Search PubMed⌕ Search

Biomedical subjects

L Castro

Publications and source records attributed to L Castro.

At least 55 records · Page 3Linked to original sources
PubMed1996

The effect of thigh-length support stockings on the hemodynamic response to ambulation in pregnancy.

OBJECTIVE: Our purpose was to determine the effect of thigh-length support stockings on hemodynamic response when pregnant subjects change from the sitting to the lateral recumbent position and then after standing with ambulation. STUDY DESIGN: Eighteen subjects in the late second and early third trimester of pregnancy acted as their own controls. The cardiovascular status of the subjects was assessed by a noninvasive technique--thoracic electrical bioimpedance before and after wearing support stockings for 1 week. Urine catecholamines were measured in 13 patients before and after wearing support stocking to assess the release of catecholamines. Samples were collected after the subjects had been in the lateral recumbent position 40 minutes and again 40 minutes later after standing with ambulation. RESULTS: Heart rate and mean arterial blood pressure decreased significantly when subjects changed from the sitting to the lateral recumbent position and then increased with ambulation. Wearing compression stockings significantly increased mean arterial pressure and afterload in all three positions. Position change from lateral recumbent to standing and ambulation marginally increased urinary dopamine levels (p = 0.097) and significantly increased norepinephrine levels (p = 0.006). CONCLUSIONS: There are significant hemodynamic changes in pregnant subjects when they change from the sitting position to the lateral recumbent position and then change to standing with ambulation. Support stocking have a significant mechanical effect: they significantly increase afterload and systemic vascular resistance by preventing pooling of blood in the lower extremities. There may also be a biochemical effect that results in less catecholamine release. These results suggest that compression stockings could play an important role in supporting the circulation during ambulation.

Adult↗
PubMed1996

Pharmacokinetics of Dextran-70 in patients with cirrhosis and ascites undergoing therapeutic paracentesis.

BACKGROUND/AIM: Dextran-70 is frequently used as a plasma expander in patients with cirrhosis treated with large-volume paracentesis to prevent post-paracentesis hypovolemia, which is thought to develop after 24 h following the procedure. However, there are no studies on Dextran-70 pharmacokinetics in cirrhosis. METHODS: Nine patients with alcoholic cirrhosis and tense ascites treated with a 5-1 paracentesis were given 500 ml of Dextran-70. Blood samples to measure the plasma concentration of dextran were obtained 15 and 30 min, 1, 2, 3, 6, 12 and 24 h and 2 and 6 days after the end of the infusion. Nine healthy volunteers were studied in identical fashion after infusion of 100 ml of Dextran-70. The plasma concentration of dextran was determined by the anthrone method. A bicompartmental model was used to analyze the pharmacokinetic parameters. RESULTS: There were no significant differences between patients with cirrhosis and controls in the volume of distribution (7.7 +/- 0.6 vs. 7.3 +/- 1.21), half-life of the first and second component of plasma disappearance (2.96 +/- 0.69 and 80.3 5.9 h in patients with cirrhosis vs 2.82 +/- 0.69 and 67.1 +/- 10.7 h in controls). CONCLUSIONS: The pharmacokinetics of Dextran-70 in patients with cirrhosis and ascites after large-volume paracentesis is similar to that in controls. This may explain why Dextran-70 is less effective than albumin in preventing paracentesis-induced hypovolemia, which starts after most Dextran fraction has disappeared from plasma.

Ascites↗
PubMed1996

Megestrol acetate therapy for anorexia and weight loss in children with malignant solid tumours.

BACKGROUND: Malnutrition is very frequent in childhood cancer. Its main cause is inadequate intake for energy demands owing to lack of appetite. Megestrol acetate is a synthetic progestin that has been used for reversing anorexia in adult cancer. OBJECTIVE: To assess megestrol acetate efficacy and side-effects in treating anorexia in childhood cancer. METHODS: Thirty-five children with solid tumours were receiving antitumour therapy. Nutritional assessment was by anthropometry. Megestrol acetate efficacy was assessed by evaluating grade of appetite, energy intake and well-being. Side-effects were evaluated by means of clinical history, physical examination, lipid profile, coagulation tests and cortisol rhythm. RESULTS: When compared to baseline all the anthropometric measurements increased (P < 0.05) from the first month of megestrol acetate therapy, as well as appetite and energy intake. No significant side-effects were found. CONCLUSION: Megestrol acetate therapy is a powerful appetite stimulant which led to weight gain, composed of both fat mass and fat-free mass. Megestrol acetate is well tolerated, with few and mild side-effects. If megestrol acetate therapy is started at the onset of anorexia, the use of more expensive, invasive and complicated techniques of nutritional support may be avoided.

