Protein intake and osteosarcopenic adiposity in Korean adults aged 50 years and older.

Intake of plant-based protein and recommended protein intake are associated with a lower risk of osteosarcopenic adiposity (co-occurrence of osteopenia/osteoporosis, sarcopenia, and adiposity) in elderly Korean men. INTRODUCTION: Osteosarcopenic adiposity (OSA) syndrome is defined as the concurrent presence of osteopenia/osteoporosis, sarcopenia, and adiposity and leads to negative functional and metabolic outcomes in late adulthood. This study aimed to investigate the association between OSA and protein intake in adults aged 50 or older. METHODS: A population-based, cross-sectional survey was conducted using the Korea National Health and Nutrition Examination Survey 2008-2009 data and included 645 men and 706 women aged 50 or older. Subjects were classified into normal and OSA groups. Protein intake was analyzed using the 24-h recall method. RESULTS: There was no significant difference in the intake of total protein and animal-based protein between normal and OSA groups. However, in males, the intake of plant-based protein (p = 0.0031) was significantly lower in the OSA group than that in the normal group. Further, the protein intake in the OSA group was 0.96 g/kg/day, which was significantly lower than that in the normal group (1.06 g/kg/day; p = 0.0203). After adjusting for confounding factors, men over 65 years old who consumed less than the recommended nutrient intake (RNI) of 0.91 g/kg/day had 5.82 times higher risk of OSA compared with subjects consuming protein equal to or greater than the RNI amount (95% CI 1.81-18.66). CONCLUSION: In conclusion, a protein intake of RNI or more is associated with a lower risk of OSA in Korean elderly men.

Sequence variations of the locus-specific 5' untranslated regions of SLA class I genes and the development of a comprehensive genomic DNA-based high-resolution typing method for SLA-2.

The genetic diversity of the major histocompatibility complex (MHC) class I molecules of pigs has not been well characterized. Therefore, the influence of MHC genetic diversity on the immune-related traits of pigs, including disease resistance and other MHC-dependent traits, is not well understood. Here, we attempted to develop an efficient method for systemic analysis of the polymorphisms in the epitope-binding region of swine leukocyte antigens (SLA) class I genes. We performed a comparative analysis of the last 92 bp of the 5' untranslated region (UTR) to the beginning of exon 4 of six SLA classical class I-related genes, SLA-1, -2, -3, -4, -5, and -9, from 36 different sequences. Based on this information, we developed a genomic polymerase chain reaction (PCR) and direct sequencing-based comprehensive typing method for SLA-2. We successfully typed SLA-2 from 400 pigs and 8 cell lines, consisting of 9 different pig breeds, and identified 49 SLA-2 alleles, including 31 previously reported alleles and 18 new alleles. We observed differences in the composition of SLA-2 alleles among different breeds. Our method can be used to study other SLA class I loci and to deepen our knowledge of MHC class I genes in pigs.

Grain-oriented segmentation of images of porous structures using ray casting and curvature energy minimization.

We segment an image of a porous structure by successively identifying individual grains, using a process that requires no manual initialization. Adaptive thresholding is used to extract an incomplete edge map from the image. Then, seed points are created on a rectangular grid. Rays are cast from each point to identify the local grain. The grain with the best shape is selected by energy minimization, and the grain is used to update the edge map. This is repeated until all the grains have been recognized. Tests on scanning electron microscope images of titanium oxide and aluminium oxide show that their process achieves better results than five other contour detection techniques.

Role of HER3 expression and PTEN loss in patients with HER2-overexpressing metastatic breast cancer (MBC) who received taxane plus trastuzumab treatment.

