The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance

ABSTRACT: BACKGROUND: Previous studies have demonstrated that postprandial hyperglycemia attenuates brachial artery flow-mediated dilation (FMD) in prediabetic patients, in diabetic patients, and even in normal subjects. We have previously reported that postprandial hyperinsulinemia also attenuates FMD. In the present study we evaluated the relationship between different degrees of postprandial attenuation of FMD induced by postprandial hyperglycemia and hyperinsulinemia and differences in ingested carbohydrate content in non-diabetic individuals. METHODS: Thirty-seven healthy subjects with no family history of diabetes were divided into 3 groups: a 75-g oral glucose loading group (OG group) (n = 14), a test meal group (TM group) (n = 12; 400 kcal, carbohydrate content 40.7 g), and a control group (n = 11). The FMD was measured at preload (FMD0) and at 60 minutes (FMD60) and 120 (FMD120) minutes after loading. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were determined at preload (PG0, IRI0) and at 30 (PG30, IRI30), 60 (PG60, IRI60), and 120 (PG120, IRI120) minutes after loading.ResultPercentage decreases from FMD0 to FMD60 were significantly greater in the TM group ([MINUS SIGN]21.19 % [PLUS-MINUS SIGN] 17.90 %; P < 0.001) and the OG group ([MINUS SIGN]17.59 % [PLUS-MINUS SIGN] 26.64 %) than in the control group (6.46 % [PLUS-MINUS SIGN] 9.17 %; P < 0.01), whereas no significant difference was observed between the TM and OG groups. In contrast, the percentage decrease from FMD0 to FMD120 was significantly greater in the OG group ([MINUS SIGN]18.91 % [PLUS-MINUS SIGN] 16.58 %) than in the control group (6.78 % [PLUS-MINUS SIGN] 11.43 %; P < 0.001) or the TM group (5.22 % [PLUS-MINUS SIGN] 37.22 %; P < 0.05), but no significant difference was observed between the control and TM groups. The FMD60 was significantly correlated with HOMA-IR (r = [MINUS SIGN]0.389; P < 0.05). In contrast, FMD120 was significantly correlated with IRI60 (r = [MINUS SIGN]0.462; P < 0.05) and the AUC of IRI (r = [MINUS SIGN]0.468; P < 0.05). Furthermore, the percentage change from FMD0 to FMD120 was significantly correlated with the CV of PG (r = 0.404; P < 0.05), IRI60 (r = 0.401; p < 0.05) and the AUC of IRI (r = 0.427; P < 0.05). No significant correlation was observed between any other FMDs and glucose metabolic variables. CONCLUSION: Differences in the attenuation of postprandial FMD induced by different postprandial insulin levels may occur a long time postprandially but not shortly after a meal.     

Very high gravity ethanol fermentation by flocculating yeast under redox potential-controlled conditions

ABSTRACT: BACKGROUND: Very high gravity (VHG) fermentation using medium in excess of 250 g/L sugars for more than 15 % (v) ethanol can save energy consumption, not only for ethanol distillation, but also for distillage treatment; however, stuck fermentation with prolonged fermentation time and more sugars unfermented is the biggest challenge. Controlling redox potential (ORP) during VHG fermentation benefits biomass accumulation and improvement of yeast cell viability that is affected by osmotic pressure and ethanol inhibition, enhancing ethanol productivity and yield, the most important techno-economic aspect of fuel ethanol production. RESULTS: Batch fermentation was performed under different ORP conditions using the flocculating yeast and media containing glucose of 201 [PLUS-MINUS SIGN] 3.1, 252 [PLUS-MINUS SIGN] 2.9 and 298 [PLUS-MINUS SIGN] 3.8 g/L. Compared with ethanol fermentation by non-flocculating yeast, different ORP profiles were observed with the flocculating yeast due to the morphological change associated with the flocculation of yeast cells. When ORP was controlled at [MINUS SIGN]100 mV, ethanol fermentation with the high gravity (HG) media containing glucose of 201 [PLUS-MINUS SIGN] 3.1 and 252 [PLUS-MINUS SIGN] 2.9 g/L was completed at 32 and 56 h, respectively, producing 93.0 [PLUS-MINUS SIGN] 1.3 and 120.0 [PLUS-MINUS SIGN] 1.8 g/L ethanol, correspondingly. In contrast, there were 24.0 [PLUS-MINUS SIGN] 0.4 and 17.0 [PLUS-MINUS SIGN] 0.3 g/L glucose remained unfermented without ORP control. As high as 131.0 [PLUS-MINUS SIGN] 1.8 g/L ethanol was produced at 72 h when ORP was controlled at [MINUS SIGN]150 mV for the VHG fermentation with medium containing 298 [PLUS-MINUS SIGN] 3.8 g/L glucose, since yeast cell viability was improved more significantly. CONCLUSIONS: No lag phase was observed during ethanol fermentation with the flocculating yeast, and the implementation of ORP control improved ethanol productivity and yield. When ORP was controlled at [MINUS SIGN]150 mV, more reducing power was available for yeast cells to survive, which in turn improved their viability and VHG ethanol fermentation performance. On the other hand, controlling ORP at [MINUS SIGN]100 mV stimulated yeast growth and enhanced ethanol production under the HG conditions. Moreover, the ORP profile detected during ethanol fermentation with the flocculating yeast was less fluctuated, indicating that yeast flocculation could attenuate the ORP fluctuation observed during ethanol fermentation with non-flocculating yeast.     

