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Biomedical subjects

I Castro

Publications and source records attributed to I Castro.

At least 37 records · Page 2Linked to original sources

[Multicenter comparative study of felodipine-ER and nifedipine-OROS in the treatment of mild-to-moderate arterial hypertension].

PURPOSE: To compare the efficacy and tolerance of felodipine-ER and nifedipine OROS, both once daily, in the treatment of mild-to-moderate uncomplicated arterial hypertension (AH). METHODS: This was a multicentric, opened, randomized, paralled trial, that selected 121 patients with uncomplicated, mild to moderate essential AH (diastolic blood pressure (DBP) > or = 95 and < or = 110 mmHg; not under anti-hypertensive medication. All patients received placebo for two weeks. After that period, they would take either 5mg/day of felodipine, or 30mg/day of nifedipine OROS, both once daily, in a randomized fashion. Patients underwent laboratory tests and electrocardiogram (ECG) at the begining and at the end of the study, and heart rate and blood pressure (BP) measurements, nearly 24 hours after the last active drug dose. RESULTS: Completed the study 111 patients, 60 in the felodipine group and 51 in the nifedipine group. Compared to baseline, the average of systolic BP and DBP decreased from 162.5 +/- 14.3mmHg and from 102.2 +/- 5.1mmHg to 143.3 +/- 14.6 and 87.9 +/- 7.2mmHg, respectively, at the end of the treatment in the felodipine group; and from 160.5 +/- 16.3mmHg and 102.5 +/- 6.2mmHg to 136.1 +/- 14.2 and 86.7 +/- 7.0mmHg, respectively in nifedipine group (p < 0.0001 for all diferences). Adequate BP response to the treatment (DBP normalization or reduction > 10mmHg from baseline) occured in 47/60 (78.3%) patients in the felodipine group and in 38/51 (74.5%) in the nifedipine group (NS). Side effects, occured in approximately 15% of the cases, and were similar in both groups. These were usually moderate and transient, but were responsible for the withdrawal from the study of two cases in the felodipine group and of three cases in the nifedipine group. CONCLUSION: Felodipine-ER and nifedipine OROS, are similarly effective and generally well tolerated in patients with mild-to-moderate essential hypertension.

Adult↗

[Seronegative arthritis: reexamination of the initial diagnosis and prognosis after 10 years].

Seronegative arthritides are a heterogeneous group of diseases that includes rheumatoid arthritis with negative rheumatoid factor. Between 1980 and 1984 we studied 38 patients with seronegative arthritis. Thirty of these patients were reassessed in 1994 after 9 to 20 years of evolution. Seventeen patients had a diagnosis of seronegative rheumatoid arthritis; this diagnosis was maintained in 12, changed to seropositive rheumatoid arthritis in three, to psoriatic arthritis in one and connective tissue disease in one. Thirteen patients had a diagnosis of undifferentiated arthritis; in 1994 the diagnosis was maintained in three, seven patients were diagnosed as having a spondyloarthropathy, two as having a reactive arthritis and one as having a connective tissue disease. In 1994, nine patients fulfilled the 1991 criteria for spondyloarthritis and six of these did so on admission. Six of 12 patients with seronegative rheumatoid arthritis had an active disease or used antiinflammatory drugs and 64% had erosions on hand X ray examinations. These figures are in contrast with the enign evolution classically attributed to this disease and agree with recent reports. The usefulness of classification criteria for rheumatoid arthritis and spondyloarthritis in the initial assessment of patients with seronegative arthritis is emphasized.

Adolescent↗

[Intracardiac thrombosis in a patient with primary antiphospholipid syndrome. Report of a case].

Antiphospholipid antibody syndrome is characterized by arterial or venous thrombosis associated to the presence of antiphospholipid antibodies. We report a 32 atrial thrombus. Four months later, being with anticoagulant treatment, he had a deep venous thrombosis. A new echocardiogram did not show the atrial thrombus. The laboratory work-up confirmed an antiphospholipid syndrome. Five months later the patient has not presented new thrombotic episodes and is receiving oral anticoagulants and antiplatelet therapy.

Adult↗

Molecular mechanisms of the antihormonal and antiimplantation effects of norethisterone and its A-ring reduced metabolites.

