Heat shock protein induction in rat pancreatic islets by recombinant human interleukin 1β

Summary Interleukin 1, potentiated by tumour necrosis factor , is cytotoxic to pancreatic Beta cells in vitro. We have hypothesized that interleukin 1 induces oxygen free radicals in Beta cells. Since cytotoxicity induced by free radicals and by heat may activate the same cellular repair mechanism (the heat shock response), the aim of this study was to investigate the pattern of protein synthesis in isolated islets after exposure to interleukin 1 (150 pg/ml, 24 h), tumour necrosis factor (50 ng/ml, 24 h), heat shock (43°C, 30 min) and H₂O₂ (0.1 mmol/l, 20 min). By polyacrylamide gel electrophoresis, autoradiography, Western-blot analysis and partial peptide mapping of ³⁵S-methionine labelled islets, interleukin 1 was found to induce a 73 kilodalton protein belonging to the heat shock protein family heat shock protein 70, a heat shock protein 90, and haem oxygenase. A minor induction of heat shock protein 73 and haem oxygenase was seen after H₂O₂. Interleukin 1 did not induce heat shock proteins in rat thyroid cells, rat mesangial cells or in human monocytes. Tumour necrosis factor did not induce selective protein synthesis. Pre-exposure of islets to heat, tumour necrosis factor , or H₂O₂ did not prevent the impairment of glucose-stimulated insulin release seen after 24 h of interleukin 1 exposure. The data are compatible with free radical induction by interleukin 1. However, the heat shock response is not specific for oxidative injury, and previous studies have shown discrepant effects as to a protective effect of free radical scavengers against interleukin 1-mediated beta-cytotoxicity. Thus, a role for free radicals in this context is not definitely proven.     

Early response evaluation of neoadjuvant therapy with PET/MRI to predict resectability in patients with adenocarcinoma of the esophagogastric junction

Abdominal Radiology - Positron emission tomography (PET)/magnetic resonance imaging (MRI) is a new modality that has showed promising results for various clinical indications. Currently, evaluation...     

Diabetic ketoacidosis at the onset of type 1 diabetes is associated with future HbA1c levels

Aims/hypothesis

We investigated the long-term impact of diabetic ketoacidosis (DKA) at onset on metabolic regulation and residual beta cell function in a Danish population with type 1 diabetes.

Methods

The study is based on data from DanDiabKids, a Danish national diabetes register for children. The register provides clinical and biochemical data on patients with type 1 diabetes diagnosed in 1996–2009 and then followed-up until 1 January 2012. Repeated-measurement models were used as statistical methods.

Results

The study population comprised 2,964 children <18 years. The prevalence of DKA at diagnosis was 17.9%. Of the total subjects, 8.3% had mild, 7.9% had moderate and 1.7% had severe DKA. DKA (moderate and severe) was associated with increased HbA_1c (%) levels (0.24; 95% CI 0.11, 0.36; p?=?0.0003) and increased insulin dose-adjusted HbA_1c (IDAA_1c, 0.51; 95% CI 0.31, 0.70; p?<?0.0001) during follow-up, after adjustment for covariates. Children without a family history of diabetes were more likely to present with DKA (19.2% vs 8.8%, p?<?0.0001); however, these children had a lower HbA_1c (%) level over time (?0.35; 95% CI ?0.46, ?0.24; p?<?0.0001). Continuous subcutaneous insulin infusion (CSII) was associated with a long-term reduction in HbA_1c, changing the effect of DKA, after adjustment for covariates (p?<?0.0001).

Conclusions/interpretation

DKA at diagnosis was associated with poor long-term metabolic regulation and residual beta cell function as assessed by HbA_1c and IDAA_1c, respectively; however, CSII treatment was associated with improvement in glycaemic regulation and residual beta cell function, changing the effect of DKA at onset in our population.     

Segmental hypersensitivity and spinothalamic function in spinal cord injury pain

The mechanisms underlying central pain following spinal cord injury (SCI) are unsettled. The purpose of the present study was to examine differences in spinothalamic tract function below injury level and evoked pain in incomplete SCI patients with neuropathic pain below injury level (central pain) versus those without such pain. A clinical examination, quantitative sensory testing and magnetic resonance imaging (MRI) were performed in 10 SCI patients with below-level pain and in 11 SCI patients without neuropathic pain. Patients with and without pain had similar reductions of mechanical and thermal detection thresholds below injury level. SCI patients with central pain had sensory hypersensitivity in dermatomes corresponding to the lesion level more frequently than SCI patients without pain, but this may in part be explained by the exclusion of at-level spontaneous pain in the pain-free group. The rostral-caudal extent of the lesion measured by MRI did not differ between the two patient groups, and there were no statistically significant differences in any of the predefined areas of interest on the axial plane images. This study suggests that neuronal hyperexcitability plays a key role in central SCI pain and furthermore - in contrast to previous findings - that loss of spinothalamic functions does not appear to be a predictor for central neuropathic pain in spinal cord injury.     

Early detection of the first episode of schizophrenia and suicidal behavior

OBJECTIVE: The suicide rate in schizophrenia is high, with the risk being highest early in the course. The rate of suicide attempts before treatment onset is also high and is often the event leading up to first treatment contact. A previous report showed that the duration of untreated psychosis can be reduced through an early detection program, and that the reduction was associated with lower symptom levels at treatment initiation. Treatment programs that bring first-episode patients into treatment at lower symptom levels can have the potential to reduce risk for suicide attempts. METHOD: The authors examined consecutive patients with nonorganic, nonaffective psychosis who sought initial treatment at psychiatric treatment units in four catchment areas: two that had an early detection program and two that did not. RESULTS: The rate of severe suicidality (plans or attempts) was significantly higher in subjects from communities without the early detection program relative to those from early detection communities, even after adjustments for known predictors of suicidality. CONCLUSION: Early detection programs that bring patients into treatment at lower symptom levels may reduce suicidality risk at first treatment contact.