Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial.

We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM.

The laboratory performance of the enFLOW(®) , buddy lite(™) and ThermoSens(®) fluid warmers.

We measured heating of isotonic saline by three fluid warmers in six experiments: saline at 5 °C or 20 °C delivered at 30, 50 or 100 ml.min(-1) . At the three flow rates, the enFLOW(®) , buddy lite(™) and ThermoSens(®) systems heated 5 °C saline to mean (SD) temperatures of: 41.1 (0.5) °C, 37.7 (0.6) °C and 39.1 (0.6) °C; to 40.3 (0.8) °C, 33.9 (1.6) °C and 39.3 (0.7) °C; and to 37.1 (0.8) °C, 24.0 (1.3) °C and 37.6 (1.0) °C, respectively, p < 0.0001 for each experiment. The mean (SD) times taken to heat 5 °C saline were: 16.6 (1.7) s, 258.4 (58.9) s and 134.2 (79.6) s; 16.9 (1.8) s, 256.2 (62.2) s and 182.5 (74.5) s; and 21.5 (1.5) s, 275.9 (49.3) s and 313.5 (18.0) s, respectively, p < 0.0003 for each experiment. The results for saline at 20 °C were similar. The enFLOW system heated saline above 36 °C faster than the ThermoSens system, whereas the buddy lite often failed to achieve 36 °C.

Characterization of the AWARE 10 two-gigapixel wide-field-of-view visible imager.

System requirements for many military electro-optic and IR camera systems reflect the need for both wide-field-of-view situational awareness as well as high-resolution imaging for target identification. In this work we present a new imaging system architecture designed to perform both functions simultaneously and the AWARE 10 camera as an example at visible wavelengths. We first describe the basic system architecture and user interface followed by a laboratory characterization of the system optical performance. We then describe a field experiment in which the camera was used to identify several maritime targets at varying range. The experimental results indicate that users of the system are able to correctly identify ~10 m targets at between 4 and 6 km with 70% accuracy.

Comparison of cystatin C- and creatinine-based estimation of glomerular filtration rate according to glycaemic status in Type 2 diabetes.

AIMS: The influence of hyperglycaemia on the performance of glomerular filtration rate (GFR) estimating equations remains to be determined. We compared the performance of creatinine-based GFR with cystatin C-based GFR in patients with Type 2 diabetes according to glycaemic status. METHODS: In a cross-sectional study of 210 patients with Type 2 diabetes, we staged glycaemic status by HbA(1c) tertiles [HbA(1c) ≤ 75 mmol/mol (9.0%) (n = 70), HbA(1c) 76-95 mmol/mol (9.1-10.8%) (n = 70), HbA(1c) >95 mmol/mol (10.8%) (n = 70)] and measured GFR. Isotopic GFR was measured using renal dynamic imaging with (99m) Tc-diethylene-triamine-penta-acetic acid. Estimated GFR (eGFR) was measured using creatinine-based formulae (Cockcroft-Gault-eGFR, the Modification of Diet in Renal Disease equation-eGFR and the Chronic Kidney Disease Epidemiology Collaboration formula-eGFR) and a cystatin C-based formula (cystatin C-eGFR). RESULTS: The isotopic GFR of all patients was 93.1 ± 34.1 ml min(-1) 1.73 m(-2). All methods for estimating GFR underestimated isotopic GFR [Cockcroft-Gault-eGFR (68.8 ± 38.6 ml min(-1) 1.73 m(-2) ) (P < 0.05), Modification of Diet in Renal Disease-eGFR (74.8 ± 31.3 ml min(-1) 1.73 m(-2) ) (P < 0.05), Chronic Kidney Disease Epidemiology Collaboration-eGFR (72.9 ± 26.6 ml min(-1) 1.73 m(-2)) (P < 0.05) and cystatin C-eGFR (83.5 ± 33.2 ml min(-1) 1.73 m(-2)) (P < 0.05)]. In all patient groups, cystatin C-eGFR was less biased and more accurate than the creatinine-based formulae, especially in the group with HbA(1c) > 95 mmol/mol (10.8%) where there was no difference between cystatin C-eGFR and isotopic GFR. CONCLUSIONS: Performance of cystatin C-eGFR was superior to creatinine-based GFR in patients with Type 2 diabetes with HbA(1c) >95 mmol/mol (10.8%).