BACKGROUND: The aim of this study was to investigate the role of human epidermal growth factor receptor (HER3) and PTEN expression in patients with HER2-overexpressing metastatic breast cancer (MBC). METHODS: One hundred twenty-five MBC patients who were treated with taxane plus trastuzumab chemotherapy as first-line therapy were included in this analysis. Immunohistochemical (IHC) staining with HER3 and PTEN antibodies were conducted retrospectively. RESULTS: Patients who had negative HER3 staining (62.4%) had a better progression-free survival (PFS) than did those who had positive HER3 staining (P=0.001; median PFS, 21 vs 11 months). Patients who had a PTEN score >20 (78.1%) showed longer PFS than did those with a PTEN score ≤20 (P=0.006; median PFS, 13 vs 9 months). Patients who had a PTEN score >20 exhibited a longer overall survival (OS) than did those with a PTEN score ≤20 (P=0.005; median OS, 48 vs 25 months). HER3 negativity and PTEN loss were identified as independent risk factors for PFS. PTEN loss was identified as an independent risk factor for OS. CONCLUSION: HER3 and PTEN expressions may be predictive markers, and PTEN expression may be a predictive and prognostic biomarker for trastuzumab treatment in HER2-positive MBCs.

Gemcitabine-oxaliplatin plus prednisolone is active in patients with castration-resistant prostate cancer for whom docetaxel-based chemotherapy failed.

BACKGROUND: There has been no previous study on the activity of gemcitabine in combination with oxaliplatin (GemOx) for castration-resistant prostate cancer (CRPC). METHODS: The GemOx was preclinically tested for cytotoxic activity in human prostate cancer cell lines. Clinically, patients with CRPC who failed prior docetaxel were treated with gemcitabine 1000 mg m(-2) and oxaliplatin 100 mg m(-2) intravenously every 2 weeks and prednisolone 5 mg orally twice daily. The primary end point was the prostate-specific antigen (PSA) response rate. RESULTS: The GemOx displayed synergistic effects based on Chou and Talalay analysis. In the phase II study, 33 patients were accrued. The median dose of docetaxel exposure was 518 mg m(-2). A total of 270 cycles were administered with a median of eight cycles per patient. A PSA response rate was 55% (95% CI, 38-72) and radiologic response rate was 82% (9 out of 11). With a median follow-up duration of 20.5 months, the median time to PSA progression was 5.8 months (95% CI, 4.4-7.2) and the median overall survival was 17.6 months (95% CI, 12.6-22.6). The most frequently observed grade 3 or 4 toxicities were neutropenia (13%) and thrombocytopenia (13%). CONCLUSIONS: The GemOx is active and tolerable in patients with metastatic CRPC after docetaxel failure (NCT 01487720).

The impact of activated p-AKT expression on clinical outcomes in diffuse large B-cell lymphoma: a clinicopathological study of 262 cases.

BACKGROUND: Oncogenic phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/AKT) pathway plays a critical role in cell proliferation and growth. Phosphorylated AKT (p-AKT) has been reported to be abnormally overexpressed and to have poor prognostic impact in solid tumors. PATIENTS AND METHODS: To define the clinical implications of p-AKT expression in diffuse large B-cell lymphoma (DLBCL), we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression and investigated the impact of p-AKT expression on clinical outcomes. We assessed 262 patients with DLBCL. Based on a cutoff value of the upper limit of the third quartile of AUs, 56 patients were classified as high p-AKT and the remaining 206 patients were classified as low p-AKT. RESULTS: The high p-AKT group was closely associated with more advanced stage (stage III-IV, P = 0.02), two or more extranodal involvement (P = 0.03), lactic dehydrogenase elevation (P = 0.03), higher International Prognostic Index risk groups (high intermediate/high, P = 0.02), and the presence of B-symptoms (P = 0.01). The high p-AKT group showed substantially worse overall survival (OS) (median OS, 115.0 months versus not reached, P = 0.004) and progression-free survival (PFS) (median PFS, 25.5 versus 105.8 months, P = 0.019) compared with the low p-AKT group. Multivariate analysis revealed that high p-AKT expression retained its significant poor prognostic impact for OS (hazard ratio 1.7; 95% confidence interval, 1.0-2.7; P = 0.031). The subgroup with high p-AKT expression and concurrent Epstein-Barr virus positivity showed worst prognosis with the median OS and PFS of 15.2 and 7.4 months. CONCLUSION: DLBCL patients with high p-AKT expression showed distinct clinical features and followed a more rapidly deteriorating clinical course with worse OS and PFS. Thus, a more effective treatment option should be developed for this subset of DLBCL patients, and targeting PI3K/AKT pathway may be a promising therapeutic strategy.

