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1.
Horm Metab Res ; 47(13): 947-52, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26610199

ABSTRACT

Bilateral adrenal hyperplasia currently accounts for up to 2 thirds of cases of primary aldosteronism. As such, it represents a major opportunity for targeted medical management as opposed to unilateral surgically correctable forms of the disease. Although the majority of cases of primary aldosteronism are sporadic, bilateral adrenal hyperplasia may occur in the context of familial hyperaldosteronism where it is associated with specific germline mutations. Over the past 5 years, impressive progress has been made in our understanding of the genetic basis underlying primary aldosteronism, allowing us to identify and characterize new familial forms of the disease and to understand the mechanisms involved in the formation of aldosterone producing adenoma. In contrast, our knowledge of the genetic contribution to the development of bilateral adrenal hyperplasia, and in a larger context, to renin and aldosterone levels in the general population, is still poor. This review summarizes our current knowledge on the genetics of bilateral adrenal hyperplasia and addresses some open questions to be addressed by future research. In particular, genome-wide association studies in large populations may provide clues to understanding the genetic susceptibility underlying the development of primary aldosteronism.


Subject(s)
Adrenal Glands/pathology , Adrenogenital Syndrome/genetics , Genetic Predisposition to Disease , Germ-Line Mutation , Humans , Hyperaldosteronism/genetics , Hyperplasia
2.
Mol Cell Endocrinol ; 408: 198-204, 2015 Jun 15.
Article in English | MEDLINE | ID: mdl-25433205

ABSTRACT

Serotonin (5-hydroxytryptamine; 5-HT) is able to activate the hypothalamo-pituitary-adrenal axis via multiple actions at different levels. In the human adrenal gland, 5-HT, released by subcapsular mast cells, stimulates corticosteroid production through a paracrine mode of communication which involves 5-HT receptor type 4 (5-HT4) primarily located in zona glomerulosa. As a result, 5-HT is much more efficient to stimulate aldosterone secretion than cortisol release in vitro and administration of 5-HT4 receptor agonists to healthy individuals is followed by an increase in plasma aldosterone levels without any change in plasma cortisol concentrations. Interestingly, adrenocortical hyperplasias and tumors responsible for corticosteroid hypersecretion exhibit various cellular and molecular defects which tend to reinforce the intraadrenal serotonergic tone. These pathophysiological mechanisms, which are summarized in the present review, include an increase in adrenal 5-HT production and overexpression of 5-HT receptors in adrenal neoplastic tissues. Altogether, these data support the concept of adrenal serotonergic paracrinopathy and suggest that 5-HT and its receptors may constitute valuable targets for pharmacological treatments of primary adrenal diseases.


Subject(s)
Adrenal Cortex Neoplasms/drug therapy , Paracrine Communication/drug effects , Serotonin/pharmacology , Serotonin/therapeutic use , Steroids/biosynthesis , Animals , Humans , Hyperplasia , Models, Biological
3.
Ann Cardiol Angeiol (Paris) ; 63(3): 213-5, 2014 Jun.
Article in French | MEDLINE | ID: mdl-24952675

ABSTRACT

Itraconazole is a triazole agent used in the treatment of fungal infections and in some metastatic cancers. Its use has been associated with cardiovascular adverse events and particularly heart failure with preserved ejection fraction. We report the case of a 68-year-old male patient with a well-controlled hypertension treated with irbesartan 150mg/day since 2007. He developed a pulmonary aspergillosis on post-tuberculosis cavitary lesions treated in July 2011 with itraconazole 200mg/day. Early 2012, his antihypertensive treatment had to be gradually increased to a quadritherapy and his blood pressure was at 157/78mmHg at home. Hypokalemia was observed on several occasions as well as edema of the lower limbs. Plasma renin and plasma and urine aldosterone concentrations on treatment not interfering with the renin angiotensin system were low, associated with normal serum and urine cortisol, ACTH, SDHA and DOC, BNP and creatinine concentrations. Plasma itraconazole values were much above the therapeutic range. Left ventricular ejection fraction was preserved. There were no adrenal or renal artery abnormalities at the CT scan. Three months after stopping itraconazole, hypokalemia and edema disappeared and blood pressure was normalized with less treatment. Plasma renin and aldosterone concentrations were normalized. He had a pulmonary lobectomy for his pulmonary aspergillosis. Itraconazole may induce a resistant hypertension with low renin. The mechanisms of this adverse effect of itraconazole remain unknown.


