Universal health coverage and primary care, Thailand.

Thailand's policy on universal health coverage (UHC) has made good progress since its inception in 2002. Every Thai citizen is now entitled to essential preventive, curative and palliative health services at all life stages. Like its counterparts elsewhere, however, the policy faces challenges. A predominantly tax-financed system in a nation with a high proportion of people living in poverty will always strive to contain rising costs. Disparities exist among the different health insurance schemes that provide coverage for Thai citizens. National health expenditure is heavily borne by the government, primarily to reduce financial barriers to access for the poor. The population is ageing and the disease profiles of the population are changing alongside the modernization of Thai people's lifestyles. Thailand is now aiming to enhance and sustain its UHC policy. We examine the merits of different policy options and aim to identify the most promising and feasible way to enhance and sustain UHC. We argue that developing the existing primary care system in Thailand has the greatest potential to provide more self-sustaining, efficient, equitable and effective UHC. Primary care needs to move from its traditional role of providing basic disease-based care, to being the first point of contact in an integrated, coordinated, community-oriented and person-focused care system, for which the national health budget should be prioritized.

La politique de couverture sanitaire universelle de la Thaïlande a bien progressé depuis sa création en 2002. Chaque citoyen thaïlandais a désormais le droit à des services de santé préventifs, curatifs et palliatifs essentiels à tous les stades de sa vie. Néanmoins, à l'instar de ses équivalents dans d'autres pays, cette politique fait face à des difficultés. Un système principalement financé par l'impôt dans un pays où une forte proportion de personnes vit dans la pauvreté devra toujours s'efforcer de limiter l'augmentation des coûts. Des disparités existent entre les différents régimes d'assurance maladie qui fournissent une couverture aux citoyens thaïlandais. Les dépenses nationales de santé sont largement prises en charge par le gouvernement, principalement pour réduire les obstacles financiers qui empêchent les pauvres d'accéder aux services de santé. La population vieillit et le profil des maladies de la population évolue en même temps que les modes de vie des Thaïlandais se modernisent. La Thaïlande a désormais l'intention de renforcer sa politique de couverture sanitaire universelle et d'assurer sa pérennité. Nous examinons les avantages de différentes possibilités d'action et cherchons à identifier la solution la plus prometteuse et réalisable pour renforcer et assurer la pérennité de la couverture sanitaire universelle. Nous soutenons que le développement du système existant de soins de santé primaires en Thaïlande est la meilleure solution pour fournir une couverture sanitaire universelle plus autonome, efficiente, équitable et efficace. Les soins primaires doivent s'écarter de leur rôle traditionnel qui est de fournir des soins de base axés sur une maladie pour être le premier point de contact dans un système de soins intégré, coordonné, orienté vers la communauté et axé sur la personne, ce qui nécessite de donner une priorité élevée au budget national de santé.

La política de Tailandia sobre la cobertura sanitaria universal (CSU) ha progresado mucho desde su creación en 2002. Todos los ciudadanos tailandeses tienen ahora derecho a servicios esenciales de salud preventiva, curativa y paliativa en todas las etapas de la vida. Sin embargo, al igual que sus homólogas en otros lugares, la política se enfrenta a desafíos. Un sistema financiado en su mayoría por impuestos en un país con una alta proporción de personas que viven en la pobreza siempre tendrá que esforzarse para limitar el aumento de los costes. Existen disparidades entre los diferentes planes de seguros sanitarios que ofrecen cobertura a los ciudadanos tailandeses. El gasto nacional en salud lo soporta en gran medida el gobierno, principalmente para reducir las barreras financieras al acceso de los pobres. La población envejece y los perfiles de enfermedad de la población cambian al mismo tiempo que se modernizan los estilos de vida de los habitantes de Tailandia. Tailandia aspira ahora a mejorar y mantener su política de CSU. Se han examinado los méritos de las diferentes opciones de políticas para así identificar la manera más prometedora y factible de mejorar y sostener la CSU. Se sostiene que el desarrollo del sistema de atención primaria de salud existente en Tailandia tiene el mayor potencial para proporcionar una atención primaria de salud más autosuficiente, eficiente, equitativa y eficaz. La atención primaria debe pasar de su función tradicional de proporcionar atención básica basada en la enfermedad a ser el primer punto de contacto en un sistema de atención integral, coordinado, orientado a la comunidad y centrado en las personas, para lo cual se debe dar prioridad al presupuesto nacional de salud.

