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Biomedical subjects

L Alvarez

Publications and source records attributed to L Alvarez.

At least 163 records · Page 9Linked to original sources
PubMed1995

Aetiology and presenting symptoms in male osteoporosis.

In order to analyse the clinical characteristics and the principal causes of osteoporosis in men, 81 osteoporotic males from an out-patient rheumatology department were studied. Bone mass assessment, automated biochemical profile and biochemical markers of bone turnover were performed in all patients, and hormonal measurements were taken when a specific aetiology was not readily apparent. Sixty-three men (78%) had secondary osteoporosis and 18 (22%) primary osteoporosis. Secondary causes of osteoporosis included hypogonadism (12 patients), corticosteroid therapy (10 patients) and alcoholism (10 patients); the remaining patients had various causes of osteoporosis. Eighteen patients had primary osteoporosis, eight of them with associated hypercalciuria. Normocalciuric patients showed lower 25-hydroxyvitamin D and 1-25-hydroxyvitamin D levels than the control group, whereas hypercalciuric patients had lower parathyroid hormone and renal threshold for phosphate excretion. In 69 patients (85%), back pain was the chief complaint. Forty-five of these 69 patients (65%) had chronic back pain and 24 (35%) had subacute episodes. Fifty per cent of the patients with chronic back pain had vertebral fractures. Both patients with and without chronic back pain were found to have a similar number of vertebral fractures. In conclusion, male osteoporosis is frequently associated with major risk factors. Patients with primary osteoporosis may have associated hypercalciuria or decreased vitamin D levels. However, not all the patients for whom back pain was the chief complaint were found to have vertebral fractures.

Adult↗
PubMed1995

Direct evidence that perhexiline modifies myocardial substrate utilization from fatty acids to lactate.

Perhexiline maleate, originally classified as a calcium antagonist, is in use as an antianginal agent. The mechanism of its protective effect is unknown, but there is speculation that it involves a modification of myocardial substrate utilization, in which glycolytic sources are used rather than fatty acids. This hypothesis was tested by employing [13C]NMR isotopomer analysis to measure substrate selection in the working rat heart. Substrate utilization was measured from a mixture of substrates present at their physiological concentration, as follows: acetoacetate, glucose, lactate and long-chain fatty acids. Control perfusions were compared with those perfused with perhexiline. It was found that perhexiline increased lactate utilization, which reduced the extent of fatty acid and endogenous substrate oxidation. There was also a significant increase in cardiac output for a small and insignificant increase in oxygen consumption, which suggested an improvement in myocardial efficiency. Thus, it was confirmed by direct measurement that this drug does modify substrate oxidation, which suggests that further investigations of the role that this agent can play in the management of ischemic heart disease would be beneficial.

Acetoacetates↗
PubMed1995

Swine hearts: quantitative anatomy of the right ventricle.

The right ventricle was studied in 75 anatomically normal swine hearts, using, in all, nine geometric and volumetric parameters: ventricular-wall thickness, length of the right-ventricular inflow and outflow tracts, and volume of the right-ventricular inflow and outflow tracts. The data for these parameters were compared with previously published patterns for human hearts and volumetric data were compared with patterns of normality found in human hearts. As in the human heart, the ventricular inflow tract in swine hearts was significantly shorter than the outflow tract (P < 0.0001).

Animals↗
PubMed1995

Developmental toxicity of dibasic esters by inhalation in the rat.

Dibasic esters (DBE) are a mixture of 3 carboxylic acid esters which are used in the paint and coatings industry. In this study, groups of pregnant Crl:CD BR rats were exposed to either 0.16, 0.4, or 1.0 mg DBE/L by inhalation for 6 hr/day from Days 7 through 16 of gestation (day in which copulation plug was detected was designated Day 1G). A control group of chambered pregnant rats was exposed simultaneously to air only. All female rats were euthanized on Day 21G and the fetuses were examined. A suppression of both food consumption and the rate of body weight gain was seen in the 0.4 and 1.0 mg/L groups during the first 6 exposure days. Staining on the fur and perineal area was seen in rats exposed to 1.0 mg/L and liver weight decreases, although not statistically significant, occurred in the 2 high exposure groups. None of the reproductive parameters were altered in any of the groups and no fetal effects were detected. DBE is not a developmental toxin in the rat following inhalation exposures as high as 1.0 mg DBE/L during the period of organogenesis.

