Search PubMed⌕ Search

Biomedical subjects

A Santos

Publications and source records attributed to A Santos.

At least 163 records · Page 9Linked to original sources

Perinatal hypothyroidism impairs the normal transition of GLUT4 and GLUT1 glucose transporters from fetal to neonatal levels in heart and brown adipose tissue. Evidence for tissue-specific regulation of GLUT4 expression by thyroid hormone.

GLUT1 and GLUT4 glucose transporter expression is highly regulated in muscle and adipose tissue during perinatal life. Here we have investigated the role of thyroid hormones in the regulation of GLUT4 induction and GLUT1 repression associated to neonatal development. Perinatal hypothyroidism markedly impaired GLUT4 protein induction in heart. This effect was heart specific, and a greater expression of GLUT4 was detected in brown adipose tissue from neonatal hypothyroid rats compared with controls. These changes in GLUT4 protein expression were not detected in brown adipose tissue or heart when hypothyroidism was induced in adult rats. These results indicate that GLUT4 induction during perinatal life is highly sensitive to thyroid hormones in both heart and adipose tissue. Perinatal hypothyroidism was characterized by decreased cardiac GLUT4 mRNA concentrations. T3 injection caused a marked increase in cardiac levels of GLUT4 mRNA in hypothyroid neonates. Thus, in 13-day-old hypothyroid rats, GLUT4 mRNA levels increased 3-fold 1 h after T3 injection. Under these conditions, retinoic acid also caused a rapid increase in cardiac GLUT4 mRNA levels from hypothyroid neonates. In addition, cardiac levels of GLUT4 protein markedly increased in fetuses and in neonates 24 h after T3 injection. These findings suggest that a direct effect of thyroid hormones is the promotion of cardiac GLUT4 gene expression. GLUT1 protein expression was markedly enhanced in brown adipose tissue and heart during neonatal hypothyroidism as well as in hypothyroidism induced in adult rats. This was concomitant to greater levels of GLUT1 mRNA in hearts from hypothyroid neonates. Immunofluorescence analysis indicated that cardiomyocytes from hypothyroid pups contained an enhanced level of GLUT1 protein. Furthermore, T3 injection caused a decrease in cardiac levels of GLUT1 mRNA in hypothyroid neonates. These results indicate that thyroid hormone manipulation leads to inverse regulation of GLUT1 and GLUT4 glucose transporter gene expression in the neonatal heart. We conclude that thyroid hormones play a pivotal role controlling the transition of glucose transporter carriers from fetal to neonatal levels in heart and brown adipose tissue.

Adipose Tissue, Brown↗

Expression of insulin-like growth factor-I (IGF-I) receptor gene in rat brain and liver during development and in regenerating adult rat liver.

Insulin-like growth factor-I (IGF-I) is involved in the growth and development of liver and brain during fetal life by acting through specific plasma membrane receptors. In an attempt to determine how the changes in IGF-I receptor number are regulated during development, we have compared [125I]IGF-I binding to membrane fractions with the concentration of IGF-I receptor mRNA in rat liver and brain. IGF-I binding to liver membranes was 4.5 times higher in 20-day-old fetuses than in adult rats. After partial hepatectomy (70%) in adult rats a transient 2-fold increase of IGF-I binding to liver membranes was observed. In fetal and regenerating liver increases similar to those observed for IGF-I binding were observed in IGF-I receptor mRNA concentrations. In brain microsomes IGF-I binding was 3.5 times higher in 20-day-old fetuses than in adults. This difference reflects a similar change in the number of IGF-I receptors without modifications in the affinity of the receptor for the ligand. In contrast to the liver, no significant changes in the concentration of IGF-I receptor mRNA were observed in the developing brain when determined by hybridization solution, Northern blot or RNase protection analysis. These findings suggest that in the liver, the IGF-I receptor gene is regulated at pretranslational level during development and regeneration, while in brain it is preferentially regulated at translational or posttranslational level.

Animals↗

Lesions of the lacrimal caruncle. Clinicopathologic features.

PURPOSE: The rarity of lesions of the lacrimal caruncle, in addition to their wide variety of histopathologic types, makes an accurate clinical diagnosis difficult. To comprehensively illustrate the clinical and histopathologic features of these lesions, the authors conducted a retrospective analysis of all caruncular lesions that underwent biopsy at a large referral ophthalmologic hospital during a 33-year period. METHODS: The files of the Laboratory of Pathologic Anatomy from July 1957 through July 1990 were reviewed. The slides of 113 cases were reviewed and classified in two main categories: (1) inflammatory lesions and (2) neoplasms and pseudoneoplasms. The age and sex of the patient as well as preoperative clinical diagnosis were analyzed. RESULTS: Among the 113 patients whose surgical specimens were evaluated, there were 44 males and 69 females. The mean age was 31 years. The clinical diagnosis was accurate in only 50% of the patients. The authors found 16 different histopathologic types of lesions. Nevi accounted for 34% and papillomas for 26% of the total analyzed lesions. Only 5.3% of the lesions were found to be malignant. CONCLUSION: In this series, the authors confirm the low frequency of caruncular lesions, as well as their wide variety of histopathologic types. The authors found a wide range of ages and a slight female predominance. Nevi and papillomas were the most frequent lesions, and clinically they were properly diagnosed in most of the cases. Although malignancy was uncommon, it was suspected in only half of the cases.

