An update on the clinical pharmacology of the dipeptidyl peptidase 4 inhibitor alogliptin used for the treatment of type 2 diabetes mellitus.

Alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor that is a class of relatively new oral hypoglycaemic drugs used in patients with type 2 diabetes (T2DM), can be used as monotherapy or in combination with other anti-diabetic agents, including metformin, pioglitazone, sulfonylureas and insulin with a considerable therapeutic effect. Alogliptin exhibits favorable pharmacokinetic and pharmacodynamic profiles in humans. Alogliptin is mainly metabolized by cytochrome P450 (CYP2D6) and CYP3A4. Dose reduction is recommended for patients with moderate or worse renal impairment. Side effects of alogliptin include nasopharyngitis, upper-respiratory tract infections and headache. Hypoglycaemia is seen in about 1.5% of the T2DM patients. Rare but severe adverse reactions such as acute pancreatitis, serious hypersensitivity including anaphylaxis, angioedema and severe cutaneous reactions such as Stevens-Johnson syndrome have been reported from post-marketing monitoring. Pharmacokinetic interactions have not been observed between alogliptin and other drugs including glyburide, metformin, pioglitazone, insulin and warfarin. The present review aimed to update the clinical information on pharmacodynamics, pharmacokinetics, adverse effects and drug interactions, and to discuss the future directions of alogliptin.

Treatment of textile wastewater with membrane bioreactor: a critical review

Membrane bioreactor (MBR) technology has been used widely for various industrial wastewater treatments due to its distinct advantages over conventional bioreactors. Treatment of textile wastewater using MBR has been investigated as a simple, reliable and cost-effective process with a significant removal of contaminants. However, a major drawback in the operation of MBR is membrane fouling, which leads to the decline in permeate flux and therefore requires membrane cleaning. This eventually decreases the lifespan of the membrane. In this paper, the application of aerobic and anaerobic MBR for textile wastewater treatment as well as fouling and control of fouling in MBR processes have been reviewed. It has been found that long sludge retention time increases the degradation of pollutants by allowing slow growing microorganisms to establish but also contributes to membrane fouling. Further research aspects of MBR for textile wastewater treatment are also considered for sustainable operations of the process.

Determing the Effect of Thermal Treatment Timing on Ultra-High Performance Concrete Beams

The loss of prestressing force over time influences the long-term deflection of the prestressed concrete element. Prestress losses are inherently complex due to the interaction of concrete creep, concrete shrinkage, and steel relaxation. Implementing advanced materials such as ultra-high performance concrete (UHPC) further complicates the estimation of prestress losses because of the changes in material models dependent on curing regime. Past research shows compressive creep is "locked in" when UHPC cylinders are subjected to thermal treatment before being loaded in compression. However, the current precasting manufacturing process would typically load the element (through prestressing strand release from the prestressing bed) before the element would be taken to the curing facility. Members of many ages are stored until curing could be applied to all of them at once. This research was conducted to determine the impact of variable curing times for UHPC on the prestress losses, and hence deflections. Three UHPC beams, a rectangular section, a modified bulb tee section, and a pi-girder, were assessed for losses and deflections using an incremental time step approach and material models specific to UHPC based on compressive creep and shrinkage testing. Results show that although it is important for prestressed UHPC beams to be thermally treated, to "lock in" material properties, the timing of thermal treatment leads to negligible differences in long-term deflections. Results also show that for UHPC elements that are thermally treated, changes in deflection are caused only by external loads because prestress losses are "locked-in" following thermal treatment.

Label-free oligonucleotide biosensor based on dual-peak long period fiber grating

We report the simplification and development of biofunctionalization methodology based on one-step 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)-mediated reaction. The dual-peak long period grating (dLPG) has been demonstrated its inherent ultrahigh sensitivity to refractive index (RI), achieving 50-fold improvement in RI sensitivity over a standard LPG sensor used in low RI range. With the simple and efficient immobilization of unmodified oligonucleotides on sensor surface, dLPG-based biosensor has been used to monitor the hybridization of complementary oligonucleotides showing a detectable oligonucleotide concentration of 4 nM with the advantages of label-free, real-time, and ultrahigh sensitivity.

Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease: a randomized, controlled clinical trial

BACKGROUND Canine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, β-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180 days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress. RESULTS Twenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (p > 0.05) for any of the studied parameters. Final data analysis (supplement: n = 9; placebo: n = 10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (p < 0.001). After treatment, a significant decrease (1.53-fold; p < 0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (p < 0.05) and paraoxonase-1 (PON1) levels after 60 days of treatment (p < 0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120 days (p < 0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group. CONCLUSIONS The combined administration of the supplement with hydrolyzed diet over 180 days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI.

Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute myocardial infarction: Results from the Metocard-CNIC trial (Effect of Metoprolol in Cardioprotection during an Acute Myocardial Infarction)

