Inhibition of cellular responses to insulin in a rat liver cell line. A role for PKC in insulin resistance

The initial response of liver cells to insulin is mediated through exocytosis of Cl⁻ channel-containing vesicles and a subsequent opening of plasma membrane Cl⁻ channels. Intracellular accumulation of fatty acids leads to profound defects in metabolism, and is closely associated with insulin resistance. It is not known whether the activity of Cl⁻ channels is altered in insulin resistance and by which mechanisms. We studied the effects of fatty acid accumulation on Cl⁻ channel opening in a model liver cell line. Overnight treatment with amiodarone increased the fat content by ∼2-fold, and the rates of gluconeogenesis by ∼5-fold. The ability of insulin to suppress gluconeogenesis was markedly reduced indicating that amiodarone treatment induces insulin resistance. Western blot analysis showed that these cells express the same number of insulin receptors as control cells. However, insulin failed to activate exocytosis and Cl⁻ channel opening. These inhibitory effects were mimicked in control cells by exposures to arachidonic acid (15 μ m ). Further studies demonstrated that fatty acids stimulate the PKC activity, and inhibition of PKC partially restored exocytosis and Cl⁻ channel opening in insulin-resistant cells. Accordingly, activation of PKC with PMA in control cells potently inhibited the insulin responses. These results suggest that stimulation of PKC activity in insulin resistance contributes to the inhibition of cellular responses to insulin in liver cells.     

Diabetes education: a chance to improve well-being of Turkish people with type 2 diabetes

To examine the influence of diabetes education on well-being, 255 patients with type 2 diabetes were recruited according to whether they attended a diabetes education program (n=126) or not (n=129). In patients who had participated in the program, the mean anxiety score was significantly lower, whereas positive well-being and general well-being scores were significantly higher than for patients who had not participated. Factors related to lower well-being included: being female, taking insulin, not attending a diabetes education program and having HbA(1c) level greater than 8%. The odds of having better well-being were two-fold higher in patients participating the diabetes education program compared with those who had not. Diabetes education has a crucial role in improving the well-being of patients with type 2 diabetes. All patients with diabetes should be encouraged to attend a diabetes education program.     

Quantitative changes in mast cell populations after left ventricular assist device implantation

Mast cells have been implicated as important in tissue remodeling and fibrosis. We investigated the effect of mechanical ventricular unloading upon myocardial fibrosis and cardiac mast cell density in patients undergoing left ventricular assist device (LVAD) implantation. Paired myocardial tissue samples were obtained from 30 patients with end-stage cardiomyopathy at the time of LVAD implantation and at the time of removal and were compared with samples taken from donor hearts. Tissue sections were stained and quantitated for mast cells and myocardial fibrosis. Mast cell density (tryptase positive cells) in cardiomyopathy was higher than that in donor hearts (33.5 +/- 3.6 SEM cells/10 fields vs.15.2 +/- 2.0 SEM cells/10 fields respectively, p = 0.04) and was lower than LVAD supported hearts (33.5 +/- 3.6 SEM cells/10 fields vs. 49.8 +/- 5.7 SEM cells/10 fields respectively, p = 0.01). Mast cells are primarily localized in areas of increased interstitial fibrosis adjacent to myocardial cells and not vessels. There was statistically significant correlation between mast cells and interstitial collagen (p = 0.03) in patients before LVAD implantation that did not persist after mechanical support (p = 0.18). These results suggest that mechanical support with left ventricular assist devices induces an increase in mast cell number in the myocardium and an associated decrease in myocardial fibrosis. We believe these data demonstrate a dual role for cardiac mast cells in the increase in fibrosis in heart failure and the decrease after LVAD and its associated cardiac improvement.     

Survivin expression in non-small-cell lung carcinomas: correlation with apoptosis and other apoptosis-related proteins, clinicopathologic prognostic factors and prognosis.

