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Making beta cells from people with type 1 diabetes Research Update Dec. 27, 2016 Scientists generated functional β (beta) cells from the skin cells of people with type 1 diabetes. In type 1 diabetes, a misguided attack by the immune system leads to destruction of insulin-producing β cells found in clusters called islets in the pancreas. Although administration of insulin via injections or a pump is life-saving, it does not mimic the exquisite blood glucose (sugar) control of the pancreas. Therefore, scientists are pursuing strategies to replace the destroyed β cells. One way to do that is through islet transplantation-an experimental procedure using islets from a cadaveric donor. The procedure has shown promise for people with difficult-to-control diabetes, but has significant challenges: donor islet tissue is limited, and immunosuppressive medications, which have toxic side effects, are required to prevent rejection of tissue transplanted from another individual. Toward overcoming the first barrier, scientists recently developed a new laboratory production method to make large quantities of β cells-called stem-cell derived β (SC-β) cells-from human stem cells. This method could, with further development, be used to make β cells from a sample of cells from a person with type 1 diabetes in the quantities needed for transplantation back into that same person. These cells would likely require protection from the autoimmune attack, but might not require toxic immunosuppressive medications to prevent rejection of the tissue. To investigate this possibility, in new research, scientists used skin cells from three people with type 1 diabetes (T1D cells) and three people without diabetes (ND cells). By introducing specific factors into these cells and using the new large-scale production method they developed, they made the skin cells become stem cells-cells that could subsequently become any cell type. They then, by introducing other factors, coaxed these stem cells to become SC-β cells (T1D SC-β cells and ND SC-β cells). Cells from the two different origins showed no differences in the ability to become SC-β cells, indicating for the first time that cells from a person with type 1 diabetes could be used to make SC-β cells. Next, the scientists demonstrated that the T1D SC-β cells functioned like healthy β cells. For example, in laboratory culture, T1D SC-β cells secreted insulin in response to glucose; they also released insulin in response to diabetes drugs that are known to stimulate insulin secretion, demonstrating their potential for use in screening for new diabetes drugs. The T1D SC-β also functioned in live animals: when T1D SC-β cells were transplanted into male mice, they produced insulin in response to glucose and controlled the animals’ blood glucose levels. Many research questions remain before an SC-β cell transplant procedure will be ready for testing in humans. First, it remains possible that differences between T1D SC-β and ND SC-β cells could appear over a longer time period than in the study. Second, it is not known how the T1D SC-β cells will interact with the recipient’s immune system; for example, it is not yet clear whether these cells could still be rejected, even though they were derived from the recipient’s own cells; and it is likely that these cells would be subject to the same autoimmune attack that destroyed the person’s original β cells. Third, individual differences in type 1 diabetes may affect the production, function, or transplant success of T1D SC-β cells. Thus, further research will illuminate the potential of T1D SC-β cells as a therapy for type 1 diabetes. Nonetheless, these results mark another significant step forward toward a cell therapy for type 1 diabetes, and also provide a valuable resource for drug screening and studying the development of the disease. References Read more……>click Here< Read more…

Abstract Bladder inflammation frequently causes cystitis pain and lower urinary tract dysfunction (LUTD) such as urinary frequency and urgency. Although mast cells have been identified to play a critical role in bladder inflammation and pain, the role of mast cells in cystitis-associated LUTD has not been demonstrated. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating inflammatory condition of the urinary bladder characterized by the hallmark symptoms of pelvic pain and LUTD. In this study we investigated the role of mast cells in LUTD using a transgenic autoimmune cystitis model (URO-OVA) that reproduces many clinical correlates of IC/BPS. URO-OVA mice express the membrane form of the model antigen ovalbumin (OVA) as a self-antigen on the urothelium and develop bladder inflammation upon introduction of OVA-specific T cells. To investigate the role of mast cells, we crossed URO-OVA mice with mast cell-deficient KitW-sh mice to generate URO-OVA/KitW-sh mice that retained urothelial OVA expression but lacked endogenous mast cells. We compared URO-OVA mice with URO-OVA/KitW-sh mice with and without mast cell reconstitution in response to cystitis induction. URO-OVA mice developed profound bladder inflammation with increased mast cell counts and LUTD, including increased total number of voids, decreased mean volume voided per micturition, and decreased maximum volume voided per micturition, after cystitis induction. In contrast, similarly cystitis-induced URO-OVA/KitW-sh mice developed reduced bladder inflammation with no mast cells and LUTD detected. However, after mast cell reconstitution URO-OVA/KitW-sh mice restored the ability to develop bladder inflammation and LUTD following cystitis induction. We further treated URO-OVA mice with cromolyn, a mast cell membrane stabilizer, and found that cromolyn treatment reversed bladder inflammation and LUTD in the animal model. Our results provide direct evidence for the role of mast cells in cystitis-associated LUTD, supporting the use of mast cell inhibitors for treatment of certain forms of IC/BPS. Citation: Wang X, Liu W, O’Donnell M, Lutgendorf S, Bradley C, Schrepf A, et al. (2016) Evidence for the Role of Mast Cells in Cystitis-Associated Lower Urinary Tract Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study. PLoS ONE 11(12): e0168772. https://doi.org/10.1371/journal.pone.0168772 Editor: Jayoung Kim, Cedars-Sinai Medical Center, UNITED STATES Received: October 11, 2016; Accepted: November 16, 2016; Published: December 21, 2016 Copyright: © 2016 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by the National Institutes of Health, U01DK082344, (https://projectreporter.nih.gov/project_info_details.cfm?aid=9120858&icde=31468144&ddparam=&ddvalue=&ddsub=&cr=1&csb=default&cs=ASC Karl Kreder) and the National Institutes of Health, R01DK100891, (https://projectreporter.nih.gov/project_info_details.cfm?aid=8626530&icde=31468170&ddparam=&ddvalue=&ddsub=&cr=10&csb=default&cs=ASC) to YL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Introduction Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory condition of the urinary bladder characterized by the hallmark symptoms of pelvic pain and lower urinary tract dysfunction (LUTD) such as urinary frequency and urgency . IC/BPS patients exhibit an increased number of mast cells in the bladder and elevated levels of mast cell mediators in the Read more…