Muscle Weakness Is Associated With an Increase of Left Ventricular Mass Through Excessive Blood Pressure Elevation During Exercise in Patients With Hypertension.

Autonomic imbalance in hypertension induces excessive blood pressure (BP) elevation during exercise, thereby increasing left ventricular mass (LVM). Although muscle weakness enhances autonomic imbalance by stimulating muscle sympathetic activity during exercise, it is unclear whether muscle weakness is associated with an increase of LVM in patients with hypertension. This study aimed to investigate the relationships between muscle weakness, BP elevation during exercise, and LVM in these patients. Eighty-six hypertensive patients aged 69 ± 8 years with controlled resting BP (ie, < 140/90 mmHg) were recruited. Plasma brain natriuretic peptide (BNP), left ventricular mass index (LVMI), and knee extension muscle strength were measured. Changes in plasma noradrenaline (NORA) and brachial-ankle pulse wave velocity (ba-PWV) were assessed before and after an ergometer exercise test performed at moderate intensity (ΔNORA and ΔPWV, respectively). A difference between baseline and peak systolic BP during the exercise test was defined as BP elevation during exercise (ΔSBP). Relationships between muscle strength, ΔNORA, ΔPWV, ΔSBP, BNP, and LVMI were analyzed, and significant factors increasing LVM were identified using univariate and multivariate regression analyses. Muscle strength was negatively correlated with ΔNORA (r = -0.202, P = 0.048), ΔPWV (r = -0.328, P = 0.002), ΔSBP (r = -0.230, P = 0.033), BNP (r = -0.265, P = 0.014), and LVMI (r = -0.233, P = 0.031). LVMI was positively correlated with ΔPWV (r = 0.246, P = 0.023) and ΔSBP (r = 0.307, P = 0.004). Muscle strength was a significant independent factor associated with LVMI (ß = -0.331, P = 0.010). Our findings suggest that muscle weakness is associated with an increase of LVM through excessive BP elevation during exercise in patients with hypertension.

Improved high-fat diet-induced glucose intolerance by an oral administration of phytosphingosine.

We have previously reported that phytoceramide and phytosphingosine (PHS) stimulated the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ) in cells. PPARγ is a therapeutic target for type 2 diabetes. We found in this study that an oral administration of PHS improved diet-induced glucose intolerance in mice. Since PHS is highly expressed in yeast, PHS in fermented foods may improve diabetes.

Humulone suppresses replication of respiratory syncytial virus and release of IL-8 and RANTES in normal human nasal epithelial cells.

Respiratory syncytial virus (RSV) is the major infectious agent causing serious respiratory tract inflammation in infants and young children. However, an effective vaccine and anti-viral therapy for RSV infection have not yet been developed. Hop-derived bitter acids have potent pharmacological effects on inflammation. Therefore, we investigated the effects of humulone, which is the main constituent of hop bitter acids, on the replication of RSV and release of the proinflammatory cytokine IL-8 and chemokine RANTES in RSV-infected human nasal epithelial cells (HNECs). We found that humulone prevented the expression of RSV/G-protein, formation of virus filaments and release of IL-8 and RANTES in a dose-dependent manner in RSV-infected HNECs. These findings suggest that humulone has protective effects against the replication of RSV, the virus assembly and the inflammatory responses in HNECs and that it is a useful biological product for the prevention and therapy for RSV infection.

Novel clinical associations between time in range and microangiopathies in people with type 2 diabetes mellitus on hemodialysis.

AIMS/HYPOTHESIS: We investigated associations among glucose time in range (TIR, 70-180 mg/dL), glycemic markers and prevalence of diabetic microangiopathy in people with diabetes undergoing hemodialysis (HD). METHODS: A total of 107 people with type 2 diabetes undergoing HD (HbA1c 6.4 %; glycated albumin [GA] 20.6 %) using continuous glucose monitoring were analyzed in this observational and cross-sectional study. RESULTS: HbA1c and GA levels significantly negatively correlated with TIR, and positively correlated with time rate of hyperglycemia, but not with time rate of hypoglycemia. TIR of 70 % corresponded to HbA1c of 6.5 % and GA of 21.2 %. The estimated HbA1c level corresponding to TIR of 70 % in this study was lower than that previously reported in people with diabetes without HD. The prevalence of diabetic neuropathy was not significantly different between people with TIR ≥ 70 % and those with TIR < 70 % (P = 0.1925), but the prevalence of diabetic retinopathy in people with TIR ≥ 70 % was significantly lower than in those with TIR < 70 % (P = 0.0071). CONCLUSION/INTERPRETATION: TIR correlated with HbA1c and GA levels in people with type 2 diabetes on HD. Additionally, a higher TIR resulted in a lower rate of diabetic retinopathy. RESEARCH IN CONTEXT: What is already known about this subject? What is the key question? What are the new findings? How might this impact on clinical practice in the foreseeable future?

