5-Lipoxygenase-activating protein is the target of a novel hybrid of two classes of leukotriene biosynthesis inhibitors.

An 18-kDa leukocyte membrane protein, termed 5-lipoxygenase-activating protein (FLAP), has recently been shown to be the target of two structurally distinct classes of leukotriene biosynthesis inhibitors. These classes of inhibitors are based on indole and quinoline structures and are represented by MK-886 and L-674,573, respectively. A novel class of hybrid structure based on the indole and quinoline classes of inhibitors, termed quindoles, has recently been developed. These compounds, exemplified by L-689,037, are potent inhibitors of leukotriene biosynthesis, both in vitro and in vivo. In the present study, we have developed and characterized a potent radioiodinated photoaffinity analogue of L-689,037, termed [125I]L-691,678. This compound was used in immunoprecipitation studies with FLAP antisera to show that the quindole series of leukotriene biosynthesis inhibitors interact directly with FLAP. In addition, we show that MK-886, L-674,573, and L-689,037 specifically compete, in a concentration-dependent manner, with both [125I]L-691,678 and [125I]L-669,083, a photoaffinity analogue of MK-886, for binding to FLAP. These results suggest that these three classes of leukotriene biosynthesis inhibitors share a common binding site on FLAP, providing further evidence that FLAP represents a suitable target for structurally diverse classes of leukotriene biosynthesis inhibitors.     

Postmortem diagnosis of sudden unexpected death from Streptococcus suis type 2 infection: A case report

Streptococcus suis causes meningitis, septicemia, arthritis, endocarditis and death in both pigs and humans. Sudden death is rarely documented in the forensic field and almost all cases were diagnosed pre-mortem. Here we report a 49-year-old man who died from S. suis type 2 infection. S. suis was identified as the causative pathogen using bacterial culture, standard biochemical and coagglutination tests, specific DNA amplification by polymerase chain reaction, and histopathologic examination. We discuss the postmortem investigation of a suspected S. suis infection.     

Renal Microvascular Disease in an Aging Population: A Reversible Process?

Renal microvascular disease and tubulointerstitial fibrosis are usually demonstrated in aging in humans and animals. It has recently been proposed that renal microvascular disease is the crucial determinant of tubulointerstitial disease or fibrosis. Enhanced circulating endothelial cell loss is a biomarker that reflects glomerular endothelial injury or renal microvascular disease, and fractional excretion of magnesium (FE Mg) is a sensitive biomarker that reflects an early stage of tubulointerstitial fibrosis. In aging in humans, both of these biomarkers are abnormally elevated. In addition, a glomerular endothelial dysfunction determined by altered hemodynamics associated with peritubular capillary flow reduction is substantiated. A correction of such hemodynamic alteration with vasodilators can effectively improve renal perfusion and restore renal function. Thus, anti-aging therapy can reverse the renal microvascular disease and dysfunction associated with the aging process.     

A Mildly Altered Vascular Homeostasis in Early Stage of CKD

Background. A continuous increase in number of CKD patients entering ESRD is a growing public health threat, which reflects the present therapeutic failure usually initiating at the late stage of CKD. Objective. To study the mechanism of vascular repair in CKD patients associated with mildly impaired renal function, which included angiogenic factors such as VEFG, angiopoietin-1, and flt-1 (VEGFR1); and antiangiogenic factors such as angiopoietin-2 and KDR (VEGFR2). Results. A mild defect in angiogenic factor—namely, angiopoietin-1—was observed, whereas VEGF and flt-1 (VEGFR1) were within normal limit. Also, antiangiogenic factor—namely, angiopoietin-2—was mildly elevated, whereas KDR (VEGFR2) remained within normal limit. Conclusion. The mechanism of vascular repair appears to be adequately functional in the early stage of CKD. Therapeutic intervention at this stage can improve renal perfusion and restore renal function as indicated in normoalbuminuric, type 2 diabetic nephropathy. The authors encourage changing the conceptual view of treatment under common treatment at late stage of CKD to treatment at early stage of CKD under an environment favorable for renal regeneration.     

Improvement of Renal Function in Type 2 Diabetic Nephropathy

Background. Therapeutic failure in preventing renal disease progression in type 2 diabetic nephropathy (DN) is due to a failure in the early detection of DN by microalbuminuria and the inappropriate correction of renal hemodynamic maladjustment secondary to glomerular endothelial dysfunction. Methods. Thirty patients associated with normoalbuminuric type 2 DN were subject to the following studies: tubular function by means of fractional excretion of magnesium (FE Mg), vascular function by means of determining the circulating endothelial cell, VEGF, VEGF/TGF B ratio, and intrarenal hemodynamic studies. Results. FE Mg, circulating endothelial cells, and TGF B were abnormally elevated, and VEGF/TGF B ratio was decreased in these normoalbuminuric patients. The intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by a preferential constriction at the efferent arteriole and a reduction in peritubular capillary flow. Following treatment with vasodilators, a decrease in efferent arteriolar resistance and increase in peritubular capillary flow as well as glomerular clearance were observed. Conclusion. FE Mg appears to be a more sensitive marker than microalbuminuria for the early detection of DN. Increased endothelial cell injury is reflected by enhanced circulating endothelial cell loss in conjunction with the increased TGF B and the decreased ratio between VEGF and TGF B. This is further supported by the dysfunctioning glomerular endothelium, which is characterized by hemodynamic maladjustment and a reduction in the peritubular capillary flow. A correction of such hemodynamic maladjustment by multidrug vasodilators effectively improves renal perfusion and restores renal function in type 2 DN.     