Prospective analysis of quality of life in elderly patients treated with adjuvant chemotherapy for non-small-cell lung cancer.

BACKGROUND: Given the more comorbidities with a decline in physiologic reserve, it can be challenging to make appropriate treatment decisions in the elderly. PATIENTS AND METHODS: Here, we prospectively evaluated and compared the health-related quality of life (HRQOL) of patients aged ≥ 65 with aged <65 who were treated with a postoperative chemotherapy for completely resected stage Ib, II or IIIa non-small-cell lung cancer (NSCLC). Either four cycles of paclitaxel (Taxol)-carboplatin (PC) or vinorelbine-cisplatin (NP) was used. The HRQOL was assessed with EORTC QLQ-C30 and EORTC QLQ-LC13. RESULTS: Between October 2008 and October 2011, a total of 139 patients (aged <65, n = 73; ≥ 65, n = 66) were enrolled, and 127 (91.4%) completed the questionnaire. Overall, the quality of life (QOL) in elderly patients did not significantly deteriorate with adjuvant chemotherapy and the time trend of QOL in elderly patients was similar to that of younger patients. Although the elderly suffered from increased treatment-related adverse events involving sore mouth, peripheral neuropathy and alopecia compared with the baseline, the same time trends were also observed in younger group. The mean dose intensities (MDIs) for PC and NP regimen were not significantly different between the two age groups. CONCLUSIONS: Postoperative chemotherapy did not substantially reduce HRQOL in elderly NSCLC patients, and HRQOL during and after adjuvant chemotherapy did not significantly differ by age.

Preoperative Chemoradiotherapy With Capecitabine With or Without Temozolomide in Patients With Locally Advanced Rectal Cancer: A Prospective, Randomised Phase II Study Stratified by O6-Methylguanine DNA Methyltransferase Status: KCSG-CO17-02.

AIMS: To evaluate the clinical efficacy of adding temozolomide (TMZ) to preoperative capecitabine (CAP)-based chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and validate O6-methylguanine DNA methyltransferase (MGMT) methylation status as a predictive marker for TMZ combined regimens. MATERIALS AND METHODS: LARC patients with clinical stage II (cT3-4N0) or III (cTanyN+) disease were enrolled. They were stratified into unmethylated MGMT (uMGMT) and methylated MGMT (mMGMT) groups by methylation-specific polymerase chain reaction before randomisation and were then randomly assigned (1:1) to one of four treatment arms: uMGMT/CAP (arm A), uMGMT/TMZ + CAP (arm B), mMGMT/CAP (arm C) and mMGMT/TMZ + CAP (arm D). The primary end point was the pathological complete response (pCR) rate. RESULTS: Between November 2017 and July 2020, 64 patients were randomised. Slow accrual caused early study termination. After excluding four ineligible patients, 60 were included in the full analysis set. The pCR rate was 15.0% (9/60), 0%, 14.3%, 18.8% and 26.7% for the entire cohort, arms A, B, C and D, respectively (P = 0.0498 between arms A and D). The pCR rate was 9.7% in the CAP group (arms A + C), 20.7% in the TMZ + CAP group (arms B + D), 6.9% in the uMGMT group (arms A + B) and 22.6% in the mMGMT group (arms C + D). Grade 1-2 nausea or vomiting was significantly more frequent in the TMZ + CAP treatment groups (arms B + D) than in the CAP treatment groups (arms A + C, P < 0.001) with no difference in grade 3 adverse events. There were no grade 4 or 5 adverse events. CONCLUSION: The addition of TMZ to CAP-based chemoradiotherapy tended to improve pCR rates, particularly in those with mMGMT LARC. MGMT status may warrant further investigation as a predictive biomarker for chemotherapeutic agents and radiotherapy.

