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Biomedical subjects

G Chamorro

Publications and source records attributed to G Chamorro.

At least 37 records · Page 2Linked to original sources

Dominant lethal study of alpha-asarone in male mice.

Alpha-asarone is a hypolipidaemic agent obtained from Guatteria gaumeri, a medical plant used in Mexico to treat hypercholesteraemia and cholelithiasis. alpha-Asarone has been shown to be hepatocarcinogenic and mutagenic in a human lymphocyte assay, a murine bone marrow cell assay and in an unscheduled DNA synthesis assay. In this study, alpha-asarone was tested for dominant lethal effects in male CF1 mice. The drug was given orally at doses of 0, 10 and 30 mg/kg per day for 5 days. Males were mated weekly with eight consecutive batches of naive, nulliparous female mice. Repeated matings revealed no perceptible effect of alpha-asarone on the incidence of pregnancy. Examination of surgically exposed uteri and ovaries of pregnant females on day 13-15 of gestation revealed an increased incidence of post-implantation loss. Semen examination of a separate group of mice showed a decreased concentration and motility of spermatozoa. These results suggest a dominant lethal mutation as well as direct alpha-asarone toxicity to spermatozoa by in treated mice.

Allylbenzene Derivatives↗

Effect of furazolidone on sister-chromatid exchanges, cell proliferation kinetics, and mitotic index in vivo and in vitro.

Furazolidone is an antimicrobial compound used in human and veterinary medicine. The aim of this investigation was to determine its genotoxic capacity in vitro and in vivo. We used the human lymphocyte culture system to detect the effect of 2.0, 4.0, 6.0, 8.0, or 10.0 micrograms/ml, and the mouse bone marrow assay to determine the effect of 8.6, 30.0, or 75.0 mg/kg furazolidone. In both systems we determined the frequency of sister-chromatid exchanges (SCE), the cell proliferation kinetics (CPK), and the mitotic index (MI). The in vitro results showed a significant SCE increase starting from the second dose tested and a CPK and MI decrease starting from the third dose. The in vivo results showed a SCE increase with the two high doses tested, but no significant modification was found in the CPK and MI with the three doses tested in the experiment.

Animals↗

[Cardiovascular effects of AV interval shortening with electrical stimulation in dilated cardiomyopathy].

BACKGROUND: A temporal alteration between atrial and ventricular contraction, in which the last one would be abnormally retarded, could exist in patients with dilated cardiomyopathy. This alteration could have adverse hemodynamic effects. AIM: To study the hemodynamic modifications caused by an artificial shortening of AV interval in patients with dilated cardiomyopathy. PATIENTS AND METHODS: Nine patients with dilated cardiomyopathy were studied. Hemodynamic and tissular perfusion values, echocardiographic and radioisotopic ventricular function parameters were measured before and after six hours of AV interval shortening with electrical stimulation of the heart. RESULTS: After electrical stimulation, cardiac output increased from 3.38 +/- 0.8 to 3.87 +/- 0.79 l/min (p< 0.05). Pulmonary capillary pressure decreased from 23.8 +/- 8.9 to 19.8 +/- 9.2 mm Hg (p = NS). There were no significant changes in ventricular function parameters or in systemic and pulmonary pressures. CONCLUSIONS: Electrical shortening of AV interval in patients with dilated cardiomyopathy increases cardiac output but does not change ventricular function parameters.

Adult↗

Antifertility effects of (+)-S-2-amino-6-iodoacetamidohexanoic acid (2-AIHA) in female rats.

(+)-S-2-amino-6-iodoacetamidohexanoic acid (AIHA), an irreversible inhibitor of the ornithindecarboxylase and extrahepatic arginase enzymatic activities with antineoplasic properties, was evaluated for antifertility activity in pregnant rats by oral administration at different periods of gestation. Our results showed that doses of 10 and 20 mg/kg of AIHA orally administered produced a contraceptive effect when it was administered from days 2 to 5, and 8 to 12 of gestation, respectively. The gestation time was slightly shortened when AIHA was applied from day 15 until labor. No sign of external malformations in fetuses was observed. On the other hand, AIHA did not affect the total length of oestrous cycle at the same dosage level used to interrupt pregnancy. In ovariectomized immature rats, neither changes in uterine weight, premature vaginal opening, or cornified cells were found. However, AIHA enhanced the estradiol-induced increase in uterine weights when both were concomitantly administered.

Abortifacient Agents↗

[Head-up tilt test in healthy asymptomatic patients].

