Effects of liquefied sake lees on growth performance and faecal and blood characteristics in Japanese Black calves.

Liquefied sake lees, a by-product of Japanese sake, is rich in Saccharomyces cerevisiae, proteins, and prebiotics derived from rice and yeast. Previous studies have reported that Saccharomyces cerevisiae fermentation products improved the health, growth, and faecal characteristics of preweaning calves. This study investigated the effects of adding liquefied sake lees to milk replacer on the growth performance, faecal characteristics, and blood metabolites of preweaning Japanese Black calves from 6 to 90 days of age. Twenty-four Japanese Black calves at 6 days of age were randomly assigned to one of three treatments: No liquefied sake lees (C, n = 8), 100 g/d (on a fresh matter basis) liquefied sake lees mixed with milk replacer (LS, n = 8), and 200 g/d (on a fresh matter basis) liquefied sake lees mixed with milk replacer (HS, n = 8). The intake of milk replacer and calf starter, as well as, the average daily gain did not differ between the treatments. The number of days counted with faecal score 1 in LS was higher than in HS (P < 0.05), while the number of days with diarrhoea medication in LS and C was lower than HS (P < 0.05). The faecal n-butyric acid concentration tended to be higher in LS compared to C (P = 0.060). The alpha diversity index (Chao1) was higher in HS than in C and LS at 90 days of age (P < 0.05). The principal coordinate analysis (PCoA) using weighted UniFrac distance showed that the bacterial community structures in faeces among the treatments at 90 days of age were significantly different (P < 0.05). The plasma ß-hydroxybutyric acid concentration, an indicator of rumen development, was higher for LS than in C throughout the experiment (P < 0.05). These results suggested that adding liquefied sake lees up to 100 g/d (on a fresh matter basis) might promote rumen development in preweaning Japanese Black calves.

Effects of resistance training on arterial compliance and plasma endothelin-1 levels in healthy men.

Arterial compliance (AC) is an index of the elasticity of large arteries. Endothelial dysfunction has been reported to result in reduced arterial compliance, which represents increased arterial stiffness. A reduction in AC is elicited by high-intensity resistance training, however the mechanisms are obscure. Because a single bout of resistance exercise causes a transient increase in circulating plasma endothelin-1 in humans, some vasoconstrictors may play a role in the mechanisms. The present study aimed to investigate whether resistance training-induced decrease in AC is associated with changes in circulating vasoconstrictors levels in young men. Young sedentary men were assigned to control (n=5) or training (n=9) groups. The training group performed four-week high-intensity resistance training (weight training exercise; three sessions/week). We measured AC and plasma levels of endothelin-1, angiotensin II, and norepinephrine before and after intervention. Resistance training significantly decreased AC, whereas the changes in plasma levels of neither endothelin-1, nor angiotensin II, nor norepinephrine were significantly different between the control and the training groups. Moreover, we found no significant correlations between changes in circulating plasma levels (endothelin-1, angiotensin II, and norepinephrine) and in the AC. Despite of no alteration of the resting circulating plasma levels (endothelin-1, etc.), we cannot exclude a possibility that the tissue/local concentrations of vasoconstrictors (endothelin-1, etc.) around the vessels might be increased and also involved in a reduction of AC in the training group. Taken together, the present results suggest that circulating vasoconstrictors (endothelin-1, etc.) in plasma are not involved in a reduction in AC by the resistance training.

Estimation of the energy expenditure of grazing ruminants by incorporating dynamic body acceleration into a conventional energy requirement system.

