PGE1 abolishes the mitochondrial-independent cell death pathway induced by D-galactosamine in primary culture of rat hepatocytes

Background and Aim:  PGE₁ reduces in vivo and in vitro D-galactosamine (D-GalN)-induced cell death in hepatocytes. The present study was undertaken to elucidate the intracellular pathway by which D-GalN induces cell death in cultured hepatocytes. In addition, we evaluated if PGE₁ was able to modulate different parameters related to D-GalN-induced apoptosis in cultured rat hepatocytes.
Methods:  Hepatocytes were isolated from male Wistar rats (225–275 g) by the classical collagenase procedure. PGE₁ (1 µM) was administered 2 h before D-GalN (5 mM) in primary culture of rat hepatocytes. Apoptosis was determined by DNA fragmentation and caspase-3, -6, -8 and -9 activation in hepatocytes. Caspase activation was evaluated by the detection of the related cleaved product and its associated activity. Cell necrosis was determined by the measurement of lactate dehydrogenase (LDH) activity in culture medium. To elucidate the role of mitochondria, we measured neutral (nSMase) and acid (aSMase) sphingomyelinase, as well as the expression of cytochrome c in mitochondria and cytoplasm fractions from D-GalN treated hepatocytes.
Results:  D-GalN induced caspase-3 activation and DNA fragmentation in hepatocytes. This apoptotic response was not associated with the activation of caspase-6, -8 or -9. The use of specific inhibitors confirmed that only caspase-3 was involved in D-GalN-induced apoptosis. D-GalN did not modify nSMase and aSMase activities, nor mitochondrial cytochrome c release in hepatocytes.
Conclusions:  D-GalN induced apoptosis through caspase-3 activation but without modification of the activity of caspase-6, -8, -9, SMases or cytochrome c release. PGE₁ appears to prevent D-GalN-induced apoptosis by a mitochondria-independent mechanism.     

High sensitivity cardiac troponin T and interleukin‐6 predict adverse cardiovascular events and mortality in anticoagulated patients with atrial fibrillation

Summary. There are limited data on the prognostic role of biomarkers in anticoagulated patients with atrial fibrillation (AF). We evaluated the prognostic value of high sensitivity TnT (hsTnT) and high‐sensitivity interleukin‐6 (hsIL6) in a large cohort of AF patients taking oral anticoagulant therapy (OAC) as both biomarkers have been associated with adverse cardiovascular events. Methods: We studied 930 patients (51% male; median age 76) with permanent/ paroxysmal AF who were stabilized (for at least 6 months) on OAC (INRs 2.0–3.0). Plasma hsTnT and hsIL6 levels were quantified by electrochemiluminescense immunoassay at baseline. Patients were followed‐up for up to 2 years, and adverse events (thrombotic and vascular events, mortality and major bleeding) were recorded. Results: At follow‐up, 96 patients (3.97%/year) died whilst 107 had an adverse cardiovascular event (3.14%/year). On multivariate analysis, high hsTnT and high hsIL6 remained significantly associated with prognosis even after adjusting for CHADS₂ score: HR 2.21 (1.46–3.35, P < 0.001) for high hsTnT and 1.97 (1.29–3.02, P = 0.002) for high hsIL6, for adverse cardiovascular events. For all‐cause mortality, the HRs were 1.79 (1.13–2.83, P = 0.013) and 2.48 (1.60–3.85, P < 0.001), respectively. The integrated discrimination index (IDI) values of clinical scores (CHADS₂ and CHA₂DS₂‐VASc) were improved by the addition of hsTnT and/or hsIL6 (all P < 0.05). Conclusion: In a large ‘real world’ cohort of anticoagulated AF patients, both hsTnT and hsIL6 levels provided prognostic information that was complementary to clinical risk scores for prediction of long‐term cardiovascular events and death, suggesting that these biomarkers may potentially be used to refine clinical risk stratification in AF.     