Xanthohumol, a prenylated chalcone from Humulus lupulus L., inhibits cholesteryl ester transfer protein.

High density lipoprotein (HDL)-cholesterol levels are correlated with a low risk of atherosclerosis. The inhibition of cholesteryl ester transfer protein (CETP), which catalyses cholesterol transfer between lipoproteins, leads to an increase in HDL-cholesterol and is expected to be the next anti-atherogenic target. This study revealed that xanthohumol, a prenylated chalcone, showed the highest inhibition against CETP from screening of natural products in various plants. We investigated the inhibitory activity of some chalcones and flavanones. Naringenin chalcone showed weak CETP inhibition compared with xanthohumol. In addition, isoxanthohumol and naringenin drastically decreased the inhibitory activity. These results suggest that the prenyl group and chalcone structure of xanthohumol were responsible for the CETP inhibitory activity.

Plasma and serum prorenin concentrations in diabetes, hypertension, and renal disease.

Although the renin-angiotensin-aldosterone system plays a crucial role in fluid homeostasis and cardiovascular disease pathophysiology, measurements of plasma prorenin levels are still unavailable in clinical practice. We previously found that prorenin molecules in human blood underwent significant posttranslational modifications and were undetectable using immunological assays that utilized antibodies specifically recognizing unmodified recombinant prorenin. Using a sandwich enzyme-linked immunosorbent assay that captures posttranslationally modified prorenins with their prosegment antibodies, we measured plasma and serum prorenin concentrations in 219 patients with diabetes mellitus, hypertension and/or renal disease and compared them with those of 40 healthy controls. The measured values were not significantly different from those of the healthy controls and were 1,000- to 100,000-fold higher than previously reported levels determined using conventional assay kits. Multiple regression analyses showed that body weight, serum albumin levels, and serum creatinine levels negatively correlated with plasma prorenin levels, while the use of loop diuretics was associated with elevated plasma prorenin levels. Blood pressure, HbA1c, and plasma renin activity were not independent variables affecting plasma prorenin levels. In contrast, serum prorenin levels were unaffected by any of the above clinical parameters. The association of the plasma prorenin concentration with indices reflecting body fluid status suggests the need to scrutinize its role as a biomarker, while serum prorenins are less likely to have immediate diagnostic value.

Strenuous resistance exercise effects on magnetic resonance diffusion parameters and muscle-tendon function in human skeletal muscle.

PURPOSE: To assess the effects of strenuous exercise on magnetic resonance diffusion parameters and muscle-tendon complex function in skeletal muscle. MATERIALS AND METHODS: Six men performed ankle plantar flexion exercises with eccentric contraction. The fractional anisotropy (FA), λ(1) , λ(2) , λ(3) , mean diffusivity (MD), and T(2) values in the triceps surae muscles were measured by magnetic resonance diffusion tensor and spin-echo imaging. Passive torque of plantar flexors, maximal voluntary isometric plantar flexion torques (MVIP), and Achilles tendon stiffness during MVIP were measured by combined ultrasonography and dynamometry. Plasma creatine kinase and muscle soreness were also assessed. These parameters were measured before and 1-8 days postexercise. RESULTS: The medial gastrocnemius exhibited significantly decreased FA 2-5 days after, increased λ(2) 3 days after, and increased λ(3) 2 and 3 days after exercise. This muscle also showed significantly increased MD and T(2) values 3 days postexercise. MVIP significantly decreased 2 and 3 days postexercise, while passive torque significantly increased 2 days postexercise. Creatine kinase and muscle soreness increased 3-5 days and 1-5 days postexercise, respectively. CONCLUSION: Exercise-induced muscle damage manifested as significant changes in muscle diffusion parameters with muscle-tendon complex dysfunction and delayed-onset muscle soreness.

Phytoceramide and sphingoid bases derived from brewer's yeast Saccharomyces pastorianus activate peroxisome proliferator-activated receptors.

