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Biomedical subjects

M Pombo

Publications and source records attributed to M Pombo.

At least 19 recordsLinked to original sources
PubMed2005

Endocrine disruptors.

Man does not come into the world pre-determined. The lifetime set of environmental conditions impinging on a given individual has been termed the ambiome, which together with the genome and the proteome determines each individual's development and construction. Among the most important elements making up the ambiome are endocrine disruptors. An endocrine disruptor is a chemical substance that has adverse effects on an organism or its progeny, through the endocrine system. The number of known endocrine disruptors is large and continuously increasing, and includes both naturally occurring and synthetic substances. We are convinced that they entail genuine problems; although it is difficult to assess their magnitude and real significance, and we will certainly need some time, probably several decades, to obtain conclusive results; but even so, we consider that the existing body of evidence about effects of endocrine disruptors on human health is sufficiently worrying to justify precautionary measures.

Animals↗
PubMed2005

Papillary thyroid carcinoma after recombinant GH therapy for Turner syndrome.

Turner syndrome (TS) has been included for several years among the indications for GH treatment, generally with satisfactory outcomes. Nevertheless, the long-term effects of this treatment in non-GH deficient patients are not fully known. The incidence of thyroid carcinoma is rare in patients during childhood, it is unusual to find this neoplasia in children under sixteen years old. This article reports the cases of two Spanish patients with papillary thyroid carcinoma after GH treatment for TS. Recent studies have indicated a possible relationship between the GH-IGF axis and the pathogenesis of neoplasias, questioning the chance association of these two pathologies. In line with this, we detected GH receptor expression in the papillary carcinoma cells. Long-term prospective studies are required to clarify the possible effects of GH treatment on the risk of neoplasia.

Carcinoma, Papillary↗
PubMed2005

Genetic basis of short stature.

Growth in humans is a complex process controlled by many genetic and non-genetic factors. It is influenced by endogenous factors like genetics, hormones and metabolism as well as exogenous ones like nutrition, physical activity and psychosocial status. Growth is one of the most sensitive markers of children's health, their nutritional status and genetic background. Besides, deviation from normality may be the first manifestation of an underlying congenital or acquired pathology. Thus, it is important to know the growth process and the disorder that can disturb it. Short stature is defined as a condition in which the height of an individual is more than 2 SD below the corresponding mean height for a given age, sex and population group. This disorder is a major concern for patients and their parents, and represents a diagnostic challenge to the clinician. A correct diagnosis is particularly important in view of the availability of effective, but costly, therapy in a small subset of cases. Cytogenetic and molecular analysis can be of great value in this diagnostic process. Emphasis can be made on the advances of molecular genetics, which have characterized human genes involved in the hypothalamus-pituitary-GH axis such as GH, POU1F1, PROP1, GHRHR, GHR, IGF, IGFR, HESX1, LHX3, LHX4, among others. Our current line of investigation is related to the study of some of these genes and the genotype-phenotype relation with the aim of identifying features that add some more light on the genetic origins of short stature.

Base Sequence↗
PubMed2004

Therapeutic optimization of growth hormone deficiency in children and adolescents.

More than 40 years after the introduction of growth hormone (GH) treatment, many questions remain unanswered. Clearly, with the availability of rhGH and with current treatment protocols, treatment efficacy has improved. However, it still remains unclear whether current treatment protocols are the best possible. Before GH deficiency was recognized as a chronic disease, children only received treatment until normal adult height had been reached. However, it has recently been shown that not all GH-dependent body structures and functions normalize in parallel with height. Furthermore, in adolescents with GH deficiency, the interruption of GH substitution leads to severe hormone deficiency symptoms in adulthood. In the case of an adolescent who meets the biochemical criteria for GH deficiency in adulthood, but does not show alterations of metabolism, body structure, or emotional state, should GH treatment be started in adolescence, or only if and when the clinical syndrome becomes apparent? This is a difficult question to which there is not yet any clear answer, and we suggest that there is a need for further studies in this area. Furthermore, it will be necessary to re-evaluate the situation of patients who have completed their growth, and definitive conclusions will require controlled studies.

