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American Consumer Credit Counseling Joins Fight to Find a Cure

(Diabetes News and Information) As an advocate for finding a cure for type 1 Juvenile Diabetes American Consumer Credit Counseling ACCC recognizes the social responsibility associated with this cause Setting a lead example for all types of organizations ACCC has donated nearly 3000 to the Juvenile Diabetes Research Foundation In hope of someday eliminating the daily struggle for sufferers of the disease 3 million in the US alone……

assisTek the Global Leader Tablet ePROs Announces the Launch of a New Website at assistekcom

(Diabetes News and Information) assisTek the global leader tablet ePROs today announced the launch of their new corporate website at assisTekcom httpwwwassistekcomThe website features a video interview of site coordinators who used assisTek systems with an elderly Spanish speaking arthritic population on the Mexican border in addition to enhanced product overviews of their flagship ePRO products and services The new iPRO product……

Extra-Nuclear Signalling of Estrogen Receptor to Breast Cancer Cytoskeletal Remodelling, Migration and Invasion

by Maria Silvia Giretti, Xiao-Dong Fu, Giovanni De Rosa, Ivana Sarotto, Chiara Baldacci, Silvia Garibaldi, Paolo Mannella, Nicoletta Biglia, Piero Sismondi, Andrea Riccardo Genazzani, Tommaso Simoncini

Background

Estrogen is an established enhancer of breast cancer development, but less is known on its effect on local progression or metastasis. We studied the effect of estrogen receptor recruitment on actin cytoskeleton remodeling and breast cancer cell movement and invasion. Moreover, we characterized the signaling steps through which these actions are enacted.

Methodology/Principal Findings

In estrogen receptor (ER) positive T47-D breast cancer cells ER activation with 17?-estradiol induces rapid and dynamic actin cytoskeleton remodeling with the formation of specialized cell membrane structures like ruffles and pseudopodia. These effects depend on the rapid recruitment of the actin-binding protein moesin. Moesin activation by estradiol depends on the interaction of ER? with the G protein G?13, which results in the recruitment of the small GTPase RhoA and in the subsequent activation of its downstream effector Rho-associated kinase-2 (ROCK-2). ROCK-2 is responsible for moesin phosphorylation. The G?13/RhoA/ROCK/moesin cascade is necessary for the cytoskeletal remodeling and for the enhancement of breast cancer cell horizontal migration and invasion of three-dimensional matrices induced by estrogen. In addition, human samples of normal breast tissue, fibroadenomas and invasive ductal carcinomas show that the expression of wild-type moesin as well as of its active form is deranged in cancers, with increased protein amounts and a loss of association with the cell membrane.

Conclusions/Significance

These results provide an original mechanism through which estrogen can facilitate breast cancer local and distant progression, identifying the extra-nuclear G?13/RhoA/ROCK/moesin signaling cascade as a target of ER? in breast cancer cells. This information helps to understand the effects of estrogen on breast cancer metastasis and may provide new targets for therapeutic interventions.

Pregnancy: Gestational Diabetes and Dietary Guidelines

Abby Van der Veer, a registered dietician who specializes in dietary counseling for pregnant women, offers advice for women with gestational diabetes. She emphasizes the importance of tight control of blood sugar as a protective measure for the fetus as well as the mother. Ms. Van der Veer recommends avoidance of drinks with excess sugar and suggests better alternatives.

Fit4D Partners With The Juvenile Diabetes Research Foundation In Support of The 2008 Ride to Cure Diabetes

(Diabetes News and Information) Fit4D Fitness4Diabetics and the Juvenile Diabetes Research Foundation JDRF announce collaborative efforts to deliver high quality educational content as well as fitness nutrition and motivational coaching to participants in the 2008 JDRF Ride to Cure Diabetes Riders with diabetes will receive personalized guidance as to how to train and have a successful Ride while balancing their diet exercise……

Protein Helps ID Thyroid Cancer Nodules

Title: Protein Helps ID Thyroid Cancer Nodules
Category: Health News
Created: 5/20/2008 2:00:00 AM
Last Editorial Review: 5/20/2008

Hormone Therapy and the Risk of Cardiovascular Disease

Pamela B. Morris, MD, Director, Preventive Cardiology, Co-Director, Women’s Heart Care, Medical University of South Carolina, discusses hormone therapy and the risk of cardiovascular disease in women.

References and Resources

McGarry KA. Menopause: introduction.
Med Health R I. 2008 Mar;91(3):72.

Billeci AM, Paciaroni M, Caso V, Agnelli G.
Hormone replacement therapy and stroke. Curr Vasc Pharmacol. 2008 Apr;6(2):112-23.

Rees M, Stevenson J; British Menopause Society Council.
Primary prevention of coronary heart disease in women. Menopause Int. 2008 Mar;14(1):40-5.