Adolescent↗

Congenital hypertrophy of the retinal pigment epithelium associated with familial adenomatous polyposis.

PURPOSE: Multiple, bilateral areas of congenital hypertrophy of the retinal pigment epithelium (CHRPE) have been described in association with familial adenomatous polyposis (FAP). Histopathologic findings have suggested a generalized effect of the FAP gene on the RPE, which could impair the functional integrity of the RPE. The clinical, psychophysical, electrophysiologic, and fluorescein angiographic findings in CHRPE in subjects with FAP were assessed. METHODS: RPE function was assessed in 7 subjects with CHRPE and a family history of FAP. Four had documented FAP (mean age = 22.25 years) and the other three were siblings of affected subjects, with a 50% risk of developing FAP (mean age = 6.33 years). All subjects underwent comprehensive ophthalmologic examination. RESULTS: All subjects showed mild hyperopia (mean, +1.13 D; best corrected visual acuity, 20/20 or better). On perimetry, there were scotomas corresponding to some lesions. ERG showed normal rod, maximal, single-flash cone, and flicker responses. Light-dark ratio was within the normal range on EOG. Fluorescein angiography demonstrated normal retinal vasculature overlying the CHRPE lesions, which blocked background choroidal fluorescence. A normal choriocapillaris was observed through some hypopigmented lacuna. CONCLUSION: CHRPE has been related to generalized expression of an abnormal gene in RPE, but its functional abnormalities tend to be localized.

Adenomatous Polyposis Coli↗

Differential effect of thyroid hormone on NGFI-A gene expression in developing rat brain.

NGFI-A is an immediate early gene that is rapidly activated in quiescent cells by mitogens or in postmitotic neurons after depolarization. We have previously shown that the expression of NGFI-A in the developing rat brain is under the control of thyroid hormone. Now we report, by means of in situ hybridization histochemistry, the differential effect of thyroid hormone on NGFI-A expression in distinct brain regions depending on the developmental stage. NGFI-A messenger RNA (mRNA) content was analyzed in the piriform cortex, striatum, hippocampus, and cerebral cortex of control, hypothyroid, and T3-injected hypothyroid rats at birth and on postnatal days 5 and 15. In the newborn rats, experimental hypothyroidism is associated with reduced levels of NGFI-A mRNA in most of the brain regions studied. On postnatal day 15, the difference in NGFI-A expression between control and hypothyroid rats is less apparent in the striatum or no longer present in the piriform cortex and the hippocampus. In the cerebral cortex, hypothyroidism is associated with reduced levels of NGFI-A mRNA on postnatal day 15. The dentate gyrus is always insensitive to the thyroidal state. Administration of T3 accelerates the recovery of NGFI-A mRNA in 5- and 15-day-old rats. However, in newborn rats, the effect of the hormone is noticeable only in the piriform cortex. We also show that the reduced level of NGFI-A mRNA in hypothyroidism is accompanied by a reduction in the protein level. Convulsions induced by pentylenetetrazole administration resulted in an increased expression of the NGFI-A gene, which is of similar magnitude in control and hypothyroid rats.

Animals↗

Live adult worms detected by ultrasonography in human Bancroftian filariasis.

Ultrasonographic examination of the scrotal area was performed in 14 asymptomatic individuals with bancroftian filariasis and microfilaremia. While in seven subjects (50%) the ultrasonographic findings were normal, lymphatic dilation and tortuosity were observed in the other seven. In these vessels, structures with peculiar aleatory movements (filaria dance sign) were detected. A segment of the lymphatic tract containing these mobile intraluminal structures that was resected surgically from the left spermatic cord of one individual confirmed that these structures were living Wuchereria bancrofti adult worms (two females and one male). Our study demonstrates for the first time the feasibility of using a low-cost, widely available, noninvasive technique (ultrasonography) to detect and monitor living adult worms and lymphatic dilation in patients with bancroftian filariasis.

Adolescent↗

Treatment of traumatic optic neuropathy, a case report.

We report a case of post-traumatic optic neuropathy in which visual improvement, documented with visual evoked potentials (VEP), occurred after administration of a corticoid megadose. The presentation of a single case does not allow to extrapolate conclusions about the efficacy of the steroid treatment, but serves as an illustration for a controversial problem as the management of post-traumatic optic neuropathy.

