl-esterified amino acids, were studied. All compounds were fully characterised by a range of methods (high-field multinuclear NMR, mass spectrometry and high performance liquid chromatography (HPLC)) and were subjected to in vitro evaluation of their anti-HIV efficacy. The nature of the amino acid appeared to be extremely important for the eventual antiviral action. Of the amino acids studied, L-alanine was the most efficacious, whilst L-proline and glycine were particularly poor. However, an unnatural amino acid moiety, dimethylglycine, could substitute for alanine with little or no loss of activity.

Amides↗