Brachial Artery Flow-mediated Dilation Following Exercise with Augmented Oscillatory and Retrograde Shear Rate

ABSTRACT: BACKGROUND: Acute doses of elevated retrograde shear rate (SR) appear to be detrimental to endothelial function in resting humans. However, retrograde shear increases during moderate intensity exercise which also enhances post-exercise endothelial function. Since SR patterns differ with the modality of exercise, it is important to determine if augmented retrograde SR during exercise influences post-exercise endothelial function. This study tested the hypothesis that (1) increased doses of retrograde SR in the brachial artery during lower body supine cycle ergometer exercise would attenuate post-exercise flow-mediated dilation (FMD) in a dose-dependent manner, and (2) antioxidant vitamin C supplementation would prevent the attenuated post-exercise FMD response. METHODS: Twelve men participated in four randomized exercise sessions (90 W for 20 minutes) on separate days. During three of the sessions, one arm was subjected to increased oscillatory and retrograde SR using three different forearm cuff pressures (20, 40, 60 mmHg) (contralateral arm served as the control) and subjects ingested placebo capsules prior to exercise. A fourth session with 60 mmHg cuff pressure was performed with 1 g of vitamin C ingested prior to the session. RESULTS: Post-exercise FMD following the placebo conditions were lower in the cuffed arm versus the control arm (arm main effect: P < 0.05) and without differences between cuff pressures (20 mmHg: 5.7 [PLUS-MINUS SIGN] 2.2 %; 40 mmHg: 4.7 [PLUS-MINUS SIGN] 1.3 %; 60 mmHg: 5.4 [PLUS-MINUS SIGN] 2.4 %) (P > 0.05). Following vitamin C treatment, post-exercise FMD in the cuffed and control arm increased from baseline (P < 0.05) but were not different (control: 7.1 [PLUS-MINUS SIGN] 3.5 % vs. cuffed: 6.6 [PLUS-MINUS SIGN] 3.3 %) (P > 0.05). CONCLUSIONS: These results indicate that augmented oscillatory and retrograde SR in non-working limbs during lower body exercise attenuates post-exercise FMD without an evident dose--response in the range of cuff pressures evaluated. Vitamin C supplementation prevented the attenuation of FMD following exercise with augmented oscillatory and retrograde SR suggesting that oxidative stress contributes to the adverse effects of oscillatory and retrograde shear during exercise on FMD.     

The effects of levosimendan on brain metabolism during initial recovery from global transient ischaemia/hypoxia

ABSTRACT: BackroundNeuroprotective strategies after cardiopulmonary resuscitation are currently the focus of experimental and clinical research. Levosimendan has been proposed as a promising drug candidate because of its cardioprotective properties, improved haemodynamic effects in vivo and reduced traumatic brain injury in vitro. The effects of levosimendan on brain metabolism during and after ischaemia/hypoxia are unknown. METHODS: Transient cerebral ischaemia/hypoxia was induced in 30 male Wistar rats by bilateral common carotid artery clamping for 15 min and concomitant ventilation with 6 % O2 during general anaesthesia with urethane. After 10 min of global ischaemia/hypoxia, the rats were treated with an i.v. bolus of 24 mug kg-1 levosimendan followed by a continuous infusion of 0.2 mug kg-1 min-1. The changes in the energy-related metabolites lactate, the lactate/pyruvate ratio, glucose and glutamate were monitored by microdialysis. In addition, the effects on global haemodynamics, cerebral perfusion and autoregulation, oedema and expression of proinflammatory genes in the neocortex were assessed. RESULTS: Levosimendan reduced blood pressure during initial reperfusion (72 [PLUS-MINUS SIGN] 14 vs. 109 [PLUS-MINUS SIGN] 2 mmHg, p = 0.03) and delayed flow maximum by 5 minutes (p = 0.002). Whereas no effects on time course of lactate, glucose, pyruvate and glutamate concentrations in the dialysate could be observed, the lactate/pyruvate ratio during initial reperfusion (144 [PLUS-MINUS SIGN] 31 vs. 77 [PLUS-MINUS SIGN] 8, p = 0.017) and the glutamate release during 90 minutes of reperfusion (75 [PLUS-MINUS SIGN] 19 vs. 24 [PLUS-MINUS SIGN] 28 mumol[MIDDLE DOT]L-1) were higher in the levosimendan group. The increased expression of IL-6, IL-1ss TNFalpha and ICAM-1, extend of cerebral edema and cerebral autoregulation was not influenced by levosimendan. CONCLUSION: Although levosimendan has neuroprotective actions in vitro and on the spinal cord in vivo and has been shown to cross the blood--brain barrier, the present results showed that levosimendan did not reduce the initial neuronal injury after transient ischaemia/hypoxia.     