The estimation of energy expenditure (EE) of grazing animals is of great importance for efficient animal management on pasture. In the present study, a method is proposed to estimate EE in grazing animals based on measurements of body acceleration of animals in combination with the conventional Agricultural and Food Research Council (AFRC) energy requirement system. Three-dimensional body acceleration and heart rate were recorded for tested animals under both grazing and housing management. An acceleration index, vectorial dynamic body acceleration (VeDBA), was used to calculate activity allowance (AC) during grazing and then incorporate it into the AFRC system to estimate the EE (EE derived from VeDBA [EE]) of the grazing animals. The method was applied to 3 farm ruminant species (7 cattle, 6 goats, and 4 sheep). Energy expenditure based on heart rate (EE) was also estimated as a reference. The result showed that larger VeDBA and heart rate values were obtained under grazing management, resulting in greater EE and EE under grazing management than under housing management. There were large differences between the EE estimated from the 2 methods, where EE values were greater than EE (averages of 163.4 and 142.5% for housing and grazing management, respectively); the EE was lower than the EE, whereas the increase in EE under grazing in comparison with housing conditions was larger than that in EE. These differences may have been due to the use of an equation for estimating EE derived under laboratory conditions and due to the presence of the effects of physiological, psychological, and environmental factors in addition to physical activity being included in measurements for the heart rate method. The present method allowed us to separate activity-specific EE (i.e., AC) from overall EE, and, in fact, AC under grazing management were about twice times as large as those under housing management for farm ruminant animals. There is evidence that the conventional energy system can predict fasting metabolism and the AC of housed animals based on accumulated research on energy metabolism and that VeDBA can quantify physical activity separately from other factors in animals on pasture. Therefore, the use of the VeDBA appears to be a precise way to predict activity-specific EE under grazing conditions, and the method incorporating acceleration index data with a conventional energy system can be a simple and useful method for estimation of EE in farm ruminants on pastures.

Lower thigh muscle mass is associated with all-cause and cardiovascular mortality in elderly hemodialysis patients.

BACKGROUND/OBJECTIVES: Higher body mass index appears protective in hemodialysis patients, although it remains to be determined which component of muscle or fat mass is primarily associated with this survival advantage. SUBJECTS/METHODS: Eighty-one hemodialysis patients in our institution were prospectively followed from July 2011 to August 2015. Muscle and fat mass were evaluated by measuring the cross-sectional areas of the thigh and abdomen using computed tomography. The relationship between muscle and fat mass, and all-cause and cardiovascular mortality was studied using the Kaplan-Meier analyses and multivariate Cox proportional hazard models. RESULTS: During more than 4 years of follow-up, 26 patients (32%) died. In the Kaplan-Meier curve analyses, lower thigh muscle mass was significantly associated with all-cause and cardiovascular mortality (log-rank test, P<0.01 and P<0.001, respectively), but there was no such association with thigh fat, abdominal muscle and fat mass levels. In multivariate Cox proportional hazard models, each 0.1 cm2/kg increase in the thigh muscle area adjusted by dry weight was associated with an estimated 22% lower risk of all-cause mortality (95% confidence interval (95% CI), 0.64-0.95, P<0.05) and a 30% lower risk of cardiovascular mortality (95% CI, 0.54-0.90, P<0.01). CONCLUSIONS: Lower thigh muscle mass is significantly associated with all-cause and cardiovascular mortality in hemodialysis patients. Our findings indicate the importance of focusing on the muscle mass of lower extremities to predict the clinical outcomes of hemodialysis patients.

Factors associated with mucosal pain in patients with partial removable dental prostheses.

The aim of this study was to investigate factors associated with mucosal pain in patients with partial removable dental prostheses (PRDPs). In this hospital-based cross-sectional study, 333 patients wearing 500 PRDPs (mean age 71·4 years, men 33·3%) were consecutively recruited from prosthetic clinic of a dental hospital in Japan. Subjects rated pain intensity and frequency of denture-bearing mucosa. An examiner recorded age, gender and systemic diseases as well as dental, mucosa, denture, sensory, behavioural- and psychological-related characteristics that were possibly associated with the mucosal pain. Multivariate analyses were performed to analyse factors related to mucosal pain. Pain intensity was rated as more than score 0 (presence) in 34·2% (171/500) PRDPs, and pain was experienced after denture delivery in 42·8% (214/500) PRDPs. Logistic regression analyses showed that younger age, mucosal damage, poor mucosal condition, bone prominence, poor residual ridge, higher pain sensitivity, presence of awake bruxism, perception of oral dryness, interim denture wear and high number of missing teeth were significant independent predictors for the presence of the mucosal pain intensity and/or frequency (P < 0·05). Multiple factors are associated with mucosal pain in patients with PRDPs. Oral mucosal characteristics, age, pain sensitivity and behavioural factors seem to be more critical for mucosal pain than distribution of missing teeth and number of abutment teeth.