Subject(s)
Antifungal Agents/adverse effects , Hypertension/chemically induced , Itraconazole/adverse effects , Aged , Antifungal Agents/administration & dosage , Humans , Itraconazole/administration & dosage , Male , Pulmonary Aspergillosis/drug therapy , Withholding Treatment
5.
J Endocrinol Invest ; 33(7): 472-7, 2010.
Article in English | MEDLINE | ID: mdl-19955850

ABSTRACT

BACKGROUND/AIMS: Aldosterone and the mineralocorticoid receptor (MR) play a major role in sodium balance and blood pressure control. They are also involved in adipocyte metabolism. The aim of this study was to analyze the association between the MR p.I180V polymorphism with hypertension and markers of cardiovascular risk. DESIGN AND METHODS: Case-control study nested within a cohort of 2063 subjects followed since birth to date. All subjects (age 23-25 yr old) from the entire cohort with systolic and diastolic hypertension (no.=126) were paired with 398 normotensive controls. MR p.I180V genotype association with anthropometric and biochemical markers of cardiometabolic risk was tested. RESULTS: There was a significant association of the MR p.I180V genotype with body mass index (BMI) and LDL-cholesterol level (p<0.01). Hypertensive subjects carrying the polymorphic G allele (AG or GG genotypes) presented significantly higher BMI (30.0+/-6.0 vs 28.7+/-5.6 kg/m(2); p<0.01) and higher LDL-cholesterol (139.9+/-60.3 vs 109.9+/-35.5 mg/dl; p<0.01). The frequency of the polymorphism MR p.I180V was similar between hypertensive subjects and controls (p=0.15). CONCLUSIONS: The MR p.I180V polymorphism seems to be associated with cardiovascular risk factors including BMI and LDL-cholesterol levels. This original in vivo finding reinforces the role of MR in adipocyte biology and in cardiovascular disease.


Subject(s)
Body Mass Index , Cholesterol, LDL/blood , Hypertension/genetics , Receptors, Mineralocorticoid/genetics , Adult , Case-Control Studies , Cohort Studies , Female , Gene Frequency , Humans , Hypertension/blood , Male , Polymorphism, Genetic , Risk Factors
6.
Environ Technol ; 29(11): 1149-55, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18975847

ABSTRACT

The composting of green waste is currently of great importance to the waste industry. For this reason, large-scale compost windrows were investigated and the results compared with those from small, bench-scale experiments. In the two windrows sampled, temperature profiles differed, and greater organic matter loss was observed in the higher temperature windrow. However, enhanced organic matter degradation through elevated temperatures was not supported in the bench-scale experiment, where, under fixed temperatures (30 and 50 degrees C, respectively), no difference in both the total dry and organic matter content was observed. Analysis of particle size distributions in both sets of experiments strongly suggested that moisture-dependent effects were a confounding factor in determining the total LOI of the windrows. Analysis of beta-glucosidase activity in the bench-scale samples demonstrated that it was the assay temperature, rather than the in situ composting temperature, which was more important in determining the level of activity. No evidence for adaptation to local maxima due to variation in the thermal environment was observed.


Subject(s)
Refuse Disposal/methods , Soil/analysis , Biodegradation, Environmental , Temperature , Water , beta-Glucosidase/metabolism
7.
Climacteric ; 11(3): 258-64, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18568791

ABSTRACT

Beside their role in the control of water and electrolyte homeostasis, recent data clearly indicate that aldosterone and the mineralocorticoid receptor (MR) are involved in adipocyte biology. It has been recently shown that aldosterone promotes white and brown adipocyte differentiation in vitro through specific activation of the MR. In addition, a non-epithelial pro-inflammatory role for MR activation has been recently inferred from studies on mineralocorticoid/salt administration in experimental animal models and from clinical studies. The mineralocorticoid system could hence represent a potential target for new therapeutic strategies in obesity and the metabolic syndrome. Progesterone has high affinity for the MR and is a natural antagonist of aldosterone. Differently from classic synthetic progestins, which are devoid of antimineralocorticoid properties, progesterone and new progestogens show remarkable antimineralocorticoid effects. Here, we discuss the potential role of the antimineralocorticoid properties of progestogens in the control of body weight, adipose tissue proliferation and salt sensitivity; their therapeutic use in postmenopausal women, as well as in women affected by polycystic ovary syndrome, may open new and unexpected possibilities in the treatment of related metabolic disorders.