For more information on this physician visit:
Pamela B. Morris, M.D.

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Excessive Islet NO Generation in Type 2 Diabetic GK Rats Coincides with Abnormal Hormone Secretion and Is Counteracted by GLP-1

by Albert Salehi, Sandra Meidute Abaraviciene, Javier Jimenez-Feltstrom, Claes-Göran Östenson, Suad Efendic, Ingmar Lundquist

Background

A distinctive feature of type 2 diabetes is inability of insulin-secreting ?-cells to properly respond to elevated glucose eventually leading to ?-cell failure. We have hypothesized that an abnormally increased NO production in the pancreatic islets might be an important factor in the pathogenesis of ?-cell dysfunction.

Principal Findings

We show now that islets of type 2 spontaneous diabetes in GK rats display excessive NO generation associated with abnormal iNOS expression in insulin and glucagon cells, increased ncNOS activity, impaired glucose-stimulated insulin release, glucagon hypersecretion, and impaired glucose-induced glucagon suppression. Pharmacological blockade of islet NO production by the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) greatly improved hormone secretion from GK islets suggesting islet NOS activity being an important target to inactivate for amelioration of islet cell function. The incretin hormone GLP-1, which is used in clinical practice suppressed iNOS and ncNOS expression and activity with almost full restoration of insulin release and partial restoration of glucagon release. GLP-1 suppression of iNOS expression was reversed by PKA inhibition but unaffected by the proteasome inhibitor MG132. Injection of glucose plus GLP-1 in the diabetic rats showed that GLP-1 amplified the insulin response but induced a transient increase and then a poor depression of glucagon.

Conclusion

The results suggest that abnormally increased NO production within islet cells is a significant player in the pathogenesis of type 2 diabetes being counteracted by GLP-1 through PKA-dependent, nonproteasomal mechanisms.

An RGS-Containing Sorting Nexin Controls Drosophila Lifespan

by Jae Myoung Suh, Drew Stenesen, John M. Peters, Akiko Inoue, Angela Cade, Jonathan M. Graff

The pursuit of eternal youth has existed for centuries and recent data indicate that fat-storing tissues control lifespan. In a D. melanogaster fat body insertional mutagenic enhancer trap screen designed to isolate genes that control longevity, we identified a regulator of G protein signaling (RGS) domain containing sorting nexin, termed snazarus (sorting nexin lazarus, snz). Flies with insertions into the 5? UTR of snz live up to twice as long as controls. Transgenic expression of UAS-Snz from the snz Gal4 enhancer trap insertion, active in fat metabolic tissues, rescued lifespan extension. Further, the lifespan extension of snz mutants was independent of endosymbiont, e.g., Wolbachia, effects. Notably, old snz mutant flies remain active and fertile indicating that snz mutants have prolonged youthfulness, a goal of aging research. Since mammals have snz-related genes, it is possible that the functions of the snz family may be conserved to humans.

High Frequency of Copy Number Variations and Sequence Variants at CYP21A2 Locus: Implication for the Genetic Diagnosis of 21-Hydroxylase Deficiency

by Silvia Parajes, Celsa Quinteiro, Fernando Domínguez, Lourdes Loidi

Background

The systematic study of the human genome indicates that the inter-individual variability is greater than expected and it is not only related to sequence polymorphisms but also to gene copy number variants (CNVs). Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (21OHD) is the most common autosomal recessive disorder with a carrier frequency of 1?25 to 1?10. The gene that encodes 21-hydroxylase enzyme, CYP21A2, is considered to be one of the most polymorphic human genes. Copy number variations, such as deletions, which are severe mutations common in 21OHD patients, or gene duplications, which have been reported as rare events, have also been described. The correct characterization of 21OHD alleles is important for disease carrier detection and genetic counselling

Methodology and Findings

CYP21A2 genotyping by sequencing has been performed in a random sample of the Spanish population, where 144 individuals recruited from university students and employees of the hospital were studied. The frequency of CYP21A2 mutated alleles in our sample was 15.3% (77.3% were mild mutations, 9% were severe mutations and 13.6% were novel variants). Gene dosage assessment was also performed when CYP21A2 gene duplication was suspected. This analysis showed that 7% of individuals bore a chromosome with a duplicated CYP21A2 gene, where one of the copies was mutated.

Conclusions

As far as we know, the present study has shown the highest frequency of 21OHD carriers reported by a genotyping analysis. In addition, a high frequency of alleles with CYP21A2 duplications, which could be misinterpreted as 21OHD alleles, was found. Moreover, a high frequency of novel genetic variations with an unknown effect on 21-hydroxylase activity was also found. The high frequency of gene duplications, as well as novel variations, should be considered since they have an important involvement in carrier testing and genetic counseling.