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E Carro

Publications and source records attributed to E Carro.

At least 19 recordsLinked to original sources
PubMed2005

Therapeutic actions of insulin-like growth factor I on APP/PS2 mice with severe brain amyloidosis.

Transgenic mice expressing mutant forms of both amyloid-beta (Abeta) precursor protein (APP) and presenilin (PS) 2 develop severe brain amyloidosis and cognitive deficits, two pathological hallmarks of Alzheimer's disease (AD). One-year-old APP/PS2 mice with high brain levels of Abeta and abundant Abeta plaques show disturbances in spatial learning and memory. Treatment of these deteriorated mice with a systemic slow-release formulation of insulin-like growth factor I (IGF-I) significantly ameliorated AD-like disturbances. Thus, IGF-I enhanced cognitive performance, decreased brain Abeta load, increased the levels of synaptic proteins, and reduced astrogliosis associated to Abeta plaques. The beneficial effects of IGF-I were associated to a significant increase in brain Abeta complexed to protein carriers such as albumin, apolipoprotein J or transthyretin. Since levels of APP were not modified after IGF-I therapy, and in vitro data showed that IGF-I increases the transport of Abeta/carrier protein complexes through the choroid plexus barrier, it seems that IGF-I favors elimination of Abeta from the brain, supporting a therapeutic use of this growth factor in AD.

Amyloid beta-Peptides↗
PubMed2004

Neoplasia in solid organ transplant recipients: single-center experience.

The incidence of neoplasms among transplanted patients is increasing, being estimated at between 4% and 18% (mean = 6%). In this article we review the neoplasms in 2514 patients who underwent transplantation in our hospital between 1981 and 2002 including 1579 kidneys, 418 hearts, 430 livers, 70 lungs, and 17 pancreas. We observed 170 tumors in 117 patients. The most frequent neoplasm was skin and lip carcinoma (30 patients) followed by PTLD (18 patients). Our results concur with the literature with one exception, a low incidence of PTLD in heart transplants, which may only be explained due to the use of preventive therapy with antiretroviral drugs.

Aged↗
PubMed2004

Microspheres containing insulin-like growth factor I for treatment of chronic neurodegeneration.

The therapeutic potential of peptide growth factors as insulin-like growth factor I (IGF-I) is currently under intense scrutiny in a wide variety of diseases, including neurodegenerative illnesses. A new poly(lactic-co-glycolide)-based microsphere IGF-I controlled release formulation for subcutaneous (SC) delivery has been developed by a triple emulsion method. The resulting microspheres displayed a mean diameter of 1.5microm, with an encapsulation efficiency of 74.3%. The protein retained integrity after the microencapsulation process as evaluated by circular dichroism and SDS-PAGE. The administration of IGF-I in microspheres caused at least a 30-fold increase in IGF-I mean residence time in rats and mice when compared with the conventional SC solution. Therefore, dosing can be changed from the conventional twice a day to once every 2 weeks. Therapeutic efficacy of this new formulation has been studied in mutant mice with inherited Purkinje cell degeneration (PCD). These mice show a chronic limb discoordination that is resolved after continuous systemic delivery of IGF-I. Normal motor coordination was maintained as long as IGF-I microsphere therapy is continued. Moreover, severely affected PCD mice, with marked ataxia, muscle wasting and shortened life-span showed a significant improvement after continuous IGF-I microsphere therapy as determined by enhanced motor coordination, marked weight gain and extended survival. This new formulation can be considered of great therapeutic promise for some chronic brain diseases.

Animals↗
PubMed2002

Serum insulin-like growth factor I regulates brain amyloid-beta levels.

Levels of insulin-like growth factor I (IGF-I), a neuroprotective hormone, decrease in serum during aging, whereas amyloid-beta (Abeta), which is involved in the pathogenesis of Alzheimer disease, accumulates in the brain. High brain Abeta levels are found at an early age in mutant mice with low circulating IGF-I, and Abeta burden can be reduced in aging rats by increasing serum IGF-I. This opposing relationship between serum IGF-I and brain Abeta levels reflects the ability of IGF-I to induce clearance of brain Abeta, probably by enhancing transport of Abeta carrier proteins such as albumin and transthyretin into the brain. This effect is antagonized by tumor necrosis factor-alpha, a pro-inflammatory cytokine putatively involved in dementia and aging. Because IGF-I treatment of mice overexpressing mutant amyloid markedly reduces their brain Abeta burden, we consider that circulating IGF-I is a physiological regulator of brain amyloid levels with therapeutic potential.