Increasing Incidence of Hip Fracture in Chiang Mai,Thailand

Hip fracture is a major health problem in Thailand. This study attempted to examine the incidence, related factors, and trends of hip fracture in Chiang Mai, Thailand. All hip fracture data among patients aged 50 yr or older were collected from hospitals in Chiang Mai, Thailand from August 1, 2006 to July 3, 2007. Data from the 1997 Chiang Mai hip fracture study were used for comparison. In the study period, 690 hip fractures were reported: 203 males and 487 females (male to female ratio was 1 to 2.4), with a mean age of 76.7 yr. The estimated cumulative incidence was 181.0 per 100,000, and the adjusted incidence was 253.3 (males: 135.9; females: 367.9). A simple fall was the most common mechanism (79%) of fracture, and 80% of the hip fractures occurred in patients aged 70 yr or older. The highest incidence of hip fracture was observed in patients older than 85 yr (1239). At 6 mo postfracture, most patients (61%) used a walking aid. Compared with the 1997 data, hip fracture incidence had increased by an average of 2% per yr, and the incidence of hip fracture had increased significantly from August 1, 2006 to July 31, 2007, especially in patients older than 75 yr. In patients older than 84 yr, the incidence increased by a factor of 2. Urgent strategies for the prevention and treatment of osteoporosis, and hence hip fracture, are needed.     

Polypyrrole nanoparticles embedded nitrogen-doped graphene composites as novel cathode for long life cycles and high-power zinc-ion hybrid supercapacitors

The well-designed network structure of synthetic polypyrrole (PPy) nanoparticles embedded on a nitrogen-doped graphene (N-rGO) surface was utilized as a cathode for aqueous zinc-ion hybrid supercapacitors. Owing to the combination of the redox surface of PPy and the two-dimensional network structure of N-rGO, the PPy/N-rGO cathode affords rapid transport channels for Zn²⁺ ion adsorption/desorption and a faradaic reaction toward the synergistic composite materials. Subsequently, the constructed zinc-ion hybrid supercapacitors with the optimized PPy/N-rGO cathode composites deliver the highest capacity of 145.32 mA h g⁻¹ at 0.1 A g⁻¹ and the maximum energy density of 232.50 W h kg⁻¹ at a power density of 160 W kg⁻¹. Besides this, excellent cycling stability of 85% retention after 10 000 charge–discharge cycles at 7.0 A g⁻¹ was achieved. The high-rate capabilities with long life cycle performance of these novel zinc-ion hybrid supercapacitors could find practical use in a wide range of applications, ranging from next-generation electronic devices to large-scale stationary energy storage.

The well-designed network structure of synthetic polypyrrole (PPy) nanoparticles embedded on a nitrogen-doped graphene (N-rGO) surface was utilized as a cathode for aqueous zinc-ion hybrid supercapacitors.     

Improved microstructure and significantly enhanced dielectric properties of Al3+/Cr3+/Ta5+ triple-doped TiO2 ceramics by Re-balancing charge compensation

The charge compensation mechanism and dielectric properties of the (Al_xCr_0.05−x)Ta_0.05Ti_0.9O₂ ceramics were studied. The mean grain size slightly changed with the increase in the Al³⁺/Cr³⁺ ratio, while the porosity was significantly reduced. The dielectric permittivity of the co-doped Cr_0.05Ta_0.05Ti_0.9O₂ ceramic was as low as ε′∼ 10³, which was described by self-charge compensation between Cr³⁺–Ta⁵⁺, suppressing the formation of Ti³⁺. Interestingly, ε′ can be significantly increased (6.68 × 10⁴) by re-balancing the charge compensation via triple doping with Al³⁺ in the Al³⁺/Cr³⁺ ratio of 1.0, while a low loss tangent (∼0.07) was obtained. The insulating grains of [Cr_0.05³⁺Ta_0.05⁵⁺]Ti_0.9⁴⁺O₁₂ has become the semiconducting grains for the triple-doped Al_x³⁺[Cr_0.05−x³⁺Ta_0.05−x⁵⁺][Ta_x⁵⁺Ti_x³⁺Ti_0.9+x⁴⁺]O_12+3x/2. Considering an insulating grain with low ε′ of the Cr_0.05Ta_0.05Ti_0.9O₂ ceramic, the electron-pinned defect-dipoles and interfacial polarization were unlikely to exist supported by the first principles calculations. The significantly enhanced ε′ value of the triple-doped ceramic was primarily contributed by the interfacial polarization at the interface between the semiconducting and insulating parts, which was supported by impedance spectroscopy. This research gives an underlying mechanism on the charge compensation in the Al³⁺/Cr³⁺/Ta⁵⁺-doped TiO₂ system for further designing the dielectric and electrical properties of TiO₂-based ceramics for capacitor applications.

The dielectric properties of Cr³⁺/Ta³⁺ co-doped TiO₂ can be significantly improved by triple doping with Al³⁺ due to the re-balance of charge compensation.     

Opisthorchis viverrini： The carcinogenic human liver fluke

Opisthorchiasis caused by Opisthorchis viverrini remains a major public health problem in many parts of Southeast Asia, including Thailand, Lao PDR, Vietnam and Cambodia. The infection is associated with a number of hepatobiliary diseases, including cholangitis, obstructive jaundice, hepatomegaly, cholecystitis and cholelithiasis. Multi-factorial etiology of cholangiocarcinoma, mechanical damage, parasite secretions, and immunopathology may enhance cholangiocarcinogenesis. Moreover, both experimental and epidemiological evidences strongly implicate liver fluke infection as the major risk factor in cholangiocarcinoma, cancer of the bile ducts. The liver fluke infection is induced by eating raw or uncooked fish products that is the tradition and popular in the northeastern and northern region, particularly in rural areas, of Thailand. The health education programs to prevent and control opisthorchiasis are still required in the high-risk areas.