Apelin, vaspin, visfatin and adiponectin in large for gestational age infants with insulin resistance

Objective

To investigate the relation of circulating four adipokines (apelin, vaspin, visfatin, adiponectin) with markers of insulin sensitivity in large for gestational age (LGA) infants.

Patients and methods

Forty LGA infants (20 LGA born from diabetic mothers and 20 LGA born from non-diabetic mothers) and 34 appropriate for gestational age (AGA) infants were recruited. Hyperinsulinism and insulin resistance was evaluated using the homeostasis model assessment (HOMA-IR), fasting glucose-to-insulin ratio (FGIR), quantitative insulin-sensitivity check index (QUICK-I) from fasting samples. Plasma adiponectin and vaspin levels were determined by radioimmunoassay. Determination of visfatin and apelin levels was performed by enzyme immunoassay.

Results

HOMA-IR, apelin and visfatin levels (p < 0.001, p < 0.001, p < 0.001, respectively) were significantly elevated and adiponectin levels, FGIR and QUICK-I values. (p < 0.001, p < 0.001, p < 0.05, respectively) were significantly lower in the LGA group. Vaspin levels were higher in the LGA group than AGA neonates without a significance. The LGA infants with diabetic mother had significantly higher visfatin, apelin, HOMA-IR values, fasting insulin levels and significantly lower adiponectin, FGIR, QUICK-I values. Apelin and visfatin were correlated positively, and adiponectin was correlated negatively with birthweight, HOMA-IR values and fasting insulin levels.

Conclusion

Based on the findings of this study, it is too difficult to explain relation between birthweight and these adipocytokines, but findings of high insulin, HOMA-IR, visfatin, apelin and low adiponectin levels in the LGA neonates showed that these adipocytokines can be used as a good predictor for metabolic syndrome.     

Synthesis and antinociceptive-antimicrobial activities of some new amide derivatives of 3,5-di/-and 1,3,5-trimethylpyrazoles

Some N-(3,5-di-/1,3,5-trimethylpyrazole-4-yl)-4-substitutedbenzamide derivatives were prepared as possible antiociceptive-antimicrobial agents. New amide derivatives (3–12) were synthesized by reacting 4-amino-3,5-di and 1,3,5-trimethylpyrazoles with 4-substitutedbenzoyl chlorides. Hotplate and tail-immersion tests were used for the determination of the antinociceptive activity. Morphine, was used as a standard test drug. All compounds were administered at a dose of 100 mg/kg ip and some of them had significant antinociceptive activity in both tests. Compound 10 (N-(1,3,5-trimethylpyrazole-4-yl)-4-bromobenzamide), was the most active one in both tests among the compounds. The antinociceptive activity of the compounds 10, 11 (N-(1,3,5-trimethylpyrazole-4-yl)-4-chlorobenzamide), and 12 (N-(1,3,5-trimethylpyrazole-4-yl)-4-fluorobenzamide), started at 30 minutes and continued up to 150 minutes in the hotplate test. Also compounds were tested for their in vitro antimicrobial activity, but exhibited weak antibacterial activity.     

Systemically Circulating Viral and Tumor-Derived MicroRNAs in KSHV-Associated Malignancies

MicroRNAs (miRNAs) are stable, small non-coding RNAs that modulate many downstream target genes. Recently, circulating miRNAs have been detected in various body fluids and within exosomes, prompting their evaluation as candidate biomarkers of diseases, especially cancer. Kaposi''s sarcoma (KS) is the most common AIDS-associated cancer and remains prevalent despite Highly Active Anti-Retroviral Therapy (HAART). KS is caused by KS-associated herpesvirus (KSHV), a gamma herpesvirus also associated with Primary Effusion Lymphoma (PEL). We sought to determine the host and viral circulating miRNAs in plasma, pleural fluid or serum from patients with the KSHV-associated malignancies KS and PEL and from two mouse models of KS. Both KSHV-encoded miRNAs and host miRNAs, including members of the miR-17–92 cluster, were detectable within patient exosomes and circulating miRNA profiles from KSHV mouse models. Further characterization revealed a subset of miRNAs that seemed to be preferentially incorporated into exosomes. Gene ontology analysis of signature exosomal miRNA targets revealed several signaling pathways that are known to be important in KSHV pathogenesis. Functional analysis of endothelial cells exposed to patient-derived exosomes demonstrated enhanced cell migration and IL-6 secretion. This suggests that exosomes derived from KSHV-associated malignancies are functional and contain a distinct subset of miRNAs. These could represent candidate biomarkers of disease and may contribute to the paracrine phenotypes that are a characteristic of KS.     

