A microscopic model for helical twisting power by the optical isomers of an octahedral metal complex

A computational approach to the evaluation of helical twisting powers (HTP) of chiral metal complexes of [Ru(blade) 2 (backbone)] type is presented. The dopant contains helically attached ''blade'' ligands and an elongated ''backbone'' ligand, and some remarkably powerful examples have been reported. In this work, the observed HTP is interpreted in terms of a microscopic interaction of a dopant and host molecules with atomistic details. For this purpose, the stable structure of a triad system comprising a dopant and two host molecules was obtained by geometry optimization using Gaussian03. As a result, the host molecules interacted attractively with the dopant, being twisted in the same direction as observed experimentally. Interaction energy was assessed as a function of the dihedral angle between the two host molecules, leading to a quadratic dependence with a minimum at the equilibrium twisting angle of À32 . Based on this, the expression was derived, in which helical twisting power was given in terms of the equilibrium twisting angle of a pair of strongly interacting host molecules

Clinical effects of a selective urate reabsorption inhibitor dotinurad in patients with hyperuricemia and treated hypertension : a multicenter, prospective, exploratory study (DIANA)

Introduction Dotinurad is a newer urate-lowering agent that selectively inhibits urate transporter 1 in the renal proximal tubule and increases urinary urate excretion. Currently, little is known about the clinical efficacies of dotinurad in patients with hyperuricemia and hypertension. The aim of this study was to assess the clinical effects of a selective urate reabsorption inhibitor dotinurad on serum uric acid (SUA) levels and relevant vascular markers in patients with hyperuricemia and treated hypertension. Methods This investigator-initiated, multicenter, prospective, single-arm, open-label, exploratory clinical trial in Japan enrolled patients with hyperuricemia and treated hypertension who received a 24-week dotinurad therapy (a starting dose at 0.5 mg once daily and up-titrated to 2 mg once daily). The primary endpoint was a percentage change in the SUA level from baseline to week 24. The secondary endpoints were cardiovascular and metabolic measurements, including changes in the cardio-ankle vascular index (CAVI) and derivatives of reactive oxygen metabolites (d-ROMs) concentration at week 24. Results Fifty patients (mean age 70.5 ± 11.0 years, with 76.0% being men, and mean SUA level 8.5 ± 1.2 mg/dL) were included in the analysis. The percentage change from baseline in the SUA level at week 24 was − 35.8% (95% confidence interval [CI] − 39.7% to − 32.0%, P < 0.001), with approximately three quarters of patients achieving an SUA level of ≤ 6.0 mg/dL at week 24. The proportional changes from baseline in the geometric mean of CAVI and d-ROMs at week 24 were 0.96 (95% CI 0.92 to 1.00, P = 0.044) and 0.96 (95% CI 0.92 to 1.00, P = 0.044), respectively. Conclusion In addition to meaningful SUA-lowering effects, 24 weeks of dotinurad therapy may favorably affect arterial stiffness and oxidative stress markers, suggesting off-target vascular protection of dotinurad. Further research is expected to verify our findings and elucidate the entire off-target effects of dotinurad

Effect of febuxostat on left ventricular diastolic function in patients with asymptomatic hyperuricemia : a sub analysis of the PRIZE Study

Hyperuricemia is related to an increased risk of cardiovascular events from a meta-analysis and antihyperuricemia agents may influence to cardiac function. We evaluated the effect of febuxostat on echocardiographic parameters of diastolic function in patients with asymptomatic hyperuricemia as a prespecified endpoint in the subanalysis of the PRIZE study. Patients in the PRIZE study were assigned randomly to either add-on febuxostat treatment group or control group with only appropriate lifestyle modification. Of the 514 patients in the overall study, 65 patients (31 in the febuxostat group and 34 in the control group) who had complete follow-up echocardiographic data of the ratio of peak early diastolic transmitral flow velocity (E) to peak early diastolic mitral annular velocity (e′) at baseline and after 12 and 24 months were included. The primary endpoint was a comparison of the changes in the E/e′ between the two groups from baseline to 24 months. Interestingly, e′ was slightly decreased in the control group compared with in the febuxostat group (treatment p = 0.068, time, p = 0.337, treatment × Time, p = 0.217). As a result, there were significant increases in E/e′ (treatment p = 0.045, time, p = 0.177, treatment × time, p = 0.137) after 24 months in the control group compared with the febuxostat group. There was no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive troponin I between the two groups during the study period. In conclusions, additional febuxostat treatment in patients with asymptomatic hyperuricemia for 24 months might have a potential of preventable effects on the impaired diastolic dysfunction