Amyloid beta-Peptides↗
PubMed2001

Circulating insulin-like growth factor I mediates the protective effects of physical exercise against brain insults of different etiology and anatomy.

Physical exercise ameliorates age-related neuronal loss and is currently recommended as a therapeutical aid in several neurodegenerative diseases. However, evidence is still lacking to firmly establish whether exercise constitutes a practical neuroprotective strategy. We now show that exercise provides a remarkable protection against brain insults of different etiology and anatomy. Laboratory rodents were submitted to treadmill running (1 km/d) either before or after neurotoxin insult of the hippocampus (domoic acid) or the brainstem (3-acetylpyridine) or along progression of inherited neurodegeneration affecting the cerebellum (Purkinje cell degeneration). In all cases, animals show recovery of behavioral performance compared with sedentary ones, i.e., intact spatial memory in hippocampal-injured mice, and normal or near to normal motor coordination in brainstem- and cerebellum-damaged animals. Furthermore, exercise blocked neuronal impairment or loss in all types of injuries. Because circulating insulin-like growth factor I (IGF-I), a potent neurotrophic hormone, mediates many of the effects of exercise on the brain, we determined whether neuroprotection by exercise is mediated by IGF-I. Indeed, subcutaneous administration of a blocking anti-IGF-I antibody to exercising animals to inhibit exercise-induced brain uptake of IGF-I abrogates the protective effects of exercise in all types of lesions; antibody-treated animals showed sedentary-like brain damage. These results indicate that exercise prevents and protects from brain damage through increased uptake of circulating IGF-I by the brain. The practice of physical exercise is thus strongly recommended as a preventive measure against neuronal demise. These findings also support the use of IGF-I as a therapeutical aid in brain diseases coursing with either acute or progressive neuronal death.

Animals↗
PubMed2001

Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus.

Although the physiological significance of continued formation of new neurons in the adult mammalian brain is still uncertain, therapeutic strategies aimed to potentiate this process show great promise. Several external factors, including physical exercise, increase the number of new neurons in the adult hippocampus, but underlying mechanisms are not yet known. We recently found that exercise stimulates uptake of the neurotrophic factor insulin-like growth factor I (IGF-I) from the bloodstream into specific brain areas, including the hippocampus. In addition, IGF-I participates in the effects of exercise on hippocampal c-fos expression and mimics several other effects of exercise on brain function. Because subcutaneous administration of IGF-I to sedentary adult rats markedly increases the number of new neurons in the hippocampus, we hypothesized that exercise-induced brain uptake of blood-borne IGF-I could mediate the stimulatory effects of exercise on the adult hippocampus. Thus, we blocked the entrance of circulating IGF-I into the brain by subcutaneous infusion of a blocking IGF-I antiserum to rats undergoing exercise training. The resulting inhibition of brain uptake of IGF-I was paralleled by complete inhibition of exercise-induced increases in the number of new neurons in the hippocampus. Exercising rats receiving an infusion of nonblocking serum showed normal increases in the number of new hippocampal neurons after exercise. Thus, increased uptake of blood-borne IGF-I is necessary for the stimulatory effects of exercise on the number of new granule cells in the adult hippocampus. Taken together with previous results, we conclude that circulating IGF-I is an important determinant of exercise-induced changes in the adult brain.

Animals↗
PubMed2000

Changes in high-frequency QRS components are more sensitive than ST-segment deviation for detecting acute coronary artery occlusion.

OBJECTIVES: This study describes changes in high-frequency QRS components (HF-QRS) during percutaneous transluminal coronary angioplasty (PTCA) and compares the ability of these changes in HF-QRS and ST-segment deviation in the standard 12-lead electrocardiogram (ECG) to detect acute coronary artery occlusion. BACKGROUND: Previous studies have shown decreased HF-QRS in the frequency range of 150-250 Hz during acute myocardial ischemia. It would be important to know whether the high-frequency analysis could add information to that available from the ST segments in the standard ECG. METHODS: The study population consisted of 52 patients undergoing prolonged balloon occlusion during PTCA. Signal-averaged electrocardiograms (SAECG) were recorded prior to and during the balloon inflation. The HF-QRS were determined within a bandwidth of 150-250 Hz in the preinflation and inflation SAECGs. The ST-segment deviation during inflation was determined in the standard frequency range. RESULTS: The sensitivity for detecting acute coronary artery occlusion was 88% using the high-frequency method. In 71% of the patients there was ST elevation during inflation. If both ST elevation and depression were considered, the sensitivity was 79%. The sensitivity was significantly higher using the high-frequency method, p<0.002, compared with the assessment of ST elevation. CONCLUSIONS: Acute coronary artery occlusion is detected with higher sensitivity using high-frequency QRS analysis compared with conventional assessment of ST segments. This result suggests that analysis of HF-QRS could provide an adjunctive tool with high sensitivity for detecting acute myocardial ischemia.

