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Current Opinion in Endocrinology, Diabetes and Obesity - Current Table Of Contents

Editorial introductions.
Page: viiDOI: 10.1097/MED.0b013e32831395d5
Can lesser-known causes of obesity help build a more predictive physiological model?.
Page: 401DOI: 10.1097/MED.0b013e32831090a6Authors: Apovian, Caroline M; Mechanick, Jeffrey I
Putative environmental-endocrine disruptors and obesity: a review.
Page: 403DOI: 10.1097/MED.0b013e32830ce95cAuthors: Elobeid, Mai A a; Allison, David B a,b,c

PubMed: 0013-7227

Mutant Parathyroid Hormone-Related Protein, Devoid of the Nuclear Localization Signal, Markedly Inhibits Arterial Smooth Muscle Cell Cycle and Neointima Formation By Coordinate Upregulation of p15Ink4b and p27kip1.
Fiaschi-Taesch N, Sicari B, Ubriani K, Cozar-Castellano I, Takane KK, Stewart AF Mutant Parathyroid Hormone-Related Protein, Devoid of the Nuclear Localization Signal, Markedly Inhibits Arterial Smooth Muscle Cell Cycle and Neointima Formation By Coordinate Upregulation of p15Ink4b and p27kip1. Endocrinology. 2008 Oct 9; Authors: Fiaschi-Taesch N, Sicari B, Ubriani K, Cozar-Castellano I, Takane KK, Stewart AF Arterial expression of Parathyroid Hormone-related Protein (PTHrP) is markedly induced by angioplasty. PTHrP contains a nuclear localization signal (NLS). PTHrP mutants lacking the NLS (DeltaNLS-PTHrP) are potent inhibitors of arterial vascular smooth muscle cell (VSMC) proliferation in vitro. This is of clinical relevance, for adenoviral delivery of DeltaNLS-PTHrP at angioplasty completely inhibits arterial re-stenosis in rats. In this study, we explored the cellular mechanisms through which DeltaNLS-PTHrP arrests the cell cycle. In vivo, adenoviral delivery of DeltaNLS-PTHrP at angioplasty markedly inhibited VSMC proliferation as compared to angioplastied carotids infected with control adenovirus (Ad.LacZ). In vitro, DeltaNLS-PTHrP overexpression was associated with a decrease in phospho-pRb, and a G0/G1 arrest. This pRb underphosphorylation was associated with stable levels of cdk's 2, 4 and 6; the D, and E cyclins, p16, p18, p19 and p21, but was associated with a dramatic decrease in cdk-2 and cdk4 kinases activities. Cyclin A was reduced, but restoring cyclin A adenovirally to normal did not promote cell cycle progression in DeltaNLS-PTHrP VSMC. More importantly, p15(INK4) and p27(kip1), two critical inhibitors of the G1/S progression, were markedly increased. Normalization of both p15(INK4b) and p27(kip1) by siRNA knockdown normalized cell cycle progression. These data indicate that the changes in p15(INK4b) and p27(kip1) fully account for the marked cell cycle slowing induced by DeltaNLS-PTHrP in VSMC. Finally, DeltaNLS-PTHrP is able to induce p15(INK4) and p27(kip1) expression when delivered adenovirally to primary murine VSMC. These studies provide a mechanistic understanding of DeltaNLS-PTHrP actions, and suggest that DeltaNLS-PTHrP may have particular efficacy for the prevention of arterial re-stenosis. PMID: 18845646 [PubMed - as supplied by publisher]
11{beta}HSD2 Inhibition Causes Cerebrovascular Remodeling and Increases Infarct Size Following Cerebral Ischemia.