The head-up tilt test has demonstrated to be useful in the study of patients with syncope of unknown origin for the diagnosis of neurocardiogenic syncope. Several publications have described different methods, with different results in cases as well as in controls. We performed a prospective study in a group of normal subjects in order to evaluate the methodology used in our population and to establish its specificity. A positive test was defined as the presence of syncope or presyncope and hypotension. The examination was carried out on a tilt table, five minutes at 0 degree, then at 70 degrees during 20 min. In the absence of syncope or presyncope an i.v. infusion of isoproterenol was started afterwards in order to increase the heart rate 30-50% over the baseline values and administered during 20 min at 70 degrees. Twenty one volunteers (14 male and 7 women; mean age 26.7 +/- 3.5 years; range: 21-33 years) and body mass index 23.4 +/- 2.2 kg/m2 were examined. Mean dose of isoproterenol was 3.1 +/- 0.9 micrograms/min (3.4 +/- 1.1 in men and 2.6 +/- 0.7 micrograms/min in women, NS). During the phase without isoproterenol no subject developed hemodynamic alterations neither symptoms. One volunteer (4.8%) developed presyncope and systemic hypotension (52/28 mm Hg) accompanied with nodal rhythm after 14 min of isoproterenol at 70 degrees, and his examination was discontinued, with immediate recovery. Three other subjects developed asymptomatic transient nodal rhythm during the phase with isoproterenol and recovered spontaneously. No other complications were observed. It is concluded that head-up tilt test with isoproterenol at 70 degrees, with the used doses and heart rate increments, is highly specific (95%) to establish the diagnosis of a neurocardiogenic syncope.

Adult↗

Evaluation of the teratological potential of the new antihypertensive 5-methoxytryptamine, beta-methylcarboxylate hydrochloride (indorenate) in mice.

5-Methoxytryptamine, beta-methylcarboxylate hydrochloride (indorenate), a new antihypertensive agent, was examined for teratogenic-embryotoxic effects in the mouse at doses of 0 (control), 10, 20, 40, and 80 mg/kg/day. The compound was administered by gastric intubation on days 6-15 of gestation. On day 17, the dams were sacrificed, the number of live, dead, and resorbed fetuses recorded and mean pup weight determined. Teratological evaluation was carried out by visual inspection, alizarin red staining of the skeleton and Wilson's sections. Signs of overtoxicity in mothers were found in the high-dose groups. There were no differences between control and indorenate-treated groups in the number of implantations, live fetuses or anomalies. However, an embryotoxic effect was observed at 40 and 80 mg/kg, shown by increased resorptions and lower weight of pups at the higher dose.

5-Methoxytryptamine↗

[Cardiopulmonary exercise test in patients with chronic cardiac failure: comparison with normal subjects and reproducibility of measurements].

The aim of this work was to measure oxygen consumption and carbon dioxide production during exercise in 21 subjects with cardiac failure and 13 normal subjects. During the resting period, subjects with cardiac failure had higher ventilatory frequency and respiratory quotient than normals. During maximal exercise, the former achieved higher ventilatory frequency and oxygen ventilatory equivalent than normals. In subjects with cardiac failure and normals, anaerobic thresholds were 14.4 +/- 0.9 and 28.8 +/- 2.2 ml/kg/min respectively and peak oxygen consumptions 17.1 +/- 1 and 34.4 +/- 1.7 ml/kg/min respectively. There were less than 10% differences in parameters when tests were repeated in 10 subjects with cardiac failure. It is concluded that gas exchange testing may be a reliable and objective assessment method in patients with cardiac failure.

Adolescent↗

[Cardiovascular response to exercise at high altitude in workers chronically exposed to intermittent hypobaric hypoxia].

The isotonic work performance was assessed in 34 workers aged 35 +/- 5.8 years old that had working shifts of four days at 4500 m over the sea level and resting periods of other four days at the sea level during at least two years. Subjects were assessed in one occasion at the sea level, and at the first and fourth day of the working shift at 4500 m over the sea level. Resting arterial oxygen saturation in these three periods was 97 +/- 1.1, 88 +/- 18 and 91 +/- 1.1% respectively (p < 0.01), and markedly decreased during maximal and submaximal exercise at 4500 m over the sea level. Exercise duration in the three periods was 931 +/- 210, 775 +/- 105 and 778 +/- 105 seg respectively (p < 0.001). Heart rate in the resting period was at least 10% higher and maximal and submaximal rates were lower at high altitude. No differences in blood pressure or packed red cell volume were observed. Exercise duration correlated inversely with age (r = -0.49 p = 0.03) and directly with maximal heart rate (r = 0.44 p = 0.009) at the sea level. No correlation between aerobic capacity and other measured parameters was observed. These results show no differences in the cardiovascular response to exercise between the first and fourth day of stay at high altitude in workers chronically exposed to intermittent hypobaric hypoxia.

Adult↗

Evaluation of the toxic and teratogenic potential of the anticonvulsant drug 4-hydroxy, 4-ethyl, 4-phenylbutyramide in mice.