Comprehensive and high-resolution typing of swine leukocyte antigen DQA from genomic DNA and determination of 25 new SLA class II haplotypes.

We previously reported the development of genomic-DNA-based high-resolution genotyping methods for SLA-DQB1 and DRB1. Here, we report the successful typing of SLA-DQA using similar methodological principles. We designed a method for comprehensive genotyping of SLA-DQA using intronic sequence information of SLA-DQA exon 2 that we had obtained from 12 animals with different SLA-DQB1 genotypes. We expanded our typing to 76 selected animals with diverse DQB1 and DRB1 genotypes, 140 random animals from 7 pig breeds, and 3 wild boars. This resulted in the identification of 17 DQA alleles with 49 genotypes. Two new alleles were identified from wild boars. Combine with SLA-DQB1, and DRB1 typing results, we identified 34 SLA class II haplotypes including 25 that were previously unreported.

Involvement of Mrp2/MRP2 in the species different excretion route of benzylpenicillin between rat and human.

1. The purpose of this study was to investigate the involvement of rat Mrp2 and human MRP2 in benzylpenicillin transport using canalicular liver plasma membrane (cLPM) vesicles isolated from Sprague-Dawley or Easai hyperbilirubinemic (EHBR) rats, and MDCKII cells overexpressing MRP2. 2. The adenosine triphosphate (ATP)-dependent uptake of benzylpenicillin and oestradiol-17beta-D-glucuronide (E(2)17betaG), a representative substrate for Mrp2, into EHBR-cLPM vesicles was decreased relative to that seen with control-cLPM vesicles, which may reflect the absence of Mrp2 in the EHBR. The ATP-dependent uptake of taurocholate, which is not a substrate for Mrp2, was similar in both control and EHBR-cLPM vesicles. The concentration dependence of ATP-dependent benzylpenicillin uptake was reflected in a K(m) of 44.0 microM and a V(max) of 508.4 pmol mg(-1) min(-1). Additional inhibition studies using E(2)17betaG and methotrexate as representative substrates for Mrp2/MRP2 demonstrated the involvement of rat Mrp2, but not human MRP2, in benzylpenicillin efflux. Benzylpenicillin appears not to be a substrate for or inhibitor of other human efflux transporters such as MDR1, MRP1, MRP3, or BCRP. 3. In conclusion, rat Mrp2, but not human MRP2, plays an important role in ATP-dependent benzylpenicillin uptake in the bile canalicular membrane, which may explain why biliary excretion of benzylpenicillin is high in the rat but negligible in humans.

Decreased urinary secretion of belotecan in folic acid-induced acute renal failure rats due to down-regulation of Oat1 and Bcrp.

The effects of folic acid-induced acute renal failure on the renal excretion of belotecan were investigated in rats after intravenous administration. Both glomeruli and renal tubules were seriously damaged by folic acid-induced acute renal failure. The renal excretion clearance, CLr, of belotecan was significantly decreased by folic acid-induced acute renal failure. Furthermore, glomerular filtration rate and secretion clearance of the drug were dramatically decreased by folic acid-induced acute renal failure. In vivo renal uptake of belotecan was inhibited by p-aminohippurate, whereas renal excretion was inhibited by GF120918, but not by verapamil and bromosulphalein. This indicates that Oat1/3 and Bcrp are involved in the renal uptake and urinary excretion of belotecan, respectively. Both mRNA and protein levels of Oat1, Oat3 and Bcrp were significantly decreased in folic acid-induced acute renal failure rats. Based on the finding that belotecan is a substrate of OAT1 but not of OAT3, the decrease in CLr of belotecan in folic acid-induced acute renal failure could, therefore, mainly be attributed to the down-regulation of Oat1 and Bcrp, in addition to the decrease in glomerular filtration rate.