Compare Gastric band Surgery In France Everyone knows that an apple per day is a more healthful option than a donut and yet, given the choice, many people would still choose the donut. A new study has revealed that food choices could be down to the associations that we make with food-related stimuli. person holding an apple in one hand and a doughnut in the other Researchers explain why the urge to eat a donut is mightier than the urge to eat an apple – even though the apple is the more healthful option. Aukje Verhoeven, Sanne de Wit, and Poppy Watson, all psychologists at the University of Amsterdam in the Netherlands, conducted the research. Their findings were published in the journal Appetite. The consumption of unhealthful foods is on the rise around the world, which is contributing to the more than 1.9 billion adults who are overweight globally. Among children in the United States, more than 27 percent of calories each day come from snacks, including salted snacks, candy, desserts, and sweetened beverages. This could have hazardous consequences for their health. Learned cues affect food choices Government initiatives have focused on making people more aware of the adverse effects of eating unhealthfully. However, most people fail to adhere to the recommended food guidelines, and eating behaviors often remain unchanged. Though it is not clear why informational interventions do not work, evidence suggests that food-related stimuli in the environment may play a role in triggering unhealthful eating habits. “Health warnings often make people want to choose healthier food products, yet many still end up picking unhealthy food products,” explains Verhoeven. “We suspected this might partly be due to the fact that people learn to associate specific cues in their environment with certain food choices.” For example, seeing a large “M” sign in the environment has been linked to reward, such as eating a cheeseburger, which then prompts a craving and could trigger a trip to the restaurant. These learned associations between cues and outcomes have a significant effect on the foods that people choose to consume. “Unhealthy choices are therefore automatically activated by learned associations, making health warnings, which focus on conscious choices, ineffective,” Verhoeven adds. For FREE No Obligation Information about the cost of Gastric Band Surgery in France Click here Or Click the Image Below to visit our Special offer Page to see if you Qualify for any Discounts Read more……>click Here< Read more…

Gastric band Surgery In France All you need to know about the Primal diet Sign in Log in with your Medical News Today account to create or edit your custom homepage, catch-up on your opinions notifications and set your newsletter preferences. Sign in Register for a free account For FREE No Obligation Information about the cost of Gastric Band Surgery in France Click here Or Click the Image Below to visit our Special offer Page to see if you Qualify for any Discounts Read more……>click Here< Read more…

Genome-Wide Association Study of Primary Sclerosing Cholangitis Identifies New Risk Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG = 0.29) was significantly greater than that between PSC and Crohn’s disease (CD) (rG = 0.04) (P = 2.55 × 10-15). UC and CD were genetically more similar to each other (rG = 0.56) than either was to PSC (P < 1.0 × 10-15). Our study represents a substantial advance in understanding of the genetics of PSC. Read more......>click Here< Read more…

Gastric band Surgery In France Being overweight may be more harmful than you thought Sign in Log in with your Medical News Today account to create or edit your custom homepage, catch-up on your opinions notifications and set your newsletter preferences. Sign in Register for a free account For FREE No Obligation Information about the cost of Gastric Band Surgery in France Click here Or Click the Image Below to visit our Special offer Page to see if you Qualify for any Discounts Read more……>click Here< Read more…

Figure 1 Functional characterization of Atxn1, Ebf1, Rreb1 and Ube2e2 (a,b,e) Data is displayed as box/whisker plots where the center line represents the median, box limits contain the 25th-75th percentiles, and whiskers span max/min values.(a) Gene expression measured by qPCR in murine subcutaneous (SAT), perigonadal visceral (VAT), and pericardial (PAT) adipose tissues (n=6 mice). Statistical significance was assessed using ANOVA and Sidak’s correction for multiple comparisons.(b) Gene expression measured by qPCR in murine adipose tissues after 8 weeks of high fat feeding compared to normal chow fed controls (n=5 mice per group). Statistical significance was assigned using a two-sided T-test.(c) Gene expression measured by qPCR in cultured adipocyte progenitors isolated from the subcutaneous (SAT) or perigonadal visceral (VAT) depots (n=4 replicates). Cells were expanded to confluence and then collected at intervals after induction of adipogenic differentiation. Data displayed as mean, error bar=s.e.m. Statistical significance was assessed using ANOVA and Sidak’s correction for multiple comparisons to time 0.(d) Oil-red-o staining of progenitors isolated from subcutaneous adipose and exposed to retroviral delivery of shRNA constructs during ex vivo expansion and induction of adipogenesis. Relative to control vector carrying a scramble sequence, shRNA constructs specific for Atxn1 and Ube2e2 impaired adipogenic differentiation. Scale=1mm.(e) Oil-red-o stain was alcohol extracted and quantified at OD520 (n=9 technical replicates). Statistical significance was assessed using ANOVA and Sidak’s correction for multiple comparisons to control (Scramble). Data representative of 3 independent experiments. Read more……>click Here< Read more…