Subject(s)
Adipose Tissue/drug effects , Progestins/pharmacology , Receptors, Mineralocorticoid , Sodium Chloride, Dietary/adverse effects , Water-Electrolyte Balance/drug effects , Adipose Tissue/metabolism , Animals , Cell Differentiation/drug effects , Female , Humans , Metabolic Syndrome/drug therapy , Mineralocorticoid Receptor Antagonists/pharmacology , Obesity/drug therapy , Progestins/physiology , Receptors, Mineralocorticoid/drug effects , Receptors, Mineralocorticoid/metabolism , Water-Electrolyte Balance/physiology
10.
J Mol Endocrinol ; 33(3): 679-91, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15591027

ABSTRACT

The pituitary hormone prolactin (PRL) exerts pleiotropic effects, which are mediated by a membrane receptor (PRLR) present in numerous cell types including adipocytes. Brown adipose tissue (BAT) expresses uncoupling proteins (UCPs), involved in thermogenesis, but also secretes leptin, a key hormone involved in the control of body weight. To investigate PRL effects on BAT, we used the T37i brown adipose cell line, and demonstrated that PRLRs are expressed as a function of cell differentiation. Addition of PRL leads to activation of the JAK/STAT and MAP kinase signaling pathways, demonstrating that PRLRs are functional in these cells. Basal and catecholamine-induced UCP1 expression were not affected by PRL. However, PRL combined with insulin significantly increases leptin expression and release, indicating that PRL potentiates the stimulatory effect of insulin as revealed by the recruitment of insulin receptor substrates and the activation of phosphatidylinositol 3-kinase. To explore the in vivo physiological relevance of PRL action in BAT, we showed that leptin content was significantly increased in BAT of PRLR-null mice compared with wild-type mice, highlighting the involvement of PRL in the leptin secretion process. This study provides the first evidence for a functional link between PRL and energy balance via a cross-talk between insulin and PRL signaling pathways in brown adipocytes.


Subject(s)
Adipocytes/drug effects , Adipocytes/metabolism , Adipose Tissue, Brown/drug effects , Gene Expression Regulation/drug effects , Insulin/pharmacology , Leptin/metabolism , Prolactin/pharmacology , Adipocytes/cytology , Adipose Tissue, Brown/cytology , Adipose Tissue, Brown/metabolism , Animals , Carrier Proteins/metabolism , Cell Differentiation , Cell Line , DNA-Binding Proteins/metabolism , Ion Channels , Janus Kinase 2 , Membrane Proteins/metabolism , Mice , Mice, Knockout , Milk Proteins/metabolism , Mitochondrial Proteins , Mitogen-Activated Protein Kinases/metabolism , Protein Binding , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Receptors, Leptin , Receptors, Prolactin/deficiency , Receptors, Prolactin/genetics , Receptors, Prolactin/metabolism , STAT3 Transcription Factor , STAT5 Transcription Factor , Signal Transduction/drug effects , Trans-Activators/metabolism , Transcription, Genetic/genetics , Uncoupling Protein 1
11.
Int J Cardiol ; 97(3): 383-8, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15561322