Is there any role of thrombin activatable fibrinolysis inhibitor in the development of a hypercoagulable state in gastric cancer

ABSTRACT: BACKGROUND: The purpose of this study was to investigate plasma levels of thrombin activatable fibrinolysis inhibitor (TAFI) and TAFI's relationship with coagulation markers (prothrombin fragment 1 + 2) in gastric cancer patients. METHODS: Thirty-three patients with gastric adenocarcinoma and 29 healthy control subjects were prospectively enrolled in the study. Patients who had a history of secondary malignancy, thrombosis related disease, oral contraceptive use, diabetes mellitus, chronic renal failure or similar chronic metabolic disease were excluded from the study. A fasting blood sample was drawn from patients to determine the plasma levels of TAFI and Prothrombin Fragment 1 + 2 (F 1 + 2). In addition, data on patient age, sex, body mass index (BMI) and stage of disease were recorded. The same parameters, except stage of disease, were also recorded for the control group. Subsequently, we assessed the difference in the levels of TAFI and F 1 + 2 between the patient and control groups. Moreover, we investigated the relation of TAFI and F 1 + 2 levels with age, sex, BMI and stage of disease in the gastric cancer group. RESULTS: There were no statistical differences in any demographic variables (age, gender and BMI) between the groups (Table 1). The mean plasma TAFI levels of the gastric cancer group (69.4 [PLUS-MINUS SIGN] 33.1) and control group (73.3 [PLUS-MINUS SIGN] 27.5) were statistically similar (P = 0.62). The mean plasma F 1 + 2 level in the gastric cancer group was significantly higher than for those in the control group (549.7 [PLUS-MINUS SIGN] 325.3 vs 151.9 [PLUS-MINUS SIGN] 67.1, respectively; P < 0.001). In the gastric cancer group, none of the demographic variables (age, gender and BMI) were correlated with either TAFI or F 1 + 2 levels. Also, no significant associations were found between the stage of the cancer and either TAFI or F 1 + 2 levels. CONCLUSION: In our study, TAFI levels of gastric cancer patients were similar to healthy subjects. The results of our study suggest that TAFI does not play a role in pathogenesis of the hypercoagulable state in gastric cancer patients.     

Vocal fold composition and early glottic carcinoma infiltration

ABSTRACT: BACKGROUND: Current imaging techniques provide only limited information pertaining to the extent of infiltration of laryngeal carcinomas into vocal fold tissue layers. Therefore, it is needed to seek the contribute to the body of knowledge surrounding examination and characterization in laryngeal carcinoma infiltration. METHODS: Excised larynges were collected from 30 male laryngectomy patients with an average age of 43.5 years (ranging 36 to 55 years) and history of smoking ([GREATER-THAN OR EQUAL TO]10 years) exhibiting T1, T2, or subglottal (normal vocal fold) carcinomas. Vocal folds were preserved via freezing or immersion in paraffin. The depth of the mucosa, submucosa, and muscular layers in both normal vocal folds and tumor tissues of afflicted vocal folds was measured. RESULTS: The average depths of the mucosa, submucosa, and muscular layers in normal vocal folds were 0.15 [PLUS-MINUS SIGN] 0.06 mm, 2.30 [PLUS-MINUS SIGN] 0.59 mm, and 2.87 [PLUS-MINUS SIGN] 0.88 mm, respectively. Infiltration measurements of T1 tumors showed a depth of 1.62 [PLUS-MINUS SIGN] 0.51 mm and 1.32 [PLUS-MINUS SIGN] 0.49 mm in frozen sections and paraffin-embedded samples, respectively. Similarly, T2 tumors showed a depth of 2.87 [PLUS-MINUS SIGN] 0.68 mm and 2.58 [PLUS-MINUS SIGN] 0.67 mm in frozen sections and paraffin-embedded samples, respectively. T1 and T2 tumors occupied 24.8 [PLUS-MINUS SIGN] 10 and 48.5 [PLUS-MINUS SIGN] 15 percent of the normal vocal fold depth, respectively. CONCLUSION: This data provides a baseline for estimating infiltration of laryngeal carcinomas in vocal fold tissue layers, of particular interest to surgeons. This information may be used to assess typical depths of infiltration, thus allowing for more appropriate selection of surgical procedures based on individual patient assessment.     

Balancing selected medication costs with total number of daily injections: a preference analysis of GnRH-agonist and antagonist protocols by IVF patients

ABSTRACT: BACKGROUND: During in vitro fertilization (IVF), fertility patients are expected to self-administer many injections as part of this treatment. While newer medications have been developed to substantially reduce the number of these injections, such agents are typically much more expensive. Considering these differences in both cost and number of injections, this study compared patient preferences between GnRH-agonist and GnRH-antagonist based protocols in IVF. METHODS: Data were collected by voluntary, anonymous questionnaire at first consultation appointment. Patient opinion concerning total number of s.c. injections as a function of non-reimbursed patient cost associated with GnRH-agonist [A] and GnRH-antagonist [B] protocols in IVF was studied. RESULTS: Completed questionnaires (n = 71) revealed a mean +/[MINUS SIGN] SD patient age of 34 +/[MINUS SIGN] 4.1 yrs. Most (83.1 %) had no prior IVF experience; 2.8 % reported another medical condition requiring self-administration of subcutaneous medication(s). When out-of-pocket cost for [A] and [B] were identical, preference for [B] was registered by 50.7 % patients. The tendency to favor protocol [B] was weaker among patients with a health occupation. Estimated patient costs for [A] and [B] were $259.82 +/[MINUS SIGN] 11.75 and $654.55 +/[MINUS SIGN] 106.34, respectively (p < 0.005). Measured patient preference for [B] diminished as the cost difference increased. CONCLUSIONS: This investigation found consistently higher non-reimbursed direct medication costs for GnRH-antagonist IVF vs. GnRH-agonist IVF protocols. A conditional preference to minimize downregulation (using GnRH-antagonist) was noted among some, but not all, IVF patient sub-groups. Compared to IVF patients with a health occupation, the preference for GnRH-antagonist was weaker than for other patients. While reducing total number of injections by using GnRH-antagonist is a desirable goal, it appears this advantage is not perceived equally by all IVF patients and its utility is likely discounted heavily by patients when nonreimbursed medication costs reach a critical level.     

