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Biomedical subjects

A Santos

Publications and source records attributed to A Santos.

At least 145 records · Page 8Linked to original sources
PubMed1996

[Reduction of the antihypertensive effects of enalapril by indomethacin. Its independence from renal sodium retention].

OBJECTIVE: To evaluate in hypertensive patients whether or not the sodium-retaining effects of indomethacin can explain the indomethacin-induced attenuation of enalapril antihypertensive effects. DESIGN: Randomized, single-blinded, placebo controlled study with a placebo phase (2 weeks) followed by enalapril 20 mg/d (4 weeks, once daily) and enalapril 20 mg + indomethacin 75 mg/d (1 week). Enalapril dose increased up to 40 mg/d if inadequate response to 20 mg. PATIENTS: Twenty-four patients with mild-moderated hypertension, showing an adequate response to enalapril (20-40 mg/d). METHODS: Blood pressure evaluated by "casual" methods and by 24-hour ambulatory blood pressure monitoring, measurement of 24-hour urinary sodium excretion and fractional excretion of sodium: at the end of placebo, enalapril and enalapril + indomethacin treatments. Determination of the correlations between the changes induced by indomethacin (when added to enalapril) on the blood pressure and on sodium excretion effects of enalapril. RESULTS: Enalapril significantly reduced casual blood pressure (systolic/diastolic) by 33/18 mmHg and 24-hour blood pressure by 20/9 mmHg. When added to enalapril, indomethacin attenuated (by 50%) the antihypertensive effects of enalapril and significantly decreased the 24-hour (from 120 +/- 11 mmol to 106 +/- 10 mmol) and fractional excretion of sodium (from 1.11 +/- 0.09% to 0.75 +/- 0.06%). However, the indomethacin-induced attenuation of enalapril hypotensive effects did not correlate with indomethacin-induced changes of sodium excretion. CONCLUSIONS: When indomethacin is administrated to hypertensive patients that are well controlled with enalapril, it produces a marked attenuation of enalapril hypotensive effects and produces sodium retention. However, the amount of the attenuation of the hypotensive effects of enalapril by indomethacin are completely independent of the amount of the indomethacin-induced sodium retention. These results suggest that the mechanisms involved in interaction between both drugs at the blood pressure domain are probably localized at an extra-renal level.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

[Clinical trial with tibolone in postmenopausal replacement therapy].

Estrogen deficiency is the basic change in women around the climateric stage. This hormone deficiency is different among women regarding the age and intensity of symptoms. The hormone replacement has proved its benefit on relieve of symptoms and long term effect on prevention of cardiovascular disease and osteoporosis. A new pharmacological agent Tibolona has been studied recently as replacement therapy. This work reports the results obtained with the use of Tibolona in 36 postmenopausal women. The effectiveness and security were confirmed as well as the low occurrence of side effects. It was also apparent that this therapy had a relevant effect on the psycho-emotional component and upon the improvement of sexual satisfaction and activity.

Adult↗
PubMed1996

Human thyroglobulin reference material (CRM 457). 1st Part: Assessment of homogeneity, stability and immunoreactivity.

This paper describes the assessment of the homogeneity and stability of a purified and lyophilized human thyroglobulin (Tg), and characterizes its immunoreactivity. The purified and lyophilized Tg is intended to be used as a primary reference material to establish calibration of working serum based reference material. The programme involved the participation of 15 European laboratories and one laboratory from the United States. The homogeneity of the content of the ampoules was considered acceptable (< 9%). The stability was tested by accelerated temperature degradation showing predicted annual relative losses of 0.01% at -70 degrees C and 1.04% at -20 degrees C. The immunoreactivity of the Tg material as measured in different laboratories varied mostly according to the method used rather than the laboratory. The interlaboratory variability showed that the two commercial methods used in several laboratories (kit 1 and 2) had an interlaboratory variation (CV) of 15.9% (N = 5) and 7.1% (N = 3), respectively, whereas the total interlaboratory CV was 64.3% (N = 18). The immunoreactive Tg had dilution curves parallel with other Tg calibrators (those of the methods). Dilution curves of the Tg material after storage at various temperatures and time were parallel in both RIA and IRMA. In conclusion, we have prepared a Tg reference material which in extensive studies in several participating laboratories has demonstrated a sufficient homogeneity and stability as well as dilution curves parallel to the calibrators of all the immunoassays tested in the study. This reference material is considered the first step towards decreasing the interlaboratory variability between Tg immunoassays.

Drug Stability↗
PubMed1996

Human thyroglobulin reference material (CRM 457). 2nd Part: Physicochemical characterization and certification.