Comparison of the efficacy and safety of tramadol/acetaminophen combination therapy and gabapentin in the treatment of painful diabetic neuropathy.

AIMS: This study compared the efficacy and safety of tramadol/acetaminophen (T/A) and gabapentin in the management of painful diabetic neuropathy. METHODS: An open, randomized, comparative study was conducted. Subjects with painful symmetric neuropathy in the lower limbs and mean pain-intensity score > or = 4 on a numeric rating scale were eligible. Subjects were randomized to receive either tramadol (37.5 mg)/acetaminophen (325 mg) or gabapentin (300 mg) for 6 weeks. After 2 weeks of the titration period (1200 mg/day for gabapentin and three tablets/day for T/A), the doses were maintained if the pain was relieved. The primary efficacy outcome was a reduction in pain intensity. Secondary measures evaluated a pain relief scale, a Brief Pain Inventory, a 36-item Short Form Health Survey, average pain intensity and sleep disturbance. RESULTS: One hundred and sixty-three subjects (T/A 79; gabapentin 84) were included. At the final visit, the mean doses were 1575 mg/day for gabapentin and 4.22 tablets/day for T/A. Both groups were similar in terms of baseline pain intensity (mean intensity: T/A 6.7 +/- 1.6; gabapentin 6.3 +/- 1.6, P = 0.168). At the final visit, the mean reductions in pain intensity were similar in both groups (T/A -3.1 +/- 2.0; gabapentin -2.7 +/- 2.1, P = 0.744). Both groups had similar improvements in every Short Form Health Survey category and Brief Pain Inventory subcategory, and in the mean pain relief scores. CONCLUSION: This study suggests that the T/A combination treatment is as effective as gabapentin in the treatment of painful diabetic neuropathy in patients with Type 2 diabetes.

Valsartan increases circulating adiponectin levels without changing HOMA-IR in patients with type 2 diabetes mellitus and hypertension.

Evaluating increasing circulating adiponectin levels is becoming an important strategy in the prevention of diabetes mellitus and cardiovascular events. This study was designed to investigate the effect of the angiotensin II receptor blocker valsartan on blood adiponectin levels and insulin sensitivity in patients with type 2 diabetes and mild-to-moderate hypertension. A total of 91 Korean patients were treated with 80 mg/day valsartan for 4 weeks followed by 160 mg/day for a further 8 weeks. Blood pressure, adiponectin levels and metabolic parameters were measured before and after treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as an insulin sensitivity index. Valsartan significantly decreased mean blood pressure and increased circulating adiponectin levels. There were no differences in metabolic parameters, including HOMA-IR, glycosylated haemoglobin and lipid levels before and after treatment. These results indicated that valsartan increases circulating adiponectin levels, but does not change insulin sensitivity in patients with type 2 diabetes and mild-to-moderate hypertension.

The relationship between adipokines, metabolic parameters and insulin resistance in patients with metabolic syndrome and type 2 diabetes.

This study was designed to investigate the relationship between adipokines in metabolic syndrome and insulin resistance. Sixty male and female subjects with or without metabolic syndrome and type 2 diabetes were included. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Compared with lean control subjects, patients with metabolic syndrome and type 2 diabetes had lower circulating levels of total adiponectin and high molecular weight (HMW) adiponectin, and higher levels of leptin and interleukin-6 (IL-6). Total and HMW adiponectin and the adiponectin/leptin (A/L) ratio were negatively correlated with HOMA-IR. After adjusting for age and sex, leptin, IL-6 and tumour necrosis factor-alpha (TNF-alpha) were positively correlated with HOMA-IR. After also adjusting for body mass index, HOMA-IR was found to be independently associated with leptin, A/L ratio and TNF-alpha levels. In conclusion, decreased total adiponectin and HMW adiponectin and increased leptin and IL-6 levels are characteristic of patients with metabolic syndrome and type 2 diabetes.

[Opacification of hydrophilic intraocular lens after multiple injections of bevacizumab]. / Eintrübung einer hydrophilen Intraokularlinse nach multiplen Bevacizumab-Injektionen.

