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Biomedical subjects

C Fraga

Publications and source records attributed to C Fraga.

12 recordsLinked to original sources
PubMed1999

Vitamin D receptor ontogenesis in rat liver.

Vitamin D through its receptor (VDR) plays a major role in bone mineral metabolism. However, VDR is also present in a variety of cell lines as well as in numerous tissues, suggesting other functions of the hormone beyond bone metabolism and mineral homeostasis. At the liver level, it has been shown that vitamin D induces numerous changes (i.e. enzyme activity level, stimulation of some metabolic pathways and stimulation of the normal liver recovery after partial hepatectomy). However, some works did not find VDR in the liver, and also used liver tissue as a negative control of VDR gene expression. In this paper, we examined fetal, neonatal and adult rat tissues for the presence of VDR using a sensitive RT-PCR technique and immunohistochemistry. We found VDR mRNA and VDR protein in rat liver at all different periods of rat life. Thus, we suggest that some of the actions of vitamin D on liver could be mediated at the genomic level through the VDR, and that the use of this tissue as a negative control of VDR gene expression is clearly inappropriate.

Animals↗
PubMed1999

Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis.

Cathepsin K, a lysosomal cysteine protease critical for bone remodeling by osteoclasts, was recently identified as the deficient enzyme causing pycnodysostosis, an autosomal recessive osteosclerotic skeletal dysplasia. To investigate the nature of molecular lesions causing this disease, mutations in the cathepsin K gene from eight families were determined, identifying seven novel mutations (K52X, G79E, Q190X, Y212C, A277E, A277V, and R312G). Expression of the first pro region missense mutation in a cysteine protease, G79E, in Pichia pastoris resulted in an unstable precursor protein, consistent with misfolding of the proenzyme. Expression of five mature region missense defects revealed that G146R, A277E, A277V, and R312G precursors were unstable, and no mature proteins or protease activity were detected. The Y212C precursor was activated to its mature form in a manner similar to that of the wild-type cathepsin K. The mature Y212C enzyme retained its dipeptide substrate specificity and gelatinolytic activity, but it had markedly decreased activity toward type I collagen and a cathepsin K-specific tripeptide substrate, indicating that it was unable to bind collagen triple helix. These studies demonstrated the molecular heterogeneity of mutations causing pycnodysostosis, indicated that pro region conformation directs proper folding of the proenzyme, and suggested that the cathepsin K active site contains a critical collagen-binding domain.

Cathepsin K↗
PubMed1996

Regional changes in capillary supply in skeletal muscle of high-intensity endurance-trained rats.

The objective of this study was to test the hypothesis that an endurance training program designed to produce recruitment of all extensor muscle fiber types during each exercise bout would stimulate capillary angiogenesis throughout rat gastrocnemius and soleus muscles. Male Sprague-Dawley rats were exercise trained 5 days/wk for 12-14 wk with exercise bouts consisting of a combination of high intensity (32 m/min on a 15% incline) and long duration (90 min/day). On completion of high-intensity endurance training (HIET) or cage activity [sedentary (Sed)], rat hindquarters were vascularly isolated and perfusion fixed with a modified Karnovsky's fixative. Capillary supply was measured in soleus and gastrocnemius muscles by using Olympus Cue 2 image-analyzer software. Capillary supply was reflected in measurements of capillary-to-fiber ratio, capillary numerical density, capillary surface area density, and capillary volume density on transversely cut tissue sections. HIET increased citrate synthase activity by 20 and 42% in the medial and long heads of the triceps brachii, respectively. Sarcomere lengths were similar in gastrocnemius and soleus muscles of Sed and HIET rats after fixation. All four indexes of capillary supply were significantly greater throughout the gastrocnemius muscle of HIET rats compared with Sed values. The relative increase in capillarity was greater in white than in red gastrocnemius muscle of HIET rats. HIET also increased capillary supply of soleus muscle. However, only capillary numerical density was statistically greater (19%) in HIET soleus compared with Sed. These results support the hypothesis that this training program would produce an increase in capillary supply in all extensor muscles.

Animals↗
PubMed1995

Prooxidant and antioxidant hepatic factors in rats chronically fed an ethanol regimen and treated with an acute dose of lindane.