The FIELDS Instrument Suite for Solar Probe Plus: Measuring the Coronal Plasma and Magnetic Field, Plasma Waves and Turbulence, and Radio Signatures of Solar Transients.

NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products.

Evolutionary Dynamics of a Highly Pathogenic Type 2 Porcine Reproductive and Respiratory Syndrome Virus: Analyses of Envelope Protein-Coding Genes.

Porcine reproductive and respiratory syndrome virus (PRRSV) has long been an economically devastating swine viral disease. The recent emergence of a highly pathogenic type 2 PRRSV with high mobility and mortality in China, spreading in Vietnam, Laos, and Thailand has placed neighbouring countries at risk. This study applied a codon-based extension of the Bayesian relaxed clock model and the fixed effects maximum-likelihood method to investigate and compare the evolutionary dynamics of type 2 PRRSV for all of known structural envelope protein-coding genes. By comparing the highly pathogenic type 2 PRRSV clade against the typical type 2 PRRSV clade, this study demonstrated that the highly pathogenic clade evolved at high rates in all of the known structural genes but did not display rapid evolutionary dynamics compared with typical type 2 PRRSV. In contrast, the ORF3, ORF5 and ORF6 genes of the highly pathogenic clade evolved in a qualitatively different manner from the genes of the typical clade. At the population level, several codons of the sequence elements that were involved in viral neutralization, as well as codons that were associated with in vitro attenuation/over-attenuation, were predicted to be selected differentially between the typical clade and the highly pathogenic clade. The results of this study suggest that the multigenic factors of the envelope protein-coding genes contribute to diversifying the biological properties (virulence, antigenicity, etc.) of the highly pathogenic clade compared with the typical clade of type 2 PRRSV.

Epstein-Barr virus-associated gastric adenocarcinomas among Koreans.

Epstein-Barr virus (EBV)-associated gastric carcinomas have been reported from various regions of the world. Epstein-Barr virus appears to be pathogenetically related to some gastric carcinomas. To determine the incidence of EBV association with gastric carcinomas among Koreans, the authors have studied EBV genome expression in 89 consecutive patients with gastric carcinomas diagnosed at the Catholic University Hospitals in Seoul, Korea, using in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs), and immunohistochemistry for EBV latent membrane proteins (LMP) and CD21 antigen on paraffin sections. Thirty-seven gastric specimens with benign ulcer disease were used controls. EBV-encoded small RNAs were expressed in tumor cell nuclei in 12 patients (13.5%). None of the controls or benign portions of the cases were positive. In the positive cases, all tumor cell nuclei were uniformly stained and the staining intensity was strong. Immunohistochemistry for LMP was positive in 3 of 12 EBERs positive patients and none of EBERs negative patients. EBV latent membrane proteins was localized only in the lymphoid cells infiltrating the tumor in two patients, and tumor cells as well as infiltrating lymphoid cells in one patient. These results indicate that the rate of EBV association with gastric carcinomas in Koreans is relatively high and comparable to other Far Eastern Asian regions. The expression pattern in EBV-associated gastric carcinomas is similar to those of nasopharyngeal carcinomas in which clonality analysis using specific probes to the tandem repeat region of EBV yielded single episomal bands suggesting that EBV infection in EBV-associated gastric carcinomas are also clonal and pathogenetically related to the neoplasm. However, the mechanism of tumorigenesis remains to be elucidated.

Expression of 3 beta-hydroxysteroid/dehydrogenase/delta5-delta4/isomerase in the tracheal cartilage of the rat.