Abnormalities, Drug-Induced↗
PubMed1995

Basic fibroblast and platelet-derived growth factors as modulators of actin and alpha-actinin in chick myocardiocytes during development.

To test whether cardiac muscle is a target for regulation by peptide growth factors, we analyzed the effects of two growth factors on actin and alpha-actinin expression at the subcellular level. Sodium dodecyl sulfate-gel electrophoresis, immunoblotting, and fluorescense-activated cell sorter analysis were used to quantify the effects of basic fibroblast growth factor and platelet-derived growth factor on cultures of chick myocardiocytes during development. Cytoplasmic and cytoskeletal concentrations of actin and alpha-actinin were dependent on the stage of embryonic development and on the type of growth factor added to the culture. The most significant finding was the increase in actin and alpha-actinin expression in the cytoplasmic compartment after treatment with basic fibroblast growth factor of chick heart cells at Hamburger and Hamilton's stage 19. At stage 39, basic fibroblast growth factor induced less marked changes in the accumulation of actin and alpha-actinin. Platelet-derived growth factor decreased alpha-actinin expression slightly in the cytoskeletal compartment in more mature stages of heart development. Our findings support the hypothesis that basic fibroblast growth factor plays a role in cardiomyocyte differentiation during the early stages of development.

Actinin↗
PubMed1995

Carbon tetrachloride-induced hepatic injury is associated with global DNA hypomethylation and homocysteinemia: effect of S-adenosylmethionine treatment.

Carbon tetrachloride (CCl4) administration to rats produces hepatic cirrhosis and supplementation with S-adenosylmethionine (SAM) can partially prevent CCl4-induced liver injury. These effects are thought to be caused by oxidative stress and the subsequent formation of free radicals, but the mechanism whereby this occurs and the accurate nature of the mechanisms by which SAM exerts its protective action are not well understood. The effect of short-term administration of CCl4 on hepatic DNA methylation and on SAM and S-adenosylhomocysteine (SAH) were assessed. CCl4 administration to rats for 3 weeks resulted in hypomethylation of liver DNA, determined by comparing the extent to which DNA from livers of control or treated animals could be methylated in vitro using [3H-methyl] SAM as methyl donor. This CCl4 effect on DNA methylation was corrected by the administration of SAM (10 mg/kg/d, intramuscularly), with values of methyl groups incorporation comparable with those observed in the control animals. hepatic SAM was decreased by CCl4 (65.3 +/- 5.27 vs. 102.2 +/- 4.89 nmol/g; P < .05) and SAH was increased (69.5 +/- 14.6 vs. 29.4 +/- 3.83 nmol/g; P < .05). This led to a marked reduction of the SAM/SAH ratio (the methylation ratio) from 3.47 in control rats to 0.94 in CCl4-treated animals (P < .05). SAM treatment partially prevented (P < .05) the reduction of the ratio SAM/SAH induced by CCl4. CCl4 also induced a marked elevation of serum homocysteine levels (more than 20-fold; P < .001), which was partially prevented by SAM administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Procollagen-III peptide and chronic viral C hepatitis.

