Plos One
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Role of GLP-1 and GIP in beta cell compensatory responses to beta cell attack and insulin resistance were examined in C57BL/6 mice lacking functional receptors for GLP-1 and GIP. Mice were treated with multiple low dose streptozotocin or hydrocortisone. Islet parameters were assessed by immunohistochemistry and hormone measurements were determined by specific enzyme linked immunoassays. ⋯ The metabolic responses to streptozotocin in GLP-1RKO and GIPRKO mice were broadly similar to C57BL/6 controls, although decreases in islet numbers and size were more severe. In contrast, both groups of mice lacking functional incretin receptors displayed substantially impaired islet adaptations to insulin resistance induced by hydrocortisone, including marked curtailment of expansion of islet area, beta cell mass and islet number. Our observations cannot be explained by simple changes in circulating incretin concentrations, suggesting that intra-islet GLP-1 and GIP make a significant contribution to islet adaptation, particularly expansion of beta cell mass and compensatory islet compensation to hydrocortisone and insulin resistance.
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Various pathways have been implicated in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFPEF). Inflammation in response to comorbid conditions, such as hypertension and diabetes, may play a proportionally larger role in HFPEF as compared to HF with reduced ejection fraction (HFREF). ⋯ Inflammation mediated through TNFα and its receptors, TNFR1 and TNFR2, may represent an important component of a comorbidity-induced inflammatory response that partially drives the pathophysiology of HFPEF.
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To explore beliefs and apprehensions about disease and its treatment in patients with rheumatoid arthritis and spondyloarthritis. ⋯ Patients with rheumatoid arthritis and spondyloarthritis hold a core set of beliefs and apprehensions that reflect their level of information about their disease and are not necessarily appropriate. The physician can initiate discussion of these beliefs in order to dispel misconceptions, align treatment expectations, provide reassurance to the patient and readjust disease management. Such a dialogue would help improve standards of care in these chronic and incapacitating diseases.
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Ganglioside as a neurotrophic drug has been hitherto widely used in China, although Guillain-Barré syndrome (GBS) following intravenous ganglioside treatment was reported in Europe several decades ago. We identified 7 patients who developed GBS after intravenous use of gangliosides (ganglioside+ group) and compared their clinical data with those of 77 non-ganglioside-associated GBS patients (ganglioside- group) in 2013, aiming at gaining the distinct features of ganglioside-associated GBS. Although the mean age, protein levels in cerebrospinal fluid (CSF) and frequency of cranial nerve involvement were similar between the two groups, the Hughes Functional Grading Scale (HFGS) score and the Medical Research Council (MRC) sum score at nadir significantly differed (4.9 ± 0.4 vs 3.6 ± 1.0; 7.7 ± 5.5 vs 36.9 ± 14.5, both p<0.001), indicating a higher disease severity of ganglioside-associated GBS. ⋯ Anti-GM1 and anti-GT1a antibodies were detectable in patients with AMAN while not in patients with the demyelinating subtype of GBS. The concentrations of these antibodies in patients with AMAN were insignificantly different between the ganglioside+ and ganglioside- groups. In sum, ganglioside-associated GBS may be a devastating side effect of intravenous use of gangliosides, which usually manifests a more severe clinical course and poorer outcome.
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To date there has been limited analysis of the economic costs and benefits associated with cannabis legalisation. This study redresses this gap. A cost benefit analysis of two cannabis policy options the status quo (where cannabis use is illegal) and a legalised-regulated option was conducted. ⋯ Examining the percentiles around the two policy options, there appears to be no difference between the NSB for these two policy options. Economic analyses are essential for good public policy, providing information about the extent to which one policy is substantially economically favourable over another. In cannabis policy, for these two options this does not appear to be the case.