Factors that influence basal insulin requirement in type 2 diabetes

In clinical practice, basal insulin dosage (BID) for the treatment for type 2 diabetes given as slow-acting analogues or NPH insulin varies widely when adjusted for body weight (UI/kg). In this study, we investigated the interrelationship between BID and anthropometric, laboratory and clinical parameters. A total of 681 type 2 diabetic patients, treated with bedtime insulin in association with other antidiabetic drugs (preprandial insulin and/or oral agents), were studied. Anthropometric, clinical and biochemical parameters, as well as micro- and macrovascular complications, were evaluated. Non-alcoholic fatty liver disease (NAFLD) was assessed by liver ultrasound. BID was titrated to achieve a fasting blood glucose target of ≤6.7?mmol/L (120?mg/dL). In the multivariate analysis, BID was significantly associated with waist circumference (p?=?0.04) and the insulin treatment duration (p?=?0.004) as the type of insulin treatment ("basal-bolus" regimen vs. basal insulin only, p?相似文献   

Subclinical anthracycline cardiotoxicity in patients with acute promyelocytic leukemia in long-term remission after the AIDA protocol

Anthracycline chemotherapy remains a critical component of cancer treatment despite its established risk of cardiotoxicity. To investigate whether the AIDA protocol, which combines idarubicin, mitoxantrone, and all-trans retinoic acid (ATRA) for treatment of acute promyelocytic leukemia (APL) results in late cardiotoxicity, 34 APL patients in long-term remission were evaluated. The cumulative dose of idarubicin and mitoxantrone were 80 mg/m(2) and 50 mg/m(2), respectively. Median follow-up was 7 years. Segmental wall motion abnormalities (SWMAs) were detected in 11 AIDA patients who still presented with an ejection fraction (EF) within normal limits (EF 56% in the AIDA group vs 59% in the control group, P=.01). However, parameters of diastolic dysfunction were significantly impaired in the AIDA group (E/A ratio: 1.04 in the AIDA group vs 1.28 in the control group, P=.001; E/E' lateral ratio: 10.04 in the AIDA group vs 5.79 in the control group, P≤.001) as well as left atrial volume (52 mL in the AIDA group vs 35 mL in the control group, P<.001). Cardiac toxicity due to anthracycline therapy is often frequent. Changes in diastolic function are helpful in the detection of subclinical anthracycline cardiotoxicity in long-term cardiac follow-up despite a preserved systolic ventricular function.     

Case-control association study of 36 single-nucleotide polymorphisms within 10 candidate genes for major depression and bipolar disorder

In this study we investigated 36 single nucleotide polymorphisms within 10 genes previously associated with major depression and bipolar disorder, as well as with the response to their treatment (ABCB1, ABCB4, TAP2, CLOCK, CPLX1, CPLX2, SYN2, NRG1, 5HTR1A and GPRIN2). No association with mood disorders and clinical outcomes was observed.     

Drug-induced eruptive melanocytic nevi

Introduction: The sudden eruption of melanocytic nevi has been associated with a number of conditions, such as bullous skin diseases, immunodeficiency and immunosuppression. The exact mechanisms leading to the development of eruptive melanocytic nevi are unknown.

Areas covered: The aim of this article is to review the literature concerning eruptive melanocytic nevi following the administration of immunosuppressive drugs and other medications.

Expert opinion: The literature regarding the development of eruptive nevi in association with pharmacological therapies includes a relatively low number of reports. Prevalence of this phenomenon is likely to be underestimated, thus reporting should be encouraged in order to better define the actual significance and related clinical implications. The development of multiple melanocytic nevi during immunosuppressive treatments highlights the importance of immune system integrity in the regulation of nevi growth. The observation of eruptive nevi as an unexpected effect of targeted therapies for specific types of cancer, including melanoma, provided intriguing hints to understand the mechanisms underlying this paradoxical event. The synergistic role of additional triggers in the occurrence of drug-induced eruptive nevi has not been explored and may be an interesting area of research.     