Adolescent↗
PubMed2002

Mycobacterium fortuitum complex endocarditis-case report and literature review.

Endocarditis due to Mycobacterium fortuitum complex is a rare entity generally linked to the hospital environment. Only 18 cases have been published since 1966. Here we present a case of a female who developed an endocarditis due to Mycobacterium chelonae after valve replacement as well as a review of the literature. The course of this kind of endocarditis is generally subacute and the outcome is usually fatal. Blood cultures were positive in 75% of cases of metallic valve endocarditis, versus 20% in bioprostheses. The treatment must include antibiotics that have shown activity against these mycobacteria, such as amikacin, imipenem, cefoxitin, fluorinated quinolones and macrolides (especially clarithromycin). Surgical removal is recommended. Although the prognosis for the patient is poor, we should expect better outcomes with the use of new antibiotic regimens.

Aortic Valve Insufficiency↗
PubMed2001

Hormonal control of growth hormone secretion.

Growth hormone secretion by the somatotroph cells depends upon the interaction between hypothalamic regulatory peptides, target gland hormones and a variety of growth factors acting in a paracrine or autocrine fashion. This review will be focused on recent data regarding the mechanism by which growth hormone-releasing hormone (GHRH) influences somatotroph cell function and the physiological role played by Ghrelin and leptin in the regulation of growth hormone (GH) secretion. It is well established that binding of GHRH to its receptor leads to activation of protein kinase A (PKA). More recently, it was found that GHRH can also activate mitogen-activated protein (MAP) kinase both in pituitary cells and in a cell line overexpressing the GHRH receptor. Whether somatotroph adenomas, either with or without a GS-alpha mutation, have alterations in some of the components of the activation of the MAP kinase pathway remains to be known. The recent isolation of Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, can be considered a landmark in the GH field, which opens up the possibility of gaining greater insight into our understanding of the mechanisms involved in the regulation of GH secretion and somatic growth. Indeed, preliminary evidences indicate that this peptide exerts a marked stimulatory effect on plasma GH levels in both rats and humans. Finally, it is well known that GH secretion is markedly influenced by nutritional status. Leptin has emerged as an important adipose tissue-generated signal that is involved in the regulation of GH secretion, thus providing an integrated regulatory system of growth and metabolism. Although the effects of leptin on GH secretion in humans remain to be clarified, indirect evidences indicate that it may play an inhibitory role.

Ghrelin↗
PubMed2000

The predictive value of inguinal herniography for the diagnosis and treatment of cryptorchidism.

PURPOSE: We evaluated the role of a patent processus vaginalis for cryptorchidism as well as inguinal herniography as a predictor of the efficacy of human chorionic gonadotropin (HCG) treatment. MATERIALS AND METHODS: We studied 244 boys with unilateral and 66 with bilateral cryptorchidism. All patients underwent inguinal herniography and received HCG. Nonresponders to treatment subsequently underwent orchiopexy, when processus vaginalis status, testicular position and epididymal characteristics were assessed. RESULTS: HCG was effective for 139 of 281 testes (49.5%) with an obliterated and 0 of 95 with a patent processus vaginalis on herniography. We further evaluated herniography in accordance with orchiopexy findings of persistent unilateral and bilateral cryptorchidism in 206 boys (237 testes) after HCG. Herniography findings of processus vaginalis morphology revealed a close correlation with that reported by the surgeon after orchiopexy (p<0.000005). The incidence of a patent processus vaginalis increased as testicular position became more caudal. The processus vaginalis was obliterated in all cases of anorchia. The incidence of more severe epididymal anomalies decreased as the testicular position became more caudal. Epididymal abnormalities were more common when the processus vaginalis was patent. CONCLUSIONS: Pretreatment herniography assessment of processus vaginalis morphology is of prognostic value for predicting the efficacy of hormone treatment, the presence or absence of testes when they are nonpalpable and future fertility.