Osmond JM, Dorrance AM 11{beta}HSD2 Inhibition Causes Cerebrovascular Remodeling and Increases Infarct Size Following Cerebral Ischemia. Endocrinology. 2008 Oct 9; Authors: Osmond JM, Dorrance AM Direct mineralocorticoid receptor (MR) activation with deoxycorticosterone acetate has deleterious effects on the cerebral vasculature. Inhibition of 11beta-hydroxysteroid dehydrogenase type II (11betaHSD2) mimics the detrimental effects of elevated mineralocorticoids in the heart, but the effect of enzyme inactivation on the cerebral vasculature is unknown. Therefore, we hypothesized that systemic 11betaHSD2 inhibition with carbenoxolone (CBX) would cause remodeling of the middle cerebral artery (MCA) and increase the damage caused by cerebral ischemia. Six-week old male Sprague Dawley rats were divided into control and CBX (2.5 mg/day)+0.9% NaCl treated. After four weeks of treatment, rats were used to assess either structure and reactivity of the MCA or the response to cerebral ischemia using the MCA occlusion technique. Cerebral damage was assessed by 2, 3, 5-triphenyltetrazolium chloride staining and expressed as a percentage of the hemisphere infarcted. CBX treatment increased systolic blood pressure (153.2+/-7.3 vs 122.1+/-4.4 mmHg, p<0.05) compared to control rats. MCAs from CBX treated rats were smaller and stiffer than control MCAs over a range of intralumenal pressures, indicating inward remodeling of the vessel. CBX treatment significantly increased ischemic cerebral infarct size compared to control rats (27.1 +/- 5.4% vs. 14.8 +/- 4.2%, p<0.05). These data indicate that inhibition of 11betaHSD2, and thus disproportionate glucocorticoid activation of the MR, results in remodeling of the MCA and worsens the outcome of cerebral ischemia, further underscoring the importance of understanding the mechanism by which MR activation leads to cerebrovascular disease. PMID: 18845645 [PubMed - as supplied by publisher]
Endothelial Dysfunction in Mice with Streptozotocin-induced Type 1 Diabetes is Opposed by Compensatory Overexpression of COX-2 in the Vasculature.
Nacci C, Tarquinio M, De Benedictis L, Mauro A, Zigrino A, Carratù MR, Quon MJ, Montagnani M Endothelial Dysfunction in Mice with Streptozotocin-induced Type 1 Diabetes is Opposed by Compensatory Overexpression of COX-2 in the Vasculature. Endocrinology. 2008 Oct 9; Authors: Nacci C, Tarquinio M, De Benedictis L, Mauro A, Zigrino A, Carratù MR, Quon MJ, Montagnani M Cardiovascular complications of diabetes result from endothelial dysfunction secondary to persistent hyperglycemia. We investigated potential compensatory mechanisms in the vasculature that oppose endothelial dysfunction in diabetes. Balb/c mice were treated with streptozotocin (STZ) to induce type 1 diabetes (T1D). In mesenteric vascular beds (MVB) isolated ex vivo from mice treated with STZ for 1 week, dose-dependent vasorelaxation to acetylcholine (ACh) or sodium nitroprusside (SNP) was comparable to that in age-matched control mice (CTRL). By contrast, MVB from mice treated with STZ for 8 weeks had severely impaired vasodilator responses to ACh consistent with endothelial dysfunction. Pre-treatment of MVB from CTRL mice with L-NAME (nitric oxide (NO) synthase inhibitor) nearly abolished vasodilation to ACh. In MVB from 1-wk STZ-treated mice, vasodilation to ACh was only partially impaired by L-NAME. Thus, vasculature of mice with T1D may have compensatory NO-independent mechanisms to augment vasodilation to ACh and oppose endothelial dysfunction. Indeed, pre-treatment of MVB isolated from 1-wk STZ-treated mice with NS-398 (selective COX-2 inhibitor) unmasked endothelial dysfunction not evident in CTRL mice pre-treated without or with NS-398. Expression of COX-2 in MVB, aortic endothelial cells, and aortic vascular smooth muscle cells from STZ-treated mice was significantly increased (vs. CTRL). Moreover, concentrations of the COX-2 dependent vasodilator 6-keto PGF-1alpha was elevated in conditioned media from aorta of STZ-treated mice. We conclude that endothelial dysfunction in a mouse model of T1D is opposed by compensatory up-regulation of COX-2 expression and activity in the vasculature that may be relevant to developing novel therapeutic strategies for diabetes and its cardiovascular complications. PMID: 18845644 [PubMed - as supplied by publisher]
Lean phenotype and resistance to diet-induced obesity in VDR knockout mice correlates with induction of uncoupling protein-1 in white adipose tissue.