A comparative study on subacute toxicity of arsenic trioxide and dimethylarsinic acid on antioxidant status in Crandell Rees feline kidney (CRFK), human hepatocellular carcinoma (PLC/PRF/5), and epithelioma papulosum cyprini (EPC) cell lines

Arsenic (As) is a global contaminant of terrestrial and aquatic environments posing concern for environmental and human health. The effects of subacute concentrations of arsenic trioxide (As^III) and dimethylarsinic acid (DMA^V) were examined using Crandell Rees feline kidney (CRFK), human hepatocellular carcinoma (PLC/PRF/5), and epithelioma papulosum cyprini (EPC). Whole monolayer with suffering cells (confluence 100%, pyknosis and refractive cells; value scale = 2) led to identification of subacute As concentrations for the three cell lines. The selected As^III concentrations were 1.33 µM for CRFK and 33.37 µM for PLC/PRF/5 and EPC, at 48 hr time point. The selected DMA^V concentrations were 0.67 mM for PLC/PRF/5, 1.33 mM for CRFK, and 2.67 mM for EPC for 48 hr. Unlike the As^III test, the three cell lines did not exhibit marked susceptibility to DMA^V-mediated toxicity. Several oxidative stress biomarker levels, directly or indirectly associated with reactive oxygen species (ROS) elimination including superoxide dismutase, catalase, glutathione peroxidases, glutathione reductase, glutathione S-transferase, glyoxalase I, glyoxalase II, and total glutathione, were determined in the three cell lines at 24 and 48 hr. Antioxidant responses in metal-treated cells were significantly altered compared to controls, suggesting a perturbation of redox state. The weakening of antioxidant pathway in either healthy or tumoral cells was greater using As^III than DMA^V. Differences in level of several oxidative stress biomarkers suggest that the oxidative stress mechanism induced by As^III is distinctly different from DMA^V. Multifaceted mechanisms of action underlying ROS generation in tumor and nontumor cells versus As^III and DMA^V exposure are thus involved. Since As-mediated toxicity is quite complex, more data regarding both oxidant-enhancement and oxidant-lowering strategies may be useful to improve knowledge regarding the influence of As on human and animal cells.     

Digital breast tomosynthesis and contrast‐enhanced dual‐energy digital mammography alone and in combination compared to 2D digital synthetized mammography and MR imaging in breast cancer detection and classification

To compare diagnostic performance of contrast‐enhanced dual‐energy digital mammography (CEDM) and digital breast tomosynthesis (DBT) alone and in combination compared to 2D digital mammography (MX) and dynamic contrast‐enhanced MRI (DCE‐MRI) in women with breast lesions. We enrolled 100 consecutive patients with breast lesions (BIRADS 3‐5 at imaging or clinically suspicious). CEDM, DBT, and DCE‐MRI 2D were acquired. Synthetized MX was obtained by DBT. A total of 134 lesions were investigated on 111 breasts of 100 enrolled patients: 53 were histopathologically proven as benign and 81 as malignant. Nonparametric statistics and receiver operating characteristic (ROC) curve were performed. Two‐dimensional synthetized MX showed an area under ROC curve (AUC) of 0.764 (sensitivity 65%, specificity 80%), while AUC was of 0.845 (sensitivity 80%, specificity 82%) for DBT, of 0.879 (sensitivity 82%, specificity 80%) for CEDM, and of 0.892 (sensitivity 91%, specificity 84%) for CE‐MRI. DCE‐MRI determined an AUC of 0.934 (sensitivity 96%, specificity 88%). Combined CEDM with DBT findings, we obtained an AUC of 0.890 (sensitivity 89%, specificity 74%). A difference statistically significant was observed only between DCE‐MRI and CEDM (P = .03). DBT, CEDM, CEDM combined to tomosynthesis, and DCE‐MRI had a high ability to identify multifocal and bilateral lesions with a detection rate of 77%, 85%, 91%, and 95% respectively, while 2D synthetized MX had a detection rate for multifocal lesions of 56%. DBT and CEDM have superior diagnostic accuracy of 2D synthetized MX to identify and classify breast lesions, and CEDM combined with DBT has better diagnostic performance compared with DBT alone. The best results in terms of diagnostic performance were obtained by DCE‐MRI. Dynamic information obtained by time‐intensity curve including entire phase of contrast agent uptake allows a better detection and classification of breast lesions.     

Donor-recipient age interaction and the impact on clinical results after heart transplantation