Child↗
PubMed1999

High serum leptin levels in children with type 1 diabetes mellitus: contribution of age, BMI, pubertal development and metabolic status.

OBJECTIVE: Children with diabetes mellitus are prone to develop obesity and to experience a delay in onset of the pubertal process. In order to understand the role of leptin in these abnormalities, serum leptin levels were analysed in children with type 1 diabetes mellitus. SUBJECTS: Twenty diabetic girls, 23 diabetic boys and 66 healthy children (selected from a reference population of 706 normal children), age-, sex- and BMI-matched with diabetic patients, were studied. MEASURMENTS: Standing height, weight and BMI were determined in each child. Serum testosterone, oestradiol and leptin were measured by specific radioimmunoassays, and HBA1c by high performance liquid chromatography. RESULTS: Both diabetic girls and boys showed higher leptin levels than the normative healthy population and a group of age-, sex- and BMI-matched normal children. In an age-related analysis, leptin levels in diabetic girls rose from 7.4 +/- 1.2 and 8.1 +/- 2.1 microg/l for the 5-7.99 and 8-10.99 year groups, to 12.6 +/- 2.4 microg/l for the 11-13.99 year group, and to 15.6 +/- 4.0 microg/l in the 14-15.99 year group in parallel with body weight. Leptin concentrations were parallel but higher (P < 0.05) than those of healthy girls. Diabetic boys had lower leptin levels than girls and, in contrast with normal boys, did not show a drop after the 10-year period. Leptin levels were 4.9 +/- 2.2, 3.9 +/- 0.2, 5.5 +/- 0.6 and 5.1 +/- 0.9 microg/l for the 5-7.99, 8-10. 99, 11-13.99 and 14-15.99 year groups, respectively. When divided by pubertal stage, leptin levels in the prepuberty stage of diabetic girls (8.6 +/- 1.0 microg/l) were higher (P < 0.05) than those in the controls (4.1 +/- 0.4 microg/l). In overt puberty girls, leptin was higher (P < 0.05) for diabetic (15.9 +/- 2.9 microg/l) than for healthy girls (9.2 +/- 1.1 microg/l). In prepubertal boys, differences were observed in leptin levels (4.9 +/- 0.5 microg/l for diabetic boys and 3.4 +/- 0.6 microg/l for healthy boys). In the overt puberty stage, diabetic boys showed higher (P < 0.05) levels of leptin (5.2 +/- 0.7 microg/l) than the healthy matched controls (2.1 +/- 0.2 microg/l). A multiple step regression analysis in the diabetic children revealed no associations between leptin and other relevant variables such as glycosylated haemoglobin, daily insulin dose, or years of suffering from the disease. CONCLUSION: Serum leptin levels were higher in diabetic than in healthy children. These differences were not attributable to age, adiposity or stage of pubertal development, and were probably conditioned by the metabolic perturbation intrinsic to the diabetic state, or the chronic hyperinsulinemia.

Adolescent↗
PubMed1999

Growth hormone secretagogues: the clinical future.

Growth hormone (GH) releasing hexapeptide (GHRP)-6 and other peptidergic and non-peptidergic compounds collectively designated GH secretagogues (GHS) are potent releasers of GH in man. Their clinical future may be envisioned in three areas: therapy of GH-deficient (GHD) states, diagnosis of GHD, and non-endocrinological actions. As therapeutic agents and compared with GH itself, GHS have the disadvantage of lower potency but have a more physiological and safer profile of GH secretion. GHS administration could be indicated for states in which medium GH doses have been shown to be effective. As a diagnostic tool, the combined administration of GH releasing hormone plus GHRP-6, both at saturating doses, is currently the most powerful releaser of GH, devoid of side effects and convenient for the patient; it may also be an alternative to the insulin tolerance test for the diagnosis of GHD in adult patients. Their potential action at cardiovascular level is highly promising. Although the clinical future of GH releasing substances is appealing, probably the most relevant contribution has yet to be discovered. Once the endogenous ligand of the GHS receptor is identified, we will have an insight into the real hypothalamic control of GH secretion in man. With this knowledge it is likely that some diagnostic and therapeutic actions that are commonly undertaken will significantly change.

