β-Cell Lipotoxicity in Response to Free Fatty Acid Elevation in Prepubertal Youth: African American Versus Caucasian Contrast

Prepubertal African American (AA) youth compared with their Caucasian (C) peers have higher insulin secretion, which correlates positively with free fatty acid (FFA) concentration. In our continued efforts to explain the racial disparity in insulinemia, and because FFAs modulate insulin secretion, we hypothesized that AA youth would have a greater response to FFA-induced β-cell insulin secretion than C youth. We compared the short-term effects of FFA elevation on fasting and glucose-stimulated C-peptide–modeled insulin secretion in prepubertal normal-weight AA versus C peers during a 2-h hyperglycemic clamp (12.5 mmol/L) on two occasions: 1) infusion of normal saline and 2) infusion of 20% intralipid (IL). During IL infusion, insulin sensitivity (IS) declined comparably in AA and C youth. Glucose sensitivity of first- and second-phase insulin secretion showed a significant condition × race interaction being higher in AA youth. Disposition index, β-cell function relative to IS, declined with IL infusion in AA and C youth, with a significantly greater decrease in Cs compared with AAs. In conclusion, AA and C prepubertal youth both demonstrated a decline in β-cell function relative to IS during IL infusion, indicative of acute lipotoxicity. The greater decline in C youth compared with AAs may suggest that C youth are more susceptible to β-cell lipotoxicity than AA youth, or alternatively, that AA youth are hypersensitive to FFA stimulation of β-cell insulin secretion, consistent with our theory.Short-term exposure to elevated free fatty acid (FFA) concentrations has a stimulatory effect on β-cell function in in vitro and in vivo animal and human studies (1–8). On the other hand, chronic exposure to sustained elevations in FFAs has been shown to decrease insulin secretion and result in β-cell lipotoxicity in in vitro rat and human islet experiments (4,9,10) and in vivo human experiments (1,5,7,11,12).We previously found that prepubertal African American (AA) youth have higher insulin secretion and an upregulated β-cell function relative to insulin sensitivity (IS) compared with their Caucasian (C) peers (13). The hyperinsulinemic response in AA youth appears to be greater than the compensatory response to their lower IS, because the disposition index (DI), which is insulin secretion relative to IS, was ∼75% higher in AA than in C youth (13). Furthermore, first- and second-phase insulin concentrations during the hyperglycemic clamp correlated positively and significantly with fasting FFA levels in AAs but not Cs, despite similar plasma FFA concentrations (13). We therefore hypothesized that the higher insulin secretion in AA prepubertal youth could be driven by a greater sensitivity to the stimulatory effects of FFA on insulin secretion and β-cell function. Thus, in the present investigation we examined the effects of FFA elevation on glucose-stimulated insulin secretion in AA and C prepubertal normal-weight children, expecting to observe a heightened response in AA children.     

Instabilitätsmuster bei Akromioklavikulargelenkverletzungen vom Typ Rockwood III

Background

There is no evidence-based treatment algorithm established for acromioclavicular joint (AC joint) dislocation classified as type Rockwood III injury. Recent meta-analyses revealed no advantage of surgical treatment compared to the non-operative approach. Both surgical and non-surgical approaches have been reported with inconsistent results. Therefore, the hypothesis of the current study was that patients classified as having Rockwood grade III injury may have different degrees of horizontal AC joint instability.

Material and methods

A total of 18 consecutive patients who had sustained a dislocation of the AC joint classified as Rockwood III were evaluated radiologically to quantify the horizontal instability of the AC joint. The specific radiological investigation included lateral stress x-rays (Alexander view) und axial stress x-rays with the affected arm in a horizontal adduction position.

Results

The dynamic horizontal instability of the AC joint was found to be independent of the vertical dislocation measured in the Rockwood classification.

Conclusion

For further treatment studies Rockwood III injuries should be distinguished in patients presenting with or without a substantial horizontal AC joint instability.     

Incidence of stroke and acute renal failure in patients of postoperative atrial fibrillation after myocardial revascularization

Introduction

Postoperative atrial fibrillation is the most common arrhythmia in cardiac surgery, its incidence range between 20% and 40%.

Objective

Quantify the occurrence of stroke and acute renal insufficiency after myocardial revascularization surgery in patients who had atrial fibrillation postoperatively.

Methods

Cohort longitudinal bidirectional study, performed at Portuguese Beneficent Hospital (SP), with medical chart survey of patients undergoing myocardial revascularization surgery between June 2009 to July 2010. From a total of 3010 patients were weaned 382 patients that presented atrial fibrillation preoperatively and/or associated surgeries. The study was conducted in accordance with national and international following resolutions: ICH Harmonized Tripartite Guidelines for Good Clinical Practice - 1996; CNS196/96 Resolution, and Declaration of Helsinki.