Effect of ipragliflozin on carotid intima-media thickness in type 2 diabetes patients

Aims To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods and results In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0–10.0% (42–86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), −0.0155–0.0182] mm and 0.0015 (95% CI, −0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of −0.0001 mm (95% CI, −0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [−0.1% (95% CI, −0.2–0.1); P = 0.359]. Conclusion Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes

Effect of sitagliptin on the echocardiographic parameters of left ventricular diastolic function in patients with type 2 diabetes : a subgroup analysis of the PROLOGUE study

Background: Diabetes is associated closely with an increased risk of cardiovascular events, including diastolic dysfunction and heart failure that leads to a shortening of life expectancy. It is therefore extremely valuable to evaluate the impact of antidiabetic agents on cardiac function. However, the influence of dipeptidyl peptidase 4 inhibitors on cardiac function is controversial and a major matter of clinical concern. We therefore evaluated the effect of sitagliptin on echocardiographic parameters of diastolic function in patients with type 2 diabetes as a sub-analysis of the PROLOGUE study. Methods: Patients in the PROLOGUE study were assigned randomly to either add-on sitagliptin treatment or conventional antidiabetic treatment. Of the 463 patients in the overall study, 115 patients (55 in the sitagliptin group and 60 in the conventional group) who had complete echocardiographic data of the ratio of peak early diastolic transmitral flow velocity (E) to peak early diastolic mitral annular velocity (e′) at baseline and after 12 and 24 months were included in this study. The primary endpoint of this post hoc sub-analysis was a comparison of the changes in the ratio of E to e′ (E/e′) between the two groups from baseline to 24 months. Results: The baseline-adjusted change in E/e′ during 24 months was significantly lower in the sitagliptin group than in the conventional group (−0.18 ± 0.55 vs. 1.91 ± 0.53, p = 0.008), irrespective of a higher E/e′ value at baseline in the sitagliptin group. In analysis of covariance, sitagliptin treatment was significantly associated with change in E/e′ over 24 months (β = −9.959, p = 0.001), independent of other clinical variables at baseline such as blood pressure, HbA1c, and medications for diabetes. Changes in other clinical variables including blood pressure and glycemic parameters, and echocardiographic parameters, such as cardiac structure and systolic function, were comparable between the two groups. There was also no significant difference in the serum levels of N-terminal-pro brain natriuretic peptide and high-sensitive C-reactive protein between the two groups during the study period. Conclusions: Adding sitagliptin to conventional antidiabetic regimens in patients with T2DM for 24 months attenuated the annual exacerbation in the echocardiographic parameter of diastolic dysfunction (E/e′) independent of other clinical variables such as blood pressure and glycemic control

Application of Δ- and Λ-Isomerism of Octahedral Metal Complexes for Inducing Chiral Nematic Phases

The Δ- and Λ-isomerism of octahedral metal complexes is employed as a source of chirality for inducing chiral nematic phases. By applying a wide range of chiral metal complexes as a dopant, it has been found that tris(β-diketonato)metal(III) complexes exhibit an extremely high value of helical twisting power. The mechanism of induction of the chiral nematic phase is postulated on the basis of a surface chirality model. The strategy for designing an efficient dopant is described, together with the results using a number of examples of Co(III), Cr(III) and Ru(III) complexes with C2 symmetry. The development of photo-responsive dopants to achieve the photo-induced structural change of liquid crystal by use of photo-isomerization of chiral metal complexes is also described

High Level of Rheumatoid Factor is Associated with Hepatitis B Viremia in Patients with Chronic Hepatitis B

Hepatitis viruses are causative agents for chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. However these viruses are also associated with lymphoproliferative disorders (LPDs), such as essential mixed cryoglobulinemia and B-cell non-Hodgkin\u27s lymphoma. Indeed, hepatitis C virus infection has been confirmed to be associated with LPDs, but the pathogenic mechanism remains unclear. In this study, we investigated the relationship between hepatitis B virus (HBV) infection and LPDs in 84 patients with chronic hepatitis B (CH-B). LPD markers, such as cryoglobulinemia, high levels of rheumatoid factor (RF), hypocomplementemia, and B cell clonality, were measured and analyzed along with viral factors. Results showed that high levels of RF were observed in 39.5% of patients with CH-B. These high RF levels were not associated with abnormal levels of other LPD markers, but only with the presence of HBV DNA in the sera of these patients. Undergoing therapy with nucleotide analogues was also associated with high RF. In two patients with CH-B, decreasing levels of RF were observed during antiviral therapy. In conclusion, high RF levels are associated with HBV viremia in patients with CH-B. HBV infection also plays an important role in the genesis of LPDs in patients with viral hepatitis