Anti-Remodeling Effects of Rapamycin in Experimental Heart Failure: Dose Response and Interaction with Angiotensin Receptor Blockade

While neurohumoral antagonists improve outcomes in heart failure (HF), cardiac remodeling and dysfunction progress and outcomes remain poor. Therapies superior or additive to standard HF therapy are needed. Pharmacologic mTOR inhibition by rapamycin attenuated adverse cardiac remodeling and dysfunction in experimental heart failure (HF). However, these studies used rapamycin doses that produced blood drug levels targeted for primary immunosuppression in human transplantation and therefore the immunosuppressive effects may limit clinical translation. Further, the relative or incremental effect of rapamycin combined with standard HF therapies targeting upstream regulators of cardiac remodeling (neurohumoral antagonists) has not been defined. Our objectives were to determine if anti-remodeling effects of rapamycin were preserved at lower doses and whether rapamycin effects were similar or additive to a standard HF therapy (angiotensin receptor blocker (losartan)). Experimental murine HF was produced by transverse aortic constriction (TAC). At three weeks post-TAC, male mice with established HF were treated with placebo, rapamycin at a dose producing immunosuppressive drug levels (target dose), low dose (50% target dose) rapamycin, losartan or rapamycin + losartan for six weeks. Cardiac structure and function (echocardiography, catheterization, pathology, hypertrophic and fibrotic gene expression profiles) were assessed. Downstream mTOR signaling pathways regulating protein synthesis (S6K1 and S6) and autophagy (LC3B-II) were characterized. TAC-HF mice displayed eccentric hypertrophy, systolic dysfunction and pulmonary congestion. These perturbations were attenuated to a similar degree by oral rapamycin doses achieving target (13.3±2.1 ng/dL) or low (6.7±2.5 ng/dL) blood levels. Rapamycin treatment decreased mTOR mediated regulators of protein synthesis and increased mTOR mediated regulators of autophagy. Losartan monotherapy did not attenuate remodeling, whereas Losartan added to rapamycin provided no incremental benefit over rapamycin alone. These data lend support to investigation of low dose rapamycin as a novel therapy in human HF.     

An Aberrant Transcription Factor Network Essential for Wnt Signaling and Stem Cell Maintenance in Glioblastoma

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Mobile Phone Radiation Alters Proliferation of Hepatocarcinoma Cells

This study investigated the effects of intermittent exposure (15 min on, 15 min off for 1, 2, 3, or 4 h, at a specific absorption rate of 2 W/kg) to enhanced data rates for global system for mobile communication evolution-modulated radiofrequency radiation (RFR) at 900- and 1,800-MHz frequencies on the viability of the Hepatocarcinoma cells (Hep G2). Hep G2 cell proliferation was measured by a colorimetric assay based on the cleavage of the tetrazolium salt WST-1 by mitochondrial dehydrogenases in viable cells. Cell injury was evaluated by analyzing the levels of lactate dehydrogenase (LDH) and glucose released from lysed cells into the culture medium. Morphological observation of the nuclei was carried out by 4′,6-diamidino-2-phenylindole (DAPI) staining using fluorescence microscopy. In addition, TUNEL assay was performed to confirm apoptotic cell death. It was observed that cell viability, correlated with the LDH and glucose levels, changed according to the frequency and duration of RFR exposure. Four-hour exposure produced more pronounced effects than the other exposure durations. 1,800-MHz RFR had a larger impact on cell viability and Hep G2 injury than the RFR at 900 MHz. Morphological observations also supported the biochemical results indicating that most of the cells showed irregular nuclei pattern determined by using the DAPI staining, as well as TUNEL assay which shows DNA damage especially in the cells after 4 h of exposure to 1,800-MHz RFR. Our results indicate that the applications of 900- and 1,800-MHz (2 W/kg) RFR cause to decrease in the proliferation of the Hep G2 cells after 4 h of exposure. Further studies will be conducted on other frequency bands of RFR and longer duration of exposure.     