Adult↗
PubMed2000

Regulation of in vivo TSH secretion by leptin.

Leptin, the product of the ob gene, is a hormone secreted by adipocytes that regulates food intake and energy expenditure. The hypothalamus-pituitary-thyroid axis is markedly influenced by the metabolic status, being suppressed during food deprivation. The aim of the present study was to assess whether leptin can act as a metabolic signal connecting the adipose tissue with the pituitary-thyroid axis. We studied the effect of leptin administration (10 microg, i.c.v.) on spontaneous TSH secretion and TSH responses to TRH in euthyroid and hypothyroid food-deprived rats. Spontaneous TSH secretion was assessed over 6 h with samples taken every 7 min. Administration of leptin to food-deprived euthyroid rats led to a reversal of the inhibitory effect exerted by fasting on spontaneous TSH secretion. This stimulatory effect of leptin on spontaneous TSH appears to be dependent on the thyroid status since it could not be observed in hypothyroid rats. This data suggests that blunted spontaneous TSH secretion in food-deprived rats is a functional and reversible state, and that the decreased leptin concentrations could be the primary event responsible for the suppression of the hypothalamic-pituitary-thyroid-axis in food-deprived rats.

Animals↗
PubMed2000

Circulating insulin-like growth factor I mediates effects of exercise on the brain.

Physical exercise increases brain activity through mechanisms not yet known. We now report that in rats, running induces uptake of blood insulin-like growth factor I (IGF-I) by specific groups of neurons throughout the brain. Neurons accumulating IGF-I show increased spontaneous firing and a protracted increase in sensitivity to afferent stimulation. Furthermore, systemic injection of IGF-I mimicked the effects of exercise in the brain. Thus, brain uptake of IGF-I after either intracarotid injection or after exercise elicited the same pattern of neuronal accumulation of IGF-I, an identical widespread increase in neuronal c-Fos, and a similar stimulation of hippocampal brain-derived neurotrophic factor. When uptake of IGF-I by brain cells was blocked, the exercise-induced increase on c-Fos expression was also blocked. We conclude that serum IGF-I mediates activational effects of exercise in the brain. Thus, stimulation of the uptake of blood-borne IGF-I by nerve cells may lead to novel neuroprotective strategies.

Action Potentials↗
PubMed2000

Regulation of somatotroph cell function by the adipose tissue.

Obese subjects exhibit a marked decrease in plasma growth hormone (GH) levels. However, the mechanisms by which increased adiposity leads to an impairment of GH secretion are poorly understood. Recent evidence suggests that the adipose tissue can markedly influence GH secretion via two different signals, namely free fatty acids (FFA) and leptin. FFA appear to inhibit GH secretion mainly by acting directly at pituitary level. Interestingly, reduction in circulating FFA levels in obese subjects led to a marked increase in GH responses to different GH secretagogues. This indicates that FFA exert a tonic inhibitory effect that contributes to blunted GH secretion in obese subjects. Recent data have shown that leptin is a metabolic signal that regulates GH secretion, since the administration of leptin antiserum to adult rats led to a marked decrease in spontaneous GH secretion. However, leptin prevents,the inhibitory effect exerted by fasting on plasma GH levels. The effect of leptin in adult rats appears to be exerted at hypothalamic level by regulating growth hormone releasing hormone (GHRH), somatostatin and neuropeptide Y (NPY)-producing neurones. In addition, during fetal life or following the development of pituitary tumors, leptin can also act directly at the anterior pituitary.

Adipose Tissue↗
PubMed2000

Spatial, individual, and temporal variation of the high-frequency QRS amplitudes in the 12 standard electrocardiographic leads.

BACKGROUND: Analysis of high-frequency QRS amplitudes (HF-QRS) may provide an additional diagnostic tool in patients with heart disease, but the basic properties of these waveforms have not been sufficiently investigated. This study describes the spatial, individual, and temporal variation at rest of HF-QRS recorded with the 12 standard electrocardiographic leads in patients with ischemic heart disease. METHODS AND RESULTS: Two consecutive electrocardiographic recordings from 67 patients were signal averaged and analyzed within a bandwidth of 150 to 250 Hz. The HF-QRS values were expressed as root mean square values. There was a spatial variation in HF-QRS among the 12 leads, with higher amplitudes in V(2) through V(4), II, aVF, and III. The individual variation among the patients was large for all leads. The sum of the HF-QRS for all 12 leads in each patient ranged from 20 to 75 microV (mean 36 +/- 11 microV). The mean of the temporal variation in HF-QRS for all 12 leads between the 2 recordings was only 0.10 +/- 0. 09 microV. CONCLUSIONS: Because of the large individual variation, analysis of HF-QRS is probably most applicable in monitoring situations when it is possible to track changes in a patient over time. The temporal variation in HF-QRS at rest is small, both in patients with and those without prior myocardial infarction.