Narvaez CJ, Matthews D, Broun E, Chan M, Welsh J Lean phenotype and resistance to diet-induced obesity in VDR knockout mice correlates with induction of uncoupling protein-1 in white adipose tissue. Endocrinology. 2008 Oct 9; Authors: Narvaez CJ, Matthews D, Broun E, Chan M, Welsh J Increased adiposity is a feature of aging in both mice and humans, but the molecular mechanisms underlying age-related changes in adipose tissue stores remain unclear. In previous studies, we noted that 18 month old normocalcemic VDR knockout (VDRKO) mice exhibited atrophy of the mammary adipose compartment relative to wild type (WT) littermates, suggesting a role for VDR in adiposity. Here we have monitored body fat depots, food intake, metabolic factors and gene expression in WT and VDRKO mice on the C57Bl6 and CD1 genetic backgrounds. Regardless of genetic background, both subcutaneous and visceral white adipose tissue depots were smaller in VDRKO mice than WT mice. The lean phenotype of VDRKO mice was associated with reduced serum leptin and compensatory increased food intake. Similar effects on adipose tissue, leptin and food intake were observed in mice lacking Cyp27b1, the 1alpha-hydroxylase enzyme that generates 1,25-dihydroxyvitamin D3, the VDR ligand. Although VDR ablation did not alter expression of PPARgamma or fatty acid synthase, PCR array screening identified several differentially expressed genes in white adipose tissue from WT and VDRKO mice. Uncoupling protein-1 (ucp-1), which mediates dissociation of cellular respiration from energy production, was >25fold elevated in VDRKO white adipose tissue. Consistent with elevation in ucp-1, VDRKO mice were resistant to high fat diet induced weight gain. Collectively, these studies identify a novel role for 1,25-dihydroxyvitamin D3 and the VDR in the control of adipocyte metabolism and lipid storage in vivo. PMID: 18845643 [PubMed - as supplied by publisher]
Competitive inhibition of Oatp1c1-mediated thyroxine transport by the fenamate class of nonsteroidal anti-inflammatory drugs.
Westholm DE, Stenehjem DD, Rumbley JN, Drewes LR, Anderson GW Competitive inhibition of Oatp1c1-mediated thyroxine transport by the fenamate class of nonsteroidal anti-inflammatory drugs. Endocrinology. 2008 Oct 9; Authors: Westholm DE, Stenehjem DD, Rumbley JN, Drewes LR, Anderson GW The organic anion transporter Oatp1c1 is a high affinity thyroxine (T4) transporter with narrow substrate specificity expressed at the blood-brain barrier. A transport model using cells over-expressing Oatp1c1 was created to identify novel Oatp1c1 substrates and inhibitors. Rat Oatp1c1 was cloned and stably expressed in HEK293 cells. Oatp1c1-transfected HEK293 cells transported (125)I-labeled T4 in a time dependent manner which was completely abolished in the presence of excess unlabeled T4. Next, various compounds including inhibitors of thyroid hormone uptake were screened for inhibitory effects on Oatp1c1-mediated T4 uptake. Phenytoin (64%), indocyanine green (17%) and fenamic acid (68%) diclofenac (51%) and meclofenamic acid (33%) all reduced T4 uptake by Oatp1c1 when assayed at concentrations of 10microM. Dose response assays for the fenamic acids, iopanoic acid, indocyanine green and phenytoin revealed IC50s for Oatp1c1 T4 uptake below or near the blood plasma levels after therapeutic doses. Further kinetic assays and reciprocal plot analyses demonstrated that the fenamic acid diclofenac inhibited in a competitive manner. Finally, microvessels were isolated from adult rat brain and assessed for T4 uptake. 