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Biomedical subjects

M Castro

Publications and source records attributed to M Castro.

At least 163 records · Page 9Linked to original sources
PubMed1996

Simvastatin releases Ca2+ from a thapsigargin-sensitive pool and inhibits InsP3-dependent Ca2+ mobilization in vascular smooth muscle cells.

Simvastatin (SV), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity inhibits migration and proliferation of vascular smooth muscle cells (SMC). To investigate whether these effects of SV are related to inhibition of cell calcium mobilization, cultured SMC obtained from rat aorta were loaded with Fura-2 to determine the basal cytosolic free calcium levels ([Ca2+]i) and the agonist-stimulated Ca2+ mobilization. SV (20 mu M) transiently increased cytosolic free calcium, an effect that depends mainly on intracellular calcium release (68%). This effect of SV was markedly reduced (75%) by thapsigargin, an inhibitor of the Ca2+ ATPase of inositol 1,4,5-triphosphate (InsP3)-sensitive calcium pools. Incubation of cells with SV (15 min) inhibited the mobilization of Ca2+ by angiotensin II, platelet-derived growth factor, and vasopressin (IC50 = 5 mu M). SV did not affect inositol trisphosphate (InsP3) levels or modify its generation by angiotensin II (Ang II) and vasopressin. Furthermore, in saponin-permeabilized cells, SV abolished the release of calcium by 2,3-dideoxy-InsP3. SV reduced the effect of thapsigargin on InsP3-sensitive stores by 67%, suggesting that SV depletes these calcium pools. The inhibitory effect of SV on calcium mobilization was prevented by coincubation of cultured cells (24 h) with 1 mM mevalonic acid, the product of HMG-CoA reductase activity. These results support the notion that SV inhibits [corrected] the migration and proliferation of SMC by directly affecting cell Ca2+.

Angiotensin II↗
PubMed1996

A prospective study of pulmonary function in patients receiving mitomycin.

Mitomycin is a chemotherapeutic agent that is used to treat a variety of solid tumors. Pulmonary toxic reactions from this agent can be life threatening. We prospectively investigated the utility of pulmonary function tests (PFTs) in monitoring for the occurrence of pulmonary toxicity due to mitomycin. PFTs were obtained at baseline and after three cycles of mitomycin therapy. We analyzed the clinical course, radiologic studies, and PFT results in 133 patients with metastatic squamous cell carcinoma of the lung randomized to treatment with either mitomycin, vinblastine, and cisplatin or mitomycin alone as part of a prospective treatment protocol of the North Central Cancer Treatment Group (NCCTG). The diffusing capacity (DCO) was available in only 40 patients after the third cycle due to a high rate of progression and death from their underlying disease. After three cycles of chemotherapy, there was an average decline in the DCO of 14% (p<0.0001) and no changes were observed in expiratory flows. No differences were noted between treatment arms. A significant decline in the DCO (defined as a >20% change after correcting for hemoglobin) was noted in 11 of 40 patients (28%). This decline in the DCO was not associated with a worse prognosis (p=0.77). Seven patients (5%) developed severe pulmonary toxic reactions attributed to chemotherapy, including noncardiogenic pulmonary edema, interstitial pneumonitis, and pleural effusions. Corticosteroid therapy resulted in temporary subjective improvement in three patients. The Dco did not correlate with the development of pulmonary toxic reactions in these seven patients. In conclusion, (1) the incidence of clinically significant pulmonary toxic reactions from mitomycin is relatively low (5%), (2) mitomycin therapy resulted in a greater than 20% decline in the DCO in approximately one-fourth of patients receiving three cycles of chemotherapy, and (3) the use of serial PFTs in patients receiving mitomycin was not shown to be predictive of pulmonary toxicity.

Aged↗
PubMed1996

Frequency and clinical implications of increased pulmonary artery pressures in liver transplant patients.