A dermoid cyst fistulating with the transverse colon

We present a rare case of fistulation of a dermoid cyst with the transverse colon. We illustrate how an infected dermoid cyst can be diagnosed as an appendix abscess although the management of these is quite different. The general surgeon should be aware of this as a differential diagnosis for an appendix abscess.     

Evaluation of the effect of static magnetic field in treatment of tendon injuries in dog

To assess the effect of magnetic field in experimental tendon injuries, ten clinically healthy adult indigenous dogs were divided into two equal groups (control and experimental). The left superficial digital flexor tendon was exposed and three windows of 6 mm thickness, 3 mm length, and 2 mm intervals were made under general anesthesia. In the experimental group, the dogs were subjected to a magnetic field of 6?×?800 G for 30 days. The tendon biopsy was collected from the site of operation on the postoperative day 30. Histomorphological changes indicated low rate of inflammatory cells, high rate of mature fibroblast, and increased normal collagen fibers, and these were better in the experimental group. The biomechanical test revealed that the tendons of the dogs in the experimental group were more resistant than tendons of the dogs in the control group. The result of this study indicated that magnetic field therapy reduced edema and local swelling, enhanced proliferation of fibroblasts, and regulated arrangement of collagen fibers, providing a good noninvasive physical therapy for tendinous injuries.     

The incidence and natural history of knee osteoarthritis in the elderly,the framingham osteoarthritis study

Objective. To determine the incidence of radiographic knee osteoarthritis (OA) and symptomatic OA (symptoms plus radiographic OA), as well as the rate of progression of preexisting radiographic OA in a population-based sample of elderly persons. Methods. Framingham Osteoarthritis Study subjects who had knee radiographs and had answered questions about knee symptoms in 1983–1985 were reexamined in 1992–1993 (mean 8.1-year interval) using the same protocol. Subjects were defined as having new (incident) radiographic OA if they developed grade ≤2 OA (at least definite osteophytes or definite joint space narrowing). New symptomatic OA was present if subjects developed a combination of knee symptoms and grade ≤2 OA. Progressive OA was diagnosed when radiographs showing grade 2 disease at baseline showed grade ≤3 disease on followup. Results. Of 1,438 participants in the original study, 387 (26.9%) died prior to followup. Of the 1,051 surviving subjects, 869 (82.7%) participated in the followup study (mean ± SD age 70.8 ± 5.0 at baseline). Rates of incident disease were 1.7 times higher in women than in men (95% confidence interval [CI] 1.0–2.7), and progressive disease occurred slightly more often in women (relative risk = 1.4; 95% CI 0.8–2.5) but rates did not vary by age in this sample. Among women, approximately 2% per year developed incident radiographic disease, 1% per year developed symptomatic knee OA, and about 4% per year experienced progres- sive knee OA. Conclusion. In elderly persons, the new onset of knee OA is frequent and is more common in women than men. However, among the elederly, age may not affect new disease occurrence or progression.     

Investigation of the biological activity,mechanical properties and wound healing application of a novel scaffold based on lignin–agarose hydrogel and silk fibroin embedded zinc chromite nanoparticles

Given the important aspects of wound healing approaches, in this work, an innovative biocompatible nanobiocomposite scaffold was designed and prepared based on cross-linked lignin–agarose hydrogel, extracted silk fibroin solution, and zinc chromite (ZnCr₂O₄) nanoparticles. Considering the cell viability technique, red blood cell hemolysis in addition to anti-biofilm assays, it was determined that after three days, the toxicity of the cross-linked lignin–agarose/SF/ZnCr₂O₄ nanobiocomposite was less than 13%. Moreover, the small hemolytic effect (1.67%) and high level of prevention in forming a P. aeruginosa biofilm with low OD value (0.18) showed signs of considerable hemocompatibility and antibacterial activity. Besides, according to an in vivo assay study, the wounds of mice treated with the cross-linked lignin–agarose/SF/ZnCr₂O₄ nanobiocomposite scaffold were almost completely healed in five days. Aside from these biological tests, the structural features were evaluated by FT-IR, EDX, FE-SEM, and TG analyses, as well as swelling ratio, rheological, and compressive mechanical study tests. Additionally, it was concluded that adding silk fibroin and ZnCr₂O₄ nanoparticles could enhance the mechanical tensile properties of cross-linked lignin–agarose hydrogel, and also an elastic network was characterized for this designed nanobiocomposite.

