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Biomedical subjects

A Lorenzo

Publications and source records attributed to A Lorenzo.

At least 55 records · Page 3Linked to original sources
PubMed1994

Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red.

beta-Amyloid (beta A) is normally produced as a nontoxic soluble peptide. In Alzheimer disease, beta A aggregates and accumulates in the brain as inert diffuse plaques or compact plaques associated with neurodegenerative changes. To determine the relationship of neurotoxicity to the physical state of beta A, we created (i) nonamyloidogenic amorphous aggregates of beta A [amorphous beta A (Am-beta A)] analogous to diffuse plaques and (ii) amyloidogenic fibrils of beta A [fibrillar beta A (Fib-beta A)] analogous to compact plaques. In primary rat hippocampal culture, Fib-beta A was neurotoxic, whereas Am-beta A was not toxic. Fib-beta A caused significant loss of synapses in viable neurons, while Am-beta A had no effect on synapse number. The amyloid fibril-binding dye Congo red inhibited Fib-beta A neurotoxicity by inhibiting fibril formation or by binding to preformed fibrils. Congo red also inhibited the pancreatic islet cell toxicity of diabetes-associated amylin, another type of amyloid fibril. These results indicate that beta A neurotoxicity requires fibril formation. These findings and our previous demonstration that amylin fibrils are toxic suggest that a common cytopathic effect of amyloid fibrils may contribute to the pathogenesis of Alzheimer disease and other amyloidoses.

Amyloid↗
PubMed1994

Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus.

The 37-amino-acid polypeptide amylin is the principal constituent of the amyloid deposits that form in the islets of Langerhans in patients with type-2 diabetes mellitus, but its role in the pathogenesis of this disease is unresolved. In view of the fact that the beta-amyloid protein that forms fibrils in Alzheimer's disease is toxic to neurons, we have investigated whether amylin fibrils could be toxic to pancreatic islet cells. We show here that human amylin is toxic to insulin-producing beta-cells of the adult pancreas of rats and humans. This toxicity is mediated by the fibrillar form of the amylin peptide and requires direct contact of the fibrils with the cell surface. The mechanism of cell death involves RNA and protein synthesis and is characterized by plasma membrane blebbing, chromatin condensation and DNA fragmentation, indicating that amylin induces islet cell apoptosis. These findings indicate that amylin fibril formation in the pancreas may cause islet cell dysfunction and death in type-2 diabetes mellitus.

Adult↗
PubMed1994

EFFECTS OF BARIUM CHLORIDE ON ELECTROLYTE TRANSPORT ACROSS ISOLATED COLONS FROM NORMAL AND ALDOSTERONE-TREATED LIZARDS (GALLOTIA GALLOTI)

Addition of BaCl2 to the solution bathing colons of normal lizards did not alter the absorptive Na+ flux, but did reverse the net absorption of Cl- to become net secretion. Cl- secretion resulted from an increase in its serosal-to-mucosal movement and was positively correlated to an increase in short-circuit current. Ba2+-induced short-circuit current was dependent on the presence of both Na+ and Cl- in the serosal medium. Ba2+-induced Cl- secretion could be reversed by serosal amiloride (10(­4) mmol l-1). Colons from acutely or chronically aldosterone-treated lizards exhibited a considerably higher short-circuit current, potential difference and net Na+ absorption than did untreated colons. Net Cl- transport was unaltered by acute treatment, but was totally abolished after chronic treatment. BaCl2 rapidly decreased the potential difference, short-circuit current and tissue conductance across colons from aldosterone-treated lizards. Net Na+ transport was markedly inhibited by Ba2+ in both acutely and chronically treated tissues, but barium did not change unidirectional or net Cl- fluxes in these. The present results support the following hypotheses: (1) that BaCl2 inhibits electrogenic Na+ absorption induced by acute or chronic aldosterone treatment and (2) that Ba2+ induces an electrogenic Cl- secretion by stimulating a basolateral Na+-dependent Cl- intake in normal but not in aldosterone-treated colons. This also suggests that aldosterone could exert an antisecretory influence in colonic epithelia.