In the literature various causes of opacification of hydrophilic lenses have been described. Pronounced opacity is a complication that must be taken seriously because it can lead to explantation or exchange of the intraocular lens (IOL). The calcification of hydrophilic IOLs is often made responsible for an explantation. Despite the rapidly increasing number of intravitreal injections, they have so far not been associated with opacification of lenses. This article reports on a female patient where opacification of the hydrophilic lens was obviously associated with multiple intravitreal injections over several years. It involved a secondary calcification with calcium phosphate deposition directly under the surface of the IOL. Possible pathomechanisms are discussed. Due to the increasing number of intravitreal injections the association with IOL opacity should be further evaluated in the future. Generally, with hydrophilic lens materials it must be taken into consideration that these can become opaque following diverse interventions.

Effects of ultraviolet intensity and wavelength on the photolysis of triclosan.

The effects of ultraviolet (UV) intensity and wavelength on triclosan (TCS) photodegradation kinetic, efficiency, mechanisms and pathway were studied. The TCS photodegradation followed the pseudo-first order kinetic model at all UV intensities examined at the wavelengths of 254 and 365 nm and the photodegradation rate increased with increasing UV intensity. TCS photodegradation efficiencies of 90 to 98% and 79 to 90% were obtained at the wavelengths of 254 and 365 nm, respectively. TCS was degraded mainly by photon induced hydroxyl radicals while the direct photon reaction with TCS played a subordinate role. Chlorophenol, dichlorophenol and phenol were the intermediates detected in all experiments conducted. Dibenzodichloro-p-dioxin and dibenzo-p-dioxin were observed as the intermediates only at lower UV intensities investigated at the wavelength of 365 nm. Based on these intermediates, a complete TCS photolysis pathway was proposed for the first time.

Degradation kinetics and mechanism of RDX and HMX in TiO2 photocatalysis.

This study was undertaken to examine the photocatalytic degradation of explosives hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) with a circular photocatalytic reactor, using a UV lamp as a light source and TiO2 as a photocatalyst. The effects of various parameters, such as the RDX or HMX concentration, the amount of TiO, and the initial pH, on the photocatalytic degradation rates of explosives were examined. In the presence of both UV light and TiO2 RDX and HMX were more effectively degraded than with either UV or TiO2 alone. The degradation rates were found to obey pseudo-first-order kinetics represented by the Langmuir-Hinshelwood model. Increases in the RDX and HMX degradation rates were obtained with decreasing initial concentrations of the explosives. The RDX and HMX degradation rates were higher at pH 7 than at either pH 3 or pH 11. A dose of approximately 0.7 g l(-1) of TiO2 degraded HMX more rapidly than did higher or lower TiO2 doses. RDX (20 mg l(-1)) photocatalysis resulted in an approximately 20% decrease in TOC, and HMX (5 mg l(-1)) photocatalysis resulted in a 60%, decrease in TOC within 150 minutes. A trace amount of formate was produced as an intermediate that was further mineralized by RDX or HMX photocatalysis. The nitrogen byproducts from the photocatalysis of RDX and HMX were mainly NO3- with NO2-, and NH4+. The total nitrogen recovery was about 60% from RDX (20 mg l(-1)), and 70% from HMX (5 mg l(-1)), respectively. Finally, a mechanism for RDX/HMX photocatalysis was proposed, along with supporting qualitative and quantitative evidence.

The effects of pulsatile versus non-pulsatile extracorporeal circulation on the pattern of coronary artery blood flow during cardiac arrest.

BACKGROUND: In sudden cardiac arrest, the effective maintenance of coronary artery blood flow is of paramount importance for myocardial preservation as well as cardiac recovery and patient survival. The purpose of this study was to directly compare the effects of pulsatile versus non-pulsatile circulation to coronary artery flow and myocardial preservation in a cardiac arrest condition. METHODS: A cardiopulmonary bypass circuit was constructed in a ventricular fibrillation model using fourteen Yorkshire swine weighing 25-35 kg each. The animals were randomly assigned to group I (n=7, non-pulsatile centrifugal pump) or group II (n=7, pulsatile T-PLS pump). Extracorporeal circulation was maintained for two hours at a pump flow of 2 L/min. The left anterior descending coronary artery flow was measured with an ultrasonic coronary artery flow measurement system at baseline (before bypass) and at every 20 minutes after bypass. Serologic parameters were collected simultaneously at baseline, 1 hour, and 2 hours after bypass in the systemic arterial and coronary sinus venous blood. The Mann-Whitney U test of STATISTICA 6.0 was used to determine intergroup significances using a p value of <0.05. RESULTS: The resistance index of the coronary artery was lower in group II and the difference was significant at 40 min, 80 min, 100 min and 120 min (p<0.05). The mean velocity of the coronary artery was higher in group II throughout the study, and the difference was significant from 20 min after starting the pump (p<0.05). The coronary artery blood flow was higher in group II throughout the study, and the difference was significant from 40 min to 120 min (p<0.05) except at 80 min. Serologic parameters showed no differences between the groups at 1 hour and 2 hours after bypass in the systemic and coronary sinus blood (p=NS). CONCLUSION: In the cardiac arrest condition, pulsatile extracorporeal circulation provides more blood flow, higher flow velocity and less resistance to coronary artery than non-pulsatile circulation.