The enzyme complex 3beta-hydroxysteroid dehydrogenase isomerase/delta5-delta4 (3beta-HSD) is involved in the biosynthesis of all classes of active steroids. In this study, the presence of 3beta-HSD was defined in rat tracheal cartilage. The expression of the 3beta-HSD gene was examined by Northern blot analysis from 30-day-old rats. Western blot and immunohistochemical localization were also performed with antibodies raised against purified human placental 3beta-HSD to obtain further information on the expression of 3beta-HSD protein during fetal and postnatal periods of development in rat cartilage. Northern blot analysis using an oligonucleotide common to the 4 known 3beta-HSD isoforms showed 3beta-HSD mRNA corresponding to a transcript of 1.7 kb. Furthermore, a 42 KDa protein band was detected in the tracheal cartilage extracts by Western blot analysis. Immunostaining for 3beta-SD was observed in chondrocytes. The first expression was detected on the 17th day of fetal life by Western blot and immunohistochemistry. Immunoreactivity of 3beta-HSD showed a significant increase at 7 and 15 days after birth, and then remained unchanged through adulthood, in agreement with the data of the Western blot. Our results demonstrated the expression for 3beta-HSD in the tracheal cartilage at both the mRNA and protein levels during fetal life and postnatal development of the rat. These results suggest that 3beta-HSD may synthesize certain steroids which play major roles in differentiation and maintenance of function during development of rat cartilage.

The effects of age, education, and gender on the Mattis Dementia Rating Scale performance of elderly Chinese and American individuals.

A Chinese version of the Mattis Dementia Rating Scale (DRS) was administered to elderly individuals in Hong Kong (n = 104), and their performance on the test was compared with that of elderly participants in San Diego (n = 150). Age and education, but not gender, were significantly related to DRS performance in both groups. The effect of education was greater in the Hong Kong than in the San Diego participants, but this difference was eliminated when individuals with no formal education were removed from the Hong Kong group. Age- and education-matched groups of Hong Kong and San Diego elderly individuals differed in the pattern of DRS subtest performance they produced, even when they did not differ in total DRS score. The Hong Kong participants scored significantly higher than the San Diego participants on the Construction subscale, whereas the opposite pattern was observed on the Initiation/Perseveration and Memory subscales. These results suggest that some DRS subscales or individual subscale items may be susceptible to cultural differences between elderly Chinese and American individuals.

A Bayesian phylogeographical analysis of type 1 porcine reproductive and respiratory syndrome virus (PRRSV).

Understanding viral transmission is an important factor for the effective prevention one of the most devastating swine diseases, porcine reproductive and respiratory syndrome. Focusing on molecular epidemiology of type 1 PRRSV, this study analysed a large ORF5 dataset collected worldwide from 1991 to 2012 using a coalescent-based Bayesian Markov chain Monte Carlo approach. The results suggested that the virus diversified into unique subpopulations in Russia & Belarus and Italy approximately 100 years ago. Previously unreported consecutive diffusions of the virus were identified, which showed that some countries, such as Spain and Germany, acted as distribution sources to some extent. This study also provided statistical evidence for the existence of an ORF5-based phylogeographical structure of type 1 PRRSV, in which the virus tended to cluster by geographical locations more tightly than expected by chance. In contrast to this tight geographical structure, the evolution of the ORF5 gene, based on mapping of non-synonymous/synonymous substitutions, was best described by a non-homogeneous process that could be implicated as a mechanism for viral immune evasion.

Transport of organic cationic drugs: effect of ion-pair formation with bile salts on the biliary excretion and pharmacokinetics.

