Malnutrición por exceso y riesgo cardiometabólico en escolares de segundo y tercero medio de la comuna de Lota de Chile / Malnutrition by excess and cardiometabolc risk in second and third grade children of Lota county of Chile

Adolescent overweight is a widespread problem which increases the risk of developing metabolic diseases. The objective of this study was to associate metabolic syndrome and cardiovascular risk in a school in the district of Lota. A cross-sectional study with simple random probability sampling in 286 children, 14 and 18 years was taken. Prevalence of malnutrition was established, and Pearson correlation was performed. The correlations were: weight and height, 0.55; weight and waist circumference 0.87; weight and body mass index 0.86; height and waist circumference 0.39; height and body mass index 0.047; body mass index and waist circumference 0.80. The presence of the metabolic syndrome conditions the presence of nutritional diseases, meaning that anthropometric indicators may be suitable for identifying the presence of cardiometabolic risk in adolescents.

La malnutrición por exceso en el adolescente es un problema prevalente y aumenta el riesgo de desarrollar enfermedades metabólicas. El objetivo de este estudio fue asociar el síndrome metabólico y el riesgo cardiovascular en escolares de la comuna de Lota de Chile. Estudio de corte transversal, muestreo probabilístico aleatorio simple, se tomó una muestra de 286 niños, de 14 y 18 años de edad. Se estableció la prevalencia de malnutrición, y se realizó una correlación de Pearson. Las correlaciones fueron: peso y talla de 0.55; peso y circunferencia de cintura 0,87; el peso y el índice de masa corporal de 0,86; la talla y la circunferencia de cintura de 0,39; la talla e índice de masa corporal de 0,047; índice de masa corporal y circunferencia de cintura 0,80. El índice de masa corporal, la circunferencia de cintura y el peso, se agrupan en un diagnóstico efectivo. El síndrome metabólico posee una relación que condiciona la presencia de patologías nutricionales, significa que los indicadores antropométricos pueden ser adecuados para identificar la presencia de riesgo cardiometabólico en adolescentes.

Mutation analysis of MEN1, HRPT2, CASR, CDKN1B, and AIP genes in primary hyperparathyroidism patients with features of genetic predisposition.

OBJECTIVE: Primary hyperparathyroidism (PHPT), a common endocrine condition, is usually caused by sporadically occurring parathyroid adenoma. A subset of patients carry germline mutations in genes such as MEN1 (multiple endocrine neoplasia type 1), HRPT2 (hyperparathyroidism 2), and CASR (calcium-sensing receptor) predisposing to syndromic forms of PHPT or familial isolated hyperparathyroidism (FIHP). Recently, germline mutations in two novel genes AIP (aryl hydrocarbon receptor-interacting protein) and CDKN1B (cyclin-dependent kinase inhibitor 1B) have been found to be associated with endocrine tumors. The purpose of this study was to evaluate the role of MEN1, HRPT2, CASR, AIP, and CDKN1B genes in PHPT patients with clinical features suggestive of genetic predisposition. PATIENTS AND DESIGN: Medical records of patients treated for PHPT from 1974 to 2001 at Oulu University Hospital were reviewed. Patients with multiglandular or recurrent/persistent disease, other MEN1- related manifestations, aged 40 yr or younger at onset or with a family history of PHPT/MEN1-related tumor were invited to the study. Twenty patients with previously diagnosed MEN1 were excluded. Participants were interviewed and blood samples obtained for biochemical screening and mutation analysis of MEN1, HRPT2, CASR, AIP, and CDKN1B. RESULTS: Of the 56 invited patients, 29 took part in the study. One patient was found to carry the c. 1356_1367del12 MEN1 founder mutation. Mutations in other genes were not detected. CONCLUSIONS: Apart from MEN1, mutations in other genes predisposing to PHPT seem to be rare or non-existing in Northern Finnish PHPT patients. No evidence was found for a role of AIP or CDKN1B in PHPT predisposition.