The goal of this trial was to study the long-term effects of intravenous (IV) metoprolol administration before reperfusion on left ventricular (LV) function and clinical events. Early IV metoprolol during ST-segment elevation myocardial infarction (STEMI) has been shown to reduce infarct size when used in conjunction with primary percutaneous coronary intervention (pPCI). The METOCARD-CNIC (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction) trial recruited 270 patients with Killip class ≤II anterior STEMI presenting early after symptom onset (<6 h) and randomized them to pre-reperfusion IV metoprolol or control group. Long-term magnetic resonance imaging (MRI) was performed on 202 patients (101 per group) 6 months after STEMI. Patients had a minimal 12-month clinical follow-up. Left ventricular ejection fraction (LVEF) at the 6 months MRI was higher after IV metoprolol (48.7 ± 9.9% vs. 45.0 ± 11.7% in control subjects; adjusted treatment effect 3.49%; 95% confidence interval [CI]: 0.44% to 6.55%; p = 0.025). The occurrence of severely depressed LVEF (≤35%) at 6 months was significantly lower in patients treated with IV metoprolol (11% vs. 27%, p = 0.006). The proportion of patients fulfilling Class I indications for an implantable cardioverter-defibrillator (ICD) was significantly lower in the IV metoprolol group (7% vs. 20%, p = 0.012). At a median follow-up of 2 years, occurrence of the pre-specified composite of death, heart failure admission, reinfarction, and malignant arrhythmias was 10.8% in the IV metoprolol group versus 18.3% in the control group, adjusted hazard ratio (HR): 0.55; 95% CI: 0.26 to 1.04; p = 0.065. Heart failure admission was significantly lower in the IV metoprolol group (HR: 0.32; 95% CI: 0.015 to 0.95; p = 0.046). In patients with anterior Killip class ≤II STEMI undergoing pPCI, early IV metoprolol before reperfusion resulted in higher long-term LVEF, reduced incidence of severe LV systolic dysfunction and ICD indications, and fewer heart failure admissions.

Maternal creatine supplementation during pregnancy prevents acute and long-term deficits in skeletal muscle after birth asphyxia: a study of structure and function of hind limb muscle in the spiny mouse

BACKGROUND: Maternal antenatal creatine supplementation protects the brain, kidney, and diaphragm against the effects of birth asphyxia in the spiny mouse. In this study, we examined creatine's potential to prevent damage to axial skeletal muscles.

METHODS: Pregnant spiny mice were fed a control or creatine-supplemented diet from mid-pregnancy, and 1 d before term (39 d), fetuses were delivered by c-section with or without 7.5 min of birth asphyxia. At 24 h or 33 ± 2 d after birth, gastrocnemius muscles were obtained for ex-vivo study of twitch-tension, muscle fatigue, and structural and histochemical analysis.

RESULTS: Birth asphyxia significantly reduced cross-sectional area of all muscle fiber types (P < 0.05), and increased fatigue caused by repeated tetanic contractions at 24 h of age (P < 0.05). There were fewer (P < 0.05) Type I and IIa fibers and more (P < 0.05) Type IIb fibers in male gastrocnemius at 33 d of age. Muscle oxidative capacity was reduced (P < 0.05) in males at 24 h and 33 d and in females at 24 h only. Maternal creatine treatment prevented all asphyxia-induced changes in the gastrocnemius, improved motor performance.

CONCLUSION: This study demonstrates that creatine loading before birth protects the muscle from asphyxia-induced damage at birth.

Long-term changes in fish communities of the Ria Formosa coastal lagoon (southern Portugal) based on two studies made 20 years apart

Fish communities of the Ria Formosa coastal lagoon (south Portugal) were sampled on a monthly basis with a beach seine at 4 sites, during two different time periods: 1980-1986 and 2001-2002. Community indices, species ranking and multivariate analysis were used in order to identify changes in the fish community between the two time periods. A total of 153,511 fish representing 57 taxa were recorded. Although species composition was very similar for both sampling periods, multivariate analysis performed on annual species abundance in number and weight revealed differences in fish community structure between the two periods. Structural changes in fish community were related mostly to a sharp decrease in the abundance of Mugilidae from 1980-1986 to 2001-2002. These changes were probably associated to a decrease in organic matter contents and nutrients concentrations due to improvements in sewage treatment and better water circulation inside the lagoon. The changes in fish community structure are more evident in the inner areas of the lagoon than near the inlet. The association between changes in sewage patterns and changes in the ichthyofaunal community structure reinforces the importance of fish communities as a biological indicator of human induced changes in marine systems. (c) 2007 Elsevier Ltd. All rights reserved.

Long term performance evaluation of small-diameter vascular grafts based on polyvinyl alcohol hydrogel and dextran and MSCs-based therapies using the ovine pre-clinical animal model.

The functional and structural performance of a 5 cm synthetic small diameter vascular graft (SDVG) produced by the copolymerization of polyvinyl alcohol hydrogel with low molecular weight dextran (PVA/Dx graft) associated to mesenchymal stem cells (MSCs)-based therapies and anticoagulant treatment with heparin, clopidogrel and warfarin was tested using the ovine model during the healing period of 24 weeks. The results were compared to the ones obtained with standard expanded polyetetrafluoroethylene grafts (ePTFE graft). Blood flow, vessel and graft diameter measurements, graft appearance and patency rate (PR), thrombus, stenosis and collateral vessel formation were evaluated by B-mode ultrasound, audio and color flow Doppler. Graft and regenerated vessels morphologic evaluation was performed by scanning electronic microscopy (SEM), histopathological and immunohistochemical analysis. All PVA/Dx grafts could maintain a similar or higher PR and systolic / diastolic laminar blood flow velocities were similar to ePTFE grafts. CD14 (macrophages) and α-actin (smooth muscle) staining presented similar results in PVA/Dx/MSCs and ePTFE graft groups. Fibrosis layer was lower and endothelial cells were only detected at graft-artery transitions where it was added the MSCs. In conclusion, PVA/Dx graft can be an excellent scaffold candidate for vascular reconstruction, including clinic mechanically challenging applications, such as SDVGs, especially when associated to MSCs-based therapies to promote higher endothelialization and lower fibrosis of the vascular prosthesis, but also higher PR values.