Adult↗
PubMed2000

Leptin increases in vivo GH responses to GHRH and GH-releasing peptide-6 in food-deprived rats.

BACKGROUND: Leptin has recently been shown to have a stimulatory effect on basal GH secretion. However, the mechanisms by which leptin exert this effect are not yet clear. GHRH and GH-releasing peptide (GHRP)-6 are the two most potent GH secretagogues described to date. OBJECTIVE: To determine if leptin could also enhance in vivo GH responses to a maximal dose of GHRH. DESIGN: Leptin (10microg i.c.v.) or vehicle was administered at random before GHRH (10microg/kg i,v.) or GHRP-6 (50microg/kg i.v.), to freely-moving rats with food available ad libitum and to (48h) food-deprived rats. METHODS: Leptin and GH concentrations were measured by radioimmunoassay. Comparison between the different groups was assessed by the Mann-Whitney test. RESULTS: In comparison with fed rats, food-deprived rats showed a marked decrease in GH responses to GHRH as assessed by the area under the curve (5492+/-190ng/ml in fed rats and 1940+/-128ng/ml in fasted rats; P<0.05) and GHRP-6 (3695+/-450 in fed rats and 1432+/-229 in fasted rats; P<0.05). In comparison with its effects in vehicle-treated rats, leptin administered to food-deprived rats markedly increased GH responses to both GHRH (6625+/-613ng/ml; P<0.05) and GHRP-6 (5862+/-441ng/ml; P<0.05). CONCLUSIONS: These data suggest that the blunted GH response to GHRH and GHRP-6 in food-deprived rats is a functional and reversible state, and that the decreased leptin concentrations could be the primary defect responsible for the altered GH secretion in food-deprived rats.

Animals↗
PubMed1999

Regulation of hypothalamic somatostatin and growth hormone releasing hormone mRNA levels by inhibin.

Although it is well established that inhibin plays a major role in the regulation of the hypothalamic-pituitary-gonadal axis, its influence in the regulation of other neuroendocrine functions is still poorly understood. Recent results indicate that inhibin suppresses plasma GH levels, but its site of action is yet unknown. Therefore, in the present work we investigated the effects of inhibin on somatostatin and growth hormone releasing hormone (GHRH) mRNA levels in the hypothalamus by 'in situ' hybridization. We found that inhibin administration (4, 12 and 24 h, i.c.v.) led to an increase in somatostatin mRNA levels in the periventricular nucleus, and to a decrease in GHRH mRNA content in the arcuate nucleus of the hypothalamus. These findings indicate that inhibin regulates the hypothalamic levels of somatostatin and GHRH mRNA.

Animals↗
PubMed1999

Role of growth hormone (GH)-releasing hormone and somatostatin on leptin-induced GH secretion.

Leptin is a hormone secreted by the adipocytes that regulates food intake and energy expenditure. It is known that growth hormone (GH) secretion is markedly influenced by body weight, being suppressed in obesity and cachexia, and recent data have demonstrated that GH release is regulated by leptin levels. Although one of the sites of action of leptin is likely to be the hypothalamus, since leptin receptor mRNA is particularly abundant in several hypothalamic nuclei, the mechanisms by which leptin regulates GH secretion are not yet known. The aim of the present study was to investigate whether leptin could act at the hypothalamic level modulating somatostatin and GH-releasing hormone (GHRH) expression. The administration of anti-GHRH serum (500 microl, i.v.) completely blocked leptin-induced GH release in fasting rats. In contrast, the treatment with anti-somatostatin serum (500 microl, i.v.) significantly increased GH release in this condition. Furthermore, leptin administration (10 microg, i.c.v.) to intact fasting animals reversed the inhibitory effect produced by fasting on GHRH mRNA levels in the arcuate nucleus of the hypothalamus, and increased somatostatin mRNA content in the periventricular nucleus. Finally, leptin administration (10 microgram, i.c.v.) to hypophysectomized fasting rats increased GHRH mRNA levels, and decreased somatostatin mRNA content, indicating an effect of leptin on hypothalamic GHRH- and somatostatin-producing neurons. These findings suggest a role for GHRH and somatostatin as mediators of leptin-induced GH secretion.