Novel fluorophores: efficient synthesis and photophysical study.

[structure: see text] We have synthesized novel fluorophores by using Sonogashira reactions of 1,4-bis(dibromovinyl)benzene and 2,5-bis(dibromovinyl)thiophene with various aromatic bromides. The emission maxima of these fluorophores vary from the indigo blue to the reddish-orange region, depending on the structures of aromatic nuclei and peripheral moieties.

Dexamethasone suppresses the expansion and transdifferentiation of transplanted porcine neonatal pancreas cell clusters (NPCCs) into beta-cells in normal nude mice.

OBJECTIVES: This study was performed to investigate the effect of dexamethasone on the expansion and transdifferentiation of transplanted neonatal pancreas cell clusters (NPCCs) in vivo. METHODS: Porcine NPCCs were generated from 1 to 3-day-old neonatal pigs. After transplantation (Tx) of 4000 islet equivalents (IEqs) of NPCCs beneath the renal subcapsular space of normoglycemic nude mice, dexamethasone (Dx, 1 mg/kg) or vehicles were injected daily. Intraperitoneal glucose tolerance testing (ip-GTT) was performed at 4 weeks (n = 4) and 10 weeks (n = 7) after Tx. After harvesting the grafts, total graft and beta-cell graft mass were determined by morphometric analysis. RESULTS: Although the mean value of AUCg was elevated in the Dx-treated group at 10 weeks after Tx, the glucose levels of all the animals by ip-GTT were within the normal range. At 10 weeks after Tx, the relative volume, absolute mass of beta-cells in the graft, and total graft mass were significantly lower in the Dx-treated group (relative volume of beta-cells: 22.0% versus 35.3%, P < 0.05; beta-cells mass: 1.0 +/- 1.2 mg versus 2.2 +/- 5.6 mg, P < 0.05, total graft mass: 4.4 +/- 5.4 mg versus 6.3 +/- 1.3 mg, P < 0.05, Dx-treated versus control), but there was no difference at 4 weeks. Morphologically prominent cystic structures were observed in the Dx group at 10 weeks. CONCLUSION: Our results suggest that dexamethasone suppresses the expansion and transdifferentiation of transplanted porcine NPCCs into beta-cells in normal nude mice.

Robust motor speed control under time varying loads in moving actuator type artificial heart (AnyHeart).

The Moving Actuator type artificial heart(AnyHeart) as well as many other artificial hearts uses a motor as its power source. For controllability of control parameters such as pump rate, pump output, blood pressure profile and flow form, the precise motor speed control is important. However, because the implantable device has limited carrying capacity of hardware components in size and number, applying diverse motor control methods are not possible. In addition, the existing PI (Proportional-Integral) motor controller does not show satisfactory performance. A new controller that is sufficiently robust for the changes of load and physical system parameters has been designed and tested. The robust speed controller is based on the sliding mode control method that is applicable to a system of which the ranges of uncertainty in physical parameters are known. In a mock circulation system test, the actual speed showed good tracking characteristics in respect to the reference speed. Fast follow-up characteristics were also observed under high afterload and speed conditions. The speed error, current and power consumption were reduced by about 40%. The proposed control technique overcomes the limitations of the PI controller, and makes important improvements in both performance and stability.

A preclinical cadaver fitting study of implantable biventricular assist device-- AnyHeart.