Parafibromin immunoreactivity: its use as an additional diagnostic marker for parathyroid tumor classification.

Parafibromin is a protein product derived from the hyperparathyroidism 2(HRPT2) tumor suppressor geneand its inactivation has been coupled to familial and sporadic forms of parathyroid malignancy. In this study, we have conducted immunohistochemistry on 33 parathyroid carcinomas (22 unequivocal and 11 equivocal) using four parafibromin antibodies directed to different parts of the protein. Furthermore, for a fraction of cases, the immunohistochemical results were compared with known HRPT2 mutational status. Our findings show that 68% (15 out of 22) of the unequivocal carcinomas exhibited reduced expression of parafibromin while the 25 sporadic adenomas used as controls were entirely positive for parafibromin expression. Additionally, three out of the six carcinomas with known HRPT2 mutations showed reduced expression of parafibromin. Using all four antibodies, comparable results were obtained on the cellular level in individual tumors suggesting that there exists no epitope of choice in parafibromin immunohistochemistry. The results agree with the demonstration of a approximately 60 kDa product preferentially in the nuclear fraction by western blot analysis. We conclude that parafibromin immunohistochemistry could be used as an additional marker for parathyroid tumor classification, where positive samples have low risk of malignancy, whereas samples with reduced expression could be either carcinomas or rare cases of adenomas likely carrying an HRPT2 mutation.

Loss of parafibromin expression in a subset of parathyroid adenomas.

Inactivation of the hyperparathyroidism-jaw tumour syndrome (HPT- JT) gene, HRPT2, was recently established as a genetic mechanism in the development of parathyroid tumours. Its encoded protein parafibromin has tumour-suppressor properties that play an important role in tumour development in the parathyroids, jaws and kidneys. Inactivating HRPT2 mutations are common in HPT- JT and parathyroid carcinomas, and have been described in a few cases of parathyroid adenomas with cystic features. In this study, 46 cases of cystic parathyroid adenomas previously investigated for HRPT2 mutations were characterized with regard to MEN1 gene mutations, cyclin D1 expression and parafibromin expression. In normal tissues and cell lines, parafibromin was ubiquitously expressed. Furthermore, parafibromin was detected as a dominating nuclear and a weaker cytoplasmic signal in transfected cell lines. In the three parathyroid tumours with inactivating HRPT2 mutations parafibromin expression was not detectable, and in one of two cases with aberrantly sized parafibromin the protein was delocalized. Both high and low cyclin D1 levels were found among HRPT2-mutated and -unmutated tumours, suggesting that these events are not mutually exclusive in parathyroid tumour development. The presented data suggest that in the majority of benign parathyroid tumours the expression of parafibromin remains unaltered, while the loss of parafibromin expression is strongly indicative of gene inactivation through mutation of the HRPT2 gene.

Multiple endocrine neoplasia type 1 (MEN1): genetic and clinical analysis in the Southern Chinese.

OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is characterized by a triad of neoplasia affecting the parathyroid glands, enteropancreatic endocrine tissue and the anterior pituitary gland. DESIGN: In order to define the prevalence of MEN1 germ-line mutations in Southern Chinese patients with MEN1 syndrome, we performed direct sequencing of the entire open reading frame of the MEN1 gene for 12 index patients and their first-degree relatives. RESULTS: Six patients had familial MEN1 syndrome and six had apparently sporadic disease. Nine different germ-line mutations at the MEN1 gene were identified, including three novel mutations [248-249delTT in exon 2, K559X(AAG --> TAG) in exon 10 and IVS 2nt + 2(G --> T) in intron 2]. All patients with familial MEN1 syndrome were heterozygous carriers of a germ-line mutation and MEN1-related disorders were only evident in their first-degree relatives who also carried the mutation. All patients with an enteropancreatic lesion were mutation carriers and the absence of mutation in three apparently sporadic MEN1 patients with only hyperparathyroidism and pituitary microadenoma might represent the presence of MEN1 phenocopy. CONCLUSIONS: The finding of MEN1 germ-line mutation in all patients with familial MEN1 syndrome suggests that genetic screening should be useful in our population to identify affected individuals within a kindred and allow early detection of MEN1-related tumours.

HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome.

We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.

Homozygous inactivation of the MEN1 gene as a specific somatic event in a case of secondary hyperparathyroidism.

BACKGROUND: Most patients who have been surgically treated for secondary hyperparathyroidism (HPT) harbor at least one pathological parathyroid gland with a tumor of monoclonal origin. OBJECTIVE: To elucidate the underlying genetic mechanisms behind secondary HPT, by studying a panel of such tumors for numerical alterations. METHODS: Sixteen parathyroid glands from eight patients (median age 58 years, range 31-74 years), were screened for numerical chromosomal imbalances, using comparative genomic hybridization (CGH). Mutation analysis of the multiple endocrine neoplasia type 1 gene (MEN1) was also performed by sequencing of the coding region. RESULTS: The results show that gross chromosomal alterations occur rarely in secondary HPT. In one of the three glands analyzed from one patient, a complete loss of chromosome 11 was detected. This gland also had an inactivating nonsense mutation, E469X, of the MEN1 gene. The mutation was present neither in the other two glands, nor in the constitutional tissue of the same patient, thus confirming its somatic origin. CONCLUSIONS: The relative lack of numerical chromosomal alterations would suggest that more discrete genetic alterations are responsible for the monoclonal growth in the majority of cases of secondary HPT. Furthermore, somatic inactivation of the MEN1 tumor suppressor gene contributes to the tumorigenesis in a small proportion of the cases.

Smoking and cardiovascular disease.

Mainstream and ETS exposure are strong risk factors for cardiovascular disease in men and women. The relationships between smoking and cardiovascular disease result from multiple mechanisms that interact to contribute to atherosclerosis, vascular injury, thrombosis, and vascular dysfunction. We are only now beginning to understand how smoking contributes to the genesis and progression of cardiovascular disease. Because of the complexity of the interactions between nicotine and the components of MSS, ETS, and sidestream smoke with the vasculature, it will take a great deal of time and effort to fully unravel the mechanisms by which smoking contributes to cardiovascular disease. In addition, cardiovascular risk in female smokers is complicated by hormonal variables that may contribute to greater relative risk. It is important that health care providers, educators, and policy makers recognize the changing patterns of smoking and the impact of smoking on cardiovascular disease, and continue campaigns aimed at enhancing smoking cessation in the general population and in teens. Rigorous research is needed on the changing cultural, psychosocial, and environmental factors that influence tobacco use to improve our understanding of racial/ethnic smoking patterns, and identify strategic tobacco control opportunities. The capacity of tobacco control efforts to keep pace with patterns of tobacco use and cessation depends on timely recognition of emerging prevalence and cessation patterns and the resulting development of appropriate community-based programs to address the factors involved. Smoking trends today will determine how heavy the health burden of cardiovascular disease and others will be among communities tomorrow. Programs that aim at early intervention and reflect cultural diversity will be the cornerstone in the battle against tobacco use. Continued interest in research, educational, and prevention efforts are needed to help curb the risk of cardiovascular disease from smoking in men and women.

Heart disease during pregnancy. Which cardiovascular changes reflect disease?

Primary care physicians have an important role in timely diagnosis and appropriate treatment of gravid patients with cardiac disorders. Health of the mother and child can be optimized with thorough understanding of the pathophysiology of cardiac disorders during pregnancy, especially those with potentially serious effects, such as peripartum cardiomyopathy and acute myocardial infarction. Mitral stenosis often manifests for the first time during pregnancy. Mitral valve prolapse is usually benign but in some cases necessitates antibiotic prophylaxis for delivery. Pregnancy in women with prosthetic cardiac valves may expose mother and child to risks that can be minimized with appropriate safeguards.