Animals↗
PubMed1999

Regulation of growth hormone secretion by signals produced by the adipose tissue.

The neuroregulation of growth hormone (GH) secretion and the state of the adipose tissue reserves are closely related. GH exerts lipolytic actions on the adipose tissue and low body weight enhances secretion of GH while obesity is associated with reduced levels of GH and blocked release of GH when challenged by all stimuli. The mediators of the regulation exerted by the adipose tissue on the GH/insulin-like growth factor-I axis are not fully understood, but in the last few years two relevant factors have emerged--free fatty acids (FFA) and the adipocyte-produced hormone leptin. FFA and GH integrate a classical feedback loop and a rise in FFA blocks GH secretion. This action is rapid, dose-related and exerted at the pituitary level with no evident hypothalamic participation. A pharmacological reduction in FFA enhances secretion of GH and eliminates the GH blockade of obesity and Cushing's syndrome. The discovery of leptin has expanded our knowledge of the way in which the adipose tissue participates in some neuroendocrine actions. Obesity is associated with elevated levels of serum leptin while undernutrition and fasting lead to low leptin. In fasted rats, the pattern of GH pulsatility is eliminated with a near absence of spontaneous peaks, but the administration of leptin by the intracerebroventricular (i.c.v.) route restores the altered pattern. When fed rats receive antileptin antibodies i.c.v the normal pattern is reversed to an absence of pulses, reminiscent of the fasting state. These results are the first demonstration that, at least in experimental animals, leptin is a relevant factor in GH regulation. Leptin has no direct pituitary action and its action at the hypothalamic level appears to be mediated by neuropeptide Y, being the final step in a reduction in the somatostatin tone. On the other hand, the action of GH on leptin levels seems to be tenuous in humans, but in the near future it will be possible to investigate the action of leptin on human GH. As the hypothalamic neuroregulation of GH secretion in humans is unlike that in the rat, a crucial point for elucidation will be the actions, if any, and the mechanisms by which leptin participates in GH regulation in humans, as well as its alterations in disease states.

Adipose Tissue↗
PubMed1997

Nocturnal rise of leptin in normal prepubertal and pubertal children and in patients with perinatal stalk-transection syndrome.

We studied 24-h profiles of circulating leptin levels using a sensitive and specific radioimmunoassay in healthy pre- (Tanner 1) and pubertal boys and girls (Tanner 3-4) as well as in a group of patients with perinatal stalk-transection syndrome. Similar nyctohemeral rhythm in serum leptin levels were found in prepubertal (MESOR: 2.34 +/- 0.2 ng/ml; amplitude 0.32 +/- 0.1 ng/ml) and pubertal boys (MESOR 2.2 +/- 0.2 ng/ml; amplitude 0.38 +/- 0.07 ng/ml). Likewise, no differences were found between prepubertal (MESOR 6.6 +/- 1.07 ng/ml; amplitude 1.67 +/- 0.4 ng/ml) and pubertal girls (MESOR 4.05 +/- 0.5 ng/ml; amplitude 0.95 +/- 0.2 ng/ml). In contrast, higher MESOR (p < 0.002) and amplitude values (p < 0.005) were found in prepubertal and pubertal girls than in prepubertal and pubertal boys. Finally a significant nyctohemeral rhythm in serum leptin levels was found in patients with perinatal stalk-transection syndrome (MESOR: 9.3 +/- 2.3 ng/ml; amplitude 1.46 +/- 0.4 ng/ml). This data shows the existence of sexual dimorphism in the nyctohemeral rhythm in serum leptin levels that are not influenced by the pubertal stage or by pulsatile anterior pituitary hormone secretion.

Adolescent↗