CpG Island Methylator Phenotype in Primary Gastric Carcinoma

Gastric cancers (GC) with methylation of multiple CpG islands have a CpG island methylator phenotype (CIMP) and they can have different biological features. The aim of this study was to investigate the DNA methylation status of GCs and its association with their clinicopathological features. We evaluated the methylation status of four genes (MINT1, MINT2, MINT25 and MINT31) in 105 primary GCs using bisulfite-pyrosequencing analysis. We classified tumors as CIMP-high (CIMP-H), CIMP-low (CIMP-L) or CIMP-negative (CIMP-N) based on the methylation of MINT1, MINT2, MINT25, and MINT31. Overall, the prevalence of CIMP-H, CIMP-L and CIMP-N was 22% (23/105), 52% (55/105) and 26% (27/105), respectively. We observed a significant difference in tumor stage (stages I-II vs. stages III-IV) between CIMP-H and CIMP-N tumors (P = 0.0435). No significant differences were observed in clinicopathological characteristics (gender, age, location and tumor differentiation) among the CIMP phenotypes. The prognoses of patients with a CIMP-H tumor is likely to be better than those with CIMP-L or CIMP-N tumors, but these differences are not statistically significant (P = 0.074 and P = 0.200). Our results suggest that CIMP may define a subgroup of GCs with distinct biological features

小児鼠径ヘルニア・精系水瘤に対する腹腔鏡下鼠径ヘルニア修復術(LPEC法) : 川崎医科大学小児外科10年間の報告

嵩原らが開発した新しい小児鼠径ヘルニアの術式,Laparoscopic Percutaneus Extraperitoneal Closure(LPEC法)が2003年に報告され,標準術式として採用する施設が増えている.鼠径管構造を破壊することなくヘルニア門を閉鎖でき,従来法にはない有用性が報告されている.また,LPEC法は小児精系水瘤や直接ヘルニアなど,その他の疾患にも応用される.当科では2005年からLPEC法を導入し,2015年までの10年間で733例を経験した.今回,外鼠径ヘルニア,精系水瘤の疫学的特徴,卵巣ヘルニアと精系水瘤の内鼠径輪所見,対側腹膜鞘状突起の開存率,術中術後合併症について診療録から集計し,後方視的に検討した.また再発,対側発症例について,初回手術時と再手術時の所見から,原因を検討した.直接ヘルニアについて,内鼠径輪の形態を評価し,臨床的特徴を検討した.外鼠径ヘルニアは612例,精系水瘤は112例,直接ヘルニアが9例であった.外鼠径ヘルニア再発で従来法を行った症例が1例,精系水瘤で腹膜鞘状突起の開存がなく従来法に移行した症例が1例あり,その他の症例はLPEC法を施行した.直接ヘルニアに対し,経過観察3例,LPEC法1例,LPEC法+後壁補強4例,鼠径部切開による後壁補強1例が行われた.術中術後の合併症は認めなかった.卵巣ヘルニアの子宮円索が対側に比し短く,精系水瘤の腹膜鞘状突起がほぼ全て開存していた.外鼠径ヘルニアの再発率は3例(0.49%)で,精系水瘤において再発は認めなかった.対側発症は3例(0.49%)に認めた.LPEC法により,内鼠径輪所見の詳細な所見が明らかとなり,外鼠径ヘルニアのみならず,精系水瘤,直接ヘルニアにおいても応用が可能で,合併症,再発率についても良好な成績であった.Takahara and colleagues published a new operative method, "Laparoscopic Percutaneous Extraperitoneal Closure (LPEC)", for pediatric inguinal hernia in 2003. It has been adopted as an alternative to traditional methods in a large number of institutions in Japan. This procedure is minimally invasive and enables closure of the hernia orifice without destroying the inguinal canal structure. This is a new surgical procedure, and its advantages over traditional methods have been reported. In addition, the LPEC procedure has also been applied to other diseases, such as pediatric hydrocele and pediatric direct inguinal hernia. In our institute, LPEC has been performed for pediatric inguinal hernia and hydrocele from 2005, with 733 cases performed in the last decade. In this study, the epidemiological characteristics of pediatric inguinal hernia and hydroceles, the findings regarding the internal inguinal ring in sliding hernia of the ovary and in hydrocele, the PV patency rate, and perioperative complications were investigated retrospectively from medical records. Furthermore, the causes of recurrent hernia or contralateral hernia were investigated based on the findings at re-operations. In the LPEC procedure, laparoscopic observation can reveal the appearance and findings of the internal ring, which leads to appropriate treatment and good results with respect to complications and recurrence