ABSTRACT

OBJECTIVES: The study was designed to test whether or not the angiotensin II receptor blocker telmisartan brings about regression of left ventricular (LV) concentric hypertrophy and whether or not these changes are associated with improved diastolic filling. METHODS: An echocardiographic follow-up study was performed in 85 hypertensive patients (systolic blood pressure [SBP] >140 mmHg, diastolic blood pressure [DBP] >90 mmHg) and mild-to-moderate LV hypertrophy (LV mass index related to body surface area [LVMI] 117-150 g/m2 for men and 105-150 g/m2 for women) treated with telmisartan monotherapy 40-80 mg once daily for 1 year. Blood pressure, LVMI, left atrial (LA) volumes, and diastolic function were determined at baseline and after 3, 6, 9, and 12 months of treatment. Blood pressure was also monitored at all visits. Diastolic function was assessed by examination of transmitral inflow and pulmonary vein flow patterns. RESULTS: Telmisartan reduced blood pressure; after 12 months, the mean+/-S.D. SBP and DBP were reduced from 144+/-10 to 126+/-8 mmHg (p<0.001) and from 98+/-8 to 86+/-7 mmHg (p<0.001), respectively. The LVMI was decreased from 119+/-7 to 109+/-3 g/m2 (p<0.001) after 12 months' telmisartan treatment. All patients had diastolic dysfunction at baseline. After 12 months' telmisartan treatment, a normal pattern of transmitral inflow was present in 21% of patients. The regression of LV hypertrophy observed after 12 months was associated with increased peak early diastolic velocity/peak late diastolic velocity ratio from 0.60+/-0.18 to 0.83+/-0.20 (p<0.001), shortened isovolumic relaxation time (IVRT) from 110+/-13 to 105+/-13 ms (p<0.001), and decreased deceleration time from 229+/-30 to 215+/-28 ms (p=0.002). Univariate analysis showed that shortened IVRT was related to a reduction in the LVMI and LA maximal and minimal volumes. In the multivariate analysis, the reduction in LVMI and the reduction in LA maximal and minimal volumes were independently associated with IVRT reduction. CONCLUSIONS: Telmisartan 40-80 mg is effective in LV hypertrophy regression in hypertensive patients. The reduction in LVMI due to telmisartan monotherapy was associated with a significant improvement of diastolic filling parameters and with a significant reduction of LA volumes.


Subject(s)
Benzimidazoles/therapeutic use , Benzoates/therapeutic use , Hypertrophy, Left Ventricular/drug therapy , Benzimidazoles/administration & dosage , Benzoates/administration & dosage , Diastole/drug effects , Diastole/physiology , Female , Humans , Hypertrophy, Left Ventricular/diagnostic imaging , Male , Prospective Studies , Systole/drug effects , Systole/physiology , Telmisartan , Ultrasonography
12.
Mol Cell Endocrinol ; 217(1-2): 119-25, 2004 Mar 31.
Article in English | MEDLINE | ID: mdl-15134810

ABSTRACT

Type I pseudohypoaldosteronism (PHA1) is a rare form of mineralocorticoid resistance characterized by neonatal renal salt wasting and failure to thrive. Typical biochemical features include high levels of plasma aldosterone and renin, hyponatremia and hyperkalemia. Different mutations of the human mineralocorticoid receptor (hMR) gene have been identified in subjects affected by the autosomal dominant or sporadic form of the disease. Our laboratory has investigated a large number of subjects with familial and sporadic PHA1. Several different mutations have been detected, which are localized in different coding exons of the hMR gene. These mutations either create truncated proteins, either affect specific amino acids involved in receptor function. In this paper, we review hMR mutations described to date in PHA1 and their functional characterization. We discuss the absence of mutations in some kindreds and the role of precise phenotypic and biological examination of patients to allow for identification of other genes potentially involved in the disease.


Subject(s)
Exons/genetics , Mutation , Pseudohypoaldosteronism/genetics , Receptors, Mineralocorticoid/genetics , Aldosterone/blood , Genes, Dominant/genetics , Humans , Hypokalemia/genetics , Hypokalemia/physiopathology , Hyponatremia/genetics , Hyponatremia/physiopathology , Kidney/physiopathology , Mineralocorticoids/metabolism , Pedigree , Predictive Value of Tests , Pseudohypoaldosteronism/blood , Pseudohypoaldosteronism/congenital , Pseudohypoaldosteronism/physiopathology , Receptors, Mineralocorticoid/metabolism , Renin/blood , Salts/metabolism
13.
Minerva Cardioangiol ; 50(4): 383-8, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12147971

ABSTRACT

The first case of combined procedure of catheter-based balloon pulmonary valvuloplasty and atrial septal defect closure using Amplatzer Septal Occluder, in a patient with Noonan syndrome, is reported. The literature regarding prevalence, genetics, pattern of involvement, symptoms, diagnosis, and treatment of this syndrome is reviewed.