Heart disease during pregnancy. Which cardiovascular changes are normal or transient?

A normal, uncomplicated pregnancy causes many physiologic cardiovascular changes and symptoms. For example, maternal blood volume, heart rate, and cardiac output increase, and fatigue, orthopnea, and presyncope often occur. In general, these findings are innocuous. Physicians need to recognize those that are not typically associated with pregnancy, such as diastolic murmurs, paroxysmal nocturnal dyspnea, and syncope. Diagnostic evaluation of pregnant women must be approached cautiously to avoid risk to the fetus. Methods using ionizing radiation should be avoided whenever possible. Hypertension, one of the most common complications of pregnancy, may be transient and benign, or it may be chronic or gestational. Early recognition and intervention are beneficial to both the mother and the child.

Nicotine stimulates DNA synthesis and proliferation in vascular endothelial cells in vitro.

Nicotine is a major component of cigarette smoke and has been postulated to play an important role in atherogenesis and malignancy. Endothelial cell growth may be regulated by nicotine, yet operative mechanisms at the endothelial level are poorly understood. We studied the effects of nicotine (10(-14)-10(-4) M) on endothelial DNA synthesis, DNA repair, proliferation, and cytotoxicity by using cultures of bovine pulmonary artery endothelial cells. Assays were performed on cells incubated with nicotine in the presence and absence of hydroxyurea (an inhibitor of scheduled DNA synthesis), serum, human platelet-poor plasma, and platelet-derived growth factor and endothelial cell growth factor (PDGF and PDECGF, respectively). Nicotine significantly stimulated endothelial cell DNA synthesis and proliferation at concentrations lower than those obtained in blood after smoking (<10(-8) M). The stimulatory effects of nicotine were enhanced by serum (0.5%) and PDECGF and were blocked by the nicotinic-receptor antagonist hexamethonium. The response to nicotine was bimodal because cytotoxicity was observed at higher concentrations (>10(-6) M). This study has implications for understanding cellular mechanisms of nicotine action. The results may be important in tumor angiogenesis, atherogenesis, and vascular dysfunction in smokers.

Substance P stimulates vascular endothelial cellular reducing capacity in the presence of insulin and human plasma factors.

Substance P (SP) is an important tachykinin in vascular wall biology. In previous studies [Villablanca et al. (1994): Circ Res 75:1113-1120], the authors have demonstrated that SP is a stimulus for endothelial cell growth and proliferation in serum-free culture conditions with cell quiescent in the G0-G1 phase of the cell cycle. As mitogenic and metabolic activity may interrelate, the purpose of this study was to determine the effects of the vasoactive perivascular neuropeptide SP on changes in the metabolic function of endothelial cells, and to characterize the response, by studying cellular reducing capacity in aortic vascular endothelial cells. In addition, interactions between SP and other growth factors (insulin and non-platelet plasma factors) were investigated and compared to the responses to SP alone. Metabolic effects were determined by evaluating cellular reducing capacity by the conversion of (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) to formazan (the MTT assay). The findings demonstrated that SP alone (10 pg/ml-25 micrograms/ml) inhibited cellular reducing capacity in vascular endothelial cells. In contrast, SP in the presence of insulin (10 micrograms/ml) stimulated endothelial reducing capacity, as compared to SP alone, by twofold on average. The effect of SP and insulin was additive at < or = 0.001 microgram/ml SP, and synergistic at SP concentrations ranging within 0.01-1.0 microgram/ml. SP in the presence of human platelet-poor plasma (HPPP, 5%) stimulated endothelial reducing capacity, as compared to SP alone, by threefold on average. The effect of SP and HPPP was additive at < or = 0.01 microgram/ml SP and synergistic at SP concentrations of 0.1-25 micrograms/ml. Lastly, SP in the presence of insulin and HPPP stimulated endothelial metabolic activity, as compared to SP alone, by 14-fold on average. An additive response to SP, insulin, and HPPP was observed at the lowest SP concentration studied (10 pg/ml). At all other SP concentrations studied (0.0001-25 micrograms/ml), the responses to insulin, HPPP, and SP were synergistic. Our studies indicate that the vasoactive neuropeptide substance P may synergize with insulin and HPPP in regulating endothelial cell metabolism. In addition, our findings suggest that the mechanisms by which SP stimulates cellular metabolism are different from the mechanisms by which it stimulates cell growth.