10microM fenamate concentrations inhibited T4 microvessel uptake with a similar hierarchical inhibition profile (fenamic acid (43%), diclofenac (78%) and meclofenamic acid (85%) as observed for Oatp1c1 transfected cells. Oatp1c1 is expressed luminally and abluminally in the BBB endothelial cell and exhibits bidirectional transport capabilities. Together, these data suggest that Oatp1c1 transports fenamates into, and perhaps across, brain barrier cells. PMID: 18845642 [PubMed - as supplied by publisher]
Identification of novel trophoblast invasion-related genes: Heme oxygenase-1 controls motility via PPAR{gamma}
Bilban M, Haslinger P, Prast J, Klinglmüller F, Woelfel T, Haider S, Sachs A, Otterbein LE, Desoye G, Hiden U, Wagner O, Knöfler M Identification of novel trophoblast invasion-related genes: Heme oxygenase-1 controls motility via PPAR{gamma} Endocrinology. 2008 Oct 9; Authors: Bilban M, Haslinger P, Prast J, Klinglmüller F, Woelfel T, Haider S, Sachs A, Otterbein LE, Desoye G, Hiden U, Wagner O, Knöfler M Invasion of cytotrophoblasts into uterine tissues is essential for placental development. To identify molecules regulating trophoblast invasion, mRNA signatures of purified villous (CTB, poor invasiveness) and extravillous (EVT, high invasiveness) trophoblasts isolated from first trimester human placentae and villous explant cultures, respectively, were compared using GeneChip analyses yielding 991 invasion/migration related transcripts. Several genes involved in physiological and pathologic cell invasion, including ADAM-12,-19,-28 as well as Spondin-2, were upregulated in EVT. Pathway prediction analyses identified several functional modules associated with either the invasive or the non-invasive trophoblast phenotype. One of the genes which were downregulated in the invasive mRNA pool, heme oxygenase-1 (HO-1), was selected for functional analyses. Real-time PCR analyses, Western blottting, and immunofluorescene of first trimester placentae and differentiating villous explant cultures demonstrated downregulation of HO-1 in invasive EVT as compared to CTB. Modulation of HO-1 expression in loss-of as well as gain-of function cell models (BeWo and HTR8/SVneo, respectively) demonstrated an inverse relationship of HO-1 expression with trophoblast migration in transwell and wound healing assays. Importantly, HO-1 expression led to an increase in protein levels and activity of the nuclear hormone receptor PPARgamma. Pharmacological inhibition of PPARgamma abrogated the inhibitory effects of HO-1 on trophoblast migration. Collectively, our results demonstrate that gene expression profiling of EVT and CTB can be used to unravel novel regulators of cell invasion. Accordingly, we identify heme oxygenase-1 as a negative regulator of trophoblast motility acting via upregulation of PPARgamma. PMID: 18845641 [PubMed - as supplied by publisher]
Transcription of Steroidogenic Acute Regulatory protein (STAR) in the rodent ovary and placenta: alternative modes of cyclic adenosine 3', 5'-monophosphate dependent and independent regulation.