Analysis of the relationship between end-to-end distance and activity of single-chain antibody against colorectal carcinoma

ABSTRACT: We investigated the relationship of End-to-end distance between VH and VL with different peptide linkers and the activity of single-chain antibodies by computer-aided simulation. First, we developed (G4S)n (where n = 1-9) as the linker to connect VH and VL, and estimated the 3D structure of single-chain Fv antibody (scFv) by homologous modeling. After molecular models were evaluated and optimized, the coordinate system of every protein was built and unified into one coordinate system, and End-to-end distances calculated using 3D space coordinates. After expression and purification of scFv-n with (G4S)n as n = 1, 3, 5, 7 or 9, the immunoreactivity of purified ND-1 scFv-n was determined by ELISA. A multi-factorial relationship model was employed to analyze the structural factors affecting scFv: rn=ABn[MINUS SIGN]ABO2+CDn[MINUS SIGN]CDO2+BCn[MINUS SIGN]BCst2. The relationship between immunoreactivity and r-values revealed that fusion protein structure approached the desired state when the r-value = 3. The immunoreactivity declined as the r-value increased, but when the r-value exceeded a certain threshold, it stabilized. We used a linear relationship to analyze structural factors affecting scFv immunoreactivity.     

Pharmacokinetic analysis of topical tobramycin in equine tears by automated immunoassay

ABSTRACT: BACKGROUND: Ophthalmic antibiotic therapy in large animals is often used empirically because of the lack of pharmacokinetics studies. The purpose of the study was to determine the pharmacokinetics of topical tobramycin 0.3% ophthalmic solution in the tears of normal horses using an automated immunoassay analysis. RESULTS: The mean tobramycin concentrations in the tears at 5, 10, 15, 30 minutes and 1, 2, 4, 6 hours after administration were 759 ([PLUS-MINUS SIGN]414), 489 ([PLUS-MINUS SIGN]237), 346 ([PLUS-MINUS SIGN]227), 147 ([PLUS-MINUS SIGN]264), 27.6 ([PLUS-MINUS SIGN]28.4), 14.8 ([PLUS-MINUS SIGN]66.6), 6.7 ([PLUS-MINUS SIGN]18.6), and 23.4 ([PLUS-MINUS SIGN]73.4) mg/L. Mean tobramycin concentration was maintained above the MIC90 for commonly isolated bacteria for 68.5 min. CONCLUSION: A single dose of topical tobramycin resulted in therapeutic concentrations of tobramycin in the tears for 1 h after administration. Therapeutic levels of tobramycin remained in equine tears 6 times longer than was reported in rabbit tears.     

Scaling-up from an implementation trial to state-wide coverage: results from the preliminary Melbourne Diabetes Prevention Study

ABSTRACT: BACKGROUND: The successful Greater Green Triangle Diabetes Prevention Program (GGT DPP), a small implementation trial, has been scaled-up to the Victorian state-wide 'Life!' programme with over 10,000 individuals enrolled. The Melbourne Diabetes Prevention Study (MDPS) is an evaluation of the translation from the GGT DPP to the Life! programme. We report results from the preliminary phase (pMDPS) of this evaluation. METHODS: The pMDPS is a randomised controlled trial with 92 individuals aged 50 to 75 at high risk of developing type 2 diabetes randomised to Life! or usual care. Intervention consisted of six structured 90-minute group sessions: five fortnightly sessions and the final session at 8 months. Participants underwent anthropometric and laboratory tests at baseline and 12 months, and provided self-reported psychosocial, dietary, and physical activity measures. Intervention group participants additionally underwent these tests at 3 months. Paired t tests were used to analyse within-group changes over time. Chi-square tests were used to analyse differences between groups in goals met at 12 months. Differences between groups for changes over time were tested with generalised estimating equations and analysis of covariance. RESULTS: Intervention participants significantly improved at 12 months in mean body mass index ([MINUS SIGN]0.98 kg/m2, standard error (SE) = 0.26), weight ([MINUS SIGN]2.65 kg, SE = 0.72), waist circumference ([MINUS SIGN]7.45 cm, SE = 1.15), and systolic blood pressure ([MINUS SIGN]3.18 mmHg, SE = 1.26), increased high-density lipoprotein-cholesterol (0.07 mmol/l, SE = 0.03), reduced energy from total ([MINUS SIGN]2.00%, SE = 0.78) and saturated fat ([MINUS SIGN]1.54%, SE = 0.41), and increased fibre intake (1.98 g/1,000 kcal energy, SE = 0.47). In controls, oral glucose at 2 hours deteriorated (0.59 mmol/l, SE = 0.27). Only waist circumference reduced significantly ([MINUS SIGN]4.02 cm, SE = 0.95).Intervention participants significantly outperformed controls over 12 months for body mass index and fibre intake. After baseline adjustment, they also showed greater weight loss and reduced saturated fat versus total energy intake.At least 5% weight loss was achieved by 32% of intervention participants versus 0% controls. CONCLUSIONS: pMDPS results indicate that scaling-up from implementation trial to state-wide programme is possible. The system design for Life! was fit for purpose of scaling-up from efficacy to effectiveness.Trial registrationAustralian and New Zealand Clinical Trials Registry ACTRN12609000507280.     