Journal Article↗
PubMed1994

[Effects of pharmacological doses of polyunsaturated fatty acids of the series 3 on the concentration of plasma lipoproteins].

Cardiovascular disease is one of the main causes of death in developed countries. Its incidence may be modified through dietary changes, this being supported by the low incidence of the disease among populations with high intake of fatty fishes. The aim of this work was to study the modifications on plasmatic levels of polyunsaturated fatty acids omega 3 after an additional supply of fish oils and to assess its effect on the metabolism of lipids and lipoproteins. The study was conducted on 8 healthy volunteers, their age ranging between 24 and 37 years. They received, during 30 days and in tablets of 500 mg, 7.5 gr/24 h of fish oil concentrate which supplied 2.5 gr/24 h of fatty acids omega 3. After 12 hours of fasting, blood samples were taken before and after the intake of this concentrate. Methyl esters from fatty acids omega 3 were assessed through gas chromatography; cholesterol, triglycerides, LDL, VLDL, HDLt, HDL2 and HDL3, through several enzymatic techniques; and lipoprotein(a) Lp(a), through ELISA. The statistical analysis was conducted using the Student's method for matched data. After 30 days of supplement, we observed: a significant increase in the plasmatic percentage of fatty acids omega 3 (EPA + DHA) along with a significant decrease of triglycerides, VLDL and HDL3 and a significant increase of HDL2, We did not observe any significant changes in cholesterol, LDL and HDLt. With respect to Lp(a), after one month of dietary supplement, its plasmatic levels did not change. Our results supports the clinical usefulness of the dietary supplementation with fatty acid omega 3 for the management of hypertriglyceridemias.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Effects of dietary oil (olive/sunflower) on the plasmatic apolipoprotein profile].

UNLABELLED: FOUNDATIONS: The dietary oil provides a significant portion of the caloric intake in the form of fat, although there is some controversy with respect to the potential positive action of each type of oil. In this study, the effect on the lipo-apoprotein profile of monounsaturated fatty acids (MUFA) provided by olive oil and the polyunsaturated fatty acids (PUFA) provided by girasol oil are compared in a population with high risk of arteriosclerosis, as it is the aged population. METHODOLOGY: 44 aged patients living in the same institution, 21 males and 23 females (age: 79 +/- 6 years), and following two different diets during 3 months, with olive and girasol oils, respectively, participated in the study. Both diets were isocaloric: 2.300 kcal/day, 17% proteins, 33% lipids (30 g/day of oil), and 50% carbohydrates. Plasmatic concentrations of cholesterol (C), triglycerides (TG), c-LDL, c-VLDL, c-HDL2, c-HDL3 and lipoprotein a (Lp[a]), as well as apoproteins A1, B, CII, CIII and E, were assessed. Applied statistics: Student's t test for matched samples. RESULTS: C and TG plasmatic levels did not changed, whereas levels of c-LDL decreased significantly, as well as levels of polyunsaturated fatty acids (135 +/- 43 and 124 +/- 33 mg/dl., p < 0.009) and levels of apo B (151 +/- 47 and 139 +/- 36 mg/dl., p < 0.009). Levels of c-HDL increased significantly (49 +/- 14 and 52 +/- 16 mg/dl., p < 0.01) as well as levels of apo A1 (190 +/- 32 and 205 +/- 41 mg/dl., p < 0.01). Levels of apo CIII (8.2 +/- 2.8 and 9.9 +/- 3.2 mg/dl., p < 0.008) and apo E (3.2 +/- 1.1 and 3.7 +/- 0.9 mg/dl., p < 0.01) also increased in men. Women did not showed any significant variations in lipoproteins, although apo A1 and apo E increased slightly and apo B decreased, although not significantly, with the polyunsaturated fat. The levels of Lp(a) did not changed. CONCLUSIONS: In the aged population following a standard diet, without overloads, the PUFAs induced positive changes in the lipoapoprotein profile when compared to a previous diet with MUFA. Those changes were more evident in men than in women.

Aged↗
PubMed1992

Time lapse study of neurite growth in hypothalamic dissociated neurons in culture: sex differences and estrogen effects.