Yivgi-Ohana N, Sher N, Melamed-Book N, Eimerl S, Koler M, Manna PR, Stocco DM, Orly J Transcription of Steroidogenic Acute Regulatory protein (STAR) in the rodent ovary and placenta: alternative modes of cyclic adenosine 3', 5'-monophosphate dependent and independent regulation. Endocrinology. 2008 Oct 9; Authors: Yivgi-Ohana N, Sher N, Melamed-Book N, Eimerl S, Koler M, Manna PR, Stocco DM, Orly J Steroid hormone synthesis is a vital function of the adrenal cortex, serves a critical role in gonadal function, and maintains pregnancy if normally executed in the placenta. The substrate for the synthesis of all steroid hormones is cholesterol and its conversion to the first steroid, pregnenolone, by the cholesterol side chain cleavage cytochrome P450 (CYP11A1, P450scc) enzyme complex takes place in the inner mitochondrial membranes. Steroidogenic acute regulatory protein (STAR) facilitates the rate limiting transfer of cholesterol from the outer mitochondrial membrane to P450scc located in the inner organelle membranes. The current study explored the mechanisms controlling transcription of the star gene in primary cell cultures of mouse placental trophoblast giant (TG) cells and rat ovarian granulosa cells examined throughout the course of their functional differentiation. Our findings show that the cis-elements required for star transcription in the rodent placenta and the ovary are centered in a relatively small proximal region of the promoter. In placental TG cells, cAMP is required for activation of the star promoter and the cis-elements mediating a maximal response were defined as cAMP Response Element 2 (CRE2) and GATA. EMSA studies show that placental CREB-1 and ATF-2 bind to a -81/-78 sequence, while GATA-2 binds to a -66/-61 sequence. In comparison, patterns of star regulation in the ovary suggested tissue-specific and developmental controlled modes of star transcription: during the follicular phase, FSH/cAMP induced CREB-1 dependent activity, while upon luteinization STAR expression becomes cAMP and CREB independent, a functional shift conferred by FRA-2 displacement of CREB-1 binding and the appearance of a new requirement for C/EBPbeta and SF-1 that bind to upstream elements (-117/-95). These findings suggest that during evolution the promoters of the star gene acquired non-consensus sequence elements enabling expression of a single gene in different organs, or allowing dynamic temporal changes corresponding to progressing phases of differentiation in a given cell type. PMID: 18845640 [PubMed - as supplied by publisher]
PROTEIN FEEDING PROMOTES REDISTRIBUTION OF ENDOGENOUS GLUCOSE PRODUCTION TO THE KIDNEY AND POTENTIATES ITS SUPPRESSION BY INSULIN.
Pillot B, Soty M, Gautier-Stein A, Zitoun C, Mithieux G PROTEIN FEEDING PROMOTES REDISTRIBUTION OF ENDOGENOUS GLUCOSE PRODUCTION TO THE KIDNEY AND POTENTIATES ITS SUPPRESSION BY INSULIN. Endocrinology. 2008 Oct 9; Authors: Pillot B, Soty M, Gautier-Stein A, Zitoun C, Mithieux G The aim of this study was to assess in rats the effect of protein-feeding on: 1) the distribution of endogenous glucose production (EGP) among gluconeogenic organs; 2) the repercussion on the insulin sensitivity of glucose metabolism. We used gene expression analyses, a combination of glucose tracer dilution and arteriovenous balance to quantify specific organ release, and hyperinsulinemic euglycemic clamps to assess EGP and glucose uptake. Protein feeding promoted a dramatic induction of the main regulatory gluconeogenic genes (glucose-6 phosphatase and phosphoenolpyruvate carboxykinase) in the kidney, but not in the liver. As a consequence, the kidney glucose release was markedly increased, compared to rats fed on a normal starch-diet. Protein feeding ameliorated the suppression of EGP by insulin and the sparing of glycogen storage in the liver, but had no effect on glucose uptake. Combined with the previously reported induction of gluconeogenesis in the small intestine, the present work strongly suggests that a redistribution of glucose production among gluconeogenic organs might occur upon protein feeding. This phenomenon is in keeping with the improvement of insulin sensitivity of EGP, most likely involving the hepatic site. These data shed a new light on the improvement of glucose tolerance, previously observed upon increasing the amount of protein in the diet, in type 2 diabetic patients. PMID: 18845639 [PubMed - as supplied by publisher]
Deletion of the G protein-coupled Receptor GPR30 Impairs Glucose Tolerance, Reduces Bone Growth, Increases Blood Pressure, and Eliminates Estradiol-stimulated Insulin Release in Female Mice.