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate lipid and glucose metabolism. PPARα is highly expressed in the liver and controls genes involved in lipid catabolism. We previously reported that synthetic sphingolipid analogs, part of which contains shorter-length fatty acid chains than natural sphingolipids, stimulated the transcriptional activities of PPARs. Sphingosine and dihydrosphingosine (DHS) are abundant sphingoid bases, and ceramide and dihydroceramide are major ceramide species in mammals. In contrast, phytosphingosine (PHS) and DHS are the main sphingoid bases in fungi. PHS and phytoceramide exist in particular tissues such as the epidermis in mammals, and involvement of ceramide species in PPARß activation in cultured keratinocytes has been reported. The purpose of the present study is to investigate whether natural sphingolipids with C18 fatty acid and yeast-derived sphingoid bases activate PPARs as PPAR agonists. METHOD: Lipids of brewer's yeast contain PHS- and DHS-based sphingolipids. To obtain the sphingoid bases, lipids were extracted from brewer's yeast and acid-hydrolyzed. The sphingoid base fraction was purified and quantified. To assess the effects of sphingolipids on PPAR activation, luciferase reporter assay was carried out. NIH/3T3 and human hepatoma (HepG2) cells were transfected with expression vectors for PPARs and retinoid × receptors, and PPAR responsive element reporter vector. When indicated, the PPAR/Gal4 chimera system was performed to enhance the credibility of experiments. Sphingolipids were added to the cells and the dual luciferase reporter assay was performed to determine the transcriptional activity of PPARs. RESULTS: We observed that phytoceramide increased the transcriptional activities of PPARs significantly, whereas ceramide and dihydroceramide did not change PPAR activities. Phytoceramide also increased transactivation of PPAR/Gal4 chimera receptors. Yeast-derived sphingoid base fraction, which contained PHS and DHS, or authentic PHS or DHS increased PPAR-dependent transcription. Additionally, phytoceramide stimulated PPARα activity in HepG2 hepatocytes, suggesting that phytoceramide activates genes regulated by PPARα. CONCLUSIONS: Phytoceramide and yeast-derived sphingoid bases activate PPARs, whereas ceramide and dihydroceramide do not change the PPAR activity. The present findings suggest that phytoceramide acts as a PPAR ligand that would regulate PPAR-targeted genes.

Differences in Muscle Activities and Kinematics between Forefoot Strike and Rearfoot Strike in the Lower Limb during 180° Turns.

BACKGROUND: A forefoot strike (FFS) could be a safer landing technique than a rearfoot strike (RFS) during a cutting motion to prevent anterior cruciate ligament (ACL) injury. PURPOSE: This study aimed to determine the joint angles, ground reaction force (GRF), and muscle activity levels associated with FFS and RFS landings during 180° turns. STUDY DESIGN: Cross-sectional study. METHODS: Fourteen male soccer players from the University of Tsukuba football (soccer) club participated in this study. The FFS consisted of initial contact with the toes on the force plates followed by the rearfoot; meanwhile, the initial contact was performed with the heels on the force plates followed by the forefoot for the RFS. Ankle, knee, and hip joint angles were recorded using a three-dimensional motion capture system. GRFs were measured using a force plate. Gluteus medius (GM), rectus femoris (RF), vastus medialis (VM), vastus lateralis (VL), semitendinosus (ST), biceps femoris (BF), tibialis anterior (TA), and lateral gastrocnemius (GL) activities were measured by electromyography. RESULTS: The activities of GM, GL, and ST from initial contact to early periods during landing into the ground with the FFS are larger than those with RFS. In addition, the results showed significant differences in lower-limb angles and GRFs between the FFS and RFS. CONCLUSION: These results suggest that there might be differences in ACL injury risk during a 180° turn between the FFS and the RFS pattern. An investigation into the grounding method that prevents injury is necessary in future studies. LEVELS OF EVIDENCE: Level 3b.

Hemodialysis-Related Glycemic Disarray Proven by Continuous Glucose Monitoring; Glycemic Markers and Hypoglycemia.