Animals↗
PubMed1999

Regulation of serum leptin levels by gonadal function in rats.

The aim of this study was to investigate the regulation of serum leptin levels by gender and gonadal steroid milieu. Thus, we measured serum leptin levels by radioimmunoassay in (a) intact male and female rats, (b) female rats at different stages of the estrous cycle and (c) ovariectomized or orchidectomized rats. Gonadectomized groups were or were not implanted with silastic capsules (10 or 30 mm in length, 1.519mm internal diameter; 3.06 mm external diameter) containing estradiol or testosterone and decapitated two weeks later. We found (i) intact female rats weighing 50 g, 250 g and 300 g exhibited higher serum leptin concentrations than intact male rats of similar body weight; (ii) leptin concentrations were not affected by the phase of the estrous cycle; (iii) two weeks after gonadectomy serum leptin concentrations increased in both male (from 4.47+/-1.87 to 8.76+/-1.24 ng/ml) and female (from 1.97+/-0.46 to 5.29+/-0.51 ng/ml) rats. The ovariectomy-induced increase in serum leptin levels was not dependent, at least completely, on changes in body weight since it could be observed when comparisons were made between ovariectomized rats and intact rats in estrus matched for body weight. In contrast the effect of orchidectomy on serum leptin levels appears to be dependent on changes in body weight since it was no longer observed when comparisons were made with a group of intact male rats matched for body weight. In conclusion, these results suggest that serum leptin concentrations are controlled by gonadal function either directly or as a consequence of changes in body weight.

Animals↗
PubMed1998

Interaction between leptin and neuropeptide Y on in vivo growth hormone secretion.

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes that regulates food intake and energy expenditure. Leptin has recently been shown to play a stimulatory role on GH secretion. The aim of the present study was to investigate whether leptin regulation of GH secretion was mediated by hypothalamic neuropeptide Y (NPY). We assessed the effect of leptin administration (10 microg, i.c.v.) and/or NPY (4 microg, i.c. v.) on fasted rats. Furthermore we administered leptin antiserum (10 microl, i.c.v.), anti-NPY serum (5 microl, i.c.v.) or normal rabbit serum (10 microl, i.c.v.) to freely moving fed rats. Spontaneous GH secretion was assessed over 6 h with blood samples taken every 15 min. Fed rats treated with anti-NPY serum exhibited a normal ultradian GH rhythm. However, administration of anti-NPY serum (5 microl, i.c.v., at 120 min) completely reversed the suppression induced by antileptin serum (10 microl, i.c.v., at 0 min) on plasma GH levels (area under the curve, AUC, 168 +/- 72 vs. 1,287 +/- 430 ng/ml/6 h; p < 0.01). In fasted rats, following NPY administration, GH levels remained suppressed throughout the 6 h studied. Besides, NPY administration completely blunted leptin-induced GH secretion as assessed by the AUC (28.5 +/- 11 vs. 520 +/- 220 ng/ml/6 h; p < 0. 01). Thus, it is possible that NPY mediates the effects of leptin on GH secretion. Alternatively, leptin and NPY could act through parallel pathways to alter GH release with NPY overcoming the stimulatory effect exerted by leptin on plasma GH levels.

Animals↗
PubMed1998

Inhibin suppresses in vivo growth hormone secretion.

Although the effects of inhibin on gonadotropin synthesis and secretion have been extensively studied, the role of inhibin in the neuroregulation of in vivo growth hormone (GH) secretion still remains to be elucidated. In the present work, we investigated the effects of inhibin on spontaneous GH secretion in three different groups of conscious adult male rats: intact, gonadectomized, and dihydrotestosterone (DHT)-treated gonadectomized animals. We found that inhibin administration (100 microg/kg, i.v.) led to a marked suppression in spontaneous GH secretion in all the groups studied. This significant decrease was assessed by the area under the curve in intact (311.1 +/- 163.3 vs. 3,882.1 +/- 1,084.6 ng/ml/6 h, p < 0. 01), gonadectomized (416.6 +/- 120.9 vs. 2,078.5 +/- 298.4 ng/ml/6 h, p < 0.01) and gondadectomized rats treated with DHT (755.0 +/- 102. 3 vs. 4,539.3 +/- 1,670.6 ng/ml/6 h, p < 0.01). Furthermore, intravenous inhibin significantly reduced in vivo GH responses to GHRH (10 microg/kg, i.v.) in both intact and gonadectomized rats. These findings suggest a role of inhibin on in vivo GH secretion in the male rat.

Animals↗