Adolescent↗
PubMed1996

Serological survey of small mammals in a vesicular stomatitis virus enzootic area.

Small mammals were captured in a Costa Rican dairy farm located in a vesicular stomatitis virus (VSV) enzootic focus, in order to determine which species were naturally infected by this virus. Monthly captures were performed from March 1989 to February 1990. Eighty-four individuals belonging to the orders Rodentia (n = 52), Insectivora (n = 31) and Marsupialia (n = 1) were captured. Only Sigmodon hispidus had neutralizing antibodies to VSV; among 21 animals, six had antibodies to Indiana, one to New Jersey, and two to both serotypes. In addition, groups of 40 sentinel mice (Mus musculus, strain C3H) were placed in cages distributed throughout the farm. Each group was exposed for 1 mo over a period of 1 yr. None of 312 sentinel mice developed antibodies against either VSV serotype. Based on these results, we believe that S. hispidus might be part of the natural cycle of VSV in this enzootic focus. Caged Mus musculus do not seem appropriate for monitoring VSV activity in this area.

Animals↗
PubMed1996

Calcium channel blockers inhibit the antidipsogenic effect of central injections of zinc in rats.

Previous data from our laboratory have indicated that acute third ventricle injections of Zn2+ elicit a significant antidipsogenic response in rats in three different situations; dehydration, and central angiotensinergic or cholineric stimulation. In the present study we analyzed whether this response depends on voltage-dependent calcium channels. Dehydrated (14 h of water deprivation, overnight) animals received 2-microliters i.c.v. injections of zinc acetate (Zn(Ac)2; 300 pmol/rat) after pretreatment with the voltage-dependent calcium channel blockers gadolinium (Gd3+; 0.03, 3.0 and 30 pmol/rat) or verapamil (VER; 0.027, 0.05 and 0.11 pmol/rat). Both blockers reserved the antidipsogenic effect of third ventricle injections of Zn2+ in a dose-dependent manner. After 120 min, animals pretreated with saline receiving Zn(Ac)2 drank 3.10 +/- 0.57 ml/100 g body weight while those pretreated with Gd3+ at the highest dose displayed a water intake of 5.45 +/- 0.41 ml/100 body weight (P < 0.01). Animals pretreated with the vehicle of VER receiving Zn(Ac)2 drank 3.15 +/- 0.45 ml/100 g while animals pretreated with VER at the highest dose receiving Zn(Ac)2 drank 6.16 +/- 0.62 ml/100 g (P < 0.01). The antidipsogenic effect of Zn(Ac)2 seems to be specific since the metal (same dose and injection procedures) did not modify food intake in rats after 24 h of food deprivation. It is suggested that Zn2+ exerts its antidipsogenic effect by activation of mechanism(s) depending on the functional integrity of voltage-dependent calcium channels.

Animals↗
PubMed1995

Autologous blood donation in cardiac patients.

Despite the advantages of autologous blood transfusion, doubt still remains about its safety in cardiac patients. We report our experience with 439 cardiac patients who donated a total of 1692 units of blood before coronary, valvular, or congenital cardiac operations. During the collections, patients were continuously monitored with ECG, blood pressure, and heart rate. In 22 collections we observed vasovagal reactions, which represents an incidence of 1.3% of the total number of collections. The patients recovered quickly and only in 3 cases was volume replacement with saline needed. There were no other complications which could be related to the preoperative autologous donation program. We feel that, with careful selection of the patients and of the circumstances surrounding the collection of blood, autologous blood donation in cardiac patients is a safe and beneficial experience.

Adolescent↗
PubMed1994

Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide.

Mitochondrial and cytosolic aconitases have been indicated as major targets of .NO- and O2-.-mediated toxicity in cells due to the oxidant-mediated disruption of the [4Fe-4S] prosthetic group. However, under circumstances in which both .NO and O2-. are generated, their almost diffusion-controlled combination reaction (k = 6.7 x 10(9) M-1 s-1), leading to the formation of peroxynitrite anion (ONOO-), can out-compete the direct reactions of .NO and O2-. with aconitase and even the enzymatic dismutation of O2-. by superoxide dismutase. In this work, we report that ONOO- reacts with isolated pig heart mitochondrial aconitase at 1.4 x 10(5) M-1 s-1, resulting in a significant loss of enzymatic activity. Aconitase activity was totally recovered after postincubation with thiols and ferrous iron, indicating that ONOO- reactions with the enzyme involve the perturbation of the labile Fe alpha to yield the inactive [3Fe-4S] cluster, which is also evident by spectral changes. On the other hand, anaerobic exposure of isolated aconitase to high concentrations of .NO (> 100 microM) led to a moderate inhibition of the enzyme, which could be fully overcome by .NO displacement under an argon-saturated atmosphere, in agreement with the formation of a reversible inhibitory complex between .NO and the active site of aconitase. Superoxide inactivated mitochondrial aconitase at (3.5 +/- 2) x 10(6) M-1 s-1, a reaction rate 3 orders of magnitude slower than its reaction rate with .NO. O2-. could represent the main mechanism of inactivation of the enzyme in systems in which it is formed without significant concomitant production of .NO. Our results imply that the mechanisms by which .NO and O2-. inactivate aconitase in cell systems may not be simple due to their direct reactions with the iron-sulfur cluster, but may rely on the formation of ONOO-.