A multifunctional, Korean-made artificial heart (AnyHeart) was developed, and prior to its clinical application, a cadaver-fitting study was performed. The study proposed to determine the optimal cannulation approach, implantation technique and route of the cannula to minimize the organ compression of AnyHeart. The anatomical feasibility and a variety of surgical techniques were evaluated using ten preserved, human cadavers. Implanting AnyHeart with ease is possible using various approaches, including a median sternotomy, and a right or left lateral thoracotomy. The lateral thoracotomy approach is shown to be safe and reproducible, especially in patients who have already undergone an operation that used a median sternotomy. The results of this study will guide improvements in the designs of cannulae and AnyHeart for future clinical applications.

Applications of the pulsatile flow versatile ECLS: in vivo studies.

INTRODUCTION: T-PLS (Twin-Pulse Life Support) is the first commercial pulsatile ECLS (Extra Corporeal Life Support) device (1). The dual sac structure of T-PLS can effectively reduce high membrane oxygenator inlet pressure and hemolysis. To verify both the use of T-PLS for ECLS and the advantages of T-PLS, we tested various models. METHOD AND RESULTS: In the partial CPB (cardio pulmonary bypass) model (swine), T-PLS (N = 6), and Biopump (N = 2), a single pulsatile pump (N = 2), were compared. In the case of single pulsatile flow, during pump systole, pressure increased to 700 - 800 mmHg at the inlet port of the membrane oxygenator. fHb, a hemolysis measurement value, was about 80 mg/dL at 3 hours. On the contrary, because of T-PLS's dual sac system, the pressure of T-PLS had a maximum value of about 250 mmHg and fHb was similar to that of the commercial centrifugal pumps. In the total CPB model (bovine, N = 6), the heart was stopped via cardioplegia (Kcl). T-PLS flow was maintained at 3.0-4.5 L/min. T-PLS functioned like a natural heart, having a pulse pressure of 26-43 mmHg and a pulse rate of 40-60 bpm (beats per minute). In the emergency case model (canine, N = 6), T-PLS was started 10 minutes after cardiac arrest from electronic shock. In spite of cardiac arrest for a period of 40 minutes, the heart was recovered after defibrillation. In the ARDS (Acute Respiratory Distress Syndrome) model (canine, N = 6), minimal ventilator parameters were set: tidal volume 130 ml, respiration rate = bpm, FiO2 = 10%. Three hours after starting T-PLS, PO2 of the carotid artery blood (after 2 hours: 195 +/- 89.4; after 3 hours: 258 +/- 99.3 mmHg) was above half the value of the femoral artery but was within normal range. CONCLUSION: It is suggested that a portable pulsatile ECLS like T-PLS may be used as a CPB device and as an alternative CPR (cardiopulmonary resuscitation) device in the case of cardiac arrest. Due to the pulsatile flow, oxygenated blood is delivered to the patient without overloading the ARDS patients heart.

Photocatalytic degradation of explosives contaminated water.

This study was undertaken to examine the degradation of TNT, RDX and HMX in a circular photocatalytic reactor with TiO2 as a photocatalyst. We examined the impact of parameters such as the initial concentration, initial pH of solution on rates of photocatalized transformation, and the mineralization. The results showed that photocatalysis is an effective process for the degradation of TNT, RDX and HMX. They could be comoletely degraded in 150 min with 1.0 g/L TiO2 at pH 7. An increase in the photocatalytic degradation of HMX was noticed with decreasing initial HMX. The rates of RDX and HMX degradation were greater in neutral pH than in acidic and alkaline conditions. In case of TNT degradation, the rate of degradation was the fastest at pH 11. Approximately 82% TOC decrease in the TNT degradation was achieved after 150 min, whereas TOC decrease in RDX and HMX was 24% and 59%, respectively. Nitrate, nitrite, and ammonium ions were detected as the nitrogen byproducts from the photocatalysis, and more than 50% of the total nitrogen was recovered as nitrate ion in every explosives.

Successful extracorporeal membrane oxygenation for right heart failure after heart transplantation-2 case reports and literature review.

After heart transplantation (HT), transient right heart failure (RHF) is common. If it does not improve with appropriate medical therapy, we must consider mechanical support. Recently, extracorporeal membrane oxygenation (ECMO) has shown better results than a right ventricular assist device or retransplantation. Two HT patients with hypertrophic cardiomyopathy had cold ischemic times beyond >240 minutes. After HT, their right heart function worsened and was unresponsive to medical therapy. After our application of ECMO, weaning was successful and the patients were discharged without complication. Early application of ECMO for RHF after HT is a good option.