Factors influencing the priority of access to food and their effects on the carcass traits for Japanese Black (Wagyu) cattle.

The factors influencing the priority of access to food and the effects of the priority of access to food on their carcass traits were analyzed for Japanese Black (Wagyu) cattle in a semi-intensive fattening production system. The records of 96 clinically healthy steers and heifers were analyzed. The calves at ∼3 to 4 months of age were allocated to pens with four animals per pen; all four animals in the same pen were of the same sex and of similar body size. The ranking of the animals' priority of access to food (1st, 2nd, 3rd and 4th), which was determined by the farm manager, was used as an indicator of social dominance in the present study. Four models including sire line, maternal grandsire line and the difference in the animals' birth dates as fixed effects were used to analyze factors influencing the priority of access to food. Ranking was represented by ordinal scores (highest=4, lowest=1) in Model 1, and the binary scores were assigned in Model 2 (highest=1; 2nd, 3rd and 4th=0), Model 3 (1st and 2nd=1; 3rd and 4th=0) and Model 4 (1st, 2nd and 3rd=1; lowest=0). The results showed that the difference in the animals' birth dates had a significant effect on the establishment of the priority of access to food in Model 3 (P<0.05), suggesting that animals born earlier may become more dominant in the pen. The maternal grandsire line tended to affect the social rank score in Models 2 and 3 (P<0.10). Our results indicated that the maternal grandsire line may affect the temperament of calves through their mothers' genetic performance and thereby more aggressive calves may be more dominant and have higher priority of access to food. On the other hand, there was a significant effect of the priority of access to food on beef marbling score (BMS; P<0.05), and the priority of access to food also tended to influence the carcass weight (P=0.09). The highest BMS was observed for animals with the first rank of the priority of access to food (P<0.05), and the higher-ranking animals had the tendency to be heavier carcass than the lower-ranking animals. Our findings emphasized the importance of information about the priority of access to food determined by farmers' own observation on implementing best management practices in small-scaled semi-intensive beef cattle production systems.

Note: Fabrication of resolution target for super-resolution microscopy.

We fabricated a resolution target for super-resolution microscopes (SRMs). The target was constructed by scattering a dyed photo-resist on a glass cover plate and used UV nano-imprinting to transfer minute line-and-space patterns on to the photo-resist layer. Using this resolution target, an image obtained from a SRM and its properties was evaluated quantitatively.

Uric acid, indoxyl sulfate, and methylguanidine activate bulbospinal neurons in the RVLM via their specific transporters and by producing oxidative stress.

Patients with chronic renal failure often have hypertension, but the cause of hypertension, other than an excess of body fluid, is not well known. We hypothesized that the bulbospinal neurons in the rostral ventrolateral medulla (RVLM) are stimulated by uremic toxins in patients with chronic renal failure. To investigate whether RVLM neurons are sensitive to uremic toxins, such as uric acid, indoxyl sulfate, or methylguanidine, we examined changes in the membrane potentials (MPs) of bulbospinal RVLM neurons of Wister rats using the whole-cell patch-clamp technique during superfusion with these toxins. A brainstem-spinal cord preparation that preserved the sympathetic nervous system was used for the experiments. During uric acid, indoxyl sulfate, or methylguanidine superfusion, almost all the RVLM neurons were depolarized. To examine the transporters for these toxins on RVLM neurons, histological examinations were performed. The uric acid-, indoxyl sulfate-, and methylguanidine-depolarized RVLM neurons showed the presence of urate transporter 1 (URAT 1), organic anion transporter (OAT)1 or OAT3, and organic cation transporter (OCT)3, respectively. Furthermore, the toxin-induced activities of the RVLM neurons were suppressed by the addition of an anti-oxidation drug (VAS2870, an NAD(P)H oxidase inhibitor), and a histological examination revealed the presence of NAD(P)H oxidase (nox)2 and nox4 in these RVLM neurons. The present results show that uric acid, indoxyl sulfate, and methylguanidine directly stimulate bulbospinal RVLM neurons via specific transporters on these neurons and by producing oxidative stress. These uremic toxins may cause hypertension by activating RVLM neurons.