Norethisterone (NET) has been used as a contragestational postcoital agent. It is biotransformed to 5 alpha dihydro-NET (5 alpha-NET) and 3 beta,5 alpha tetrahydro-NET (3 beta,5 alpha-NET) in target tissues. The participation of these metabolites in NET effects is unknown. We have examined the antiimplantation and antiprogestational effects of NET and its metabolites, in adult mated female rabbits, by assessing the number of implantation sites and the expression products of the uteroglobin (UTG) gene in the uterus, and by comparing them with those of RU-486 and estradiol. Steroids were daily administered s.c. at several doses for 7 consecutive days, starting 24 hr after coitus. To assure that fertilization occurred in all animals, the presence of early pregnancy factor was determined. The results demonstrated that high doses (5 mg/kg) of NET reduced both implantation and the expression of the UTG gene. On the other hand, lower doses (1.5 mg/kg) of 5 alpha-NET produced an antiimplantation effect and suppressed UTG synthesis and its mRNA. These effects were similar to those of RU-486. At lower doses (1 mg/kg), both estradiol and the estrogenic metabolite 3 beta,5 alpha-NET were also effective in inhibiting implantation and UTG gene expression. The overall results suggest that NET metabolites exert antiimplantation and antiprogestational effects through their interaction with progesterone and estrogen receptors, and provide an explanation for the molecular mechanisms involved in the postcoital contraceptive action of NET.

Animals↗

Norethisterone metabolites modulate the uteroglobin and progesterone receptor gene expression in prepubertal rabbits.

Norethisterone (NET) is a synthetic progestin, used as a contraceptive agent, that is biotransformed at target tissues into 5 alpha-NET and 3 beta,5 alpha-NET, which possess different pharmacological properties. The effects of these metabolites on the expression of uteroglobin (UG) and progesterone receptor (PR) genes, both regulated by progesterone (P4), were evaluated in the uterus of prepubertal female rabbits that were simultaneously treated with P4 (1.0 mg) for 5 consecutive days. As determined by Western and Northern blot analyses, 5 alpha-NET inhibited the P4-induced UG gene expression in a dose-dependent manner. A similar inhibition was observed with the administration of RU-486. The estrogenic agent 3 beta,5 alpha-NET and estradiol at a dose of 1.0 mg also inhibited the UG gene expression induced by P4. Both 5 alpha-NET and 3 beta,5 alpha-NET blocked the PR down-regulation induced by P4 as assessed by Western and Northern blot methods. The inhibition of UG synthesis and PR down-regulation by 5 alpha-NET and 3 beta,5 alpha-NET indicates that these NET metabolites possess antiprogestational properties.

Animals↗

[Adequacy of of pacemakers responsive to the volume-minute ventilation rate in heart transplantation patients].

PURPOSE: To evaluate in the late post-operative period (PO) the chronotropic response to exercise of patients submitted to orthotopic cardiac transplantation (CT) and the implant of a cardiac pacemaker (PM). METHODS: A rate response ventricular PM (VVI+R) which uses minute ventilation (MV) as a sensor was implanted in five patients in the early PO of CT due to chronotropic incompetence. The patients were 31 to 64 years old and the indication to implant of PM was low ventricular escape rhythm following atrial taquicardia/bradycardia (one case) or sinus bradycardia (4 cases). The study was performed by means of paired exercise tests using Naughton protocol in order to compare the heart rate in VVI (prefixed heart rate) and VVIR+MV (rate response) mode. The duration of the exercise was compared between the two modes of stimulation. RESULTS: In VVI mode the heart rate was significantly lower than in VVIR+MV mode for comparable periods of exercise (101 +/- 12 ppm vs 132 +/- 4 ppm; p < 0.05); in VVIR+MV mode the patients had a prolonged time of exercise as compared to VVI mode (15 +/- 7 min vs 12 +/- 7 min; NS). CONCLUSION: The MV rate response PM provided patients with satisfactory heart during exercise and may be an adequate option to patients submitted to CT who present chronotropic incompetence.

Adult↗

Two distinct factors bind to the rabbit uteroglobin TATA-box region and are required for efficient transcription.