Subject(s)
Angioplasty, Balloon , Cardiac Catheterization , Heart Septal Defects, Atrial/therapy , Noonan Syndrome/therapy , Pulmonary Valve Stenosis/therapy , Female , Humans , Middle Aged
14.
Minerva Cardioangiol ; 50(1): 69-73, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11830721

ABSTRACT

A case of endoluminal repair of vein and artery axillary rupture after reduction of shoulder dislocation in an 83-year-old woman is reported. The lesions were repaired successfully with two cover stents (JOSTENT and Passager). Endovascular treatment of such vascular injuries seems to be feasible and safe, though further investigation is warranted.


Subject(s)
Angioplasty , Axillary Artery/injuries , Axillary Artery/surgery , Axillary Vein/injuries , Axillary Vein/surgery , Shoulder Dislocation/complications , Aged , Aged, 80 and over , Female , Humans
15.
Minerva Cardioangiol ; 49(6): 369-76, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11733731

ABSTRACT

BACKGROUND: Patent ductus arteriosus (PDA) is the second most common congenital heart disease. A large number of surgical and transcatheter techniques for the interruption or closure of PDA has been reported. The aim of this study was to assess the immediate and short-term results of transcatheter closure of PDA using the new, self-expandable, self-centering, and repositionable Amplatzer Duct Occluder device. METHODS: We attempted occlusion of PDA with the Amplatzer Duct Occluder in seven consecutive patients, one child and six adults, four females and three males, between September 1999 and January 30th 2000. All PDAs but one were approached from the femoral venous site; the Amplatzer Duct Occluder size was selected in order to be 2 mm larger than the duct's diameter at its narrowest site and the mean PDA diameter was 5.4+/-2.5 mm (range 3-9). All patients underwent physical examination, chest X-ray and echocardiography within 48 hours and on first and third month after PDA occlusion. RESULTS: Four patients had a megaphone type (type A), and three had an elongated, conical type (type E) PDA. Four patients had immediate, complete angiographic closure of the ductus 10 minutes after the procedure, one had a trace shunt and two had small shunts which all disappeared within 48 hours. The average fluoroscopy time and procedural time were 34.4+/-10.6 min (range 21-50) and 105+/-38.9 min (range 75-190) respectively. There were no complications at follow-up. CONCLUSIONS: Transcatheter closure of PDA using the new Amplatzer Duct Occluder is an easy and effective technique. Moreover it is safe even in the presence of wide PDAs.


Subject(s)
Ductus Arteriosus, Patent/therapy , Adolescent , Adult , Aged , Cardiac Catheterization , Cardiology/instrumentation , Equipment Design , Female , Follow-Up Studies , Humans , Male , Middle Aged
18.
J Biol Chem ; 276(42): 38911-20, 2001 Oct 19.
Article in English | MEDLINE | ID: mdl-11495902

ABSTRACT

The mineralocorticoid receptor (MR), a ligand-dependent transcription factor, mediates aldosterone actions in a large variety of tissues. To explore the functional implication of MR in pathophysiology, transgenic mouse models were generated using the proximal human MR (hMR) promoter to drive expression of hMR in aldosterone target tissues. Tissue-specific analysis of transgene expression in two independent transgenic animal (TG) lines by ribonuclease protection assays revealed that hMR is expressed in all mineralocorticoid-sensitive tissues, most notably in the kidney and the heart. TG exhibit both renal and cardiac abnormalities. Enlarged kidneys were histologically associated with renal tubular dilation and cellular vacuolization whose prevalence increased with aging. Renal clearance studies also disclosed a significant decrease in urinary potassium excretion rate in TG. hMR-expressing animals had normal blood pressure but developed mild dilated cardiomyopathy (increased left ventricle diameters and decreased shortening fraction), which was accompanied by a significant increase in heart rate. Differential gene expression analysis revealed a 2- to 5-fold increase in cardiac expression of atrial natriuretic peptide, serum- and glucocorticoid-induced kinase, and early growth response gene 1 as detected by microarrays; renal serum- and glucocorticoid-induced kinase was also induced significantly. Altogether, TG exhibited specific alteration of renal and cardiac functions, thus providing useful pathophysiological models to gain new insights into the tissue-specific mineralocorticoid signaling pathways.