More than 40% of clinically used drugs are organic cations (OCs), which are positively charged at a physiologic pH, and recent reports have established that these drugs are substrates of membrane transporters. The transport of OCs via membrane transporters may play important roles in gastrointestinal absorption, distribution to target sites, and biliary and/or renal elimination of various OC drugs. Almost 40 years ago, a molecular weight (Mw) threshold of 200 was reported to exist in rats for monoquaternary ammonium (mono QA) compounds to be substantially (e.g., >10% of iv dose) excreted to bile. It is well known that some OCs interact with appropriate endogenous organic anions in the body (e.g., bile salts) to form lipophilic ion-pair complexes. The ion-pair formation may influence the affinity or binding of OCs to membrane transporters that are relevant to biliary excretion. In that sense, the association of the ion-pair formation with the existence of the Mw threshold appears to be worthy of examination. It assumes the ion-pair formation of high Mw mono QA compounds (i.e., >200) in the presence of bile salts in the liver, followed by accelerated transport of the ion-pair complexes via relevant bile canalicular transporter(s). In this article, therefore, the transport of OC drugs will be reviewed with a special focus on the ion-pair formation hypothesis. Such information will deepen the understanding of the pharmacokinetics of OC drugs as well as the physiological roles of endogenous bile salts in the detoxification or phase II metabolism of high Mw QA drugs.

Chunggan extract (CGX), methionine-and choline-deficient (MCD) diet-induced hepatosteatosis and oxidative stress in C57BL/6 mice.

In the present study, we aimed to evaluate the hepatoprotective and antioxidant effects of Chunggan extract (CGX) in an animal model of hepatosteatosis. The C57BL/6N mice were fed either methionine- and choline-sufficient (MCS) diet (n = 10) or a methionine- and choline-deficient (MCD) diet (n = 50) for 4 weeks, and then they were treated orally with CGX (100 or 200 mg/kg), ursodeoxycholic acid (80 mg/kg, as a positive control), or distilled water (DW, MCS diet group, and MCD diet group) for the final 2 weeks (once per day). The MCD diet induced severe hepatic injury with the typical features of hepatosteatosis in both serum and hepatic tissues. CGX treatment significantly attenuated these alterations in the serum levels including triglyceride (TG), aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin. Moreover, CGX also efficiently prevented from the hepatic TG accumulation in the hepatic tissue, evidenced by histopathological findings, compared with the MCD diet. In addition, CGX treatment significantly ameliorated the excessive oxidative stress and antioxidant markers in the serum as well as the hepatic levels of reactive oxygen species, the levels of malondialdehyde, the protein carbonyl, and total antioxidant capacity, and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. In conclusion, our results indicate the experimental relevance of CGX for potential clinical application in patients with hepatosteatotic disorders and a possible mechanism related to its antioxidant properties.

Efficacy of ramosetron in the treatment of male patients with irritable bowel syndrome with diarrhea: a multicenter, randomized clinical trial, compared with mebeverine.

BACKGROUND: The 5-HT(3) receptor antagonists are known to be effective for the treatment of diarrhea-predominant irritable bowel syndrome (IBS), but not widely used yet. The aim of this study was to compare the efficacy and safety of ramosetron, a 5-HT(3) receptor antagonist, and mebeverine in male patients with IBS with diarrhea (IBS-D). METHODS: This study was performed in a multicenter, randomized, open-label design. Data of 343 male patients with IBS-D who were randomized to either a 4-week treatment of ramosetron 5µg once daily or a 4-week treatment of mebeverine 135 mg three times daily were analyzed by the intent-to-treat analysis. The primary efficacy parameter was the proportion of patients with adequate relief of IBS symptoms at the last week of treatment. The secondary endpoints were changes in each symptom score and the safety profiles. KEY RESULTS: The responder rates for global IBS symptoms, abdominal pain/discomfort and abnormal bowel habits in the ramosetron and mebeverine groups significantly increased during the treatment period. The severity scores of abdominal pain/discomfort and urgency, the stool form score, and the stool frequency in both treatment arms were significantly reduced, compared with the baselines. There were no significant differences in the responder rates (37%vs 38% on ITT analysis) and adverse event profiles between the ramosetron and mebeverine groups. Neither severe constipation nor ischemic colitis was reported by ramosetron-treated patients. CONCLUSIONS & INFERENCES: Ramosetron 5µg once daily is as effective as mebeverine three times daily in male patients with IBS-D.