Given the important aspects of wound healing approaches, in this work, an innovative biocompatible nanobiocomposite scaffold was designed and prepared based on cross-linked lignin–agarose hydrogel, extracted silk fibroin solution, and zinc chromite (ZnCr₂O₄) nanoparticles.     

1型糖尿病患儿的课堂注意力：稳定血糖的效果

目的:观察评估通过使用胰岛素泵以稳定血糖,是否可以改善1型糖尿病患儿的课堂注意力。试验设计:对4例患有1型糖尿病且血糖水平不稳定的患儿在课堂中的表现进行为期10d的观察。在放置胰岛素泵,控制血糖后再观察10d。利用改良多基线设计血糖控制水平是否与患儿专注于功课和走神行     

Bronchography in the recognition of congenital cystic bronchiectasis.

Congenital cystic bronchiectasis is an uncommon disease. Most of the reported cases have been in infants and young children. This paper presents four cases of older children and younger adults who had congenital cystic bronchiectasis. Distribution of the disease is lobar or may even involve an entire lung. Bronchography plays an important role in the diagnosis of congenital cystic bronchiectasis. The three important bronchographic signs of congenital cystic bronchiectasis are: (1) absence of contrast filling of the bronchial glands duct; (2) contrast filling of numerous cysts which communicate directly with the bronchial tree; and (3) nonvisualization of normal lung parenchyma within the area of involvement.     

Inhibition of lipolysis improves insulin sensitivity in protease inhibitor-treated HIV-infected men with fat redistribution

BACKGROUND: Fatty acid concentrations are increased in patients with HIV and fat redistribution and may contribute to insulin resistance in this population. OBJECTIVE: We determined the effects of acute inhibition of lipolysis on insulin sensitivity in HIV-infected patients with fat redistribution who were receiving a protease inhibitor. DESIGN: Seven HIV-infected men [age: 45 +/- 2 y; body mass index (in kg/m(2)): 28.8 +/- 1.9] with a fasting insulin concentration > or= 104 pmol/L (15 micro IU/mL), combined visceral adiposity and peripheral lipoatrophy, and receiving a protease inhibitor were studied. Tolbutamide-modified frequently sampled intravenous-glucose-tolerance tests (FSIGTTs) were performed after randomized double-blind administration of acipimox (500 mg at -90 and 0 min), a potent inhibitor of lipolysis, and placebo. The subjects completed 2 FSIGTTs separated by 3-7 d. RESULTS: At baseline, fasting insulin and fatty acid concentrations were 27.6 +/- 5.0 micro IU/mL and 0.83 +/- 0.08 mmol/L (normal range: 0.1-0.6 mmol/L), respectively. Fatty acid concentrations were significantly reduced after acipimox compared with placebo (fatty acid area under the curve: acipimox = 73 +/- 8 compared with placebo = 122 +/- 12 mmol x 270 min/L, P = 0.002). Acipimox treatment resulted in a significant increase in the insulin sensitivity index (acipimox = 1.63 +/- 0.5 compared with placebo = 0.88 +/- 0.3 x 10(-4) x min(-1) x micro IU/mL, P = 0.015). CONCLUSIONS: Acute inhibition of lipolysis and reduction in fatty acid concentrations are associated with improved insulin sensitivity in patients with HIV lipodystrophy and hyperinsulinemia. Further studies are needed to determine whether long-term antilipolytic strategies to reduce fatty acid concentrations may be useful in treating the metabolic disturbances associated with HIV lipodystrophy.