Complications Following Endoscopic Retrograde Cholangiopancreatography: Minimal Invasive Surgical Recommendations

Background

ERCP has a complication rate ranging between 4% and 16% such as post-ERCP pancreatitis, hemorrhage, cholangitis and perforation. Perforation rate was reported as 0.08% to 1% and mortality rate up to 1.5%. Besides, injury related death rate is 16% to 18%. In this study we aimed to present a retrospective review of our experience with post ERCP-related perforations, reveal the type of injuries and management recommendations with the minimally invasive approaches.

Methods

Medical records of 28 patients treated for ERCP-related perforations in Okmeydani Training and Research Hospital between March 2007 and March 2013 were reviewed retrospectively. Patient age, gender, comorbidities, ERCP indication, ERCP findings and details were analyzed. All previous and current clinical history, laboratory and radiological findings were used to assess the evaluation of perforations.

Results

Between March 2007 and March 2013, 2972 ERCPs were performed, 28 (0.94%) of which resulted in ERCP-related perforations. 10 of them were men (35.8%) and 18 women (64.2%). Mean age was 53.36±14.12 years with a range of 28 to 78 years. 14 (50%) patients were managed conservatively, while 14 (50%) were managed surgically. In 6 patients, laparoscopic exploration was performed due to the failure of non-surgical management. In 6 of the patients that ERCP-related perforation was suspected during or within 2 hours after ERCP, underwent to surgery primarily. There were two mortalities. The mean length of hospitalization stay was 10.46±2.83 days. The overall mortality rate was 7.1%.

Conclusion

Successful management of ERCP-related perforation requires immediate diagnosis and early decision to decide whether to manage conservatively or surgically. Although traditionally conventional surgical approaches have been suggested for the treatment of perforations, laparoscopic techniques may be used in well-chosen cases especially in type II, III and IV perforations.     

Isoform switching facilitates period control in the Neurospora crassa circadian clock

A striking and defining feature of circadian clocks is the small variation in period over a physiological range of temperatures. This is referred to as temperature compensation, although recent work has suggested that the variation observed is a specific, adaptive control of period. Moreover, given that many biological rate constants have a Q₁₀ of around 2, it is remarkable that such clocks remain rhythmic under significant temperature changes. We introduce a new mathematical model for the Neurospora crassa circadian network incorporating experimental work showing that temperature alters the balance of translation between a short and long form of the FREQUENCY (FRQ) protein. This is used to discuss period control and functionality for the Neurospora system. The model reproduces a broad range of key experimental data on temperature dependence and rhythmicity, both in wild‐type and mutant strains. We present a simple mechanism utilising the presence of the FRQ isoforms (isoform switching) by which period control could have evolved, and argue that this regulatory structure may also increase the temperature range where the clock is robustly rhythmic.     

Optimization of citric acid production from a carrot juice-based medium by <Emphasis Type="Italic">Yarrowia lipolytica</Emphasis> using response surface methodology

In this study, diluted and fortified carrot juice was used for modelling and optimization of citric acid production by a new mutant strain, Yarrowia lipolytica K-168. Protein concentrate obtained from fine flour -a byproduct of semolina production- was used as a nitrogen source in the fermentation medium. Interactive effects of selected independent variables, initial total sugar concentration, initial pH, initial concentration of protein concentrate obtained from fine flour of semolina and temperature, on the growth and citric acid production of the yeast were investigated. An experimental design including 30 experiments was conducted by using the method of central composite design. Modelling the effects of these independent variables on maximum citric acid concentration, maximum citric acid production rate, citric acid yield, the ratio of maximum citric acid concentration to maximum isocitric acid concentration and specific growth rate were performed by response surface methodology. The variations of all of the responses with the independent variables were defined by a quadratic model. Numeric optimization was performed by using the desireability function. The conditions with 190.83 g/L initial sugar concentration, 5.90 initial pH, 0.07 g/L initial concentration of fine flour protein concentrate and 27.86 °C were determined as optimal conditions for citric acid production. The maximum citric acid concentration reached to 80.53 g/L in optimal conditions.