Subject(s)
Heart/physiology , Immediate-Early Proteins , Kidney/physiology , Mice, Transgenic , Nuclear Proteins , Receptors, Mineralocorticoid/biosynthesis , Animals , Blotting, Northern , DNA, Complementary/metabolism , DNA-Binding Proteins/biosynthesis , Early Growth Response Protein 1 , Humans , Kidney/metabolism , Male , Mice , Models, Genetic , Myocardium/metabolism , Oligonucleotide Array Sequence Analysis , Promoter Regions, Genetic , Protein Serine-Threonine Kinases/biosynthesis , Receptors, Mineralocorticoid/genetics , Recombinant Proteins/metabolism , Signal Transduction , Sodium-Potassium-Exchanging ATPase/biosynthesis , Time Factors , Tissue Distribution , Transcription Factors/biosynthesis
19.
Mol Endocrinol ; 15(9): 1586-98, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11518808

ABSTRACT

Aldosterone effects are mediated by the MR, which possesses the same affinity for mineralocorticoids and glucocorticoids. In addition to the existence of mechanisms regulating intracellular hormone availability, we searched for human MR splice variants involved in tissue-specific corticosteroid function. We have identified a new human MR isoform, hMRDelta5,6, resulting from an alternative splicing event skipping exons 5 and 6 of the human MR gene. hMRDelta5,6 mRNAs are expressed in several human tissues at different levels compared with wild-type human MR, as shown by real time PCR. Introduction of a premature stop codon results in a 75-kDa protein lacking the entire hinge region and ligand binding domain. Interestingly, hMRDelta5,6 is still capable of binding to DNA and acts as a ligand-independent transactivator, with maximal transcriptional induction corresponding to approximately 30-40% of aldosterone-activated wild-type human MR. Coexpression of hMRDelta5,6 with human MR or human GR increases their transactivation potential at high doses of hormone. Finally, hMRDelta5,6 is able to recruit the coactivators, steroid receptor coactivator 1, receptor interacting protein 140, and transcription intermediary factor 1alpha, which enhance its transcriptional activity. Ligand-independent transactivation and enhancement of both wild-type MR and GR activities by hMRDelta5,6 suggests that this new variant might play a role in modulating corticosteroid effects in target tissues.


Subject(s)
Adrenal Cortex Hormones/metabolism , Alternative Splicing/genetics , Receptors, Mineralocorticoid/genetics , Trans-Activators/genetics , Amino Acid Sequence , Animals , Base Sequence , Cells, Cultured , Humans , Molecular Sequence Data , Protein Isoforms , Rabbits , Receptors, Mineralocorticoid/metabolism , Trans-Activators/metabolism , Transcription, Genetic/genetics
20.
Cardiovasc Intervent Radiol ; 24(2): 111-2, 2001.
Article in English | MEDLINE | ID: mdl-11443396

ABSTRACT

A 58-year-old man with a history of severe invalidating claudicatio intermittens underwent femoropopliteal bypass with a human umbilical vein graft. Seven years later he presented with a painful enlarging mass in the middle portion of his right thigh. The duplex scan showed a pseudoaneurysm of the body of the prosthesis, which was confirmed by angiography. As an alternative to surgical management, Wallgraft endoprosthesis was used for endoluminal exclusion of the pseudoaneurysm. To our knowledge, this technique has never been used before in such a case.


Subject(s)
Aneurysm, False/surgery , Angioplasty , Blood Vessel Prosthesis Implantation , Blood Vessel Prosthesis/adverse effects , Saphenous Vein/surgery , Aneurysm, False/etiology , Humans , Male , Middle Aged
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