The role of survivin that regulates the biological behavior of non-small-cell lung carcinoma (NSCLC) is still controversial. We aimed to investigate survivin expression in NSCLC and to define any correlation with expressions of p53, bcl-2, bax, apoptotic index (AI), tumor cell proliferation, clinicopathologic variables, and overall survival. Tumors of 63 patients with NSCLC were examined for expressions of survivin, p53, bcl-2, bax, and Ki-67 by immunohistochemistry. AI was also evaluated. Results for each antibody were correlated with each other, and with clinicopathologic variables including age, sex, histologic subtype, TNM (T: primary tumor, N: regional lymph node metastasis, M: distant metastasis) stage, lymph node status, smoking history, and prognosis. Nuclear survivin expression was inversely correlated with p53 expression (P = 0.04, r = - 0.367), and tumor stage (P = 0.03, r = - 0.273), and positively correlated with tumor cell proliferation (P = 0.009, r = 0.329). Cytoplasmic survivin expression positively correlated with smoking history (P = 0.02, r = 0.282). Survivin/bax ratio was inversely correlated with AI (r: - 0.004). By Kaplan-Meier analysis, TNM stage (P < or = 0.001), lymph node metastasis (P = 0.04), and Ki-67 index (P < or = 0.001) were associated with survival, whereas survivin was not. In multivariate analysis, only TNM stage was an independent predictor. Although survivin and other apoptosis-related protein expressions fail to predict the clinical outcome, the present findings suggest that survivin is involved in tumor cell apoptosis and proliferation and may play a role in critical steps of cancer progression in NSCLC.     

Dental technician's pneumoconiosis: mineralogical analysis of two cases

Pneumoconiosis was diagnosed by open lung biopsy in two dental technicians who had interstitial lung disease. Mineralogical analysis was performed to investigate the origin of the dust that had been inhaled. A marked accumulation of silicon and phosphorus was found in both cases. The hard metals chromium and cobalt were also found. Dental technician's pneumoconiosis is a complex pneumoconiosis in which such dust and hard metals may play a role.     

Alpha-lipoic acid may ameliorate testicular damage by targeting dox-induced altered antioxidant parameters,mitofusin-2 and apoptotic gene expression

In the study, the ameliorating effects of alfa lipoic acid (ALA) against doxorubicin-induced testicular apoptosis, oxidative stress and disrupted mitochondrial fusion were investigated in male rats. Rats were divided into four groups as control, doxorubicin (DOX), DOX + ALA and ALA. A single dose of 15 mg/kg DOX was administered i.p to the DOX and DOX + ALA groups. 50 mg/kg ALA was given to the DOX + ALA and ALA groups by oral gavage every other day. After 28 days, rat testes and serum samples were collected and analysed. Administration of DOX alone caused a decrease in body and relative testicular weights, seminiferous tubule diameter and germinal epithelium thickness, Johnsen's score and serum testosterone levels. DOX treatment led to severe testicular damage such as tubular degeneration, and atrophic tubules. Also, the activities of superoxide dismutase and glutathione peroxidase were reduced, while the level of malondialdehyde was increased in the testis. The mRNA levels of apoptotic-related genes (CASP3, TP53, BAX, BCL2) and apoptotic index were increased, while mitofusin-2 decreased. DOX caused an increase in CASP3 and a decrease in mitofusin-2 immunoreactivities. Treatment with ALA markedly improved all of DOX-induced biochemical, histochemical and molecular alterations in rat testis. Consequently, ALA has a therapeutic role in ameliorating DOX-induced testicular damage in rats.     