Mårtensson UE, Salehi SA, Windahl S, Gomez MF, Swärd K, Daszkiewicz-Nilsson J, Wendt A, Andersson N, Hellstrand P, Grände PO, Owman C, Rosen CJ, Adamo ML, Lundquist I, Rorsman P, Nilsson BO, Ohlsson C, Olde B, Leeb-Lundberg LM Deletion of the G protein-coupled Receptor GPR30 Impairs Glucose Tolerance, Reduces Bone Growth, Increases Blood Pressure, and Eliminates Estradiol-stimulated Insulin Release in Female Mice. Endocrinology. 2008 Oct 9; Authors: Mårtensson UE, Salehi SA, Windahl S, Gomez MF, Swärd K, Daszkiewicz-Nilsson J, Wendt A, Andersson N, Hellstrand P, Grände PO, Owman C, Rosen CJ, Adamo ML, Lundquist I, Rorsman P, Nilsson BO, Ohlsson C, Olde B, Leeb-Lundberg LM In vitro studies suggest that the G protein-coupled receptor GPR30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined if GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum insulin-like growth factor-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media:lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice including estradiol-stimulated insulin release. PMID: 18845638 [PubMed - as supplied by publisher]

PubMed: 0804-4643

Monogenic polycystic ovary syndrome due to a mutation in the lamin A/C gene is sensitive to thiazolidinediones but not to metformin.
Gambineri A, Semple RK, Forlani G, Genghini S, Grassi I, Hyden CS, Pagotto U, O'Rahilly S, Pasquali R Related Articles Monogenic polycystic ovary syndrome due to a mutation in the lamin A/C gene is sensitive to thiazolidinediones but not to metformin. Eur J Endocrinol. 2008 Sep;159(3):347-53 Authors: Gambineri A, Semple RK, Forlani G, Genghini S, Grassi I, Hyden CS, Pagotto U, O'Rahilly S, Pasquali R CONTEXT: Despite the very high prevalence of the polycystic ovary syndrome (PCOS), the underlying pathogenetic mechanism has remained obscure. OBJECTIVE: To determine the cause of two sisters' PCOS associated with severe insulin resistance. DESIGN: Clinical case report. Methods Two sisters who presented with hyperandrogenism and menstrual disorders in the context of PCOS, and were subsequently found to be severely insulin resistant. Physical examination revealed muscular hypertrophy with a paucity of fat in the extremities, trunk and gluteal regions, in spite of excess fat deposits in the face, neck and dorsocervical region. Known genes involved in familial partial lipodystrophy were screened. At the same time, metformin (1700 mg/day) was commenced. After 2-3 years of uninterrupted therapy, lack of clinical improvement led to the introduction of pioglitazone (30 mg/day). RESULTS: Both sisters were found to be heterozygous for the R482Q mutation in the lamin A/C gene (LMNA) gene, establishing the definitive diagnosis as Dunnigan-type familial partial lipodystrophy complicated by severe insulin resistance and secondary PCOS. Treatment with pioglitazone resulted in progressive amelioration of insulin resistance, hyperinsulinaemia and hyperandrogenaemia. Menses also improved, with restoration of a eumenorrhoeic pattern, and the framework of ultrasound PCO was in complete remission. CONCLUSIONS: Assessment of insulin sensitivity and adipose tissue topography should be a key part of the initial evaluation of patients with PCOS. Identifying such forms of PCOS with monogenic insulin resistance as the primary pathogenic abnormality may have practical implications for therapy, since they respond to thiazolidinediones, but not to metformin. PMID: 18728124 [PubMed - indexed for MEDLINE]
Methylenetetrahydrofolate reductase C677T polymorphism is associated with central adiposity and increased androgenicity in healthy postmenopausal women.