OBJECTIVE: To characterize the pulmonary hemodynamics and identify predictors of pulmonary hypertension in a group of patients before liver transplantation and to determine whether pulmonary hypertension in these patients is related to survival. MATERIAL AND METHODS: In 362 patients before their first liver transplantation (between 1985 and 1993), the clinical history, laboratory data, and results of pulmonary function tests were recorded. Pulmonary artery (PA) catheterization was performed after induction of anesthesia at the time of transplantation. Monthly follow-up was maintained. RESULTS: A hyperdynamic circulation was often present -- an increased mean cardiac output (7.6 L/min), increased mean PA pressure (20.9 mm Hg), correlation of mean PA pressure with cardiac output (r = 0.25; P<0.001), and decreased mean pulmonary vascular resistance (60 dynes times s/cm5). Mean PA pressures were more than 25 mm Hg in 72 patients (20%). Pulmonary hypertension (defined as mean PA pressure of more than 25 mm Hg and pulmonary vascular resistance in excess of 120 dynes times s/cm5) occurred in 15 patients (4%). Pulmonary function tests revealed obstruction in 7%, restriction in 18%, and low diffusing capacity in 46%. By univariate analysis, lower forced expiratory volume in 1 second, forced vital capacity, and total lung capacity were the only preoperative factors associated with pulmonary hypertension (P<0.05). Survival was significantly lower in patients with acute fulminant hepatitis (P<0.001), the group with the highest mean PA pressure, than in those with other diagnoses. Increased PA pressures or mild to moderate pulmonary hypertension was not found to be associated with a worse survival by univariate or multivariate analysis. CONCLUSION: Increased PA pressure is common in liver transplant patients (20%). "True" pulmonary hypertension occurred in only 4% of our patients and was not associated with an adverse outcome.

Adolescent↗
PubMed1996

Ulcerative colitis in children under 10 years of age: medical and surgical treatment.

Ulcerative colitis is seen with increasing frequency in paediatric age and its diagnosis is made more difficult by atypical cases. Sixty-five patients with UC were seen at our institute and all of them underwent medical treatment. In all patients the disease extended to the whole colon (pancolitis). Eleven patients (average age 9 yrs) underwent surgical correction by Endorectal Pull Through (EPT) 8 straight and 3 with ileal reservoir. One straight EPT had to be converted to Brooke ileostomy because of unacceptable stool frequency. In the rest of the patients the disease is well controlled with medical treatment. After 2 years of follow up surgical complications, continence, stool frequency and quality of life were evaluated: results indicate that surgical complications rate is the same as in other reported series; furthermore, continence and stool frequency are good with all surgical techniques eve though straight pull-through may require a period of adaptation the length of which varies considerably. Our results confirm that children with pancolitis and severe symptoms should be offered prolonged medical treatment prior to undertake surgical correction.

Adolescent↗
PubMed1996

[Anesthesia in 3 cases of Marfan's syndrome].

We report the cases of 3 patients with Marfan's syndrome with a wide range of clinical signs and severe cardiovascular involvement. The first case was an 18-year-old man who received general anesthesia during laparotomy for acute abdomen. Surgery was uneventful, even though emergency conditions precluded a full preoperative workup. In the second case (herniorrhaphy in a 36-year-old man) and the third (total hip replacement in a 23-year-old woman), surgery was scheduled, permitting heart function testing, assessment of previous treatment, premedication and adjustment of length of the surgical table. Surgery was likewise uneventful in the second and third cases.

Adolescent↗
PubMed1996

Regulation of corticotropin-releasing hormone secretion by ACTH at different times after adrenalectomy.

This study was undertaken to determine the short-loop negative feedback at the hypothalamic site after adrenalectomy (ADX), when the hypothalamic-pituitary axis was a different set-points. Rats were submitted to the experimental procedure 3 h and 1, 3 and 14 days after bilateral ADX or sham surgery under ether anesthesia by the dorsal approach. ADX rats were supplied with 1.5% NaCl. After decapitation, plasma samples were collected and corticosterone (B) and adrenocorticotrophic hormone (ACTH) concentrations were determined by radioimmunoassay (RIA). Using in vitro incubation of the median basal hypothalamus (MBH) fragment we studied the hypothalamic corticotrophin-releasing hormone (CRH) release under basal conditions and under the inhibitory effect of ACTH. Hypothalamic CRH secretion, determined by direct RIA, without extraction and reported as pg CRH/MBH per 1 h incubation, was inhibited by ACTH administration in a dose-dependent manner, as demonstrated by a significant negative correlation obtained by linear regression analysis of CRH secretion as a function of ACTH dose. However, the percentage of inhibition of CRH secretion was higher at 1 and 3 days than at 14 days after ADX. In conclusion, these in vitro studies demonstrated that ACTH suppressed basal CRH secretion in a dose-dependent manner, an effect compatible with a short-loop feedback mechanism. Furthermore, we demonstrated variable suppressibility of CRH secretion by ACTH at different times after ADX.

Adrenalectomy↗
PubMed1996

Annotated list of species of marine crustaceans (Decapoda and Stomatopoda) from Golfo Dulce, Costa Rica.

The present study is an annotated list of the marine crustaceans (Decapoda and Stomatopoda) from Golfo Dulce, Costa Rica, collected during the RV Victor Hensen Cruise 1993-1994, at depths ranging from 20 to 260 m. Stomatopoda was represented by one family and two species. Decapoda was represented by 12 families and 21 species. Two new records for Costa Rica, Cancer johngarthi and Lysmata californica are reported. This increases the reported marine crustaceans of Golfo Dulce to three species of Stomatopoda and sixty-six of Decapoda (a complete checklist in included). A list of species reported in the literature from the gulf is also included.