Pyrosequencing survey of the microbial diversity of 'narezushi', an archetype of modern Japanese sushi.

AIMS: This study aimed to analyse microbiota of the fermented food 'narezushi', an archetype of modern Japanese sushi. The pyrosequencing technique was used to analyse sequences of 16S ribosomal DNA contained in six narezushi products. METHODS AND RESULTS: The V1-V2 regions of the 16S ribosomal DNA were amplified from different narezushi products using PCR, and approximately 120,000 sequences were phylogenetically assigned at the genus level, using the Ribosomal Database Project classifier. In all samples, the microbial populations consisted of more than 90% Lactobacillales, mainly Lactobacillus or Pediococcus, reflecting their crucial role in narezushi fermentation. There were more than 700 operational taxonomy units in all samples, with Shannon-Wiener index varying from 1.69 to 2.60. CONCLUSIONS: The microbiota of all narezushi products were shown to consist largely of Lactobacillales populations. Interestingly, different species were found to be dominant in each product. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides an insight into the bacterial composition of fermented fish-based foods, which are consumed worldwide. Significant differences in the dominant species were observed between products, possibly because of the starter-free production process.

Validity of mid-arm muscular area measured by anthropometry in nonobese patients with increased muscle atrophy and variation of subcutaneous fat thickness.

BACKGROUND: The anthropometric measurement of mid-arm muscular area (MAMA) involves overestimation because of various assumptions, this overestimation being progressive with increasing adiposity. However, the effects of muscle atrophy and variation of the subcutaneous fat thickness have remained uncertain. OBJECTIVES: The validity of MAMA estimated by anthropometry was examined by comparing with MAMA measured by computed tomography (CT) in a nonobese population. The effects of muscle atrophy and variation of the subcutaneous fat thickness on the validity of MAMA were examined by new indices. SUBJECTS/METHODS: The relative MAMA was compared between the anthropometric and CT methods in 45 patients. New indices were introduced for assessing muscle deformity (muscle deformity index, MDI) and subcutaneous fat variation (SFVI). The effects of MDI, SFVI and age on the difference of MAMA between the anthropometric and CT methods were investigated. RESULTS: MDIs were positively correlated with age in males (r=0.47, P<0.05) and females (r=0.66, P<0.001). SFVI was positively correlated with age only in females (r=0.54, P<0.01). Even in these patients, the relative MAMA estimated by anthropometry was significantly associated with that measured by CT (r=0.85, P<0.0001 in males and r=0.90, P<0.0001 in females). A Bland-Altman plot indicated that the difference between both methods was relatively small, although increased adiposity might be a source of overestimation for anthropometric MAMA measurement. CONCLUSIONS: MAMA estimated by anthropometry was a reliable indicator of muscle mass in patients with muscle atrophy and varying thickness of subcutaneous fat in lean patients.

Novel TiO(2)/ZnO multilayer mirrors at 'water-window' wavelengths fabricated by atomic layer epitaxy.

We propose that novel oxide superlattice structures of crystalline TiO(2)/ZnO on sapphire substrates can be used for multilayer mirrors with high reflectivity at 2.734 nm. In the experimental study, both rutile TiO(2)(200) and wurtzite ZnO(001) thin films were grown epitaxially on the same sapphire (001) substrate by atomic layer epitaxy (ALE) at 450 °C. We also demonstrated that the novel oxide superlattice structure of 10-bilayer TiO(2)/ZnO on a sapphire substrate gave a high reflectivity of 29.4% at 2.74 nm.