The clinical impact of Prostate Imaging–Reporting and Data System classification in patients with haemospermia undergoing multiparametric magnetic resonance imaging of the prostate

In this study, we evaluated the role of the Prostate Imaging–Reporting and Data System (PI-RADS) classification of multiparametric magnetic resonance imaging (mpMRI) to determine the likelihood of prostate cancer (PCa) in patients with haemospermia. Fifty-one patients presenting with haemospermia between 2018 and 2020 were included in this retrospective study. Forty-two of the patients (82.4%) were over 40 years, and the median prostate-specific antigen (PSA) level was 1.4 ng/ml. Fourteen of the patients (27.5%) had recurrent haemospermia. All patients underwent mpMRI, and assessments were classified according to PI-RADS v2. The mpMRI revealed PI-RADS one to four lesions in 10 (19.6%), 30 (58.8%), 6 (11.8%) and 5 (9.8%) patients respectively. One patient with PI-RADS 3 and five with PI-RADS 4 lesions underwent cognitive fusion prostate biopsy depending on MRI findings, and two patients with PI-RADS 4 lesions were diagnosed with PCa. Patients with haemospermia and risk factors, that is aged over 40 years, a high PSA level or familial history of PCa, need a more thorough evaluation with mpMRI.     

Carbamazepine-induced sperm disorders can be associated with the altered expressions of testicular KCNJ11/miR-let-7a and spermatozoal CFTR/miR-27a

Male infertility is a global health problem, and the underlying molecular mechanisms are not clearly known. Ion channels and microRNAs (miRNAs), known to function in many vital functions in cells, have been shown to play a significant role in male infertility through changes in their expressions. The study aimed to evaluate the alterations of testicular and/or spermatozoal potassium voltage-gated channel subfamily J member 11 (KCNJ11), Cystic fibrosis transmembrane conductance regulator (CFTR), miR-let-7a and miR-27a expressions in carbamazepine-related male infertility. Here, we showed that carbamazepine reduced sperm motility, increased abnormal sperm morphology, and impaired hormonal balance as well as increased relative testis weight and decreased relative seminal vesicle weight. On the other hand, downregulated KCNJ11 and upregulated miR-let-7a expressions were determined in testis (p < .05). Also, downregulated KCNJ11 and upregulated CFTR and miR-27a expressions were found in spermatozoa (p < .05). Interestingly, altered testicular KCNJ11 and miR-let-7a expressions were correlated with decreased sperm motility and elevated sperm tail defect. Besides, spermatozoal CFTR and miR-27a expressions positively correlated with sperm tail defects. The results indicated a significant relationship between ion channel and/or miRNA expression alterations and impaired sperm parameters due to carbamazepine usage.     

Radiological and clinical comparisons of the patients with rheumatoid arthritis operated with rigid and dynamic instrumentation systems due to lumbar degenerative spinal diseases

BackgroundIt is extremely difficult to treat spine disorders with stabilization in patients with rheumatoid arthritis. Because revision rates are significantly higher in rigid stabilization. To date, there is no data about patients with rheumatoid arthritis treated with dynamic stabilization. Our aim was to compare the radiological and clinical results of patients with rheumatoid arthritis who underwent lumbar rigid stabilization or dynamic stabilization with Polyetheretherketone rod (PEEK).MethodsPatients with degenerative lumbar spine disease with rheumatoid arthritis who underwent dynamic stabilization between 2013 and 2015 and rigid stabilization between 2010 and 2012 were evaluated radiologically for adjacent segment disease, proximal junctional kyphosis, system problem (nonunion, screw loosening, instrumentation failure, pull out). It was also compared according to both the revision rates and the Visual Analog Scale and Oswestry Disability Index scores at the 12th month and 24th month.ResultsThe difference of decrease in Visual Analog Scale and Oswestry Disability Index scores from preoperative to 12th month between patients who underwent dynamic stabilization and rigid stabilization was statistically insignificant. However, there was a significant difference of increase in Visual Analog Scale and Oswestry Disability Index scores between the 12th month and 24th month of patients who underwent rigid stabilization, compared with patients with dynamic stabilization. In patients with dynamic stabilization, the problems of instrumentation were seen less frequently. Revision rates were high in patients with rigid stabilization when compared the patients with dynamic stabilization.ConclusionRadiological and clinical outcomes in patients with rheumatoid arthritis operated with dynamic stabilization are more significant when compared to rigid stabilization. These patients have lower pain and disability scores in their follow up periods. Revision rates are lower in patients with dynamic stabilization.