The toxicity profiles of the phenyl alcohol amides: 4-hydroxy, 4-ethyl, 4-phenylbutyramide (HEPB) and two lower homologous: 3-hydroxy, 3-ethyl, 3-phenylpropionamide (HEPP) and 2-hydroxy, 2-ethyl, 2-phenylacetamide (HEPA) were studied in mice. TD50 value was determined by oral administration and LD50 by oral and intraperitoneal routes. The results indicate that HEPP is less toxic than the others, both of which had very similar toxicity. Furthermore, the teratogenic potential of HEPB was investigated in mice after oral administration. The compound was administered on days 6-15 of gestation at doses of 0, 5, 25, 50 or 100 mg/kg of weight. On day 17 of pregnancy the mice were sacrificed and the pups examined. An increase of body weight in both mothers and fetuses was observed at 25 and 50 mg/kg and a decrease was found in mothers receiving 100 mg/kg, as a sign of maternal toxicity. Considering the litter data, embryotoxicity and fetotoxicity were only shown at the highest dose. However, the HEPB treatment did not result in malformations of live fetuses or resorptions when the implantations were considered as the individual entity.

Abnormalities, Drug-Induced↗

alpha-Asarone toxicity in long-term cultures of adult rat hepatocytes.

In this work we studied the toxic effects of alpha-asarone, a hypolipidemic active principle of Guatteria gaumeri Greenman, on long-term cultures of adult rat hepatocytes cultivated on a feeder layer of 3T3 cells. The exposure for one and two weeks to alpha-asarone (1-50 micrograms/ml) produced intracytoplasmic lipid droplets and at higher concentrations (25-50 micrograms/ml) retraction of the hepatocyte cords and cell detachment. Ultrastructurally, the treated cultures (10 micrograms/ml) showed enlargement and vacuolization of the mitochondria in addition to lipid droplets. The triacylglycerol content increased up to 2.3-fold in the cultures treated for one week with 50 micrograms/ml, whereas the protein content per culture, a rough estimate of cell number and viability, decreased by up to 53% in the cultures treated for two weeks with 50 micrograms/ml. The synthesis and secretion of proteins, measured by the incorporation of [3H]-leucine into cellular and secreted macromolecules, decreased also in the cultures exposed. After one and two week exposure to 50 micrograms/ml of alpha-asarone, the secretion of labeled proteins decreased by 53 and 67%, respectively, whereas the synthesis of cellular and total proteins decreased by 48-67%, respectively. The secretion of proteins was the most sensitive parameter of alpha-asarone toxicity. The mean inhibitory dose (ID50), i.e, that producing 50% inhibition in the incorporation of the labeled precursor, was 22.12 and 5.04 micrograms/ml after one and two weeks exposure, respectively. Our results show that long-term exposure to micromolar concentrations of alpha-asarone produces morphologic and ultrastructural alterations, triacylglycerol accumulation (fatty liver), and inhibition of protein synthesis and secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗

Inhibition of lipid synthesis and secretion in long-term cultures of adult rat hepatocytes by alpha-asarone.

In this work we studied the effect of alpha-asarone, a hypolipidemic active principle of Guatteria gaumeri Greenman, on hepatic lipid metabolism using adult rat hepatocytes cultured on a feeder layer of 3T3 cells. These cultures synthesize and secrete for at least two weeks various lipids from [14C]-acetic and [14C]-oleic acid. Exposure for one or two weeks to 10 micrograms/ml of alpha-asarone decreased the secretion of various lipids to the culture medium; triacylglycerol secretion was inhibited by 80-97%, phospholipid secretion by 70-87%, cholesterol by 64-70%, and cholesterol esters by 50-92%. The incorporation of [14C]-acetic acid into cellular lipids decreased by 30-81% and that of [14C]-oleic acid into phospholipids by 25-47% whereas the incorporation of [14C]-oleic acid into triglycerides and cholesterol esters increased 3.2 fold and by 28-36%, respectively. Similarly, the activities of glycerol-3-phosphate dehydrogenase and malic enzyme, marker enzymes of glycerolipid and fatty acid synthesis, decreased by 22-50% and 30-76%, respectively. Our results show that the exposure of the 3T3-hepatocyte cultures to micromolar concentrations of alpha-asarone significantly inhibits lipid secretion and probably lipid synthesis. They also suggest that at least part of the hypolipidemic effect could be due to a decrease in the secretion of lipids (i.e., lipoproteins) by the hepatocytes.

3T3 Cells↗

[Tilt test: hemodynamic responses in patients with syncope or presyncope of unknown etiology].