Mixed-lineage-leukemia (MLL) fusion protein collaborates with Ras to induce acute leukemia through aberrant Hox expression and Raf activation.

Mixed-lineage-leukemia (MLL) fusion oncogenes are closely involved in infant acute leukemia, which is frequently accompanied by mutations or overexpression of FMS-like receptor tyrosine kinase 3 (FLT3). Earlier studies have shown that MLL fusion proteins induced acute leukemia together with another mutation, such as an FLT3 mutant, in mouse models. However, little has hitherto been elucidated regarding the molecular mechanism of the cooperativity in leukemogenesis. Using murine model systems of the MLL-fusion-mediated leukemogenesis leading to oncogenic transformation in vitro and acute leukemia in vivo, this study characterized the molecular network in the cooperative leukemogenesis. This research revealed that MLL fusion proteins cooperated with activation of Ras in vivo, which was substitutable for Raf in vitro, synergistically, but not with activation of signal transducer and activator of transcription 5 (STAT5), to induce acute leukemia in vivo as well as oncogenic transformation in vitro. Furthermore, Hoxa9, one of the MLL-targeted critical molecules, and activation of Ras in vivo, which was replaceable with Raf in vitro, were identified as fundamental components sufficient for mimicking MLL-fusion-mediated leukemogenesis. These findings suggest that the molecular crosstalk between aberrant expression of Hox molecule(s) and activated Raf may have a key role in the MLL-fusion-mediated-leukemogenesis, and may thus help develop the novel molecularly targeted therapy against MLL-related leukemia.

Effect of parental genotypes and paternal heterosis on litter traits in crossbred goats.

The effect of parental genotype and paternal heterosis on litter size (LS), total litter birth weight (TLW) and average litter birth weight (ALW) was analysed utilizing data from a crossbreeding programme involving the exotic German Fawn goats and local Katjang goats in Malaysia. In this study, these traits were regarded as traits of the litter to consider the effect of service sire genotype. The results revealed that LS was significantly influenced by the genotype of sire. The genotypes of sire and dam had significant effects on TLW and ALW. Estimates of crossbreeding parameter showed significant and negative influence of paternal heterosis on TLW and ALW while there was no significant effect of paternal heterosis on LS. The results of this study stress the need to reconsider the use of local males in the tropics.

Identification of TSC-22 as a potential tumor suppressor that is upregulated by Flt3-D835V but not Flt3-ITD.

Transforming growth factor-beta (TGF-beta)-stimulated clone-22 (TSC-22) was originally isolated as a TGF-beta-inducible gene. In this study, we identified TSC-22 as a potential leukemia suppressor. Two types of FMS-like tyrosine kinase-3 (Flt3) mutations are frequently found in acute myeloid leukemia: Flt3-ITD harboring an internal tandem duplication in the juxtamembrane domain associated with poor prognosis and Flt3-TKD harboring a point mutation in the kinase domain. Comparison of gene expression profiles between Flt3-ITD- and Flt3-TKD-transduced Ba/F3 cells revealed that constitutive activation of Flt3 by Flt3-TKD, but not Flt3-ITD, upregulated the expression of TSC-22. Importantly, treatment with an Flt3 inhibitor PKC412 or an Flt3 small interfering RNA decreased the expression level of TSC-22 in Flt3-TKD-transduced cells. Forced expression of TSC-22 suppressed the growth and accelerated the differentiation of several leukemia cell lines into monocytes, in particular, in combination with differentiation-inducing reagents. On the other hand, a dominant-negative form of TSC-22 accelerated the growth of Flt3-TKD-transduced 32Dcl.3 cells. Collectively, these results suggest that TSC-22 is a possible target of leukemia therapy.

Acute renal infarction in a patient with left atrial myxoma.

