Urban water security - what does it mean?

This research is focussed on understanding what urban water security means–a surprisingly elusive concept given the global shift from rural to urban living. We first make the case for a distinct urban water security definition. We then identify 25 unique water security definitions, of which three relate to the urban context but all with scope for improvement. Applying novel indices, we assess the prevalence, complexity and evolution of themes and dimensions within all definitions and find a stable spectrum of themes; but note a shifting emphasis towards environmental and social dimensions, away from quality and quantity of supply. Overall the definitions are becoming more comprehensive by simply listing more outcomes to be achieved. Instead of this ‘shopping-list’ approach, we propose a simplified urban water security definition with a focus on agreement of needs with community stakeholders, while using the themes to guide what the objectives might be

Nutrient-stimulated insulin secretion in mouse islets is critically dependent on intracellular pH

BACKGROUND: Many mechanistic steps underlying nutrient-stimulated insulin secretion (NSIS) are poorly understood. The influence of intracellular pH (pH(i)) on insulin secretion is widely documented, and can be used as an investigative tool. This study demonstrates previously unknown effects of pH(i)-alteration on insulin secretion in mouse islets, which may be utilized to correct defects in insulin secretion. METHODS: Different components of insulin secretion in mouse islets were monitored in the presence and absence of forced changes in pH(i). The parameters measured included time-dependent potentiation of insulin secretion by glucose, and direct insulin secretion by different mitochondrial and non-mitochondrial secretagogues. Islet pH(i )was altered using amiloride, removal of medium Cl(-), and changing medium pH. Resulting changes in islet pH(i )were monitored by confocal microscopy using a pH-sensitive fluorescent indicator. To investigate the underlying mechanisms of the effects of pH(i)-alteration, cellular NAD(P)H levels were measured using two-photon excitation microscopy (TPEM). Data were analyzed using Student's t test. RESULTS: Time-dependent potentiation, a function normally absent in mouse islets, can be unmasked by a forced decrease in pH(i). The optimal range of pH(i )for NSIS is 6.4–6.8. Bringing islet pH(i )to this range enhances insulin secretion by all mitochondrial fuels tested, reverses the inhibition of glucose-stimulated insulin secretion (GSIS) by mitochondrial inhibitors, and is associated with increased levels of cellular NAD(P)H. CONCLUSIONS: Pharmacological alteration of pH(i )is a potential means to correct the secretory defect in non-insulin dependent diabetes mellitus (NIDDM), since forcing islet pH(i )to the optimal range enhances NSIS and induces secretory functions that are normally absent

Critical Role of Gap Junction Coupled K(ATP) Channel Activity for Regulated Insulin Secretion

Pancreatic β-cells secrete insulin in response to closure of ATP-sensitive K(+) (K(ATP)) channels, which causes membrane depolarization and a concomitant rise in intracellular Ca(2+) (Ca(i)). In intact islets, β-cells are coupled by gap junctions, which are proposed to synchronize electrical activity and Ca(i) oscillations after exposure to stimulatory glucose (>7 mM). To determine the significance of this coupling in regulating insulin secretion, we examined islets and β-cells from transgenic mice that express zero functional K(ATP) channels in approximately 70% of their β-cells, but normal K(ATP) channel density in the remainder. We found that K(ATP) channel activity from approximately 30% of the β-cells is sufficient to maintain strong glucose dependence of metabolism, Ca(i), membrane potential, and insulin secretion from intact islets, but that glucose dependence is lost in isolated transgenic cells. Further, inhibition of gap junctions caused loss of glucose sensitivity specifically in transgenic islets. These data demonstrate a critical role of gap junctional coupling of K(ATP) channel activity in control of membrane potential across the islet. Control via coupling lessens the effects of cell–cell variation and provides resistance to defects in excitability that would otherwise lead to a profound diabetic state, such as occurs in persistent neonatal diabetes mellitus

Amiloride derivatives enhance insulin release in pancreatic islets from diabetic mice

BACKGROUND: Amiloride derivatives, commonly used for their diuretic and antihypertensive properties, can also cause a sustained but reversible decrease of intracellular pH (pH(i)). Using dimethyl amiloride (DMA) on normal rodent pancreatic islets, we previously demonstrated the critical influence of islet pH(i )on insulin secretion. Nutrient-stimulated insulin secretion (NSIS) requires a specific pH(i)-range, and is dramatically enhanced by forced intracellular acidification with DMA. Furthermore, DMA can enable certain non-secretagogues to stimulate insulin secretion, and induce time-dependent potentiation (TDP) of insulin release in mouse islets where this function is normally absent. The present study was performed to determine whether pH(i)-manipulation could correct the secretory defect in islets isolated from mice with type 2 diabetes. METHODS: Using two mouse models of type 2 diabetes, we compared a) pHi-regulation, and b) NSIS with and without treatment with amiloride derivatives, in islets isolated from diabetic mice and wild type mice. RESULTS: A majority of the islets from the diabetic mice showed a slightly elevated basal pH(i )and/or poor recovery from acid/base load. DMA treatment produced a significant increase of NSIS in islets from the diabetic models. DMA also enabled glucose to induce TDP in the islets from diabetic mice, albeit to a lesser degree than in normal islets. CONCLUSION: Islets from diabetic mice show some mis-regulation of intracellular pH, and their secretory capacity is consistently enhanced by DMA/amiloride. Thus, amiloride derivatives show promise as potential therapeutic agents for type 2 diabetes

Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure

We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Energy expenditure and brown adipose tissue metabolism in Asxl2ΔLysM mice were protected from the suppressive effects of HFD, a phenomenon associated with relatively increased catecholamines likely due to their suppressed degradation by macrophages. White adipose tissue of HFD-fed Asxl2ΔLysM mice also exhibited none of the pathological remodeling extant in their control counterparts. Suppression of macrophage Asxl2 expression, via nanoparticle-based siRNA delivery, prevented HFD-induced obesity. Thus, ASXL2 controlled the response of macrophages to dietary factors to regulate metabolic homeostasis, suggesting modulation of the cells\u27 inflammatory phenotype may impact obesity and its complications

Platelet rich plasma injection grafts for musculoskeletal injuries: a review

In Europe and the United States, there is an increasing prevalence of the use of autologous blood products to facilitate healing in a variety of applications. Recently, we have learned more about specific growth factors, which play a crucial role in the healing process. With that knowledge there is abundant enthusiasm in the application of concentrated platelets, which release a supra-maximal quantity of these growth factors to stimulate recovery in non-healing injuries. For 20 years, the application of autologous PRP has been safely used and documented in many fields including; orthopedics, sports medicine, dentistry, ENT, neurosurgery, ophthalmology, urology, wound healing, cosmetic, cardiothoracic, and maxillofacial surgery. This article introduces the reader to PRP therapy and reviews the current literature on this emerging treatment modality. In summary, PRP provides a promising alternative to surgery by promoting safe and natural healing. However, there are few controlled trials, and mostly anecdotal or case reports. Additionally the sample sizes are frequently small, limiting the generalization of the findings. Recently, there is emerging literature on the beneficial effects of PRP for chronic non-healing tendon injuries including lateral epicondylitis and plantar fasciitis and cartilage degeneration (Mishra and Pavelko, The American Journal of Sports Medicine 10(10):1–5, 2006; Barrett and Erredge, Podiatry Today 17:37–42, 2004). However, as clinical use increases, more controlled studies are needed to further understand this treatment