The aim of this work was to assess the hemodynamic responses to the tilt test of 51 patients with syncope (n = 31) or presyncope (n = 20) of unknown etiology. A protocol with an inclination of 70 degrees (20 min) with or without isoproterenol (mean dose of 3.6 +/- 0.3 ug/min), was used. Forty five percent of patients had a positive test, 18 with isoproterenol at 70 degrees (group 1A) and 5 without isoproterenol (group 1B); 28 patients had a negative test (group 2). These groups did not differ in age or sex distribution. Basal heart rate was 76.2 +/- 2x'. At the end of the test it was 73.4 +/- 5.7 in group 1A, 78.0 +/- 7.5 in group 1B and 120.4 +/- 3.3 in group 2 (p < 0.01). Systolic blood pressure decreased to 78.1 +/- 4.8 mmHg in group 1A, to 76.2 +/- 9.9 in group 1B and did not decrease in group B (130.0 +/- 5.7 mmHg, p < 0.01). The required dose of isoproterenol was higher in group 1A than in group 2 (4.4 +/- 0.3 vs 3.1 +/- ug/min, p < 0.01). It is concluded that the tilt test reproduced symptoms and accompanying hemodynamic mechanisms in a high proportion of patients with syncope of unknown etiology. This test should be incorporated in the diagnostic workup of these patients.

Adolescent↗

[Surgery of acute mitral valve insufficiency].

Between January 1980 and December 1990, 16 patients with acute mitral insufficiency were operated on an emergency basis at our institution. They represented 1.8% of all mitral surgical cases. All of them were in acute pulmonary edema and 7 in cardiogenic shock. The etiology was ischemic in 6, degenerative in 4, infectious in 3, degenerative and infectious in 2 and traumatic in 1. The pathologic mechanism was chordal rupture in 8 patients (5 anterior) and papillary muscle rupture in the other 8 (5 posterior). A mitral valve replacement was performed in all cases. Two patients died and 7 had morbidity in the postoperative period. One patient died 6 months after surgery of congestive heart failure. Ten patients are in NYHA functional class I at a mean follow-up of 48.1 months. Acute mitral insufficiency has different etiologies and pathologic mechanisms. In spite of the severe clinical condition of these patients, mitral valve replacement has good immediate and long-term results.

Acute Disease↗

[Dissection of the ascending aorta (type A): diagnostic aspects, surgical treatment and long-term follow-up].

Aortic replacement is the treatment of choice and improves the natural history of dissections involving the ascending aorta. Forty patients (23 male), aged 49.4 years, have been operated at the hospital Clínico de la Universidad Católica. Twenty six presented with acute dissections. Angiography conformed the dissection in 63.3% and computed axial tomography in 84.6% of patients; lately, transesophageal echocardiography has become the most sensitive diagnostic method. Twenty three patients (57.5%) were subjected to emergency operations and 17 to semielective procedures. In 24 patients (60%) ascending aorta was replaced and in 16 a composite graft was used. Operative mortality was 27.5%. Univariate analysis showed that the period in which the operation was performed and the presence of limb ischemia were the only independent predictors of operative mortality. Long term follow up was achieved in 26 patients (89.6%). Actuarial 5 year survival without considering operative mortality was 87.9%. It is concluded that patients with acute dissections involving the ascending aorta should be operated as soon as the imaging diagnosis is complete and, since this is a palliative procedure, a close follow up is required for early detection of complications.

Adult↗

[Risk of chronic oral anticoagulant treatment in elderly patients].

To assess age-related risks of long term anticoagulation, the records of 348 patients followed up at our university hospital outpatient anticoagulation clinic during a seven year period were reviewed. There were 129 patients, under 56 years of age, 144 from 56 to 69 and 75 over 70 years old. The total observation period was 1089 patient-years (3.3 yrs per pt). 64% of the patients had adequate anticoagulation level (prothrombin time < 35%, INR 2.2-4.5) 70 to 100% of the observation period. Prothrombin time was slightly, but significantly higher in the elderly group. During this period 21 patients developed major bleeding complications (1.84/100 pt yrs), 8 of them with fatal intracranial hemorrhages, and 20 embolic complications (1.93/100 pt yrs), 3 of them fatal. No significant differences in the incidence of both bleeding and embolic complications were observed in the three groups. The results of this retrospective follow-up study suggest that long term anticoagulation can be carried out in elderly pts with risk of hemorrhagic and embolic complications similar to those observed in the general population.

Acenocoumarol↗

Cytogenetic and teratogenic evaluation of letimide.

Letimide is a new efficient analgesic salicylate derivative. In this study we evaluated its cytogenetic and teratogenic potential. For chromosomal aberrations and sister chromatid exchange analysis we tested 250, 375, 500 and 625 micrograms/ml of letimide in human lymphocyte cultures in vitro, and for the in vivo cytogenetic study analysing the same parameters we studied the effects of 30, 50 and 100 mg/kg in mouse bone marrow cells. The teratogenic study was performed at dosages of 50, 100 and 200 mg/kg/d of letimide in mice. The results agree with the systems studied previously, showing no significant effect in the rate of aberrations, sister chromatid exchanges or congenital malformations induced by this new analgesic.

Adult↗