The rabbit uteroglobin gene is expressed in a variety of epithelial cell types like the lung Clara cells and the glandular and luminal epithelial cells of the endometrium. Expression in Clara cells is on a high constitutive level, whereas expression in the rabbit endometrium is under tight hormonal control. One important element of the rabbit uteroglobin gene mediating its efficient transcription in two epithelial cell lines from human endometrium (Ishikawa) and lung (NCI-H441) is its noncanonical TATA box (TACA). Here, we show that two factors (TATA core factor [TCF] and TATA palindrome factor [TPF]) different from the TATA-box binding protein bind to the DNA major groove at two adjacent sites within the uteroglobin TATA-box region and that one of them (TCF) is specifically expressed in cell lines derived from uteroglobin-expressing tissues. The binding sites for TCF and TPF, respectively, are both required for efficient transcription in Ishikawa and NCI-H441 cells. Mutation of the TACA box, which we show is a poor TATA box in functional terms, to a canonical TATA motif does not affect TCF and TPF binding. Therefore, we suggest that the function of the unusual cytosine could be to reduce rabbit uteroglobin expression in cells lacking TCF and that the interaction of TATA-box binding protein with the weak TACA site is facilitated in TCF- and TPF-positive cells.

Animals↗

Endometrial expression of progesterone receptor and uteroglobin genes during early pregnancy in the rabbit.

The progesterone receptor (PR) plays a pivotal role in the maturation process of the secretory endometrium, implantation and maintenance of pregnancy in rabbits. To determine the dynamics of PR gene expression and its physiological significance, the endometrial expression of PR and PR mRNA were evaluated and compared with the expression of the progesterone-regulated uteroglobin (UG) gene during 0-5 days post-coitus in rabbits. The results of immunoblot experiments indicated the presence of PR in endometrial cell extracts from days 1-4 of pregnancy with maximum PR immunostaining on day 2, followed by a marked diminution until its complete disappearance on day 5. When endometrial PR mRNA content was assessed by Northern blots, the results were similar to those of PR immunostaining, with maximal concentrations on the second day after mating. However, PR mRNA levels were still high on day 3, despite the concomitant decrease in immunostainable PR. Endometrial UG gene expression, on the other hand, exhibited a different time sequence. Thus, the UG content in uterine flushings progressively increased from day 3 after mating, reaching maximal levels on the fifth day. The endometrial UG mRNA content presented a similar profile, as its maximum concentration occurred on days 4-5. The overall results indicate that endometrial PR is down-regulated at both the mRNA and protein levels, possibly by endogenous progesterone during early pregnancy. The striking observation that maximal expression of endometrial UG gene products occurred when PR and its mRNA are no longer detectable suggests an important role for this progesterone-binding uterine protein during the preimplantation period.

Animals↗

[Evaluation of the use of amiodarone in outpatients].

From the group of patients follow-up at the arrhytmias out-patients clinic of the Institute of Cardiology from Rio Grande do Sul, Brasil, one hundred (100) patients were selected in order to evaluate the efficacy, benefits and side effects of short term use (minimum of 3 months) of amiodarone. During the period of study, the authors had found that average doses of amiodarone (200 mg/day) were highly effective for ventricular and supraventricular in addition, they also noticed a very low incidence of side-effects independent of the cardiopathy.

Adult↗

Calcium antagonists and heat-induced hepatic injury.

Several laboratories have demonstrated the value of the isolated perfused rat liver as a suitable model for heat-induced hepatic injury in vivo. Membrane changes caused by perfusion of rat livers at 42 degrees C for 90 min were similar to those induced by toxic chemicals or hypoxia. In an evaluation of several categories of drugs reported to reduce cell injury, calcium antagonists (nifedipine, dantrolene, and verapamil), were evaluated for their therapeutic potential for heat injury. Isolated rat livers were perfused at 42 degrees C for 90 min with and without calcium antagonists. Livers were also perfused at 37 degrees C. Potassium and transaminase leakage, bile production and ultrastructure were used to evaluate their responses. Neither of the three calcium antagonists significantly improved any of the functional parameters measured. However, dantrolene produced dilated or vesicular rough endoplasmic reticulum in the heated livers. These changes suggest selective intracellular action on endoplasmic reticulum of heated livers. Ring-shaped mitochondria and vesicular endoplasmic reticulum were observed in the heated, verapamil-treated livers, but these could not be quantitatively distinguished from controls. Nifedipine did not appear to alter intracellular membranes, but did increase bile production.

Animals↗