This report describes the characterization of a purified human thyroglobulin (Tg) reference material, and details the procedures used in its certification. The purified Tg is intended to be used as a primary reference material to establish calibration of working serum based reference material for immunoassay procedures. The programme involved the participation of 15 European laboratories and one laboratory from the United States. The physicochemical characterization showed by polyacrylamide gel electrophoresis and immunoblotting that the purified Tg had for the major part the expected molecular size of 660 kDa with traces of lower molecular forms. The amino acid composition was close to that demonstrated for the cDNA and the content of iodine was in keeping with a moderately to highly iodinated Tg. The mass concentration in reference material RM 457 is certified to be (0.324 +/- 0.018) g/L on the basis of protein determined by the Lowry method and supported by nitrogen determination, absorbance measurement, and amino acid analysis. This reference material is considered the first step towards decreasing the interlaboratory variability between Tg methods of measurement.

Amino Acids↗
PubMed1995

Increased survival after major thermal injury: the effect of growth hormone therapy in adults.

BACKGROUND: Advances in the management of patients with major thermal injury have resulted in a progressive increase in survival rates. We report preliminary data evaluating the safety and potential efficacy of human growth hormone (HGH) administration in a high-risk population of burned patients. METHODS: From 1989 to 1993, 69 patients sustaining major burns (defined as patient age plus percentage of body surface area with deep second- and third-degree burns > or = 90) were evaluated. Patients routinely received anti-inflammatory pharmacotherapy including antioxidants, an endotoxin binder, and cyclooxygenase blockade. Half of the 54 patients who survived more than 7 days received HGH to enhance wound healing. Injury severity, morbidity, and mortality for patients receiving HGH was compared to the 27 patients not receiving HGH. RESULTS: For the entire population (n = 69), average age was 56 +/- 23 years, body surface area burned was 58% +/- 24%, and 30% sustained smoke inhalation. Actual mortality was 41%, significantly less than the more than 70% mortality rate predicted from reported outcome data. Patients receiving HGH were well matched with the group not receiving HGH with respect to extent of injury, burn management, pharmacotherapy, and in-hospital morbidity. Mortality of the patients receiving HGH was 11%, significantly less than the 37% mortality rate of the patients without HGH (p = 0.027). CONCLUSION: Compared to standard predictors of burn mortality our small patient group appears to have an improved survival rate, suggesting that the use of anti-inflammatory agents appears safe and potentially beneficial. Patients receiving HGH exhibited minimal drug-related complications and mortality rates were improved when this population was compared with both predicted mortality rates and a well-matched control population of concurrently treated patients. Prospective blinded trials are now necessary to confirm these findings in a larger patient group.

Adolescent↗
PubMed1995

Thyroid hormone-regulated brain mitochondrial genes revealed by differential cDNA cloning.

Thyroid hormone (T3) plays a critical role in the development of the central nervous system and its deficiency during the early neonatal period results in severe brain damage. However the mechanisms involved and the genes specifically regulated by T3 during brain development are largely unknown. By using a subtractive hybridization technique we have isolated a number of cDNAs that represented mitochondrial genes (12S and 16S rRNAs and cytochrome c oxidase subunit III). The steady state level of all three RNAs was reduced in hypothyroid animals during the postnatal period and T3 administration restored control levels. During fetal life the level of 16S rRNA was decreased in the brain of hypothyroid animals, suggesting a prenatal effect of thyroid hormone on brain development. Since T3 does not affect the amount of mitochondrial DNA, the results suggest that the effect of T3 is at transcriptional and/or postranscriptional level. In addition, the transcript levels for two nuclear-encoded mitochondrial cytochrome c oxidase subunits: subunits IV and VIc were also decreased in the brains of hypothyroid animals. Hypothyroidism-induced changes in mitochondrial RNAs were followed by a concomitant 40% decrease in cytochrome c oxidase activity. This study shows that T3 is an important regulator of mitochondrial function in the neonatal brain and, more importantly, provides a molecular basis for the specific action of this hormone in the developing brain.

Animals↗
PubMed1995

Contact endoscopy during microlaryngeal surgery: a new technique for endoscopic examination of the larynx.

By means of a microcolpohysteroscope during microlaryngoscopy, the cells of superficial layers of the vocal cord epithelium, previously stained with methylene blue, were observed in vivo and in situ. Several parameters were evaluated: regularity of the epithelium, dimensions and color of the nucleus, nucleus-cytoplasm ratio, nucleus and cytoplasm contours, and presence of the nucleolus, mitosis, cytoplasmic inclusions, keratosis, and koilocytes, among others. The normal squamous epithelium of the vocal cord has a homogeneous cell arrangement, with a spheroid and isochromic nucleus, and a uniform nucleus-cytoplasm ratio. Specific cellular epithelial patterns in different disorders were observed, namely, chronic laryngitis, keratosis, dysplasia, papilloma, and malignant tumor. The present study on contact endoscopy during microlaryngeal surgery reports our first results with this original technique, performed in 68 patients.

Adolescent↗
PubMed1995

Effect of perinatal hypothyroidism on the developmental regulation of rat pituitary growth hormone and thyrotropin genes.