Lambrinoudaki I, Kaparos G, Papadimitriou D, Sergentanis TN, Creatsa M, Alexandrou A, Logothetis E, Christodoulakos G, Kouskouni E Related Articles Methylenetetrahydrofolate reductase C677T polymorphism is associated with central adiposity and increased androgenicity in healthy postmenopausal women. Eur J Endocrinol. 2008 Sep;159(3):233-41 Authors: Lambrinoudaki I, Kaparos G, Papadimitriou D, Sergentanis TN, Creatsa M, Alexandrou A, Logothetis E, Christodoulakos G, Kouskouni E OBJECTIVE: To assess the association of genetic polymorphisms related to cardiovascular disease (CVD) risk with anthropometric parameters and indices of androgenicity in healthy postmenopausal women. DESIGN: Cross-sectional study in a University Menopause Clinic. METHODS: The following polymorphisms were assessed in 84 healthy postmenopausal women: glycoprotein IIIa Leu33Pro, apolipoprotein E2/E3/E4, methylenetetrahydrofolate reductase (MTHFR) Ala222Val, apolipoprotein B Arg3500Gln, paraoxonase 1 Gln192Arg, plasminogen activator inhibitor 1 4G/5G, cholesterol-7 alpha-hydroxylase A-204C, and cholesterol ester transfer protein (TaqIB) B1/B2. Hormonal assays included FSH, LH, 17-beta-estradiol, testosterone, sex hormone-binding globulin (SHBG), DHEA sulfate, Delta-4-androstenedione (Delta4A), free androgen index (FAI), free estrogen index (FEI), and homocysteine (Hcy). The anthropometric components were body mass index (BMI) and waist-to-hip ratio (WHR). RESULTS: MTHFR Ala222Val polymorphism was positively associated with testosterone, FAI, and FEI (P=0.001, P=0.0004, and P=0.014 respectively) and negatively with SHBG (P=0.047). Furthermore, women bearing this polymorphism had higher BMI and WHR compared with women with the wild-type variant (P=0.027 and P=0.044 respectively). CONCLUSIONS: MTHFR Ala222Val polymorphism is associated with increased androgenicity and elevated BMI and WHR in healthy postmenopausal women. The significance of this association with respect to the CVD risk of postmenopausal women remains to be elucidated in future studies. PMID: 18728123 [PubMed - indexed for MEDLINE]
The effect of weight loss after gastric banding on the molecular distribution of serum adiponectin.
Leth H, Kroustrup JP, Larsen JF, Andersen KK, Flyvbjerg A, Frystyke J Related Articles The effect of weight loss after gastric banding on the molecular distribution of serum adiponectin. Eur J Endocrinol. 2008 Sep;159(3):357 Authors: Leth H, Kroustrup JP, Larsen JF, Andersen KK, Flyvbjerg A, Frystyke J The above article has been retracted by the authors, as they have withdrawn the data upon which it was based. The retraction was made before the article reached its final form in the publication process. However, the authors' manuscript, prior to copy editing, page layout and proofing, was initially made available online upon acceptance as an Accepted Preprint. PMID: 18684858 [PubMed - indexed for MEDLINE]
Should we treat all subjects with subclinical thyroid disease the same way?
Biondi B Related Articles Should we treat all subjects with subclinical thyroid disease the same way? Eur J Endocrinol. 2008 Sep;159(3):343-5 Authors: Biondi B PMID: 18647822 [PubMed - indexed for MEDLINE]
Thyroid and the environment: exposure to excessive nutritional iodine increases the prevalence of thyroid disorders in Sao Paulo, Brazil.