Aconitate Hydratase↗
PubMed1994

Impairment of spatially directed attention in patients with probable Alzheimer's disease as measured by eye movements.

OBJECTIVE: To investigate changes in spatially directed attention in patients with a diagnosis of probable Alzheimer's disease (AD). BACKGROUND: Impaired attention in patients with probable AD has not been the subject of extensive research. Yet recent reports suggest that attentional deficits may be an important early feature of the disease in a subset of patients. SETTING: University hospital center studying dementia and aging. SUBJECTS: Ten mild to moderately impaired patients diagnosed as having probable AD, by National Institute of Neurologic and Communicative Diseases and Stroke criteria, and 11 healthy age- and education-matched controls. MEASURES: Eye movements were recorded as subjects participated in two experiments designed to measure spatially directed attention. Subjects were instructed to (1) attend to and fixate a target appearing randomly to the right or left of a central marker and (2) direct attention to and fixate a target appearing randomly in one of four peripheral locations. RESULTS: Patients with probable AD exhibited fewer accurate trials and longer saccade latencies in both tasks. As a group, patients performed worse in the second task that placed increased demands on attention. However, the performance of patients in this second experiment varied. Four patients performed significantly worse than all other patients, while three patients performed as well as controls. Errors in the second task were reviewed to identify specific types of attentional deficits. Six empirically derived error patterns were classified into one of two major categories: perseveration and impersistence. Seven of 10 patients made greater than 50% errors of perseveration, and three of 10 made greater than 50% errors of impersistence. CONCLUSIONS: Impairment of attention may be an early feature of AD and a prominent clinical characteristic of some patients. The differences observed in error types made by patients may reflect the varied distribution of neuropathologic changes affecting structures that mediate aspects of attention. The architecture of eye movements can be used as a physiologic measure that should provide useful information for the diagnosis and clinicopathologic subtyping of patients with AD.

Aged↗
PubMed1994

Inhibition of mitochondrial electron transport by peroxynitrite.

Mammalian mitochondria are sensitive targets of the cytotoxic effects of superoxide (O.2-) and nitric oxide (.NO). In turn, when superoxide and nitric oxide are simultaneously produced, they rapidly react with each other yielding the highly oxidizing peroxynitrite anion (ONOO-) which may be also toxic to mammalian mitochondria. In this study we report that peroxynitrite exposure to rat heart mitochondria resulted in significant inactivation of electron carriers such as succinate dehydrogenase and NADH dehydrogenase as well as the mitochondrial ATPase. As a result of enzyme inactivation, peroxynitrite lead to a profound inhibition of glutamate/malate- and succinate-supported oxygen consumption but did not cause mitochondrial uncoupling. Secondary to inhibiting mitochondrial electron transport, peroxynitrite induced an enhanced succinate-stimulated hydrogen peroxide formation by heart mitochondria. Most of the damaging effects against mitochondria can be ascribed to peroxynitrite anion itself and not to hydroxyl radical-like oxidant yielded during the proton-catalyzed decomposition of peroxynitrite, as hydroxyl radical scavengers provided a rather modest protection. Our observations indicate that mitochondria may constitute a key intracellular loci for the toxic effects of peroxynitrite under the various pathological conditions in which peroxynitrite appears to play a contributory role.

Animals↗
PubMed1994

Pregnant rats are refractory to the natriuretic actions of atrial natriuretic peptide.