A 24-year-old male first attended our hospital with acute onset of right flank pain radiating to the right lower quadrant of the abdomen. A contrast-enhanced computer tomography (CT) scan showed renal infarction, and he was admitted immediately for treatment. On admission, the right lower abdominal pain diminished gradually. On the second day in hospital, a left atrial echogenic mass was detected which filled the left atrial cavity; it appeared to be a left atrial myxoma measuring 3.9+/-4.9 cm. The patient was immediately transferred and underwent emergency surgery. Histologic examination confirmed the diagnosis of myxoma. Post-operatively, he recovered well and was discharged from hospital without any further specific treatment.

ER stress (PERK/eIF2alpha phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation.

Expanded polyglutamine 72 repeat (polyQ72) aggregates induce endoplasmic reticulum (ER) stress-mediated cell death with caspase-12 activation and vesicular formation (autophagy). We examined this relationship and the molecular mechanism of autophagy formation. Rapamycin, a stimulator of autophagy, inhibited the polyQ72-induced cell death with caspase-12 activation. PolyQ72, but not polyQ11, stimulated Atg5-Atg12-Atg16 complex-dependent microtubule-associated protein 1 (MAP1) light chain 3 (LC3) conversion from LC3-I to -II, which plays a key role in autophagy. The eucaryotic translation initiation factor 2 alpha (eIF2alpha) A/A mutation, a knock-in to replace a phosphorylatable Ser51 with Ala51, and dominant-negative PERK inhibited polyQ72-induced LC3 conversion. PolyQ72 as well as ER stress stimulators upregulated Atg12 mRNA and proteins via eIF2alpha phosphorylation. Furthermore, Atg5 deficiency as well as the eIF2alpha A/A mutation increased the number of cells showing polyQ72 aggregates and polyQ72-induced caspase-12 activation. Thus, autophagy formation is a cellular defense mechanism against polyQ72-induced ER-stress-mediated cell death by degrading polyQ72 aggregates, with PERK/eIF2alpha phosphorylation being involved in polyQ72-induced LC3 conversion.

Diffusion Tensor Imaging and 3D Tractography of the Cervical Spinal Cord Using the ECG-Gated Line-scan Technique. A Feasibility Study.

Diffusion tensor (DT) magnetic resonance (MR) imaging in addition to conventional MR images provide valuable information on the brain. This study compared line scan DT imaging with and without the ECG-gating technique to estimate clinical usefulness of the line scan diffusion tensor image (LSDTI) with ECG-gating in evaluating spinal cord diseases in vivo. First, five healthy volunteers participated in the comparison study. LSDWI was performed in three to five sagittal sections with a pulsed-field-gradient diffusion preparation pulse employing two different b-values (0 and 700 s/mm(2)) along six directions. Apparent diffusion coefficient (ADC) maps and fractional anisotropy (FA) were calculated and three-dimensional tract reconstruction and color schemes of the spinal cord were obtained. Image quality and the acquisition time of each LSDTI were compared. Second, LSDTI with ECG-gating was performed in eighteen patients with cervical spinal cord disorders and evaluated by two neuroradiologists. Images with the ECG-gated technique were all superior to those without ECG-gating. Mean extended time for LSDTI with ECG-gating was approximately two minutes. In clinical use, the ADC and FA of spinal cord in patients with cervical spondylotic myelopathy statically changed. Moreover, demonstration of fibers was correlated with clinical symptoms. ECG-gating technique is preferable to LSDTI. The ADC and FA measurements and 3D fiber tracking of LSDTI with ECG-gating are promising methods to estimate cervical spinal cord pathology in clinical use.

Low-dose prednisolone ameliorates acute renal failure caused by cholesterol crystal embolism.