Frequency of poor quality of life and predictors of health related quality of life in cirrhosis at a tertiary care hospital Pakistan

ABSTRACT: BACKGROUND: Cirrhosis produces variety of symptoms which eventually lead to a negative impact on Health Related Quality of Life (HRQOL). The general aim of this study was to evaluate the magnitude of poor HRQOL and to assess factors related with HRQOL in patients with CLD in Pakistan. FINDINGS: This was a cross sectional study conducted in gastroenterology outpatient clinics of Aga Khan University Hospital, Karachi on adult patients with cirrhosis. In this study chronic liver disease questionnaire (CLDQ) was used to assess HRQOL of these patients and CLDQ score was used as an outcome measure to determine factors related with HRQOL. 273 participants were recruited in the study; 155 (57%) were males. Mean age of participants was 49 [PLUS-MINUS SIGN] 11 years. The most common cause for cirrhosis was viral infection 247(91.5%). Mean Model for End Stage Liver Disease (MELD) score was 12.6 [PLUS-MINUS SIGN] 6.8 and 2/3 of patients 209 (76.6%) had advanced cirrhosis in Child Turcot Pugh (CTP) B or C stage. Poor HRQOL was seen in 187(69%; 95% C.I.: 63%, 74%) of the participants. Mean CLDQ score was 4.36 [PLUS-MINUS SIGN]1.1. Amongst all of the domains, fatigue domain had lower CLDQ score. Hemoglobin (beta = 0.09 [SE = 0.04]), Albumin (beta = 0.32[SE = 0.09]), Diastolic Blood Pressure (DBP) (beta = 0.01[0.005) prior history of decompensation (beta = 0.98[SE = 0.39] were significant factors associated with HRQOL in patients with liver cirrhosis. CONCLUSION: Frequency of poor health related quality of life determined by CLDQ score is high in patients with liver cirrhosis. Hemoglobin, serum albumen, prior history of decompensation (like encephalopathy and upper gastro intestinal bleed), are associated with health related quality of life.     

Rate of cardiac arrhythmias and silent brain lesions in experienced marathon runners: rationale, design and baseline data of the Berlin Beat of Running study

ABSTRACT: BACKGROUND: Regular exercise is beneficial for cardiovascular health but a recent meta-analysis indicated a relationship between extensive endurance sport and a higher risk of atrial fibrillation, an independent risk factor for stroke. However, data on the frequency of cardiac arrhythmias or (clinically silent) brain lesions during and after marathon running are missing.Methods/ DesignIn the prospective observational "Berlin Beat of Running" study experienced endurance athletes underwent clinical examination (CE), 3 Tesla brain magnetic resonance imaging (MRI), carotid ultrasound imaging (CUI) and serial blood sampling (BS) within 2-3 days prior (CE, MRI, CUI, BS), directly after (CE, BS) and within 2 days after (CE, MRI, BS) the 38th BMW BERLIN-MARATHON 2011. All participants wore a portable electrocardiogram (ECG)-recorder throughout the 4 to 5 days baseline study period. Participants with pathological MRI findings after the marathon, troponin elevations or detected cardiac arrhythmias will be asked to undergo cardiac MRI to rule out structural abnormalities. A follow-up is scheduled after one year. RESULTS: Here we report the baseline data of the enrolled 110 athletes aged 36-61 years. Their mean age was 48.8 [PLUS-MINUS SIGN] 6.0 years, 24.5 % were female, 8.2 % had hypertension and 2.7 % had hyperlipidaemia. Participants have attended a mean of 7.5 [PLUS-MINUS SIGN] 6.6 marathon races within the last 5 years and a mean of 16 [PLUS-MINUS SIGN] 36 marathon races in total. Their weekly running distance prior to the 38th BMW BERLIN-MARATHON was 65 [PLUS-MINUS SIGN] 17 km. Finally, 108 (98.2 %) Berlin Beat-Study participants successfully completed the 38th BMW BERLIN-MARATHON 2011. DISCUSSION: Findings from the "Berlin Beats of Running" study will help to balance the benefits and risks of extensive endurance sport. ECG-recording during the marathon might contribute to identify athletes at risk for cardiovascular events. MRI results will give new insights into the link between physical stress and brain damage.Trial registrationclinicaltrials.gov NCT01428778.     

