β-cell-specific glucocorticoid reactivation attenuates inflammatory β-cell destruction

Progression and severity of type 1 diabetes is dependent upon inflammatory induction of nitric oxide production and consequent pancreatic β-cell damage. Glucocorticoids (GCs) are highly effective anti-inflammatory agents but have been precluded in type 1 diabetes and in islet transplantation protocols because they exacerbated insulin resistance and suppressed β-cell insulin secretion at the high-doses employed clinically. In contrast, physiological-range elevation of GC action within β-cells ameliorated lipotoxic β-cell failure in transgenic mice overexpressing the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (MIP-HSD1^tg/+ mice). Here, we tested the hypothesis that elevated β-cell 11beta-HSD1 protects against the β-cell destruction elicited by streptozotocin (STZ), a toxin that dose-dependently mimics aspects of inflammatory and autoimmune β-cell destruction. MIP-HSD1^tg/+ mice exhibited an episodic protection from the severe hyperglycemia caused by a single high dose of STZ associated with higher and sustained β-cell survival, maintained β-cell replicative potential, higher plasma and islet insulin levels, reduced inflammatory macrophage infiltration and increased anti-inflammatory T regulatory cell content. MIP-HSD1^tg/+ mice also completely resisted mild hyperglycemia and insulitis induced by multiple low-dose STZ administration. In vitro, MIP-HSD1^tg/+ islets exhibited attenuated STZ-induced nitric oxide production, an effect reversed with a specific 11beta-HSD1 inhibitor. GC regeneration selectively within β-cells protects against inflammatory β-cell destruction, suggesting therapeutic targeting of 11beta-HSD1 may ameliorate processes that exacerbate type 1 diabetes and that hinder islet transplantation.

Diabetes management in care homes:steps in the right direction?

Aims: Previous research has identified several inadequacies in management of diabetes within care homes many of which were highlighted in Diabetes UK’s report Diabetes in care homes:awareness, screening, training. The aim of this study was to see if this was still the case and to identify specific areas for improvement. Methods: Thirty care homes in Birmingham were invited to participate in the study. Data were collected using a standard questionnaire based on the Diabetes UK national survey of care homes comprising questions relating to screening, self-management, care planning and local authority support. All returned responses were analysed. Results: Responses were received from 20 of the 30 care homes approached. The mean percentage of residents with diabetes in the care homes sampled was 13.7%. None of the homes screened for diabetes on admission and only 5% screened residents annually.80% of homes acknowledged providing diabetes-specific training to staff. Residents in 95% of homes had a medical review in the last 12 months: 70% with a GP, 20% with a diabetes specialist nurse/nurse. 65% of homes provided support for self-management.45% of care homes did not have individualised care plans for residents with diabetes. 35% of managers reported poor support and guidance from their local authority.Conclusions: Improvements were noted in the care provided to individuals with diabetes living in care homes in Birmingham. Aspects relating to screening, individualised care plans and support to care home staff still need attention.

CloudMPL:a domain specific language for describing management policies for an autonomic cloud infrastructure

To benefit from the advantages that Cloud Computing brings to the IT industry, management policies must be implemented as a part of the operation of the Cloud. Among others, for example, the specification of policies can be used for the management of energy to reduce the cost of running the IT system or also for security policies while handling privacy issues of users. As cloud platforms are large, manual enforcement of policies is not scalable. Hence, autonomic approaches for management policies have recently received a considerable attention. These approaches allow specification of rules that are executed via rule-engines. The process of rules creation starts by the interpretation of the policies drafted by high-rank managers. Then, technical IT staff translate such policies to operational activities to implement them. Such process can start from a textual declarative description and after numerous steps terminates in a set of rules to be executed on a rule engine. To simplify the steps and to bridge the considerable gap between the declarative policies and executable rules, we propose a domain-specific language called CloudMPL. We also design a method of automated transformation of the rules captured in CloudMPL to the popular rule-engine Drools. As the policies are changed over time, code generation will reduce the time required for the implementation of the policies. In addition, using a declarative language for writing the specifications is expected to make the authoring of rules easier. We demonstrate the use of the CloudMPL language into a running example extracted from a management energy consumption case study.

Modes of action of antibacterial agents

This chapter describes the modes of action of the major antibiotics and synthetic agents used to treat bacterial infections. Particular attention is given to the biochemical mechanisms by which the agents interfere with biosynthetic processes and the basis for their selective antibacterial action. Interference with the biosynthesis and assembly of structural components of the bacterial cell wall provides the basis for many important groups of antibiotics, including the agents targeting steps in peptidoglycan synthesis. Other agents exploit more subtle differences between bacteria and mammalian cells in fundamental processes such as DNA, RNA and protein synthesis.