While acute lindane treatment and chronic ethanol feeding to rats have been associated with hepatic oxidative stress, the possible roles of these stresses in the pathogenesis of hepatic lesions reported in acute lindane intoxication and in those observed in some models of chronic alcoholism have not been established. Our previous studies in rats chronically fed ethanol regimens and then treated with a single intraperitoneal (i.p.) dose of lindane (20 mg/kg) showed that while lindane per se was invariably associated with hepatic oxidative stress, chronic ethanol feeding only produced this stress when the dietary level of vitamin E was relatively low. Chronic ethanol pretreatment did not significantly affect the lindane-associated oxidative stress, and neither chronic ethanol feeding nor acute lindane, single or in combination, produced any histologic and biochemical evidence of liver damage. In the present experiment, the acute dose of lindane was increased to 40 mg/kg, and we have studied a larger number of prooxidant and antioxidant hepatic factors. Male Wistar rats (115.5 +/- 5.4 g) were fed ad lib for 11 weeks a calorically well-balanced and nutritionally adequate basal diet, or the same basal diet plus a 32% ethanol/25% sucrose solution, also ad lib, and were then injected i.p. with a single dose of lindane or with equivalent amounts of corn oil. The results indicated that acute lindane treatment to naive rats increased practically all the prooxidant hepatic factors examined (cytochromes P450 and b5, NADPH cytochrome c reductase, NADPH oxidase), as well as the generation of microsomal superoxide radical and thiobarbituric acid reactive substances of liver homogenates, but did not modify any of the antioxidant hepatic factors studied. Conversely, the chronic administration of ethanol alone did not significantly affect the prooxidant hepatic factors but reduced some of the antioxidants (i.e., the activities of GSH-Px and the contents of alpha-tocopherol and ubiquinols 9 and 10). Although chronic ethanol pretreatment further increased the superoxide generation induced by lindane per se, it did not increase but generally reduced the effects of lindane per se on the other prooxidant factors studied. Furthermore, although acute lindane administration to ethanol-pretreated rats was associated with decreases in GSH and catalase (not affected by ethanol or lindane treatment alone), it did not substantially modify the reducing effects of ethanol feeding per se on GSH-Px, alpha-tocopherol, and ubiquinols. Once again, neither chronic ethanol feeding nor lindane treatment, single or in combination, was associated with any evidence of liver damage.

Animals↗
PubMed1995

Effect of multiple-dose activated charcoal on the clearance of high-dose intravenous aspirin in a porcine model.

STUDY OBJECTIVE: To study the effect of multiple-dose activated charcoal (MDAC) on salicylate clearance in pigs given high-dose i.v. aspirin. DESIGN: In a crossover design, six fasted pigs received 300 mg/kg i.v. aspirin followed by no treatment or MDAC (1 g/kg hourly for 6 doses by gastrostomy). Serum salicylate samples were obtained every 30 minutes for 6 hours. RESULTS: The mean peak salicylate concentrations were 47.4 +/- 6.2 mg/dL and 48.4 +/- 3.9 mg/dL (P = .74), and the areas under the time-serum salicylate concentration curve over 6 hours were 171,000 +/- 24,000 mg.minute/L and 188,000 +/- 18,000 mg.minute/L for the control and treatment arms, respectively (P = .22). This study had a 90% power to detect a 30% difference between arms. CONCLUSION: MDAC does not enhance the clearance of salicylate after administration of high-dose i.v. aspirin.

Animals↗
PubMed1993

Lysine clonixinate in minor dental surgery: double-blind randomized parallel study versus paracetamol.

Lysine clonixinate (LC), an effective and well tolerated non-morphinic analgesic whose mechanism of action is basically due to the inhibition of cyclo-oxygenase, was assessed with a double-blind randomized dummy design versus paracetamol (P) on 200 patients suffering from pain after minor dental surgery. Patients received according to their needs 1 or 2 tablets of 125 mg lysine clonixinate or 500 mg paracetamol every 8 h during 48 h or until pain relief. Both groups, each composed of 100 patients, were comparable in terms of demographic conditions (t test), initial symptoms (chi-square test), characteristics of the extracted dental pieces, surgical complications and wound treatment (chi-square test). Pain intensity scores and daily average intake of tablets (3.4/day) documented in the patients' diary revealed no statistically significant differences between the two treatments (chi-square test). It was found that spontaneous pain measured using a visual analogue scale (VAS) decreased significantly in both treatment groups at the 24-h control examination. The following values were observed in the LC group: baseline 4.38 +/- 1.7; 24-h * 1.20 +/- 1.4; 48-h * 0.36 +/- 1.2. In the P group the values were: baseline 4.28 +/- 1.6; 24-h * 1.11 +/- 1.4; 48-h * 0.30 +/- 0.7 (*p < 0.05). Other variables like facial swelling and night pain, evaluated on a score from 0 to 4 and symptom presence or absence respectively, showed a similar response.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1989

Reasons for the variability in growth hormone (GH) responses to GHRH challenge: the endogenous hypothalamic-somatotroph rhythm (HSR).

