Involvement of thioredoxin-interacting protein (TXNIP) in glucocorticoid-mediated beta cell death

Aim/hypothesis  

Glucocorticoid hormones (GCs) are widely used to treat a variety of inflammatory and immune diseases. However, their long-term administration is associated with adverse metabolic effects, including glucose intolerance and diabetes. Our objective was to elucidate the mechanisms by which GCs affect beta cell survival with a specific emphasis on the role of the thioredoxin-interacting protein (TXNIP) in beta cell apoptosis.     

Association between childhood nephrotic syndrome and hemophagocytic lymphohistiocytosis

Background

Hemophagocytic lymphohistiocytosis (HLH) is caused by an excessive activation of nonmalignant macrophages. Renal lesions have been described in association with, but always after, HLH diagnosis.

Case-diagnosis

We describe a previously healthy 26-month-old girl who presented originally with steroid-responsive nephrotic syndrome (NS), but after 4 months, on the first NS relapse, experienced numerous complications (many of them reported to accompany NS as single events). Clinical and laboratory signs of HLH evolved with time and led to deterioration of her condition and death, within 5 months of her original presentation.

Conclusions

To our knowledge, this is the first report of NS antedating the presentation of HLH.     

Plasma neutrophil gelatinase-associated lipocalin as a biomarker for acute kidney injury in critically ill patients with suspected sepsis

Objectives

The aim of this study was to investigate the diagnostic utility of plasma neutrophil gelatinase-associated lipocalin (NGAL) as an early objective biomarker to predict acute kidney injury (AKI) in critically ill patients with suspected sepsis, for whom procalcitonin (PCT) was used for the diagnosis and staging of sepsis.

Design and methods

Plasma NGAL was measured using the Triage NGAL Test (Alere, Inc., San Diego, CA, USA) in 231 samples obtained from patients with suspected sepsis. The results of NGAL were compared with those of Elecsys BRAHMS PCT (Roche Diagnostics, Basel, Switzerland). Renal failure was assessed using the renal subscore of Sepsis-related Organ Failure Assessment (SOFA) score. AKI was defined according to the Acute Kidney Injury Network criteria.

Results

The concentrations of plasma NGAL were significantly different according to the five groups of PCT concentration (P < 0.0001) and the renal subscore of SOFA score (P < 0.0001). Plasma NGAL was significantly increased in the patients with AKI compared with those without AKI (416.5 ng/mL vs. 181.0 ng/mL, P = 0.0223).

Conclusion

Plasma NGAL seems to be a highly sensitive and objective predictor of AKI in patients with sepsis. Plasma NGAL can be added for the diagnosis and staging of renal failure in sepsis.     

Association between transmucosal depth of osseointegrated implants and malodor production

PURPOSE: The aim of the present study was to test the association between transmucosal depth of 2-stage dental implants and malodor production. MATERIALS AND METHODS: Fifty-nine 2-stage implants were tested in 14 patients. Measurements were conducted 3 to 4 weeks following second-stage surgery. Measurements included healing abutment malodor scored using a subjective scale, volatile sulfide compounds levels measured using a sulfide monitor (Halimeter), and microbial sampling for anaerobic growth and malodor production. RESULTS: All the malodor-related parameters measured in this study were significantly associated with the transmucosal depth. A significant increase in severity was observed concomitant with the increase in transmucosal depth. CONCLUSION: Based upon the data from this study of 59 two-stage implants in 14 patients, it appears that transmucosal depth of 2-stage dental implants may be an important factor affecting the presence of anaerobic bacterial population and resulting malodor production within the implant-abutment interface.     

Frequency and natural history of inherited bone marrow failure syndromes: the Israeli Inherited Bone Marrow Failure Registry

Background

Inherited bone marrow failure syndromes are rare genetic disorders characterized by bone marrow failure, congenital anomalies, and cancer predisposition. Available single disease registries provide reliable information regarding natural history, efficacy and side effects of treatments, and contribute to the discovery of the causative genes. However, these registries could not shed light on the true incidence of the various syndromes. We, therefore, established an Israeli national registry in order to investigate the relative frequency of each of these syndromes and their complications.

Design and Methods

Patients were registered by their hematologists in all 16 medical centers in Israel. We included patients with Fanconi anemia, severe congenital neutropenia, Diamond-Blackfan anemia, congenital amegakaryocytic thrombocytopenia, dyskeratosis congenita, Shwachman-Diamond syndrome, and thrombocytopenia with absent radii.

Results

One hundred and twenty-seven patients diagnosed between 1966 and 2007 were registered. Fifty-two percent were found to have Fanconi anemia, 17% severe congenital neutropenia, 14% Diamond-Blackfan anemia, 6% congenital amegakaryocytic thrombocytopenia, 5% dyskeratosis congenita, 2% Shwachman-Diamond syndrome, and 2% thrombocytopenia with absent radii. No specific diagnosis was made in only 2 patients. Of the thirty patients (24%) developing severe bone marrow failure, 80% had Fanconi anemia. Seven of 9 patients with leukemia had Fanconi anemia, as did all 6 with solid tumors. Thirty-four patients died from their disease; 25 (74%) had Fanconi anemia and 6 (17%) had severe congenital neutropenia.

Conclusions

This is the first comprehensive population-based study evaluating the incidence and complications of the different inherited bone marrow failure syndromes. By far the most common disease was Fanconi anemia, followed by severe congenital neutropenia and Diamond-Blackfan anemia. Fanconi anemia carried the worst prognosis, with severe bone marrow failure and cancer susceptibility. Diamond-Blackfan anemia had the best prognosis. The data presented provide a rational basis for prevention programs and longitudinal surveillance of the complications of inherited bone marrow failure syndromes.     

Omega-3 treatment of childhood depression: a controlled, double-blind pilot study

OBJECTIVE: Major depressive disorder in children may be more common than previously thought, and its therapeutics are unclear. Because of success in a previous study on omega-3 fatty acids in adult major depressive disorder, the authors planned a pilot study of omega-3 fatty acids in childhood major depression. METHOD: Children who entered the study were between the ages of 6 and 12. Ratings were performed at baseline and at 2, 4, 8, 12, and 16 weeks using Children's Depression Rating Scale (CDRS), Children's Depression Inventory (CDI), and Clinical Global Impression (CGI). Children were randomized to omega-3 fatty acids or placebo as pharmacologic monotherapy. Twenty-eight patients were randomized, and 20 completed at least 1 month's ratings. RESULTS: Analysis of variance showed highly significant effects of omega-3 on symptoms using the CDRS, CDI, and CGI. CONCLUSIONS: Omega-3 fatty acids may have therapeutic benefits in childhood depression.