AIMS: The prognosis of renal cholesterol crystal embolism (CCE) is poor. Although various treatments for CCE have been attempted, there is no optimal therapy. We tested the effect of low-dose prednisolone (PS) on CCE-related acute renal failure (ARF). PATIENTS AND METHODS: 7 patients (mean age 69 years) diagnosed with CCE-related ARF were treated with oral PS at 15-20 mg/day for 2-4 weeks, which was then tapered at 5 mg/day over 2-4 weeks, followed by 5 mg/day maintenance dose. Recurrent ARF during PS tapering was treated with a larger dose of PS. RESULTS: Inciting factors were identified in four patients: coronary angiography (n=3) and cerebral angiography (n=1). On admission, serum creatinine (SCr) was 2.1 +/- 0.3 mg/dl (mean +/- SEM). SCr and eosinophil count before treatment were 4.2 +/- 0.4 mg/dl and 682 +/- 73/microl, respectively. PS therapy improved ARF in all cases at week 2 (SCr 3.8 +/- 0.5 mg/dl) parallel to a decrease in eosinophilia (116 +/- 30/microl), and at week 4 (3.1 +/- 0.4 mg/dl and 134 +/- 20/microl, respectively). At last follow-up, renal function was improved or maintained in 5 patients compared with that at week 4 post-treatment. One patient died of lung cancer. Another required LDL apheresis and hemodialysis but died due to CCE-related multi-organ failure. A third patient had recurrent ARF and was re-treated with a larger dose of PS, which resulted in an immediate decrease in SCr. However, the patient developed acute renal dysfunction due to congestive heart failure, and required hemodialysis. CONCLUSIONS: Low-dose PS improved CCE-related ARF, probably through amelioration of inflammatory reaction surrounding affected renal vessels.

beta-Glucosidase inhibitory activities of phenylpropanoid glycosides, vanicoside A and B from Polygonum sachalinense rhizome.

The phenylpropanoid glycosides, vanicoside A and B, isolated from rhizomes of giant knotweed (Polygonum sachalinense) showed beta-glucosidase inhibitory activity, with IC(50) values of 59.8 and 48.3 mug/ml (59.9 and 50.5 muM), respectively. In contrast, p-coumaric acid and ferulic acid, corresponding to phenylpropanoyl moieties of vanicosides, exhibited very little inhibition.

Beneficial action of candesartan cilexetil plus amlodipine or ACE inhibitors in chronic nondiabetic renal disease.

Although multiple antihypertensive agents are required to control blood pressure (BP) in chronic renal disease, it remains undetermined whether the combination therapy with angiotensin receptor blockers (ARB) plus calcium antagonists or angiotensin-converting enzyme inhibitors (ACEI) confers more preferable action on renal disease than the ARB monotherapy. In the present study, we compared the effect of the combination therapy with ARB plus calcium antagonists/ACEI on proteinuria with that of the ARB monotherapy in chronic nondiabetic renal disease. At 1 month of the drug treatment, the candesartan monotherapy (n=19) reduced BP from 154+/-3/93+/-2 to 146+/-3/88+/-2 mmHg (P<0.05), and a similar magnitude of BP reductions was observed with the combination therapy with candesartan plus ACEI/amlodipine (from 153+/-2/95+/-2 to 144+/-2/88+/-2 mmHg, P<0.05, n=39). The depressor action of these therapies was sustained throughout the 12-month treatment. In contrast, the reduction in proteinuria was greater with the combination therapy (-52+/-3% at 12 months, n=39) than with the candesartan monotherapy (-25+/-3%, n=19), although the baseline values of proteinuria were nearly the same in the candesartan monotherapy group (1.74+/-0.22 g/day) and the combination therapy group (2.10+/-0.19 g/day, P>0.2). Of note, the proteinuria-sparing effect did not differ between the candesartan+ACEI group and the candesartan+amlodipine group. In conclusion, the present study suggests more beneficial action of the combination therapy with ARB plus ACEI/amlodipine than the ARB monotherapy in nondiabetic renal disease. Since the reduction in BP was achieved to the same level, the distinct proteinuria-sparing action of these therapies is attributed to BP-independent mechanisms, which should vary depending on the agents used.