Camargo RY, Tomimori EK, Neves SC, G S Rubio I, Galrão AL, Knobel M, Medeiros-Neto G Related Articles Thyroid and the environment: exposure to excessive nutritional iodine increases the prevalence of thyroid disorders in Sao Paulo, Brazil. Eur J Endocrinol. 2008 Sep;159(3):293-9 Authors: Camargo RY, Tomimori EK, Neves SC, G S Rubio I, Galrão AL, Knobel M, Medeiros-Neto G OBJECTIVE: To evaluate the prevalence of chronic autoimmune thyroiditis (CAT) and iodine-induced hypothyroidism, hyperthyroidism (overt and subclinical), and goiter in a population exposed to excessive iodine intake for 5 years (table salt iodine concentrations: 40-100 mg/kg salt). Design This was a population-based, cross-sectional study with 1085 participants randomly selected from a metropolitan area in São Paulo, Brazil, and conducted during the first semester of 2004. METHODS: Thyroid ultrasound examination was performed in all participants and samples of urine and blood were collected from each subject. Serum levels of thyroid-stimulating hormone, free thyroxine, and anti-thyroid peroxidase (TPO) antibodies, urinary iodine concentration, thyroid volume, and thyroid echogenicity were evaluated. We also analyzed table salt iodine concentrations. RESULTS: At the time the study was conducted, table salt iodine concentrations were within the new official limits (20-60 mg/kg salt). Nevertheless, in 45.6% of the participants, urinary iodine excretion was excessive (above 300 microg/l) and, in 14.1%, it was higher than 400 microg/l. The prevalence of CAT (including atrophic thyroiditis) was 16.9% (183/1085), women were more affected than men (21.5 vs 9.1% respectively, P=0.02). Hypothyroidism was detected in 8.0% (87/1085) of the population with CAT. Hyperthyroidism was diagnosed in 3.3% of the individuals (36/1085) and goiter was identified in 3.1% (34/1085). CONCLUSIONS: Five years of excessive iodine intake by the Brazilian population may have increased the prevalence of CAT and hypothyroidism in subjects genetically predisposed to thyroid autoimmune diseases. Appropriate screening for early detection of thyroid dysfunction may be considered during excessive nutritional iodine intake. PMID: 18586897 [PubMed - indexed for MEDLINE]
Evaluation of the sensitivity to chemotherapeutics or thiazolidinediones of primary anaplastic thyroid cancer cells obtained by fine-needle aspiration.
Antonelli A, Ferrari SM, Fallahi P, Berti P, Materazzi G, Marchetti I, Ugolini C, Basolo F, Miccoli P, Ferrannini E Related Articles Evaluation of the sensitivity to chemotherapeutics or thiazolidinediones of primary anaplastic thyroid cancer cells obtained by fine-needle aspiration. Eur J Endocrinol. 2008 Sep;159(3):283-91 Authors: Antonelli A, Ferrari SM, Fallahi P, Berti P, Materazzi G, Marchetti I, Ugolini C, Basolo F, Miccoli P, Ferrannini E OBJECTIVE: Anaplastic thyroid cancer (ATC) is often unoperable and chemotherapy and radiotherapy are the main treatments. Until now 'primary ATC cell cultures' (ANA) have been developed from surgical biopsies. The possibility to obtain ANA from fine-needle aspiration (FNA-ANA) and to test their sensitivity to different drugs could increase the effectiveness of treatments and avoid unnecessary surgical procedures. DESIGN: To obtain FNA-ANA from six ATC patients before undergoing surgery and to evaluate the chemosensitivity of FNA-ANA to chemotherapeutic agents and thiazolidinediones (TZD). METHODS AND RESULTS: FNA-ANA from the six ATC patients were cultured in RPMI 1640 and propagated in DMEM. Chemosensitivity was evaluated by inhibiting the proliferation with increasing concentrations of five different chemotherapeutic agents (bleomycin, cisplatin, gemcitabine, etoposide, and carboplatin) or TZD (rosiglitazone). Chemotherapeutic agents significantly inhibited (P<0.0001) FNA-ANA proliferation, such as TZD (P<0.001); etoposide was the most effective in reducing cell growth. Another ANA culture for each patient was obtained from a biopsy specimen; the results for the chemosensitivity tests were similar to those obtained with FNA-ANA. The (V600E)BRAF mutation was observed in two ATC patients; the inhibition of proliferation by drugs was similar in tumors with or without (V600E)BRAF mutation. CONCLUSIONS: Our study demonstrates 1) the possibility to obtain FNA-ANA, and opens the way to the use of FNA-ANA to test the chemosensitivity to different drugs (chemotherapeutic agents or TZD; and possibly the radiosensitivity) in each patient, avoiding unnecessary surgical procedures and the administration of inactive chemotherapeutics; and 2) that etoposide is highly effective in reducing ATC cell growth in vitro. PMID: 18583391 [PubMed - indexed for MEDLINE]

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