OBJECTIVE: There is a high risk of asymptomatic hypoglycemia associated with hemodialysis (HD) using glucose-free dialysate; therefore, the inclusion of glucose in the dialysate is believed to prevent intradialytic hypoglycemia. However, the exact glycemic fluctuation profiles and frequency of asymptomatic hypoglycemia using dialysates containing >100 mg/dL glucose have not been determined. RESEARCH DESIGN AND METHODS: We evaluated the glycemic profiles of 98 patients, 68 of whom were men, with type 2 diabetes undergoing HD (HbA1c 6.4 ± 1.2%; glycated albumin 20.8 ± 6.8%) with a dialysate containing 100, 125, or 150 mg/dL glucose using continuous glucose monitoring. RESULTS: Sensor glucose level (SGL) showed a sustained decrease during HD, irrespective of the dialysate glucose concentration, and reached a nadir that was lower than the dialysate glucose concentration in 49 participants (50%). Twenty-one participants (21%) presented with HD-related hypoglycemia, defined by an SGL <70 mg/dL during HD and/or between the end of HD and their next meal. All these hypoglycemic episodes were asymptomatic. Measures of glycemic variability calculated using the SGL data (SD, coefficient of variation, and range of SGL) were higher and time below range (<70 mg/dL) was lower in participants who experienced HD-related hypoglycemia than in those who did not, whereas time in range between 70 and 180 mg/dL, time above range (>180 mg/dL), HbA1c, and glycated albumin of the two groups were similar. CONCLUSIONS: Despite the use of dialysate containing 100-150 mg/dL glucose, patients with diabetes undergoing HD experienced HD-related hypoglycemia unawareness frequently. SGL may fall well below the dialysate glucose concentration toward the end of HD.

Dietary iso-α-acids prevent acetaldehyde-induced liver injury through Nrf2-mediated gene expression.

Acetaldehyde is the major toxic metabolite of alcohol (ethanol) and enhances fibrosis of the liver through hepatic stellate cells. Additionally, alcohol administration causes the accumulation of reactive oxygen species (ROS), which induce hepatocyte injury-mediated lipid peroxidation. Iso-α-acids, called isohumulones, are bitter acids in beer. The purpose of this study was to investigate the protective effects of iso-α-acids against alcoholic liver injury in hepatocytes in mice. C57BL/6N mice were fed diets containing isomerized hop extract, which mainly consists of iso-α-acids. After 7 days of feeding, acetaldehyde was administered by a single intraperitoneal injection. The acetaldehyde-induced increases in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were suppressed by iso-α-acids intake. Hepatic gene expression analyses showed the upregulation of detoxifying enzyme genes, glutathione-S-transferase (GST) and aldehyde dehydrogenase (ALDH). In vitro, iso-α-acids upregulated the enzymatic activities of GST and ALDH and induced the nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nfe2l2; Nrf2), a master regulator of antioxidant and detoxifying systems. These results suggest that iso-α-acid intake prevents acetaldehyde-induced liver injury by reducing oxidative stress via Nrf2-mediated gene expression.

Assessment of the accuracy of an intermittent-scanning continuous glucose monitoring device in patients with type 2 diabetes mellitus undergoing hemodialysis (AIDT2H) study.

FreeStyle Libre has been approved for use in patients undergoing hemodialysis (HD) in Japan, unlike Europe and the United States; however, evidence regarding its accuracy in such patients is sparse. Forty-one participants with type 2 diabetes undergoing HD were recruited. The overall mean absolute relative difference and mean absolute difference were 23.4% and 33.9 mg/dL, respectively. Sensor glucose levels and capillary glucose levels were significantly correlated (r = 0.858, P < .01), although the sensor glucose levels were significantly lower than the capillary glucose levels. The accuracy of FreeStyle Libre in patients undergoing HD became deteriorated with the days of usage. The percentage of sensor results in Zones A and B in the consensus error grid analysis and in the Clarke error grid analysis were 99.7% and 99.0%, respectively. Its insufficient accuracy necessitates adjunct usage of FreeStyle Libre with self-monitoring of blood glucose in patients undergoing HD.

Comparison of accuracy between flash glucose monitoring and continuous glucose monitoring in patients with type 2 diabetes mellitus undergoing hemodialysis.