Animals↗
PubMed1995

Effect of etofibrate on bile production in the normolipidemic rat.

1. The effect of etofibrate, the ethandiol-1,2 diester of nicotinic and clofibric acids on bile production was studied in male rats that received a daily dose of 300 mg of etofibrate/kg body weight by stomach tube for 10 days and were compared with control rats receiving the medium. 2. The bile duct was cannulated, animals were intravenously given 1 microCi (4-14C)-cholesterol/100 b.w. and bile was collected at different intervals for a total of 4 hr. 3. Etofibrate treatment decreased plasma cholesterol and triglyceride concentrations and increased the bile flow. The cummulative amount of both bile volume and total bile radioactivity secreted increased linearly in all the animals; the respective slopes being higher in etofibrate treated rats than in controls. 4. The main labelled component found in the bile was always bile acids rather than cholesterol and the proportion of each of these compounds was similar in both groups. Neither was any difference between the groups found in the concentration of bile acids, cholesterol and phospholipids nor in the cholesterol/(bile+phospholipid) ratio. 5. Besides other factors, the present results indicate that an increase in bile flow and biliary cholesterol excretion in its free form and after its conversion into bile acids should contribute to the hypocholesterolemic effect of etofibrate.

Animals↗
PubMed1995

Time-course of hypothalamic CRH and pituitary ACTH contents, and pituitary responsiveness to CRH stimulation after bilateral adrenalectomy.

The pituitary ACTH and hypothalamic CRH alterations at different periods after adrenalectomy (ADX) or Sham ADX were studied by measurement of ACTH and CRH contents by radioimmunoassay (RIA) in rats. We also studied the corticotroph alterations by immunohistochemistry and the in vitro pituitary responsiveness to CRH. Plasma ACTH presented a triphasic response after ADX. Anterior pituitary (AP) ACTH content decreased 3 h and 1 day after surgery, then rose over this period. Immunohistochemistry demonstrated an initial degranulation of the corticotrophs with a progressive increase in cells immunostained for ACTH and a positive correlation (r = 0.88) with AP ACTH content measured by RIA. Hypothalamic CRH content decreased after ADX, but returned to sham value 3 weeks later. Basal ACTH secretion in incubation medium was correlated with the AP ACTH content observed in vivo. The pituitary responsiveness to CRH was not the same at all times after ADX. It was absent 1 day after, presented an increase of 51%, 117% and 26% when compared with the basal ACTH output 3 h, 3 and 14 days after ADX, respectively. Our data suggest that after ADX the corticotroph undergoes a transitory decrease in ability to secrete ACTH after store depletion. During a later phase, however, there is a relative hyporesponsiveness of the corticotroph to CRH stimulation. These data indicate that CRH may be acting on a down-regulated pituitary or more additional factors play a role in the sensitization of the pituitary after ADX.

Adrenalectomy↗
PubMed1995

Pulmonary tuberous sclerosis.

We describe the clinical presentation, pulmonary function tests, chest radiograph, and computed tomography findings, response to hormonal treatment, and duration of survival of nine patients with pulmonary involvement in tuberous sclerosis complex with follow-up over an average of 17 years (range, 1 to 35 years) since diagnosis. All patients were female, and the average age at onset of symptoms was 16 years (range, 3 months to 39 years); pulmonary symptoms did not develop until an average age of 33 years (range, 22 to 46 years). There was an average delay of 8 years before the correct diagnosis was made. The most common presenting clinical features were seizures, pneumothorax, bleeding into a renal angiomyolipoma, dyspnea, and typical skin changes. Pulmonary function tests commonly demonstrated obstruction to airflow and reduced single-breath diffusing capacity. Chest radiograph and computed tomography characteristically demonstrated diffuse interstitial infiltrates with cystic changes. Two asymptomatic patients with mild pulmonary involvement have remained in stable condition without hormonal therapy. The remaining seven patients had moderate to severe airflow obstruction; of these, five underwent hormonal therapy. Three patients had a clinical response to treatment. Two patients who did not receive hormonal treatment died of progressive respiratory failure. Most patients with pulmonary involvement in tuberous sclerosis have a slowly declining clinical course. Although the available data are limited, they suggest that a trial of hormonal therapy is recommended both for symptomatic patients and for those with declining pulmonary function. Tuberous sclerosis complex should be suspected in all patients with the diagnosis of lymphangioleiomyomatosis.

Adult↗