Association of Alanine Aminotransferase Levels (ALT) with the Hepatic Insulin Resistance Index (HIRI): a cross-sectional study

ABSTRACT: BACKGROUND: The association between serum alanine aminotransferase (ALT) levels and hepatic insulin resistance (IR) has been evaluated with the hyperinsulinemic-euglycemic clamp. However, there is no information about the association of ALT with the Hepatic Insulin Resistance Index (HIRI). The aim of this study was to evaluate the association between serum ALT levels and HIRI in subjects with differing degrees of impaired glucose metabolism. METHODS: This cross-sectional study included subjects that had an indication for testing for type 2 diabetes mellitus (T2DM) with an oral glucose tolerance test (OGTT). Clinical and biochemical evaluations were carried out including serum ALT level quantification. HIRI was calculated for each participant. Correlation analyses and lineal regression models were used to evaluate the association between ALT levels and HIRI. RESULTS: A total of 324 subjects (37.6 % male) were included. The mean age was 40.4 [PLUS-MINUS SIGN] 14.3 years and the mean body mass index (BMI) was 32.0 [PLUS-MINUS SIGN] 7.3 kg/m2. Individuals were divided into 1 of 5 groups: without metabolic abnormalities (n = 113, 34.8 %); with the metabolic syndrome (MetS, n = 179, 55.2 %), impaired fasting glucose (IFG, n = 85, 26.2 %); impaired glucose tolerance (IGT, n = 91, 28.0 %), and T2DM (n = 23, 7.0 %). The ALT (p < 0.001) and HOMA2-IR (p < 0.001) values progressively increased with HIRI quartiles, while ISI-Matsuda (p < 0.001) progressively decreased. After adjustment for sex, age, and BMI, we identified a significant correlation between HIRI and ALT in persons with the MetS (r = 0.22, p = 0.003), IFG (r = 0.33, p < 0.001), IGT (r = 0.37, p < 0.001), and T2DM (r = 0.72, p < 0.001). Lineal regression analysis adjusting for age, HDL-C, TG and waist circumference (WC) showed an independent association between ALT and HIRI in subjects with the MetS (beta = 0.07, p = 0.01), IFG (beta = 0.10, p = 0.02), IGT (beta = 0.09, p = 0.007), and T2DM (beta = 0.31, p = 0.003). This association was not identified in subjects without metabolic abnormalities. CONCLUSIONS: ALT levels are independently associated with HIRI in subjects with the MetS, IFG, IGT, and T2DM. The ALT value in these subjects may be an indirect parameter to evaluate hepatic IR.     

Postprandial endothelial function does not differ in women by race: an insulin resistance paradox?

Insulin resistance is associated with endothelial dysfunction. Because African-American women are more insulin-resistant than white women, it is assumed that African-American women have impaired endothelial function. However, racial differences in postprandial endothelial function have not been examined. In this study, we test the hypothesis that African-American women have impaired postprandial endothelial function compared with white women. Postprandial endothelial function following a breakfast (20% protein, 40% fat, and 40% carbohydrate) was evaluated in 36 (18 African-American women, 18 white women) age- and body mass index (BMI)-matched (age: 37 ± 11 yr; BMI: 30 ± 6 kg/m(2)) women. Endothelial function, defined by percent change in brachial artery flow-mediated dilation (FMD), was measured at 0, 2, 4, and 6 h following a meal. There were no significant differences between the groups in baseline FMD, total body fat, abdominal visceral fat, and fasting levels of glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, or serum estradiol. Although African-American women were less insulin-sensitive [insulin sensitivity index (mean ± SD): 3.6 ± 1.5 vs. 5.2 ± 2.6, P = 0.02], both fasting triglyceride (TG: 56 ± 37 vs. 97 ± 49 mg/dl, P = 0.007) and incremental TG area under the curve (AUC(0-6hr): 279 ± 190 vs. 492 ± 255 mg·dl(-1)·min(-1)·10(-2), P = 0.008) were lower in African-American than white women. Breakfast was associated with a significant increase in FMD in whites and African-Americans, and there was no significant difference in postprandial FMD between the groups (P > 0.1 for group × time interactions). Despite being insulin-resistant, postprandial endothelial function in African-American women was comparable to white women. These results imply that insulin sensitivity may not be an important determinant of racial differences in endothelial function.     

The detection of hTERC amplification using fluorescence in situ hybridization in the diagnosis and prognosis of cervical intraepithelial neoplasia: a case control study