Adult↗

Epidemiology of hepatitis C in central Portugal. Prevalence of anti-HCV in the population of the Coimbra District.

Anti-hepatitis C virus antibody (anti-HCV) screening was performed in a sample of the adult population of the Coimbra District. 657 persons were included (267 male and 390 female, mean age of 42.7 + 13.1 years), aleatorily chosen from four characteristic regions. Anti-HCV was detected using an ELISA-2 test and all positive sera were also tested with RIBA-2. General prevalence of anti-HCV was 0.46%. All positive patients live in urban areas and presented risk factors for HCV infection. Anti-HCV was found in 33.3% of intravenous drug abusers, in 1.8% of transfused individuals, in 1.33% of alcoholics (higher than 80 g/d alcohol ingestion), in 1% of cases with history of surgical operations, and in 0.65% of persons who lived in risk regions for hepatitis B. We conclude that anti-HCV prevalence is low in our region. We think it is important to perform other studies on larger samples of general population and to study risk groups.

Adult↗

[Bone density and osteoporosis. An opinion].

Osteoporosis is a serious health problem for women over 45 years of age. It is divided in type I, affecting mainly cancellous bone and type II, affecting cancellous and cortical bone. Type I osteoporosis is related mainly with menopause, meanwhile, type II osteoporosis is related with ageing in both sexes. Osteoporosis has a major impact in the quality of life and the independence of the individuals, being the best treatment its prevention. All women at the beginning of the menopause should receive hormonal replacement treatment and calcium, in order to avoid type I osteoporosis, since treatment for women with established osteoporosis is aimed to halt the process of bone loss. Bone density may be measured in a reliable way by different techniques, allowing to the practitioner an accurate and reproducible measurement in different segments of the body. The main indications for bone densitometry suggested by the NOF are commented, as well as, the variability that may occur in different populations and the concept of normal values of bone density.

Adult↗

Two inbred rat sublines that differ in spontaneous yawning behavior also differ in their responses to cholinergic and dopaminergic drugs.

This work compares the sensitivities of high-yawning (HY) and low-yawning (LY) sublines of Sprague-Dawley rats to dopaminergic and cholinergic yawning-inducing drugs. HY animals are significantly more sensitive to apomorphine and (-)3PPP than LY animals. Physostigmine is a less effective yawning-inducer in HY than in LY rats. With pilocarpine no differences were detected between both sublines in regard to its yawning-inducing activity. Since yawning behavior is subject to dopaminergic (inhibitory) and cholinergic (excitatory) influences, it is suggested that the genetic differences between these sublines affect the dopaminergic pathways that normally regulate yawning frequency.

Animals↗

Insertional inactivation of the WT1 gene in tumour cells from a patient with WAGR syndrome.

The WT1 gene was analysed using DNA from a Wilms' tumour derived from a patient with the WAGR syndrome using single strand conformation polymorphism analysis and polymerase chain reaction sequencing. A 14-bp insertion was found in the intron part of the splice donor site of exon 7 and was a tandem duplication of an upstream exon sequence. This mutation would be expected to disrupt the correct processing of the WT1 mRNA and is predicted to result in a non-functional protein. This observation further supports the role of WT1 in Wilms' tumorigenesis in patients with constitutional 11p13 deletions.

Abnormalities, Multiple↗

Multiple regulation of S14 gene expression during brown fat differentiation.

S14 is a gene known to be under thyroid hormone control. Its mRNA concentration is very high in lipogenic tissues, and although the precise function of the protein is still unknown, indirect data suggest its implication in triglyceride synthesis. S14 gene expression is up-regulated by thyroid hormone in liver, white adipose tissue, and lactating mammary gland. However, in brown fat, the level of this sequence is increased 3-fold in the hypothyroid animal. We have used primary cultures of brown preadipocytes differentiated to fully mature brown adipocytes to investigate the influence of cellular differentiation and hormonal stimulation on S14 gene expression. Steady state levels of S14 mRNA rose from nondetectable levels in preadipocytes to reach a maximum in fully mature adipocytes. Treatment of brown adipocytes cultures with T3 did induce S14 gene expression. This induction reflects in part a posttranscriptional stabilization of the messenger by T3. Insulin, insulin-like growth factor-I, and inositol phosphate-glycan also increase the level of S14 mRNA. Norepinephrine (NE) plays a major role in the regulation of S14 gene, and 24 h after its addition, NE elicited a 20-fold decrease in mRNA S14 concentrations. An elevated intracellular concentration of cAMP is a strong negative effector of S14 gene expression, and neither NE nor cAMP action is totally overcome by T3. As happens in vivo, glucose is a potent stimulator of S14 mRNA; however, there is a lag time of several hours before its effects can be detected. The increase in S14 gene expression with the maturation stage of the cell suggests an important role for S14 in adipocyte differentiation.

Adipose Tissue, Brown↗