Dialyzability of Faropenem in Infected Patients on Chronic Hemodialysis

The aim of this study was to evaluate the profile of dialyzability of an oral penem antibiotic, faropenem (FRPM), in hemodialysis (HD) patients with infections. Eight patients took one tablet of FRPM (200 mg) every 12 h during an inter‐dialysis period, and another tablet at 1–5 h before the beginning of the HD session. Blood samples were obtained during the HD session (3–4 h). Plasma FRPM concentrations in the arterial side were 4.8 ± 2.5 and 2.8 ± 1.0 µg/mL before and at the end of HD session, respectively, which are above the 50% minimal inhibitory concentrations of FRPM against the major pathogen (0.015–2 µg/mL). Dialyzer clearance and elimination fraction of FRPM were 14.9 ± 6.8 mL/min per m² and 20.4 ± 9.9%, respectively. About 2% of FRPM was removed from the body during a single HD session. The infection‐related symptoms, the white blood cell count and the level of C‐reactive protein were improved by FRPM without any adverse effects. These data suggest that the dialyzability of FRPM is relatively low, and the amount of the drug removed by a single HD session is small. FRPM 200 mg twice daily might provide an effective and safe dosage regimen without additional dosing at the end of the HD session.     

Structures and conductivities of stable and metastable Li5GaS4 solid electrolytes

Understanding the differences in the structures and defects in the stable crystalline phase and metastable phase is important for increasing the ionic conductivities of a solid electrolyte. The metastable phase often has higher conductivity than the stable phase. In this study, metastable lithium thiogallate, Li₅GaS₄, was synthesized via mechanochemistry and stable Li₅GaS₄ was obtained by heating the metastable phase. The metastable Li₅GaS₄ sample was found to have an antifluorite-type crystal structure with cationic disorder, while the stable phase was found to have a monoclinic crystal structure, similar to that of another solid electrolyte, Li₅AlS₄. In both the structures, the Ga³⁺ cations were surrounded by four S²⁻ anions in tetrahedral coordination. The conductivity of the metastable phase was determined to be 2.1 × 10⁻⁵ S cm⁻¹ at 25 °C, which is 1000 times greater than that of the monoclinic phase. The high conductivity of the metastable phase was achieved owing to cation disorder in the crystal structure.

A metastable antifluorite-type Li₅GaS₄ electrolyte prepared by a mechanochemical process exhibits the highest conductivity of 2.1 × 10⁻⁵ S cm⁻¹ at 25 °C, which is three orders of magnitude higher than that of the heated Li₅GaS₄ samples with the stable phase.     

Combined administration of lauric acid and glucose improved cancer‐derived cardiac atrophy in a mouse cachexia model

Cancer‐derived myocardial damage is an important cause of death in cancer patients. However, the development of dietary interventions for treating such damage has not been advanced. Here, we investigated the effect of dietary intervention with lauric acid (LAA) and glucose, which was effective against skeletal muscle sarcopenia in a mouse cachexia model, on myocardial damage. Treatment of H9c2 rat cardiomyoblasts with lauric acid promoted mitochondrial respiration and increased ATP production by Seahorse flux analysis, but did not increase oxidative stress. Glycolysis was also promoted by LAA. In contrast, mitochondrial respiration and ATP production were suppressed, and oxidative stress was increased in an in vitro cachexia model in which cardiomyoblasts were treated with mouse cachexia ascites. Ascites‐treated H9c2 cells with concurrent treatment with LAA and high glucose showed that mitochondrial respiration and glycolysis were promoted more than that of the control, and ATP was restored to the level of the control. Oxidative stress was also reduced by the combined treatment. In the mouse cachexia model, myocardiac atrophy and decreased levels of a marker of muscle maturity, SDS‐soluble MYL1, were observed. When LAA in CE‐2 diet was orally administered alone, no significant rescue was observed in the cancer‐derived myocardial disorder. In contrast, combined oral administration of LAA and glucose recovered myocardial atrophy and MYL1 to levels observed in the control without increase in the cancer weight. Therefore, it is suggested that dietary intervention using a combination of LAA and glucose for cancer cachexia might improve cancer‐derived myocardial damage.     

DHMEQ, a novel nuclear factor-kappaB inhibitor, induces selective depletion of alloreactive or phytohaemagglutinin-stimulated peripheral blood mononuclear cells, decreases production of T helper type 1 cytokines, and blocks maturation of dendritic cells

Dehydroxymethylepoxyquinomicin (DHMEQ), a novel nuclear factor κB (NF-κB) inhibitor, has been shown to be active against variety types of solid tumours as well as haematological malignant cells. This study explored the anti-inflammatory effects of DHMEQ in vitro. DHMEQ inhibited the proliferation of phytohaemagglutinin (PHA)-stimulated or alloreactive peripheral blood mononuclear cells (PBMC) in mixed lymphocyte cultures as measured using a 3-(4,5-dimethylithiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay. In contrast, DHMEQ did not affect the viability of resting PBMC. In addition, real-time polymerase chain reaction showed that DHMEQ decreased PHA-stimulated expression of T helper type 1 (Th1) cytokines, including interleukin-2, interferon-γ, and tumour necrosis factor α, in PBMC as well as Jurkat T-lymphoblastic leukaemia cells, and also decreased levels of p65 isoforms of NF-κB in the nucleus. Furthermore, we found that DHMEQ inhibited the endocytic capacity of dendritic cells (DCs) and down-regulated the expression of cell surface antigen CD40, suggesting that DHMEQ blocked the maturation as well as the function of DCs. Taken together, the results suggest that DHMEQ may be useful for treatment of inflammatory diseases, including graft-versus-host disease after allogenic haematopoietic stem cell transplantation.     

Characterization of the hog cholera virus 5′ terminus

Hog cholera virus (HoCV) 5 terminus of the ALD and GPE(–) strains were analyzed by using rapid amplification of cDNA end method (5RACE). An additional nine nucleotides were found at the 5 termini of genomic RNA in the ALD and GPE(–) strains of HoCV. These nine nucleotides were also conserved in BVDV and were suggested to form a hairpin structure at the 5 terminus by computer-assisted analysis. It seems possible that the secondary structure and/or the 5 terminus sequence has a significant role in the HoCV virus genome.     

Age <40Years is an independent prognostic factor predicting inferior overall survival in patients treated with breast conservative therapy

To evaluate the effect of age at diagnosis on the treatment outcome after breast conservative therapy (BCT), retrospective analysis was done for 378 patients undergoing BCT for early breast cancer. Patients were divided into two groups according to their age: 'younger' (<40years, n=108) and 'older' (≥40years, n=270). Multivariate analysis was performed on the variables including tumor characteristics, the use of systemic therapy, and age to assess risk factors for local-regional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival rates (OS). The median follow-up duration was 94months. The 8-year LRRFS, DMFS, and OS for younger and older groups were 88.1% and 96.5% (p=0.0022); 85.7% and 93.7% (p=0.0310); 89.2% and 95.9% (p=0.0205), respectively. On multivariate analysis, younger age was the only significant predictor of poor LRRFS (p=0.0022). Younger age and ER negativity showed borderline significance for DMFS (p=0.0828 and 0.0618, respectively). Younger age had trend toward inferior OS (p=0.0702). In conclusion, age younger than 40years was associated with inferior LRRFS in early breast cancer patients treated with BCT. There was also a trend for inferior DMFS and OS in younger patients. Age at diagnosis should be considered for individualized patient management.