UNLABELLED: Chronic hepatitis develops in at least half of persons acutely infected with hepatitis C virus (HCV). Ten to 25% of these patients will develop cirrhosis. Serum procollagen-III peptide (PIIIP) may be of value in predicting the development of chronic active fibrogenic liver disease. It has been reported that in chronic viral C hepatitis, the levels of hepatitis C virus-RNA (HCV-RNA) correlate directly with the severity of hepatic histology and inversely with response to interferon therapy. OBJECTIVES: The aims of this study were to correlate the level of PIIIP with HCV-RNA concentrations, ALT values, and histological severity in patients with chronic viral C hepatitis. METHODS: Eighty-six patients with chronic C hepatitis were divided into three groups: group I (n = 34), mild chronic active hepatitis, group II (n = 25), moderate to severe chronic active hepatitis, and group III (n = 27), cirrhosis. HCV-RNA was measured by Quantiplex, and PIIIP was measured by radioimmunoassay-gnostic assay. RESULTS: Mean +/- SD level of ALT in group I was 114 +/- 48 U/L, group II was 169 +/- 115 U/L, and group III was 160 +/- 94 U/L. The mean +/- SD level of HCV-RNA in group I was 110 +/- 130 x 10(5) Eq/ml, in group II was 140 +/- 140 x 10(5) Eq/ml, and in group III was 70 +/- 80 x 105 Eq/ml. The mean +/- SD level of PIIIP in group I was 0.6 +/- 0.2 U/ml, in group II was 0.9 +/- 0.4 U/ml, and in group III was 1.2 +/- 0.6. There was a significant difference in the levels of PIIIP among the three groups (p = 0.0001). There was no correlation among ALT, HCV-RNA, and PIIIP in any of the three groups. CONCLUSIONS: PIIIP peptide determinations in patients with chronic viral C hepatitis are reflective of histological severity and may provide relatively noninvasive means of following disease progression.

Alanine Transaminase↗
PubMed1994

Expression of rat liver S-adenosylmethionine synthetase in Escherichia coli results in two active oligomeric forms.

A cDNA containing the complete coding sequence for rat liver S-adenosylmethionine synthetase was cloned into the prokaryotic expression vector pT7-7 and expressed in Escherichia coli BL21(DE3). A major additional band corresponding to a protein of 48 kDa was detected on SDS/PAGE after induction with isopropyl beta-D-thiogalactopyranoside. This protein was distributed in both the soluble and insoluble fractions and accounted for approx. 30% of the total bacterial protein. The soluble enzyme was fully active, as revealed by assays in vitro of S-adenosylmethionine synthetase activity. In addition, transformed bacteria exhibited highly increased levels of intracellular S-adenosylmethionine. Two active forms of the recombinant enzyme, with apparent molecular masses of 210 kDa and 110 kDa, were detected when cytosolic extracts of the transformed cells were fractionated by gel-filtration chromatography. It is concluded that the expressed S-adenosylmethionine synthetase polypeptide assemble as tetramers and dimers.

Animals↗
PubMed1994

Posterior temporal epilepsy: electroclinical features.

In the course of evaluating children with posterior temporal lobe epilepsy with subdural electrodes, we observed that their seizures commonly arose from basal rather than convexity foci and that they followed a stereotyped clinical sequence. Seizures characteristically began with behavioral arrest that coincided with basal temporal seizure discharges and progressed to motor signs as the seizure activity spread to the ipsilateral cortical convexity. Behavioral automatisms were observed in approximately half the patients, but were never the first or most prominent ictal manifestation. Focal lesions were identified preoperatively in 7 patients. We performed tailored temporal lobe resections in 14 patients, 10 (71%) of whom were seizure free (N = 9) or had occasional auras (N = 1) at a mean follow-up of 2 years. These findings suggest that in childhood, posterior temporal seizures frequently arise from basal cortex and have a consistent and recognizable ictal and electrographic semiology. In medically refractory patients, tailored temporal resection is an effective therapy.

Adolescent↗
PubMed1994

Prevention of thrombus formation on biomaterials exposed to blood using different antiplatelet drugs: experimental study in dogs.

An ex vivo shunt, established in dogs between both femoral arteries and right atrium, has been used to quantify the platelet deposition on six prosthetic materials used in the construction of cardiovascular prostheses: highly porous knitted Dacron (intervascular HP 800, 1400 mL/cm2/min/120 mm Hg), low-porosity woven Dacron (intervascular LP 200, 200 mL/cm2/min/120 mm Hg), double velour knitted Dacron, Avcothane 51 elastomere, and the mesothelial and epipericardial surfaces of bovine pericardium. In the search for a method to prevent platelet thrombi formation on these materials, we studied four groups of dogs: group 1 (control), group 2 (5 mg/kg body weight (BW)/day acetylsalicylic acid), group 3 (20 mg/kg BW/day acetylsalicylic acid), and group 4 (5 mg/kg BW/day acetylsalicylic acid plus 5 mg/kg BW/day dipyridamole). Platelets were labeled with 111In-oxine. The least thrombogenic material was Avcothane 51 elastomere. The only effective treatment for reduction of platelet deposition on the six materials was 5 mg/kg BW/day of acetylsalicylic acid. The dose used in group 3 only decreased the deposition of platelets on three of the six materials studied. The treatment employed in group 4 did not significantly reduce the deposition of platelets on any of the materials when compared with the control group.