Inducible receptors.

While regulation of receptor function is known to occur at many levels (e.g. transcriptional, post-translational), it is generally perceived that a tissue either expresses or does not express a particular receptor in an all-or-none fashion. Many pathological (e.g. tissue injury) and physiological (e.g. angiogenesis) processes have, however, been shown to be associated with the transcriptional induction of specific receptors. Induced receptors are not confined to any particular class, but range from G protein-coupled receptors to receptor tyrosine kinases. The potential implications of de novo receptor expression are profound with respect to potential novel therapeutic targets in specific disease states. Further, this observation may explain unexpected side-effects in the pharmacotherapy of existing disease states. In this article Lucy Donaldson, Michael Hanley and Amparo Villablanca discuss circumstances under which de novo receptor induction has been described, potential mechanisms of induction and the implications for pharmacology.

17beta-estradiol stimulates substance P receptor gene expression.

The actions of substance P (SP), a widely distributed tachykinin neuropeptide, are mediated by the NK1 receptor, a seven trans-membrane spanning domain cell surface receptor coupled to heterotrimeric G-proteins. SP regulates cellular processes in the CNS, placenta and vasculature including permeability, inflammation, mitogenesis and transformation. Examples of sexual dimorphism in tissue distribution and expression of SP and the SP receptor (SPR) in various organ systems (breast, uterus, brain) suggest the SPR may be under hormonal control. Using Northern blot analysis of SPR mRNA levels, we studied the effects of 17beta-estradiol (E2) on SPR gene expression in AR42J (rat pancreatic acinar) cells which constitutively express high levels of SPR. E2 (100 nM) led to a 2.5-fold increase in SPR mRNA levels (4.7 kb band) which was time- and concentration-dependent. The increase was inhibited by the RNA polymerase inhibitor actinomycin D (5 microg/ml) but not by the translational inhibitor cycloheximide (10 microg/ml). In addition, the antiestrogen tamoxifen (1 microM) blocked the stimulatory effect of E2 on SPR mRNA. Increased SPR mRNA levels in response to E2 were linearly related to increased [3H]SP binding to the SPR. This study has implications for understanding molecular mechanisms of hormonal control of receptor gene expression.

Coronary heart disease in women. Gender differences and effects of menopause.

Gender differences in coronary heart disease (CHD) are significant, not only with regard to mortality and morbidity but in the presentation, course, diagnosis, and treatment of CHD. To date, however, little research specific to women has been done. Until the results of ongoing and future studies become available, women and their physicians will have to rely on observational epidemiologic data to guide management decisions. While the current state of incomplete knowledge may make physicians uncomfortable about dealing with CHD in women, failure to act will only continue to result in the death of some 500,000 women annually. Therefore, it is incumbent on all healthcare professionals to reevaluate their approach to CHD in women and to place greater emphasis on more timely diagnosis and appropriate treatment. An understanding of gender differences in CHD, together with new data from current and future investigative studies, should lead to improved outcomes for women with CHD.

Substance P increases microvascular permeability via nitric oxide-mediated convective pathways.

