Browsing by Author "Campino, C."

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    Central Obesity and the Metabolic Syndrome Are Associated with Portal and Not Systemic Hypercortisolism Supported by the Raise of Urinary Corticosteroid Metabolites
    (2010) Baudrand, R.; Campino, C.; Carvajal, C. A.; Olivieri, O.; Guidi, G.; Faccini, G.; Pasini, F.; Sateler, J.; Cornejo, J.; San Martin, B.; Dominguez, J. M.; Mosso, L. M.; Owen, G.; Kalergis, A. M.; Fardella, C.; NCD Risk Factor Collaboration (NCD-RisC)
    Background: There is paucity of information about bone metabolism during pregnancy or breast feeding in teenagers. Aim: To study bone turnover at the end of pregnancy and during breast feeding in teenagers and correlate it with environmental, hormonal or nutritional variables. Subjects and methods: Thirty teenagers during their breast feeding period after a first pregnancy and 30 nulliparous girls matched for age, age of menarche and body mass index were assessed three weeks after delivery (period 1), at six months of breast feeding (period 2) and one year after the lactating period (period 3). Calcium intake and plasma calcium, phosphorus, alkaline phosphatases, parathormone, estradiol and prolactin were measured. Calcium, creatinine and hydroxypyroline were also measured in a morning urine samples. Results: Lactating and control girls were aged 16.3+/-0.8 and 16.1+/-0.7 years old respectively. Calcium intake in lactating and control girls was 798+/-421 and 640+/-346 g/day respectively in period 1, 612+/-352 and 592+/-309 mg/day in period 2 and 495+/-180 and 456+/-157 g/day in period 3. During periods 1 and 2, lactating girls had higher alkaline phosphatases (161+/-37 compared to 119+/-28 U/l and 149+/-37 compared to 106+/-23 U/l), parathormone (4.3+/-2.6 compared to 2/8+/-0.8 ng/dl and 3.6+/-1.6 compared to 3.0+/-0.9 ng/dl) and urinary hydroxyproline (95+/-16 compared to 63+/-15 mg/g creatinine and 84+/-19 compared to 59+/-15 mg/g creatinine). No differences were observed in period 3. No correlation between bone turnover variables, body mass index or hormonal parameters, was observed. Conclusions: In teenagers, there is an increase in bone turnover at the end of pregnancy, that persists during the lactating period. These changes are not relaxed to nutritional or hormonal variables.
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    Immune System Alterations by Aldosterone During Hypertension: From Clinical Observations to Genomic and Non-Genomic Mechanisms Leading to Vascular Damage
    (2013) Munoz-Durango, N.; Barake, M. F.; Letelier, N. A.; Campino, C.; Fardella, C. E.; Kalergis, A. M.
    Hypertension is traditionally considered a disease in which elevated blood pressure contributes to inflammation and activation of the immune system, leading to cardiovascular injury and end-organ damage. Here, we discuss the effects of aldosterone on the immune system and aldosterone's contribution to vascular pathogenesis. Studies in human have suggested a broader role for aldosterone, beyond elevating blood pressure. Recent clinical data support the notion that aldosterone can directly alter the function of the immune system and cause vascular-damaging inflammation. Clinical observations have been reproduced in experimental models of hypertension, further supporting the idea that an aberrant immune response contributes to the onset of hypertension. Such studies have shown that myeloid cells are required to induce the disease and IL-17-producing CD4(+) T cells may contribute to maintaining aldosterone-mediated hypertension. In addition, regulatory T cells diminish the inflammatory damage caused by aldosterone during hypertension. This is a very active area of research that could lead to new therapeutic targets for treating hypertension.
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    New splicing mutation of MEN1 gene affecting the translocation of menin to the nucleous
    (2006) Tala, H. P.; Carvajal, C. A.; Gonzalez, A. A.; Garrido, J. L.; Tobar, J.; Solar, A.; Campino, C.; Arteaga, E.; Fardella, C. E.