ABSTRACT: BACKGROUND: Currently the routine non-invasive screening methods for cervical intraepithelial neoplasia (CIN) and cervical cancer are Thinprep cytology test (TCT) and human papillomavirus testing. However, both methods are limited by the high false positive and false negative rates and lack of association with patients' prognosis, especially for the early detection of pro-malignant CIN. The aim of the study was to investigate the role of genomic amplification of human telomerase gene (hTERC) in the diagnosis and prognosis of CIN. METHODS: The study group consisted of specimens of exfoliated cervical cells from 151 patients, including 27 with CIN I, 54 with CIN II/III, 17 with carcinoma in situ, and 28 with invasive squamous carcinoma, as well as 25 patients who were at 2-year follow-up after either Loop Electrosurgical Excision treatment (n = 11) or radical surgery (n = 14). hTERC amplification was detected by dual-color interphase fluorescence in situ hybridization (FISH), and the results were compared with TCT and histologic examination. The final diagnosis was determined by the pathological examination. The control group consisted of specimens of exfoliated cervical cells from 40 normal women. RESULTS: The percentage of cervical exfoliated cells with positive hTERC amplification and incidence rates of hTERC amplification were 9.2% [PLUS-MINUS SIGN] 4.6% and 44.4% (12/27) respectively in patients with CIN I; 16.0% [PLUS-MINUS SIGN] 14.4% and 85.1% (46/54) in patients with CIN II/III; 19.7% [PLUS-MINUS SIGN] 13.3% and 88.3% (15 /17) in patients with carcinoma in situ; 47.0% [PLUS-MINUS SIGN] 25.2% and 100% (28/28)in patients with invasive squamous carcinoma. There was statistically significant difference between the control and study group (P <0.01), and between the patients with various diseases within the study group (P <0.05). CONCLUSION: The detection of genomic amplification of hTERC using FISH is a non-invasive and effective approach for CIN.     

Ambulatory ECG-based T-wave alternans and heart rate turbulence can predict cardiac mortality in patients with myocardial infarction with or without diabetes mellitus

ABSTRACT: BACKGROUND: Many patients who survive a myocardial infarction (MI) remain at risk of sudden cardiac death despite revascularization and optimal medical treatment. We used the modified moving average (MMA) method to assess the utility of T-wave alternans (TWA) and heart rate turbulence (HRT) as risk markers in MI patients with or without diabetes mellitus (DM). METHODS: We prospectively enrolled 248 consecutive patients: 96 with MI (post-MI patients); 77 MI with DM (post-MI + DM patients); 75 controls without cardiovascular disease (group control). Both TWA and HRT were measured on ambulatory electrocardiograms (AECGs). HRT was assessed by two parameters [BOX DRAWINGS LIGHT HORIZONTAL] turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO [GREATER-THAN OR EQUAL TO]0% and TS [LESS-THAN OR EQUAL TO]2.5 ms/R-R interval were met. The endpoint was cardiac mortality. RESULTS: TWA values differed significantly between MI and controls. Post-MI + DM patients had higher TWA values than post-MI patients (58 [PLUS-MINUS SIGN] 21 muV VS 52 [PLUS-MINUS SIGN] 18 muV, P = 0.029). Impaired HRT--increased TO and decreased TS were observed in MI patients with or without DM. During follow-up of 578 [PLUS-MINUS SIGN] 146 days, cardiac death occurred in ten patients and three of them suffered sudden cardiac death (SCD). Multivariate analysis determined that a HRT-positive outcome [HR (95% CI): 5.01, 1.33--18.85; P = 0.017], as well as the combination of abnormal TWA ([GREATER-THAN OR EQUAL TO]47 muV) and positive HRT had significant association with the endpoint [HR (95% CI): 9.08, 2.21--37.2; P = 0.002)]. CONCLUSION: This study indicates that AECGs-based TWA and HRT can predict cardiac mortality in MI patients with or without DM. Combined analysis TWA and HRT may be a convenient and useful method of identifying patients at high risk for cardiovascular death.     

Effect of ascorbic acid treatment on conduit vessel endothelial dysfunction in patients with hypertension

Hypertension is associated with low plasma ascorbic acid levels and impaired endothelial function. Recent evidence suggests that increased vascular oxidative stress contributes to the pathophysiology of endothelial dysfunction and hypertension. We recently showed that chronic oral ascorbic acid therapy lowers blood pressure in hypertensive patients. We hypothesized that it would also improve endothelial vasomotor function. In a randomized, double-blind, placebo-controlled study, we examined the effect of acute (2 g po) and chronic (500 mg/day for 1 mo) ascorbic acid treatment on brachial artery flow-mediated dilation in 39 patients with hypertension. Compared with 82 age- and gender-matched normotensive controls, these patients had impaired endothelium-dependent, flow-mediated dilation of the brachial artery [8.9 +/- 6.1 vs. 11.2 +/- 5.7% (SD), P < 0.04]. After therapy, plasma ascorbic acid concentrations increased acutely from 50 +/- 12 to 149 +/- 51 micromol/l and were maintained at 99 +/- 33 micromol/l with chronic treatment (both P < 0.001). As previously reported, chronic ascorbic acid therapy reduced systolic and mean blood pressure in these patients. However, acute or chronic ascorbic acid treatment had no effect on brachial artery endothelium-dependent, flow-mediated dilation or on endothelium-independent, nitroglycerin-mediated dilation. These results demonstrate that conduit vessel endothelial dysfunction secondary to hypertension is not reversed by acute or chronic treatment with oral ascorbic acid. The effects of this treatment on resistance vessel vasomotor function warrant further investigation.     