INTRODUCTION: We evaluated the accuracy and clinical utility of flash glucose monitoring (FGM) in comparison with continuous glucose monitoring (CGM) and self-monitoring blood glucose (SMBG) in patients with type 2 diabetes (T2D) undergoing hemodialysis (HD). METHODS: Simultaneous FGM (FreeStyle LibrePro), CGM (iPro2) and SMBG were performed on 13 T2D research subjects. RESULTS: There were good overall correlations between SMBG and FGM (64.7% and 30.8% within the A and B of Parkes Error Grid, respectively) and between SMBG and CGM (87.9% and 11.0% within the A and B, respectively). However, during HD, correlations between SMBG and FGM were only 49.7% and 37.2% within the A and B, respectively, while correlations of SMBG and CGM were 72.8% and 22.2% within the A and B, respectively. The percentage of FGM not in Zone A + B was more than 4 times higher than for CGM. The overall mean absolute relative difference (MARD) for FGM was 18.2%, this significantly higher than 11.2% for CGM. During HD, MARD for FGM was 22.8%, significantly higher than 15.0% for CGM. CONCLUSION: FGM has good clinical agreement in T2D patients undergoing HD. However, the accuracy of FGM relative to SMBG was worse than that of CGM.

Omega-3 Polyunsaturated Fatty Acids Inhibit the Function of Human URAT1, a Renal Urate Re-Absorber.

The beneficial effects of fatty acids (FAs) on human health have attracted widespread interest. However, little is known about the impact of FAs on the handling of urate, the end-product of human purine metabolism, in the body. Increased serum urate levels occur in hyperuricemia, a disease that can lead to gout. In humans, urate filtered by the glomerulus of the kidney is majorly re-absorbed from primary urine into the blood via the urate transporter 1 (URAT1)-mediated pathway. URAT1 inhibition, thus, contributes to decreasing serum urate concentration by increasing net renal urate excretion. Here, we investigated the URAT1-inhibitory effects of 25 FAs that are commonly contained in foods or produced in the body. For this purpose, we conducted an in vitro transport assay using cells transiently expressing URAT1. Our results showed that unsaturated FAs, especially long-chain unsaturated FAs, inhibited URAT1 more strongly than saturated FAs. Among the tested unsaturated FAs, eicosapentaenoic acid, α-linolenic acid, and docosahexaenoic acid exhibited substantial URAT1-inhibitory activities, with half maximal inhibitory concentration values of 6.0, 14.2, and 15.2 µM, respectively. Although further studies are required to investigate whether the ω-3 polyunsaturated FAs can be employed as uricosuric agents, our findings further confirm FAs as nutritionally important substances influencing human health.

Inhibitory effect of Citrus flavonoids on the in vitro transport activity of human urate transporter 1 (URAT1/SLC22A12), a renal re-absorber of urate.

As hyperuricemia is a cause of urate-related diseases such as gout, the anti-hyperuricemic and/or uricosuric activity of food ingredients is receiving increased attention. Here, we examined the inhibitory activities of seven Citrus flavonoids against URAT1, a renal transporter involved in urate re-uptake from urine. We found that naringenin and nobiletin strongly inhibited URAT1, and may therefore serve as an anti-hyperuricemic food ingredient that can reduce the risk of urate-related diseases.

[Two cases of inoperable advanced bileduct cancer treated effectively with a gemcitabine/cisplatin combination].

We report two cases of inoperable advanced bileduct cancer that responded well to combined gemcitabine (GEM)/cisplatin (CDDP) therapy. A 70-year-old woman was admitted to the hospital because of jaundice; PTCD was performed, followed by laparotomy, however, the tumor was found to be inoperable because of extensive direct invasion of the surrounding organs. Then, after insertion of a stent, the patient was started on combined chemotherapy with GEM 1,000 mg/m2 on days 1, 8 and CDDP 70 mg/m2 on day 1 administered once every 3 weeks. After 4 courses, thrombocytopenia appeared. Therefore, chemotherapy was continued for another three courses with GEM 800 mg/m2 on days 1, 15 and CDDP 50 mg/m2 on day 1 every 4 weeks. After 7 courses the serum CEA level returned to normal range, and marked reduction of the tumor size was observed on CT. The patient has been able to maintain a good quality of life without occurrence of any severe adverse effects. A 61-year-old woman was admitted to the hospital because of icterus, and was diagnosed to have lower bile duct cancer with liver metastasis. After insertion of a stent, she was started on combined chemotherapy with GEM 1,000 mg/m2 on days 1, 8 and CDDP 70 mg/m2 on day 1 administered once every 3 weeks. After completion of 4 courses, the patient developed thrombocytopenia and a feel- ing of dullness. Therefore, chemotherapy was continued for the next three courses with GEM 800 mg/m2 on days 1, 15 and CDDP 50 mg/m2 on day 1, administered every 4 weeks. This treatment was associated with a fall of the serum CA19-9 level to within normal range, and marked improvement of the liver metastasis was also noted. Combined GEM/ CDDP therapy improves the QOL of inoperable bile duct cancer patients and offers promise as pre-operative chemotherapy.