Animals↗
PubMed1994

S-adenosyl-L-methionine synthetase and methionine metabolism deficiencies in cirrhosis.

Methionine metabolism impairment in human liver disease has been related with an alteration in SAM-synthetase. This deficiency is produced by a post-translational event since human liver cirrhosis presents normal levels of SAM-synthetase mRNA in spite of a more than 50% diminution in its activity. A series of different experiments on the structure and activity of this enzyme have provided strong evidence that SAM-synthetase is regulated by reduced/oxidized glutathione ratio. Restoration of glutathione levels by the addition of S-adenosyl-methionine or glutathione esters in various experimental conditions (buthionine sulfoximine and carbon tetrachloride intoxication) resulted in a normalization of the SAM-synthetase diminution caused by the toxics and an attenuation of the morfological alteration produced in the liver, including fiber production. This findings might have pharmacological implications in the treatment of liver diseases, since the possible beneficial effect of long term administration of SAM could include a reduction of fiber production.

Animals↗
PubMed1994

Influence of dimethyl sulphoxide on intermediate filament proteins in human rhabdomyosarcoma cell lines: modulation at subcellular level.

The effects of dimethyl sulphoxide have been investigated on differentiation in human rhabdomyosarcoma cell lines obtained from typically malignant, poorly differentiated tumours. The expression of cell differentiation marker proteins (desmin and vimentin) was assessed in cell lines A-204, A-673 and RD, and the modifications in expression after 3, 8 and 24 h of induction with 1.25% dimethyl sulphoxide were recorded. Protein expression in both the cytoplasm and cytoskeleton was significantly altered by treatments lasting 8 and 24 h, the most noteworthy changes being increased desmin and decreased vimentin expression. The results clearly indicate that dimethyl sulphoxide induced changes typical of differentiation in rhabdomyosarcoma cell lines A-673 and RD; less marked changes were observed in line A-204.

Blotting, Western↗
PubMed1994

Modulation of contractile proteins in embryonic and fetal chick cardiac cells by phorbol ester, gamma-interferon, 5-azacytidine and diacylglycerols.

We studied changes in the concentration of tropomyosin, actin, desmin and vimentin in cultured myocardiocytes from Hamburger and Hamilton's stages 29 and 39 chick embryos (HH29 and HH39) (1), treated with 12-o-tetradecanoyl-phorbol-13-acetate (TPA), 5-azacytidine (AZA), gamma interferon (INF) and diacylglycerols (DAG). In embryonic myocardiocytes at HH29, the first three agents modified the intracellular distribution of the thin filament proteins tropomyosin and actin, increasing their cytoplasmic concentration and decreasing their cytoskeletal concentration. The concentration of the intermediate filament proteins desmin and vimentin increased in both subcellular fractions after treatment with these drugs. In fetal myocardiocytes at HH39, total protein content decreased after treatment with these drugs. Cytoplasmic and cytoskeletal concentrations of actin and tropomyosin decreased to different degrees after treatment with TPA, AZA or DAG in HH39 myocardiocytes. TPA, AZA and DAG decreased desmin in the cytoplasmic and cytoskeletal fractions. These findings suggest that the drugs tested alter the normal protein composition in cultured myocardiocytes, and have different effects depending on the developmental stage in which the embryo is treated.

Animals↗
PubMed1994

Application of new coatings for vascular grafts based on polyacrylic systems with antiaggregating activity.