    Multiple endocrine neoplasia type 1 (MEN1) is a syndrome inherited in an autosomal dominant trait caused by the inactivation of the tumor suppressor gene MEN1. Objective: To communicate a family with a new heterozygous germ line mutation in the intronic region of MEN1 gene and to study its influence in the menin expression. Patients and Methods: We studied 5 members of a family with symptomatic hyperparathyroidism (HIPT). One of them had also a neuroendocrine pancreatic tumor, and 2 had non-functional multinodular cortical adrenal hyperplasia compatible with the diagnosis of MEN1. After the mutation was identified, HSP9211 restriction enzyme was used to determine both zygosity and segregation of the mutation. RT-PCR from leukocyte's isolated mRNA and western blot from pancreatic tumor tissue were performed. In vitro studies were done in Chinese hamster ovary (CHO) cells transfected with reporter minigenes carrying the coding regions spanning exon (EX)-intron 9 and EX10 with the mutant and the wild type sequences. Results: We identified a heterozygous G-to-T substitution in the intron-EX junction (IVS9-1 G > T) of MEN1 gene in the index case and the family members. The mRNA from patient's leukocytes was larger (934 bp) in comparison to the normal transcript (717 bp). Immunoblot analysis demonstrated that wild type (67 kDa) and two additional mutant proteins (similar to 55 and similar to 90 kDa) were expressed in the pancreatic tissue. The in vitro study showed a 45% nuclear localization of the mutated menin signal and a 95% in the wild type protein. Conclusions: We identified a new intronic heterozygous germ line mutation (IVS9-1G > T) of MEN1 gene in a family affected by MEN1 syndrome. This mutation alters the splice acceptor site of intron 9 that promotes an incorrect splicing, generating aberrant proteins without the nuclear localization signals necessary for the normal menin translocation to the nucleus.
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    Visceral Hypercortisolism Observed in Central Obesity and Metabolic Syndrome Is Associated with Insulin Resistance and Beta Cell Dysfunction.
    (2010) Baudrand, R.; Campino, C.; Carvajal, C. A.; Olivieri, O.; Guidi, G.; Faccini, G.; Pasini, F.; Sateler, J.; Cornejo, J.; San Martin, B.; Dominguez, J. M.; Tabilo, C.; Mosso, L. M.; Owen, G.; Kalergis, A. M.; Fardella, C.
    There is evidence that primary aldosteronism (PA) may be common in patients with essential hypertension (EH) when determinations of serum aldosterone (SA), plasma renin activity(PRA), and the SA/PRA ratio are used as screening. An inherited form of primary hyperaldosteronism is the glucocorticoid-remediable aldosteronism (GRA) caused by an unequal crossing over between the CYP11B1 and CYP11B2 genes that results in a chimeric gene, which has aldosterone synthase activity regulated by ACTH. The aim of this study was to evaluate the prevalence of PA and the GRA in 305 EH patients and 205 normotensive controls. We measured SA (1-16 ng/dL) and PRA (1-2.5 ng/mL . h) and calculated the SA/PRA ratio in all patients. A SA/PRA ratio level greater than 25 was defined as being elevated. PA was diagnosed in the presence of high SA levels (>16 ng/dL), low PRA levels (<0.5 ng/mL . h), and very high SA/PRA ratio (>50). Probable PA was diagnosed when the SA/PRA ratio was more than 25 but the other criteria were not present. A Fludrocortisone test was done to confirm the diagnosis. GRA was differentiated from other forms of PA by: the aldosterone suppression test with dexamethasone, the high levels of 18-hydroxycortisol, and the genetic detection of the chimeric gene. In EH patients, 29 of 305 (9.5%) had PA, 13 of 29 met all the criteria for PA, and 16 of 29 were initially diagnosed as having a probable PA and confirmed by the fludrocortisone test. Plasma potassium was normal in all patients. The dexamethasone suppression test was positive for GRA in 10 of 29 and 18-hydroxycortisol levels were high in 2 of 29 patients who had also a chimeric gene. In normotensive subjects, 3 of 205 (1.46%) had PA, and 1 of 205 had a GRA. In summary, we found a high frequency of normokalemic PA in EH patients. A high proportion of PA suppressed SA with dexamethasone, but only a few had a chimeric gene or high levels of 18-hydroxycortisol. These results emphasize the need to further investigate EH patients.