Relationship between upper and lower limb conduit artery vasodilator function in humans

Brachial artery flow-mediated dilation (FMD) is a strong predictor of future cardiovascular disease and is believed to represent a "barometer" of systemic endothelial health. Although a recent study [Padilla et al. Exp Biol Med (Maywood) 235: 1287-1291, 2010] in pigs confirmed a strong correlation between brachial and femoral artery endothelial function, it is unclear to what extent brachial artery FMD represents a systemic index of endothelial function in humans. We conducted a retrospective analysis of data from our laboratory to evaluate relationships between the upper (i.e., brachial artery) vs. lower limb (superficial femoral n = 75; popliteal artery n = 32) endothelium-dependent FMD and endothelium-independent glyceryl trinitrate (GTN)-mediated dilation in young, healthy individuals. We also examined the relationship between FMD assessed in both brachial arteries (n = 42). There was no correlation between brachial and superficial femoral artery FMD (r(2) = 0.008; P = 0.46) or between brachial and popliteal artery FMD (r(2) = 0.003; P = 0.78). However, a correlation was observed in FMD between both brachial arteries (r(2) = 0.34; P < 0.001). Brachial and superficial femoral artery GTN were modestly correlated (r(2) = 0.13; P = 0.007), but brachial and popliteal artery GTN responses were not (r(2) = 0.08; P = 0.11). Collectively, these data indicate that conduit artery vasodilator function in the upper limbs (of healthy humans) is not predictive of that in the lower limbs, whereas measurement of FMD in one arm appears to be predictive of FMD in the other. These data do not support the hypothesis that brachial artery FMD in healthy humans represents a systemic index of endothelial function.     

Plasma nitrite reserve and endothelial function in the human forearm circulation

Attenuation of endothelium-derived nitric oxide (NO) synthesis is a hallmark of endothelial dysfunction. Early detection of this disorder may have therapeutic and prognostic implications. Plasma nitrite mirrors acute and chronic changes in endothelial NO-synthase activity. We hypothesized that local plasma nitrite concentration increases during reactive hyperemia of the forearm, reflecting endothelial function. In healthy subjects (n = 11) plasma nitrite and nitrate were determined at baseline and during reactive hyperemia of the forearm using reductive gas-phase chemiluminescence and flow-injection analysis, respectively. Endothelium-dependent dilation of the brachial artery was measured as flow-mediated dilation (FMD) using high-resolution ultrasound. Results were compared to patients with endothelial dysfunction as defined by reduced FMD (n = 11). Reactive hyperemia of the forearm increased local plasma nitrite concentration from 68 +/- 5 to 126 +/- 13 nmol/L (p < 0.01), whereas in endothelial dysfunction nitrite remained unaffected (116 +/- 12 to 104 +/- 10 nmol/L; n.s.), corresponding to nitrite reserves of 94 +/- 21 and -8 +/- 4%. This was accompanied by a significantly greater increase in brachial artery diameter (FMD: 8.5 +/- 0.4% vs 2.9 +/- 0.5%, for healthy subjects and endothelial dysfunction, respectively; p < 0.001). This observation suggests that nitrite changes reflect endothelial function. Assessment of local plasma nitrite during reactive hyperemia may open new avenues in the diagnosis of vascular function.     

Analysis of using the tongue deviation angle as a warning sign of a stroke

ABSTRACT: BACKGROUND: The symptom of tongue deviation is observed in a stroke or transient ischemic attack. Nevertheless, there is much room for the interpretation of the tongue deviation test. The crucial factor is the lack of an effective quantification method of tongue deviation. If we can quantify the features of the tongue deviation and scientifically verify the relationship between the deviation angle and a stroke, the information provided by the tongue will be helpful in recognizing a warning of a stroke. METHODS: In this study, a quantification method of the tongue deviation angle was proposed for the first time to characterize stroke patients. We captured the tongue images of stroke patients (15 males and 10 females, ranging between 55 and 82 years of age); transient ischemic attack (TIA) patients (16 males and 9 females, ranging between 53 and 79 years of age); and normal subjects (14 males and 11 females, ranging between 52 and 80 years of age) to analyze whether the method is effective. In addition, we used the receiver operating characteristic curve (ROC) for the sensitivity analysis, and determined the threshold value of the tongue deviation angle for the warning sign of a stroke. RESULTS: The means and standard deviations of the tongue deviation angles of the stroke, TIA, and normal groups were: 6.9 [PLUS-MINUS SIGN] 3.1, 4.9 [PLUS-MINUS SIGN] 2.1 and 1.4 [PLUS-MINUS SIGN] 0.8 degrees, respectively. Analyzed by the unpaired Student's t-test, the p-value between the stroke group and the TIA group was 0.015 (>0.01), indicating no significant difference in the tongue deviation angle. The p-values between the stroke group and the normal group, as well as between the TIA group and the normal group were both less than 0.01. These results show the significant differences in the tongue deviation angle between the patient groups (stroke and TIA patients) and the normal group. These results also imply that the tongue deviation angle can effectively identify the patient group (stroke and TIA patients) and the normal group. With respect to the visual examination, 40% and 32% of stroke patients, 24% and 16% of TIA patients, and 4% and 0% of normal subjects were found to have tongue deviations when physicians "A" and "B" examined them. The variation showed the essentiality of the quantification method in a clinical setting. In the receiver operating characteristic curve (ROC), the Area Under Curve (AUC, = 0.96) indicates good discrimination. The tongue deviation angle more than the optimum threshold value (= 3.2[DEGREE SIGN]) predicts a risk of stroke. CONCLUSIONS: In summary, we developed an effective quantification method to characterize the tongue deviation angle, and we confirmed the feasibility of recognizing the tongue deviation angle as an early warning sign of an impending stroke.