The goal of these studies was to examine the effects of substance P, a tachykinin neuropeptide, on pathways of microvascular permeability. Individual frog mesenteric venular capillaries were cannulated, and albumin apparent permeability coefficients (Ps) were determined by quantitative fluorescence microscopy. Ps of albumin (PsAlb) rose from 6.8 +/- 1.8 (SE) cm.s-1.10(7) at control to 22.3 +/- 2.3 cm.s-1.10(7) when substance P (10(-11) M) was perfused. The effect of increased microvessel permeability induced by substance P (10(-11) M) was blocked with the nonpeptide substance P receptor antagonist CP-96,345 and NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. PsAlb increased 0.99 cm.s-1.10(7) for every cmH2O increase in microvessel pressure after treatment of the vessel with substance P, demonstrating coupling of albumin flux to transvascular water flow. In conclusion, the mechanism of increased microvessel permeability in response to substance P appears to be the result of receptor-mediated increase in nitric oxide production and formation of water-filled convective pathways presumably located between adjacent endothelial cells.

Growth-promoting effects of substance P on endothelial cells in vitro. Synergism with calcitonin gene-related peptide, insulin, and plasma factors.

The purpose of this study was to determine the effects of the vasoactive perivascular neuropeptide substance P (SP) on the growth and function of vascular endothelial cells in serum-free culture conditions with cells quiescent in the G0-G1 phase of the cell cycle and to characterize the response. In addition, interactions between SP and other growth factors and neuropeptides including insulin, platelet factors, neurokinin A, neurokinin B, and calcitonin gene-related peptide (CGRP) were studied on endothelial cell growth and compared. Growth effects were determined by stimulation of tritiated thymidine incorporation into DNA and cell proliferation. SP exhibited differential effects on cell growth that were a function of concentration, incubation time, interaction with other growth factors, and cell culture conditions. DNA synthesis in response to SP showed a bell-shaped distribution with a maximal effect that was 10.5-fold over control at 500 micrograms/mL of SP after 48 hours of incubation. The effect showed marked synergism with insulin (10 micrograms/mL) and with CGRP (0.01 to 10 micrograms/mL), which is colocalized with SP in vivo. Insulin and CGRP alone had no significant effect on endothelial cell growth. Furthermore, no synergism was observed between SP and platelet-derived growth factor or platelet-derived endothelial cell growth factor. Endothelial cell proliferation increased in response to SP to 2.6-fold over control at 48 hours, was maximal at 10 micrograms/mL SP, and also demonstrated synergism with insulin (10 micrograms/mL). Our studies indicate that neuropeptides play a significant role in regulating endothelial cell growth and proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchial vasodilation by histamine in sheep: characterization of receptor subtype.

Histamine has been shown to mediate features of pulmonary allergic reactions including increased tracheobronchial blood flow. To determine whether the increase in blood flow was due to stimulation of H1- or H2-histamine receptors, we gave histamine base (0.1 micrograms/kg iv) or histamine dihydrochloride as an aerosol (10 breaths of 0.5% "low dose" or 5% "high dose") before and after H1- or H2-receptor antagonists. Blood velocity in the common bronchial branch of the bronchoesophageal artery (Vbr) was continuously measured using a chronically implanted Doppler flow probe. Pretreatment with H2-receptor antagonists cimetidine, ranitidine, or metiamide did not affect the increase in Vbr induced by intravenous histamine [106 +/- 45% (SD)]. Addition of the H1-receptor antagonists diphenhydramine or chlorpheniramine, however, reduced the Vbr response to 16 +/- 22, 21 +/- 28, 23 +/- 23, and 37 +/- 32% of the unblocked responses (P less than 0.05) when intravenous histamine was given at 3, 10, 20, and 30 min, respectively, after the H1 antagonist. At 40, 50, and 60 min the H1-receptor blockade appeared to attenuate, but subsequent continuous infusion of chlorpheniramine (2 mg.kg-1.min-1) then blocked the histamine response for 60 min. Low-dose histamine aerosol did not change mean arterial or pulmonary arterial pressures, cardiac output, or arterial blood gases but increased Vbr transiently from 15.2 +/- 3.4 to 37.6 +/- 8.4 (SE) cm/s. After chlorpheniramine, the Vbr response to histamine, 16.3 +/- 2.2 to 22.6 +/- 3.6 cm/s, was significantly reduced (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)