We studied the effects of thyroid hormone (T3) on GH, TSH, and T3 receptor (TR) gene expression as well as deiodinase activities during rat pituitary development. By reverse transcriptase-polymerase chain reaction, GH and TSH beta transcripts were detectable on fetal day 15. Although with certain differences, the expression of both GH and TSH beta genes was under T3 control during fetal and neonatal life. Differences in plasma, but not pituitary, TSH concentrations were observed between control and hypothyroid animals throughout the period studied. Both TR alpha and TR beta genes were expressed in the fetal pituitary. TR alpha 1, TR beta 2, and c-erbA alpha 2 transcripts displayed a developmental profile different from that of TR beta 1. Thyroid hormone repressed TR alpha 1, TR beta 2, and c-erbA alpha 2 and stimulated TR beta 1. Type I and type II deiodinase activities (5'DI and 5'DII, respectively) had different ontogenic patterns; 5'D-II was the predominant activity in fetuses, with levels similar to those in adults, whereas the level of 5'D-I was low and increased with age. T3 stimulated 5'D-I and decreases 5'D-II. These results demonstrate that in somatotroph and thyrotroph cells, the mechanisms responsible for T3 action are mature and active very early in development and suggest an involvement of this hormone in the establishment and/or maintenance of the somatotroph and thyrotroph phenotype.

Animals↗
PubMed1995

Contact endoscopy of the vocal cord: normal and pathological patterns.

Contact endoscopy allows an in vivo and in situ study of the superficial layers of the vocal cord epithelium. This technique offers access to some characteristics of the epithelium cells: dimension and shape of the nuclei, nucleus/cytoplasm ratio, keratosis, presence of nucleolus, mitosis and koylocites. Contact endoscopy was performed during microlaryngoscopies in 92 patients with benign, pre-malign and malign pathology of the vocal cords. Systematic confrontation with pathological examination and laryngectomy specimens studied by histology and electron microscopy were used to improve the interpretation of contact endoscopy findings. Based on this correlation it has been possible to analyse the transition of the squamous and ciliated epithelium of the vocal cord as well as to delineate some pathological patterns, e.g. chronic laryngitis, keratosis, dysplasia, tumor and papilloma.

Adolescent↗
PubMed1995

Measurement of trough-to-peak ratios of four anti-hypertensive drugs on the basis of 24 h ambulatory blood pressure monitoring: different methods may give different results.

With 24 h ambulatory blood pressure monitoring (ABPM), the trough-to-peak (T/P) ratios (corrected for placebo) of atenolol 100 mg, cilazapril 2.5 mg, enalapril 20 mg and nifedipine-GITS 30 mg administered once daily for 4 weeks were determined in four groups of hypertensive patients. T/P ratios were calculated by three different methods: directly from the curves that averaged all individual 24 h profiles (A); averaging all individual T/P ratios after ABPM data were averaged for each patient over either 1 h intervals (B) or 3 h intervals (C). Methods B and C produced different values of T/P which, for each drug, were significantly higher with method C. With method A, nifedipine appeared to have the higher T/P. With methods B and C (which in contrast to method A, permitted statistical comparisons), differences between nifedipine and the other drugs were not significant. Meanwhile, method B appears to adhere most closely to FDA guidelines by taking more into account the interindividual variability of BP profile. Thus, we suggest that precise guidelines for measuring T/P on the basis of ABPM are needed, whereas for the comparison between drugs, both the mean value of the T/P and its variance must be determined.

Adult↗
PubMed1994

Changes in tyrosine hydroxylase gene expression in mesencephalic catecholaminergic neurons of immature and adult male rats perinatally exposed to cannabinoids.

We have previously reported that the perinatal exposure of pregnant rats to cannabinoids affected the activity of tyrosine hydroxylase (TH) in the striatum of their male offspring at peripubertal ages. In the present work, we examined whether this effect was accompanied by modifications in TH gene expression. The amount of TH-mRNA--measured by Northern blot analysis with a specific TH probe--in the mesencephalon of 15- and 20-day-old male rats perinatally exposed to hashish extracts was higher than that measured in aged-matched controls. No differences appeared at 30 and 40 days after birth, a priori because they correspond to ages after the hashish withdrawal occurring on day 24 after birth. However, a significant decrease in the amount of TH-mRNA was observed in adult animals (70 days of life) perinatally exposed to hashish. The increase in TH-mRNA concentrations observed in hashish-exposed 15-day-old animals corresponded to an increase in the amount of TH protein, measured by Western blot analysis, in the mesencephalon, with no differences in the striatum. However, the amount of TH protein in both tissues was not modified by perinatal hashish treatment in adult animals, where TH-mRNA amounts had been decreased. In summary, perinatal cannabinoid exposure enhances the expression of the TH gene in mesencephalic catecholaminergic neurons during early peripubertal ages, coinciding with hashish treatment. Normality was found after hashish withdrawal and an interesting decrease in the amount of TH-mRNA appeared in adulthood, although with no reflection on the amount of TH protein.

Animals↗