Normal pregnant women and rats undergo a volume expansion. Atrial natriuretic peptide (ANP) is involved in volume homeostasis and is stimulated in response to volume expansion in nonpregnant animals, resulting in natriuresis and diuresis. The conscious, chronically catheterized rat was used to measure mean arterial blood pressure (MABP) and renal responses to administered ANP (160 ng.kg-1.min-1 i.v.) to determine if the actions of ANP are altered by pregnancy. These experiments examined virgin (n = 7) and pregnant rats, studied on gestational days 7-9 (n = 9) and 15-17 (n = 7). Renal clearance studies (with inulin and p-aminohippurate) were conducted in control conditions and during 60 min of ANP infusion. After the ANP infusion, plasma ANP concentrations were measured in virgin and pregnant rats. MABP fell with ANP infusion to similar absolute values in virgins (112 +/- 2 to 80 +/- 6 mmHg), 7- to 9-day pregnant (114 +/- 2 to 91 +/- 3 mmHg), and 15- to 17-day pregnant (107 +/- 2 to 88 +/- 4 mmHg) rats although the percent decline in MABP in 15- to 17-day pregnant rats was less than in virgins. Plasma ANP concentrations were similar in all groups. ANP had no effect on glomerular filtration rate, renal plasma flow, or renal vascular resistance in virgin or pregnant rats. ANP increased sodium excretion in virgins and in 7- to 9-day pregnant rats (+102 +/- 27 and +135 +/- 47%, respectively) but not in 15- to 17-day pregnant animals (+23 +/- 22%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Endothelium-derived relaxing factor inhibition and the pressor response to norepinephrine in the pregnant rat.

OBJECTIVE: To determine whether endothelium-derived relaxing factor (EDRF) plays a role in the blunted pressor response to norepinephrine that is characteristic of normal pregnancy. METHODS: Eleven pregnant (mean +/- standard error of the mean 18 +/- 1 days of gestation) and 11 virgin conscious, unrestrained Sprague-Dawley rats with long-term indwelling vascular catheters were studied. Mean arterial pressure (MAP) and heart rate were measured in response to continuous infusions of either vehicle (5% dextrose) or increasing concentrations of norepinephrine (25, 100, and 200 ng/kg/minute) before and after administration of NG-monomethyl-L-arginine (LNMMA), a specific inhibitor of EDRF synthesis. RESULTS: Baseline MAP was lower in pregnant than in virgin rats (96 +/- 3 versus 105 +/- 3 mmHg; P < .05). Before LNMMA administration, the pregnant rats exhibited a significantly blunted pressor response to increasing concentrations of norepinephrine compared to that of virgin rats (P < .005). Given alone, LNMMA produced a greater increase in baseline MAP in virgin rats than in pregnant rats (rise in MAP of 44 +/- 2 versus 31 +/- 2 mmHg; P < .001). However, LNMMA abolished the blunted pressor response to norepinephrine in the pregnant animals and did not significantly affect the pressor response to norepinephrine in virgin rats. Heart rate responses to increasing concentrations of norepinephrine in the presence and absence of LNMMA were not significantly different in the two groups of animals. CONCLUSION: Stimulated EDRF production may contribute to the blunted pressor response to norepinephrine characteristic of pregnancy in the rat.

Analysis of Variance↗
PubMed1993

Effect of percutaneous transluminal coronary angioplasty on circulating endothelin levels.

Percutaneous transluminal coronary angioplasty (PTCA) is frequently associated with vasoconstriction involving large vessels as well as microcirculation, but the potential mechanisms remain poorly defined. In this study, we tested the hypothesis that endothelial disruption during PTCA is associated with an increase in circulating levels of endothelin, a potent endothelium-derived vasoconstrictor peptide. Circulating levels of endothelin and other potential vasoactive mediators such as atrial natriuretic factor, epinephrine and norepinephrine were measured immediately before and after PTCA in 23 patients with coronary artery disease. Although there was no change in the endothelin levels after angiography alone (43 +/- 5 vs 44 +/- 7 pg/ml, p = 0.5), there was a significant increase after PTCA (32 +/- 8 to 37 +/- 10 pg/ml, p < 0.005). The increase in endothelin was associated with a significant increase in atrial natriuretic factor (78 +/- 57 to 129 +/- 131 ng/ml, p = 0.01) and a decrease in epinephrine and norepinephrine levels (111 +/- 64 to 59 +/- 36 pg/ml, p = 0.005, and 1,131 +/- 500 to 811 +/- 311 pg/ml, p = 0.003, respectively). Circulating levels of endothelin did not correlate with the percent coronary stenosis before or after PTCA or the presence or absence of angiographically visible thrombus. These findings suggest that endothelial injury during PTCA may be associated with increased circulating levels of endothelin and its counter-regulatory hormone, atrial natriuretic factor, and also with a reciprocal decrease in epinephrine and norepinephrine levels. Thus, these humoral changes may modulate changes in coronary vascular tone after PTCA.

Adult↗
PubMed1993

Consumption of EGF by A431 cells: evidence for receptor recycling.