To evaluate the impact of donor-recipient age matching on clinical outcomes after heart transplantation, a total of 509 patients (January 1990-December 2018, mean follow-up 111 ± 80 months) were stratified into 4 groups (young-R/young-D, young-R/old-D, old-R/young-D, old-R/old-D) according to the recipient (young-R < 60, old-R ≥ 60 years) and the donor (young-D < 50, old-D ≥ 50 years) age. No difference was found among 30-day mortality (P = .11) and postoperative complications between groups. Both unadjusted and adjusted survival was significantly higher for group young-R/young-D than that of other groups, in which survival was similar [adjusted HR for mortality of 2.0(1.2-3.4), 2.1(1.4-3.8) and 2.5(1.6-4.1) for groups old-R/young-D, young-R/old-D, old-R/old-D, respectively]. Compared to other groups, the incidence of grade ≥ 2 CAV was significantly lower in old-R/young-D group [adjusted HR 0.4(0.2-0.7)]. Among young recipients, the rate of acute grade ≥ 2 rejection episodes was higher in those receiving an old donor graft (P = .04). Old recipient groups were more affected by neoplasms and severe renal failure than young recipient groups (P < .01). Employment of hearts from donors ≥50 years of age adversely affects survival in recipients <60 years of age but does not influence outcomes in older recipients. Also, donor and recipient ages seem to have opposite effects on incidence of rejections and CAV of high grade.     

Differential recognition of a tyrosine-dependent signal in the basolateral and endocytic pathways of thyroid epithelial cells

Trafficking of receptors is of crucial importance for the physiology of most exocrine and endocrine organs. It is not known yet if the same mechanisms are used for sorting in the exocytic and endocytic pathways in the different epithelial tissues. In this work, we have used a deletion mutant of the human neurotrophin receptor p75(hNTR) that is normally localized on the apical membrane when expressed in Madin-Darby canine kidney cells. This internal 57-amino acid deletion of the cytoplasmic tail leads to a relocation of the protein from the apical to the basolateral membrane and to rapid and efficient endocytosis. These events are mediated by a signal localized within 9 amino acids of the mutated cytoplasmic tail that is strictly dependent on a tyrosine residue (Tyr-308). We have analyzed the basolateral sorting efficiency and endocytic capacity of this signal in Fischer rat thyroid (FRT) cells, in which basolateral and endocytic determinants have not yet been identified. We found that this targeting signal can mediate efficient transport to the basolateral membrane also in FRT cells with similar tyrosine dependence as in MDCK cells. In contrast to MDCK cells, this Tyr-based signal was not able to mediate coated pits localization and endocytosis in FRT cells. These data represent the first characterization of basolateral/endocytic signals in thyroid epithelial cells. Furthermore, our results indicate that requirements for tyrosine-dependent basolateral sorting signals are conserved among cell lines from different tissues but that the recognition of the colinear endocytic signal is tissue specific.     

L-folic acid supplementation in healthy postmenopausal women: effect on homocysteine and glycolipid metabolism

CONTEXT: Hyperhomocysteinemia as well as alterations of glycemic and lipidic metabolism are recognized as risk factors for cardiovascular diseases. OBJECTIVE: The aim of this study was to examine the effect of L-folic acid supplementation on homocysteine (Hcy) and related thiols, such as cysteine (Cys) and Cys-glycine (Cys-Glyc) pathways and their relationship to glucose, insulin, and lipidic metabolism in normoinsulinemic postmenopausal women. DESIGN: This study was a randomized placebo, not double-blind, trial. SETTING: The study was performed in an academic research center. PATIENTS OR OTHER PARTICIPANTS: Twenty healthy postmenopausal women were selected. No patient was taking drugs known to affect lipid or glucose metabolism. INTERVENTION(S): Patients underwent two hospitalizations before and after 8 wk of L-acid folic (7.5 mg/d) or placebo administration. The glycemic metabolism was studied by an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Hcy metabolism was studied by a standardized oral methionine-loading test. MAIN OUTCOME MEASURE(S): Hcy, Cys, and Cys-Glyc, basally and after a methionine loading test, were measured. Basal insulin, glucose, and peptide C levels as well as area under the curve for insulin, area under the curve for peptide, hepatic insulin extraction, and metabolic index were assayed. The total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels and the cholesterol/HDL and LDL/HDL ratios were also measured. RESULTS: The total basal Hcy concentration and the plasma postmethionine loading Hcy values were significantly decreased (P < 0.01) in L-folic acid-treated patients, whereas postmethionine loading Cys-Glyc levels were markedly increased (P < 0.02). Furthermore, L-folic acid intake induced a significant improvement in carbohydrate metabolism through an increase in fractional hepatic insulin extraction (P < 0.05) and peripheral insulin sensitivity (P < 0.02) in normoinsulinemic women. HDL levels considerably increased, inducing an improvement in other atherosclerotic indexes, such as cholesterol/HDL and LDL/HDL ratios (P < 0.03). CONCLUSIONS: These results show that folic acid supplementation lowers plasma Hcy levels and improves insulin and lipid metabolism, reducing the risk of cardiovascular disease.