Association of Lifelong Intake of Barley Diet with Healthy Aging: Changes in Physical and Cognitive Functions and Intestinal Microbiome in Senescence-Accelerated Mouse-Prone 8 (SAMP8).

Barley intake reportedly reduces the risk of cardiovascular disease, but effects on the systemic phenotypes during healthy aging have not yet been examined. Therefore, we examined the effects of barley on the lifespan; behavioral phenotypes, such as locomotor activity, and cognitive functions, and intestinal microbiome in the senescence-accelerated mouse-prone 8 (SAMP8) mouse. We prepared two mild high-fat diets by adding lard, in which the starch components of AIN-93G were replaced by rice or barley "Motchiriboshi." SAMP8 (four weeks old, male) mice were fed AIN-93G until eight weeks old, and then rice (rice group) or barley diet (rice: barley = 1:4, barley group) until death. Changes in aging-related phenotypes, object and spatial recognition, locomotor and balancing activities, and the intestinal microbiome were recorded. Moreover, plasma cholesterol levels were analyzed at 16 weeks old. Barley intake prolonged the lifespan by approximately four weeks, delayed locomotor atrophy, and reduced balancing ability and spatial recognition. Barley intake significantly increased the medium and small particle sizes of high-density lipoprotein (HDL) cholesterol, which is associated with a reduced risk of total stroke. The Bacteroidetes to Firmicutes ratio in the barley group was significantly higher than that in the rice group during aging. Thus, lifelong barley intake may have positive effects on healthy aging.

Plasma Cystine Levels and Cardiovascular and All-Cause Mortality in Hemodialysis Patients.

Oxidative stress accelerates the development of cardiovascular disease. Plasma cystine, a thiol oxidative stress marker, is related to several established factors for cardiovascular disease risk and prognosis. Although a comprehensive oxidative stress index is clinically required for hemodialysis patients with high oxidative stress, there are few reports concerning thiol oxidative stress markers predicting their prognosis. We investigated the relationship between plasma amino acids including cystine levels and cardiovascular disease-related and all-cause mortality in 132 maintenance hemodialysis patients. Higher cystine levels were associated with old age, longer hemodialysis duration, hemodialysis-associated hypotension, higher cardiothoracic ratio, higher blood urea nitrogen, and lower ankle-brachial index. Multivariate Cox regression analysis revealed that high plasma cystine was independently related with both cardiovascular disease mortality and all-cause mortality. Thus, high plasma cystine levels predict the prognosis of hemodialysis patients. High cystine levels necessitate a careful investigation for the cause of oxidative stress and comorbidities like vascular injury.

Molecular characteristics of tissue-bound semicarbazide-sensitive amine oxidase (SSAO) in guinea pig tissues.

Various mammalian tissues contain a tissue-bound amine oxidizing enzyme distinct from mitochondrial outer membrane enzyme, monoamine oxidase (MAO, EC 1.4.3.4), termed semicarbazide-sensitive amine oxidase (SSAO, EC 1.4.3.6). An increase in SSAO activity was found in patients suffering from vascular disorders such as diabetes and diabetic complications. It has previously been shown that 2-bromoethylamine (2-BEA) is a potent, and selective suicidal inhibitor of tissue-bound SSAO. The aim of this study was to investigate the interaction of this suicidal SSAO inhibitor with the tissue-bound enzyme in guinea pig lung, kidney, stomach, and heart homogenates. The conditions necessary for this inhibitor to titrate the concentrations of this enzyme were also determined. 2-BEA appears to interact with SSAO, as reported previously for this enzyme from different sources, in a manner consistent with an irreversible, "suicide" reaction. Because of this property, 2-BEA could be used to titrate the concentrations of SSAO active centers in these tissues under the appropriate conditions employed. Although some possible non-specific binding of the inhibitor to sites other than the active center of the enzyme, metabolism of this inhibitor and/or presence of enzyme subtypes was hypothesized, the molecular characteristics of SSAO in these tissues (Km, Vmax values, enzyme efficiencies, approximate enzyme concentrations, and molecular turnover numbers) towards the substrate kynuramine (0.1 mM) at pH 7.4 and 37 degrees C have been estimated.