A study has been made of the behaviour of knitted and woven Dacron mesh used in the preparation of vascular grafts when coated with either a layer of poly(2-hydroxyethyl methacrylate) or co-polymers of 2-hydroxyethyl methacrylate with 5, 10 or 20 wt% of an acrylic derivative of salicylic acid, 2-methacryloyloxybenzoic acid. In vitro studies were carried out to quantify the loss of polymer under flow conditions, and ex vivo studies were done in dogs to quantify the deposition of 111In-oxine-labelled platelets. The treated materials showed a lesser deposition of platelet thrombi when compared with the control group.

Animals↗
PubMed1994

Cytotoxic and antimicrobial screening of selected terpenoids from Asteraceae species.

Twelve pure compounds originally obtained through a systematic chemotaxonomical study with Mexican plants of the Asteraceae, were subjected to a cytotoxic and in vitro antimicrobial screening. Three different cell lines in culture (KB, KB-VI and P388) were used in the cytotoxicity assay, while antimicrobial activity was tested against Gram-positive and Gram-negative bacteria, as well as Candida albicans. Of the twelve terpenoids tested, only taraxasterol showed antimicrobial activity against Staphylococcus aureus. The significant cytotoxic activity exhibited by five sesquiterpene lactones, and the moderate cytotoxicity of an eudesmane, is discussed.

Animals↗
PubMed1994

Prevention of arterial thrombosis by a monoclonal antibody against the 100 to 109 amino acid sequence stretch of the beta-subunit of the human platelet fibrinogen receptor: a comparative study with low dose aspirin.

OBJECTIVES: The aim of this study was to compare, in dogs, the antithrombotic activity of aspirin and the murine monoclonal antibody P37, which inhibits platelet aggregation and fibrinogen binding to activated platelets. BACKGROUND: The antithrombotic activity of P37 has been somewhat predictable, given its in vitro platelet antiaggregating activity and localization at or very near the fibrinogen binding site in the platelet fibrinogen receptor, the glycoprotein IIb/IIIa or integrin alpha IIb-beta 3. METHODS: The monoclonal antibody P37 of the immunogamma-globulin-1 isotype was prepared according to previously described immunization and fusion protocols and screening assays. To compare its antiaggregating capacity with that of aspirin, experimental thrombosis was induced in all dogs by means of direct current applied to the carotid artery. Autologous platelets had previously been labeled with indium-111 oxine. The dogs were assigned to three groups: group I (n = 18) was the control group; group II (n = 12) was treated orally with 5 mg of aspirin/kg body weight per day for 7 days before induction of thrombosis, and group III (n = 10) was treated intravenously with a single dose of P37 (0.8 mg/kg). RESULTS: The indium-111 oxine activity deposited in the thrombi was 12.94 +/- 12.83% (mean +/- SD) in group I, 3.55 +/- 2.99% in group II and 0.03 +/- 0.03% in group III. The differences between groups were always statistically significant (p < 0.05). CONCLUSIONS: We conclude that a single dose (0.8 mg/kg) of P37 in a canine model of arterial thrombosis is approximately 100 times more efficient than the administration of aspirin (5 mg/kg per day) in preventing platelet deposition during thrombus formation.

Animals↗
PubMed1994

Creatine kinase isoenzymes as markers of differentiation in rhabdomyosarcoma cells in culture.

Rhabdomyosarcomas have been classified on the basis of their degree of differentiation, a feature closely related with their response to chemotherapy. We recently reported the role of creatine kinase isoenzymes as tumoral markers in the diagnosis of rhabdomyosarcoma. The present study was designed to determine whether these isoenzymes are also good markers of the degree of differentiation of these neoplasm. Dimethyl sulfoxide, a well-known differentiating agent, was used to induce myogenic differentiation. This agent increased CK-MM and/or CK-MB fractions, and decreased CK-BB isoenzyme in rhabdomyosarcoma cell lines. The variable behavior of MCK-1 macromolecule was unrelated to the degree of differentiation. Our findings suggest that CK-MM, CK-MB and CK-BB isoenzymes are good markers of the degree of differentiation in rhabdomyosarcomas and could be used as specific markers of prognostic and diagnostic value.

Biomarkers, Tumor↗