Cultures of dissociated hypothalamic cells taken from rat fetuses of 19 days of gestation were studied using time-lapse recording and sequential microphotography from 1 to 5 days in vitro (DIV) and at 7 and 21 DIV. Cultures were seeded with cells taken from fetuses grouped by sex or sexually mixed; experimental cultures were raised in medium containing 17-beta-estradiol 100 nM (E2). Cells were plated on poly-D-lysine-coated coverslips at a culture density of approximately 4,000 cells/cm2. Immunocytochemistry of cell cultures was performed using a Tau monoclonal antibody (clone Tau-1 PC1C6) and a monoclonal antibody against MAP-2 (clone AP-20). Cells started to produce lamellipodia and neuritic processes approximately 4 hr after plating. Forty-eight hours later a few neurons had defined their morphological polarity by the differentiation of an axon-like process that grows faster than the others; at 5 DIV almost all neurons had defined their axons. At this time, monoclonal antibody against MAP-2 clearly stained soma and dendrites, but not axons. Tau immunoreactivity (lots CCA101 and CCA101N from Boeringher Mannheim) was differentially distributed, with a clear predominance in axon and soma. Results on the morphometric analysis of control and E2 treated neurons provide direct evidence for the existence of sex related differences in the neurite outgrowth response of hypothalamic neurons, since cultured neurons taken from female fetuses differentiated axons later and had fewer primary neurites and shorter dendrites than neurons taken from male fetuses or sexually mixed cultures. Also, it was demonstrated in living neurons that E2 effectively enhances outgrowth and elongation in axons. The frequency distribution curves of axonal length for control and E2 treated cultures was unimodal, suggesting that the effect of E2 was a uniform increase in the axonal length of all neurons. The structural differences between neurons from both sexes and the changes induced by E2 may contribute to explain the differences in brain function found between the sexes.

Animals↗
PubMed1992

Amygdala neurons in vitro: neurite growth and effects of estradiol.

Dissociated cell cultures from embryonic rat medial amygdala were studied using sequential photography and immunocytochemical staining for cytoskeletal proteins and substance P (sP). Cultures were seeded with cells taken from fetuses grouped by sex; experimental cultures were raised in medium containing 17-beta-estradiol (E2). Forty-eight hours after plating a few neurons begin to define their morphological polarity by the differentiation of an axon-like process; at 5 days in vitro (DIV) almost all neurons had developed an axon. Tapering, daughter branch ratio and branch power coefficient coincided with identification of dendrites which could be confirmed by retrospective analysis of immunocytochemically stained cultures: at 5 DIV MAP-2 was restricted to dendrites whereas Tau immunoreactivity was differentially localized with a clear predominance in the axon. At 21 DIV neuronal shape parameters were strikingly like those of amygdaloid neurons in vivo. It was demonstrated in living neurons that E2 increased total dendritic length and that this is due to increased ramification of third or higher order dendritic segments whose individual lengths are not different from controls. Densitometric measurement of MAP-2 stained neurons showed a highly significant increase of immunoreactive material in cells grown in the presence of E2; readings for alpha-tubulin were not different between controls and E2 treated cultures. The effect of E2 on dendritic length was just as manifest in sP-positive as in sP-negative neurons. No sexual differences in morphological parameters, growth characteristics or effects of E2 were found in neurons taken from female fetuses versus neurons from male fetuses. The significance of these results for the generation of sexual differences in the amygdala in vivo is discussed and contrasted with reported results on the effects of E2 in cultures of different neural regions.

Amygdala↗
PubMed1992

[Beta-thromboglobulin levels and atherosclerosis. Its relationship with the presence of risk factors].

In order to evaluate whether plasma beta-thromboglobulin (as a marker of the degree of platelet function) in patients presenting clinically evident atherosclerosis is related to the presence or absence of different risk factors (smoking habit, arterial hypertension, hypercholesterolemia, diabetes, hypertriglyceridemia, obesity, hyperuricemia, alcoholism), 40 patients have been studied in whom mean beta-thromboglobulin levels was 54 +/- 25.56 ng/ml, which is very superior to levels considered normal. However, the presence of one or more risk factors did not lead to significant variations in b-thromboglobulin concentrations, and no differences were found either when each risk factor was considered separately. The positive correlation (r = 0.98; p less than 0.01) between beta-thromboglobulin and apo B levels is highlighted. The results suggest that platelet hyperfunction seems to be due to a greater extent to the atherosclerotic process rather than to the existence of a particular risk factor.