The aims of this study were: (1) to test the possibility that pre-GHRH plasma GH values could reflect the functional status of the hypothalamic-somatotroph rhythm (HSR) at testing, and thus explain if it is responsible for the marked variability in GH responsiveness to GHRH challenge and (2) to see if exogenous somatostatin (SS) could disrupt this endogenous HSR and thus make the GH responses homogeneous. (1) Two to 14 GHRH acute tests (GRF-29, 1 micrograms/kg, i.v. bolus) were performed in 12 normal men and 10 normal women at the same time (0830 h) at random intervals (2 to 60 days). Blood samples to measure plasma GH were drawn at 15 min intervals before and after GHRH challenge. Given that the increments in pre-GHRH plasma GH values (I = value at 0 min minus value at -15 min) were highly correlated with either GHRH-elicited peaks of GH (men, r = 0.81; women; r = 0.69; P less than 0.0001) or the rise in GH after the challenge (r = 0.685; P less than 0.0001, in the total of tests performed), three theoretical HSR phases were proposed: (A) I greater than or equal to 0.4 microgram/l Secretory Phase; (B) I less than or equal to 0, (from GH at -15 min greater than or equal to 1.5 microgram/l), Secretion Plateau; (C) I less than or equal to 0, (from GH at -15 min less than or equal to 1.5 microgram/l), Refractory Phase. Individually, 91% of the men and 86% of the women showed a constant HSR phase when tested at the same time of day independently of the intervals between tests. GH responses (peaks, mean +/- SEM, g/l) in Phase A (women, 51.5 +/- 4.1; men, 31.4 +/- 3.2) were significantly higher (P less than 0.01) than those in Phase B (women, 22.6 +/- 1.8; men, 19.7 +/- 1.5), and these than those in Phase C (women, 9.2 +/- 1.5; men, 6.2 +/- 0.5). The great dispersion observed when GH peaks were analysed as a whole disappeared (except in Phase A in women) when they were evaluated according to the HSR Phase at testing. (2) In seven men and eight women 7 min after stopping an infusion of SS (250 micrograms/h for 3 h) a new GHRH test was performed. Plasma GH variations prior to SS infusion expressed the previous HSR Phase, while the GHRH-elicited peak of GH established the Phase at the moment of testing.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Growth hormone (GH) responsiveness to GHRH in normal adults is not affected by short-term gonadal blockade.

The effects of changes in circulating gonadal steroids on GH secretion elicited by GHRH challenge (1 microgram/kg) in normal adults volunteers (aged 18-24 years), were evaluated in 10 women and 10 men before and after gonadal blockade was achieved by a GnRH agonist (1500 micrograms/day by nasal spray for 40 days). To see if the effect of testosterone on GH secretion was dependent on its aromatization to estradiol (E2), GHRH tests were performed in 7 normal men prior to administration of testosterone enanthate (250 mg im), 8 days after this treatment had began, and again after E2 receptor blockade with tamoxifen (30 mg for 2 days plus 10 mg on the third day 2 h before the GHRH test, po) administered 8 days after testosterone enanthate. The study of the functional status of the somatotropes at the time of GHRH testing was made according to our previous postulate. Short-term gonadal blockade did not affect the parameters of GH response to GHRH in neither women nor men. Thus, the functional blockade of the gonads may be advisable as an adjunct therapy in the treatment of hypothalamic GH-deficiency during the peripubertal stage. In the other group of men, administration of testosterone enanthate significantly increased GHRH-elicited GH release, but this was reverted after E2 receptor blockade. Since the hypothalamic-somatotrope rhythm was altered by both these pharmacological manipulations, it appears that testosterone acts on GH release mainly at the suprapituitary level, and that this action is secondary to its aromatization to E2.

Adolescent↗
PubMed1988

Reports and recommendations on the teaching of and training in gastroenterology in South America.

This report is based on information obtained from the medical education associations of Brazil, Colombia, and Chile. It seems that a similar policy is followed by the other countries of Latin America. The aim of the undergraduate teaching is the training of a general physician. The teaching of subspecialities is just a part of internal medicine. The education and training program should take this interrelationship into account, to prepare a general physician concerned with the biopsychosocial unity of the patient. The students must be trained for the diagnosis and management of the commonest disorders of the alimentary tract. As a speciality, gastroenterology education starts after graduation, in a 2-year program of medical residency, following a 1-year training in internal medicine. In Brazil there are courses for graduates following the medical residency program, to prepare for master's and doctor's degrees.

Education, Medical↗