We examined the extent of EGF consumption by EGFR in A431 cells. When 125I-EGF was added to A431 cell cultures at low or high density, at concentrations which corresponded to 10-fold excess of ligand over receptor on the cell surface, most of the 125I-EGF was consumed within 2 h. The amounts of 125I-EGF consumed were much greater than available EGFR on the A431 cells, by a factor of 6.5 in low-density cultures and 5.8 in high-density cultures. When the concentration of 125I-EGF was increased in low density cultures, further consumption of 125I-EGF by the A431 cells was greatly reduced, partially due to a rapid down regulation of EGFR. However, when higher concentrations of 125I-EGF were added to high density cultures, with reduced receptor down regulation, the cells continued to consume a large fraction of the EGF in the culture medium. The consumption of 125I-EGF by these cultures was in excellent agreement with the measured amount of ligand internalized into the cell. EGF consumption was far in excess of the number of EGFR down regulated or degraded. Only a minor portion of the EGFR could have been replaced during the assay period by synthesis of new EGFR or from the intracellular pool of EGFR, and the fluid-phase uptake of EGF is only temporarily increased by exposure to EGF. Our results demonstrate that EGFR in high density A431 cell cultures recycled many times. The apparent level of recycling was dependent upon the concentration of EGF and followed Michaelis-Menton kinetics for ligand concentrations as high as 215 nM. At this EGF concentration, high-density cultures consumed 45 EGF molecules per receptor over a period of 6 h.

Biological Transport↗
PubMed1993

Over-expression of transforming growth factor alpha antagonizes the anti-tumorigenic but not the differentiation actions of retinoic acid in a human teratocarcinoma cell.

All-trans retinoic acid (RA) treatment of the multipotent human teratocarcinoma (TC) cell line NTERA-2 clone D1 (abbreviated NT2/D1) induces a neuronal phenotype and other cell lineages. NT2/D1 cells basally express transforming growth factor alpha (TGF-alpha) mRNA and secreted protein. After RA-treatment TGF-alpha expression is markedly reduced. This decline in TGF-alpha expression accompanies the induction of the neuronal phenotype and a marked reduction of tumorigenicity in athymic mice. This suggested a causal link between reduced TGF-alpha expression and the induced differentiation or loss of tumorigenicity of these RA-treated TC cells. To evaluate this possibility, an RA-refractory NT2/D1 subclone was analysed. This subclone, designated NT2/D1-R1, failed to induce differentiation or to decrease TGF-alpha expression despite RA treatment. To further explore the relationship between TGF-alpha expression and RA actions in this human TC cell, a TGF-alpha cDNA was stably transfected and expressed in NT2/D1 cells. RA-treatment of independently obtained TGF-alpha over-expressing clones and a representative control transfectant only expressing the neomycin resistance gene produced a neuronal phenotype similar to parental NT2/D1 cells as assessed by morphologic, immunophenotypic, and gene expression markers of differentiation. RA-treatment of these clones also induced a G1 arrest similar to parental cells. However, only the TGF-alpha over-expressing clones that secreted high levels of TGF-alpha protein into the conditioned media before and after RA treatment still developed tumors in athymic mice despite prior exposure to these cells to RA. This finding demonstrates that TGF-alpha can inhibit the anti-tumorigenic effects of RA in human TCs. Thus, over-expression of a single growth factor that normally declines with RA treatment antagonizes the anti-tumorigenic but not the differentiation actions of RA in this human tumor cell.

Animals↗
PubMed1992

A clinical, electrophysiological, morphological and immunological study of chronic sensory neuropathy with ataxia and paraesthesia.

We have observed 9 patients (8 men and 1 woman), 58 to 77 years of age with neuropathy with only sensory symptoms and insidious onset. Five of them (4 men and 1 woman) aged 65 to 77 years, had normal serum electrophoretic profiles, while the others (all men), 58 to 74 years, had IgM monoclonal gammopathy of undetermined significance (MGUS). Clinical data were consistent with a sensory neuropathy affecting predominantly the kinesthetic sense (position and vibration sensation). The electrophysiological data indicated predominant sensory axonal neuropathy. Morphological data confirmed the primary axonal damage. Western immunoblot showed that the IgG from a patient without MGUS reacted with a 55 kD protein of dorsal root ganglion homogenate. Three of four patients with IgM MGUS were serum reactive against chondroitin sulfate C (ChS-C) in double immunodiffusion. After absorption with ChS-C the monoclonal peak completely disappeared from two patients and was decreased in the third patient. Our data indicate that immunological abnormalities are part of the pathogenesis for a subgroup of chronic neuropathy with only sensory symptoms.

Aged↗