Aged↗
PubMed1991

[Ceruloplasmin levels in patients with chronic obstructive bronchopneumopathy].

The seric levels of ceruloplasmin in a group of 20 patients suffering of chronic obstructive lung disease were studied. Levels in this group of patients (51.42 +/- 11.15 mg/dl) (p less than 0.005) were significantly higher than those of the control group (36.59 +/- 13.37 mg/dl). There was no correlation between ceruloplasmin levels and PaO2, PaCO2, SaO2, HCO3- measurements. Results show a possible oxidation reaction; owing to the fact that ceruloplasmin is a general oxidase which, combined with an antioxidant stimulus of patients with chronic respiratory insufficiency, can produce this reaction.

Aged↗
PubMed1990

[Escape rhythms after ablation of the atrioventricular junction and implantation of a pacemaker].

Escape rhythms characteristics after successful catheter ablation of the atrioventricular junction and intentional complete heart block were compared with those due to others etiologies as well as the advantage of the posterior implantation of a rate responsive pacemaker (VVIR). In 22 patients, 9 men and 13 women, with permanent AV block after fulguration and follow-up periods from 4 to 58 months, escape rhythms data studied during the procedure and at short and long-term periods, showed the following characteristics: 1) Classical parameters of valuation are not as a whole useful to evaluate subsidiary escape rhythms after electrical fulguration of the atrioventricular junction system. 2) The QRS morphology of the escape rhythm exhibited frequently right or left bundle branch block and specially the former. 3) Spontaneous variability of the escape rhythm recovery time makes this parameter unreliable. 4) Electrophysiological parameters previous to the shock and energy delivery do not predict the origin and characteristics of the subsidiary escape rhythms. 5) Active ventricular arrhythmias appearing immediately postshock are unrelated with any subsequent complication. 6) Permanent pacing increases pacemaker dependency at least temporarily. In 15 of 22 patients, a rate responsive multiprogrammable pacemaker controlled by QT interval was implanted. Cardiac performance and life-quality was improved in these patients due to the addition of several factors: 1) Control of the tachyarrhythmias. 2) Elimination of antiarrhythmic drugs and their side-effects on ventricular function. 3) Self-regulation of cardiac rate through permanent stimulation with a QT sensitive rate responsive pacemaker.

Adult↗
PubMed1990

[Results of the functional tests using calcitonin in patients with chronic diffuse hepatopathy].

A group of ten patients suffering cirrhosis who were treated with 100 U/l of calcitonin was studied with the aim of knowing whether in patients with cirrhosis the calcitonin is able to provoke the usual characteristic biologic modifications on the basis of the knowledge of their hormonal high levels accompanied of oesteopenia. Regarding their baseline determinations, no statistically significant modifications have been observed in calcium, phosphorous, alkaline phosphatase or its thermostable and thermolabile fractions, magnesium, uric acid and creatinine plasma concentrations respectively. This absence of a biological response to calcitonin could be due either to a numeric or functional damage of the hormone receptors or a diminished biodisponibility, although there are facts suggesting a lesser hormone biopotenciality in these patients.

Calcitonin↗
PubMed1989

Rat blood and brain amino acid pattern in short term experimental diabetes.

Some serum and brain amino acid variations occurring in animals with short term streptozotocin-diabetes (24 h) are studied in this work. Diabetic animals showed an increase in serum of the three branched-chain amino acids as well as an increase in free tryptophan, besides a decrease in total serum tryptophan and in the tryptophan/competitor amino acids ratio. In brain, the three branched-chain amino acids increased, but there were no variation in whole brain tryptophan. Nevertheless, by studying levels of tryptophan in different brain regions, an increase in medulla-pons was recorded. This circumstance could be explained by the increase in free serum tryptophan levels, in agreement with several authors who assign this reason for brain tryptophan.

Amino Acids↗