Results

The 2628 patients included in this study were divided into two groups: Group I, who didn''t show postoperative atrial fibrillation, with 2302 (87.6%) patients; and group II, with 326 (12.4%) who developed postoperative atrial fibrillation. The incidence of stroke in patients was 1.1% without postoperative atrial fibrillation vs. 4% with postoperative atrial fibrillation (P<0.001). Postoperative acute renal failure was observed in 12% of patients with postoperative atrial fibrillation and 2.4% in the group without postoperative atrial fibrillation (P<0.001), that is a relation 5 times greater.

Conclusion

In this study there was a high incidence of stroke and acute renal failure in patients with postoperative atrial fibrillation, with rates higher than those reported in the literature.     

Effect of photobiomodulation on expression of IL-1β in skeletal muscle following acute injury

Muscle repair is regulated by growth factors and cytokines. Low-level laser therapy (LLLT) seems to influence acute inflammation and accelerate skeletal muscle repair. This study verifies the effect of LLLT on the expression of IL-1β in the tibialis anterior (TA) muscle of rats following acute injury. Wistar rats (n?=?35) were allocated into three groups: control (without lesion and LLLT, n?=?5), injury group (n?=?15), and injury + LLLT group (n?=?15). The acute injury was induced by the contact with a cooled metal probe (3 mm in diameter) during 10 s, twice, in the same muscle area. LLLT was used three times a week using the InGaAlP laser (660 nm; beam spot of 0.04 cm², output power of 20 mW, power density of 500 mW/cm², and energy density of 5 J/cm² during 10 s). The animals were analyzed at 1, 7, and 14 days following injury. TA muscles samples were used for obtaining total RNA and performing cDNA synthesis. Real-time polymerase chain reactions were realized using IL-1β primer. There was a decrease in IL-1β expression after 7 days in LLLT group in comparison with the no treated group. In conclusion, LLLT was able to decrease IL-1β expression during the skeletal muscle repair following an acute injury.     

The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents: effects of long-term interdisciplinary therapy

To investigate the role of pro- and anti-inflammatory adipokines in the bone metabolism of non-alcoholic fatty liver disease (NAFLD) obese adolescents as well as the effects of long-term interdisciplinary therapy on metabolic-related risk factors. Forty post-puberty obese adolescents were randomly assigned into two groups: (1) NAFLD group and (2) non-NAFLD group (diagnosis by ultrasonography) and submitted to a weight loss therapy. Body composition was analyzed by air displacement plethysmography, bone mineral density (BMD) and content by dual-energy X-ray absorptiometry, blood samples were collected to measure lipid profile, hepatic enzymes, and adipokines. Leptin and adiponectin concentrations were measured by ELISA. A decrease in total body mass, BMI, body fat, visceral and subcutaneous fat, insulin concentration, HOMA-IR, total cholesterol and an increase in lean body mass were observed in both groups after therapy. It was found positive correlation between the Δ BMD and the Δ fat mass (%) (r = 0.31, P = 0.01) and negative correlations between Δ BMC with Δ HOMA-IR (r = -0.34, P = 0.02) and Δ HOMA-IR with Δ leptin (r = -0.34, P = 0.02). In addition, increased levels of adiponectin and reduction in leptin concentrations were observed in NAFLD group. In the simple regression analysis, the HOMA-IR was an independent predictor changes in BMC in total obese adolescents and in the non-NAFLD group. One year of interdisciplinary weight loss therapy for obese adolescents with or without NAFLD, could regulate bone mineral metabolism as result of an increased BMC and improved inflammatory state.     

Primary biliary cirrhosis in a rheumatoid arthritis patient treated with rituximab, a case-based review

Primary biliary cirrhosis (PBC) is an autoimmune disease in which intrahepatic bile ducts are targeted by an immune-mediated injury. This disease tends to progress to fibrosis and cirrhosis with hepatic failure. The authors report a case of a 50-year-old rheumatoid arthritis (RA) patient, with erosions and seropositive for rheumatoid factor and anti-citrullinated peptide antibodies, with 18 years disease duration refractory to prednisolone and several disease-modifying antirheumatic drugs, either conventional or biological (adalimumab and etanercept). In April 2007, she started therapy with rituximab (RTX) with good European League Against Rheumatism response achieved 9 months later. In June 2008, she was admitted with intrahepatic cholestasis, steatorrhea, and spontaneous fractures of various ribs. After excluding cholelitiasis, as well as infectious and neoplastic diseases a liver biopsy was performed that was compatible with the diagnosis of PBC. The antinuclear antibodies (1/160) were positive as well as the antimitochondrial antibodies (1/640). Other antibodies were negative such as anti-SSA and anti-SSB. Afterwards, the patient started ursodesoxycholic acid 15 mg kg^-1 day^-1 with progressive improvement of cholestatic markers. A labial salivary gland biopsy was performed and showed findings compatible with the concomitant diagnosis of Sjögren’s syndrome. Based on this clinical report, a detailed review of the clinical aspects of PBC is presented as well as its association with other immune-mediated inflammatory diseases, particularly, with RA.