Optimization of growth media components for polyhydroxyalkanoate (PHA) production from organic acids by Ralstonia eutropha

We employed systematic mixture analysis to determine optimal levels of acetate, propionate, and butyrate for cell growth and polyhydroxyalkanoate (PHA) production by Ralstonia eutropha H16. Butyrate was the preferred acid for robust cell growth and high PHA production. The 3-hydroxyvalerate content in the resulting PHA depended on the proportion of propionate initially present in the growth medium. The proportion of acetate dramatically affected the final pH of the growth medium. A model was constructed using our data that predicts the effects of these acids, individually and in combination, on cell dry weight (CDW), PHA content (%CDW), PHA production, 3HV in the polymer, and final culture pH. Cell growth and PHA production improved approximately 1.5-fold over initial conditions when the proportion of butyrate was increased. Optimization of the phosphate buffer content in medium containing higher amounts of butyrate improved cell growth and PHA production more than 4-fold. The validated organic acid mixture analysis model can be used to optimize R. eutropha culture conditions, in order to meet targets for PHA production and/or polymer HV content. By modifying the growth medium made from treated industrial waste, such as palm oil mill effluent, more PHA can be produced.Malaysia. Ministry of Science, Technology and Innovation (MOSTI

Mischformen und Überlappung des Typ-1- und des Typ-2-Diabetes. Limitationen individueller Therapieoptionen durch die bestehende Disease-Management-Programm-Systematik.  

Bei einem 67-jährigen Patienten mit Typ-2-Diabetes und Facetten des metabolischen Syndroms wurden niedrigtitrige GAD-Autoantikörper (GAD: Glutamatdekarboxylase) bei gleichzeitig negativen Befunden für die anderen Inselantikörper nachgewiesen und deshalb die Diagnose geändert auf Typ-1-Diabetes. In der Folge kam es unter einer intensivierten Insulintherapie mit maximal 137 Einheiten Insulin/Tag trotz Beibehaltung des Metformins zu einer ausgeprägten Gewichtszunahme von 18 kg in 3 Jahren. Es handelt sich hier am ehesten um einen Typ-2-Diabetes mit LADA-Phänotyp (LADA: „latent autoimmune diabetes in adults“) als Mischbild oder aber bei den niedrigtitrigen GADA (GAD-Autoantikörper) um nicht mit Diabetes assoziierte unspezifische Autoantikörper. Die DMP-Systematik (DMP: Disease-Management-Programm) kann diesen Phänotyp aber nicht abbilden, da lediglich das DMP Diabetes mellitus Typ 1 und das DMP Diabetes mellitus Typ 2 zur Verfügung stehen. Aus diesem Grund wurde der Patient erneut in das DMP Diabetes mellitus Typ 2 eingeschrieben. Zumindest für Patienten, die phänotypisch einem Typ-2-Diabetes entsprechen und niedrigtitrige Single-GADA aufweisen, wäre eine Diagnose „Typ-2-Diabetes mit β‑Zell-Autoimmunität“ zutreffender als Typ-1-Diabetes/LADA. Nach zusätzlicher Gabe von Liraglutid 1,8 mg s. c. (subkutan) nahm der Patient in kurzer Zeit 9 kg ab und konnte die Insulindosis auf zuletzt 38 Einheiten/Tag senken

Modulating the Autoimmune Response in Type 1 Diabetes: A Report on the 64th Scientific Sessions of the ADA, June 2004, Orlando, FL, USA

Type 1 diabetes mellitus results from a loss of insulin-producing β-cells in the pancreatic islets caused by an immune-mediated chronic destructive process. It is generally believed that immune tolerance to β-cells is broken by environmental factors in genetically susceptible individuals, leading to β-cell destruction that is mediated by T lymphocytes. A key assumption in the current pathogenic concept of type 1 diabetes is a defective immunoregulation affecting both central and peripheral mechanisms of tolerance induction against β-cell antigens. In animal models of type 1 diabetes, disease-protective modulation of the islet autoimmune response can be effected by various strategies including administration of islet antigens. In human type 1 diabetes, therefore, new strategies are currently being developed with the aim of actively suppressing the autoimmune process and inducing a lasting tolerance against islet antigens. In this context, inducing regulatory T cells in vivo (i.e. CD4(+)CD25(+) T cells or type 1 regulatory T cells) is currently becoming more widespread. The following report highlights some of the recent studies on immunotherapy of type 1 diabetes, presented at the 64(th) Scientific Sessions, held in June 2004, in Orlando, Florida

Elimination of Dietary Gluten and Development of Type 1 Diabetes in High Risk Subjects

Removal of dietary gluten is associated with a lower frequency of type 1 diabetes (T1D) in patients with celiac disease. Therefore, we performed a pilot study in which seven islet-antibody-positive first degree relatives of patients with T1D were placed on a gluten-free diet for 12 months, followed by gluten re-exposure for 12 months, to investigate whether this could reduce levels of circulating autoantibodies. We found that islet autoantibody levels at the end of the gluten-free period were not different to those before the commencement of the diet nor to antibody levels at the end of the gluten re-exposure period. In the present study, we have followed the 7 children formerly placed on a gluten-free diet for the manifestation of T1D for up to 5 years (mean follow-up time after fulfilling inclusion criteria: 4.8 years, SE 0.82 years) and compared them to 30 siblings and offspring of patients with T1D with similar characteristics to the intervention group (mean follow-up time: 5 years, SE 0.62 years). The cumulative 5-year risk of T1D in the intervention group did not differ from that in the prediabetic control group (42.9%, 95 CI (6.3-79.5%) vs. 49.7%, 95 CI (30.9-68.5%), p=0.87, log-rank test). These findings suggest that removing gluten from the diet over a period of one year is effective neither in the short nor in the long term in high-risk prediabetic individuals with a fully activated immune response to different islet antigens close to manifestation of T1D. These and recent data showing that exposure to dietary gluten in offspring of mothers and fathers with T1D very early in life is associated with an increased risk of developing islet antibodies also suggest that removal of dietary gluten should be tested as early as possible in children with an increased risk of islet autoimunity, i.e. before an immune response to islet antigens is established