Pharmacokinetic Analysis, Analgesic Effects, and Adverse Effects of Tapentadol in Cancer Patients with Pain.
In this study, we conducted a pharmacokinetic analysis of tapentadol (TP) in Japanese patients with cancer pain and identified covariates influencing pharmacokinetic parameters. In addition, the analgesic effects and adverse effects of TP were investigated. Data were collected from in-patients with cancer pain who had been administered TP as an extended-release formula. The median (range) estimated clearance (CL/F) and distribution volume (Vd/F) of TP were 86.7 (31.3-213.7) L/h and 1288 (189-6736) L, respectively. There was a strong negative correlation between CL/F and age, Child-Pugh score, and albumin-bilirubin (ALBI) s...
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Homma M, Kokubun H, Okuwaki K, Katada C, Hayashi N, Kanai A, Koizumi W, Atsuda K Tags: Biol Pharm Bull Source Type: research

Detection of Abacavir-Induced Structural Alterations in Human Leukocyte Antigen-B*57  : 01 Using Phage Display.
Detection of Abacavir-Induced Structural Alterations in Human Leukocyte Antigen-B*57 : 01 Using Phage Display. Biol Pharm Bull. 2020;43(6):1007-1015 Authors: Shirayanagi T, Aoki S, Fujimori S, Watanabe K, Aida T, Hirasawa M, Kumagai K, Hoshino T, Ito K Abstract The interaction of human leukocyte antigen (HLA) with specific drugs is associated with delayed-type hypersensitivity reactions, which cause severe cutaneous toxicity. Such interactions induce structural alterations in HLA complexes via several different mechanisms such as the hapten theory, p-i concept, and altered peptide repert...
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Shirayanagi T, Aoki S, Fujimori S, Watanabe K, Aida T, Hirasawa M, Kumagai K, Hoshino T, Ito K Tags: Biol Pharm Bull Source Type: research

β-Aminoisobutyric Acid Suppresses Atherosclerosis in Apolipoprotein E-Knockout Mice.
β-Aminoisobutyric Acid Suppresses Atherosclerosis in Apolipoprotein E-Knockout Mice. Biol Pharm Bull. 2020;43(6):1016-1019 Authors: Shimba Y, Katayama K, Miyoshi N, Ikeda M, Morita A, Miura S Abstract Endurance exercise training has been shown to induce peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in skeletal muscle. We recently reported that skeletal muscle-specific PGC-1α overexpression suppressed atherosclerosis in apolipoprotein E-knockout (ApoE-/-) mice. β-Aminoisobutyric acid (BAIBA) is a PGC-1α-dependent myokine secreted...
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Shimba Y, Katayama K, Miyoshi N, Ikeda M, Morita A, Miura S Tags: Biol Pharm Bull Source Type: research

Effects of Oxidation of Human Serum Albumin on the Binding of Aripiprazole.
In this study, we investigated the binding characteristics of ARP to oxidized HSA as observed in chronic disease conditions. Oxidized HSAs were prepared using chloramine-T (CT-HSA) or metal-catalyzed oxidation system (MCO-HSA) in vitro, respectively. An increase in the carbonyl content was confirmed in oxidized HSAs. From the results of circular dichroism (CD) and tryptophan fluorescence spectra, no significant structural change of oxidized HSAs was observed. These results indicate that prepared HSAs are mildly oxidized and well reflects the status of HSA during chronic diseases. However, oxidized HSAs were observed to hav...
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Sakurama K, Nishi K, Chuang VTG, Hashimoto M, Yamasaki K, Otagiri M Tags: Biol Pharm Bull Source Type: research

8-HEPE-Concentrated Materials from Pacific Krill Improve Plasma Cholesterol Levels and Hepatic Steatosis in High Cholesterol Diet-Fed Low-Density Lipoprotein (LDL) Receptor-Deficient Mice.
Abstract Eicosapentaenoic acid (EPA), one of the N-3 polyunsaturated fatty acids (n-3 PUFAs), is a major active ingredient of fish that contributes to improve dyslipidemia. Recently, we demonstrated that 8-hydroxyeicosapentaenoic acid (8-HEPE) had a more positive effect on metabolic syndrome than EPA, and that 8-HEPE induced peroxisome proliferator-activated receptor (PPAR)α activation in the liver. We investigated the effects of 8-HEPE-concentrated materials from Pacific krill on dyslipidemia and hepatic steatosis in low-density lipoprotein (LDL) receptor-deficient (LDLR-KO) mice. Eight-week-old male LDLR-K...
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Saito M, Ishida N, Yamada H, Ibi M, Hirose M Tags: Biol Pharm Bull Source Type: research

Association of Hypnotic Drug Use with Fall Incidents in Hospitalized Elderly Patients: A Case-Crossover Study.
Abstract We investigated whether use of hypnotic drugs, including benzodiazepine receptor agonists, as well as ramelteon and suvorexant are associated with fall incidents in elderly inpatients aged no less than 75 years, who were hospitalized at an acute care general hospital in Japan, between November 1st, 2016 and October 31st, 2017. Multivariate analysis results were reported as odds ratio (OR) with 95% confidence interval (CI). Following to a case-crossover study protocol, the time windows of the case and the control days were assigned to the day or the days, which are one day or 2-8 d before the fall i...
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Torii H, Ando M, Tomita H, Kobaru T, Tanaka M, Fujimoto K, Shimizu R, Ikesue H, Okusada S, Hashida T, Kume N Tags: Biol Pharm Bull Source Type: research

Ziyuglycoside II Inhibits Rotavirus Induced Diarrhea Possibly via TLR4/NF- κB Pathways.
This study aimed to investigate the roles of Ziyuglycoside II in rotavirus-induced diarrhea and the underlying molecular mechanism. We found that normal MA104 cells treated with RV became swollen and gather together. However, Ziyuglycoside II treatment inhibited cell growth in a dose- and time dependent manner and suppressed RV replication. Moreover, Ziyuglycoside II reversed RV-induced downregulation of anti-inflammatory cytokine interleukin (IL)-10 and upregulation of pro-inflammatory factors, such as interferon-γ (IFN-γ), IL-1β, IL-6, and tumor necrosis factor (TNF-α). Moreover, Ziyuglycoside II a...
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Chen X, Liu L, Chen W, Qin F, Zhou F, Yang H Tags: Biol Pharm Bull Source Type: research

Hypoglycemic Activity and the Mechanisms of Lycium Bark Extract in db/db Mice.
Abstract The extract of Lycium bark (LBE), which is the root bark of Lycium chinense, has long been used in China for hypertension, inflammation, and diabetes. LBE has been reported to ameliorate hyperglycemia in mice with alloxan-induced type 1 diabetes, but evidence on the effect of LBE in diabetes had not been enough. Therefore, we investigated the effects of LBE on type 2 diabetes using db/db mice. Nine-week-old male db/db mice were orally administered LBE (425 mg/kg) for 10 weeks. Blood samples were collected under anesthesia for the determination of blood glucose and insulin levels. The blood glucose ...
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Shimato Y, Hattori T, Ohno T Tags: Biol Pharm Bull Source Type: research

The Anti-atherogenic Activity of Beauveriolide Derivative BVD327, a Sterol O-Acyltransferase 2-Selective Inhibitor, in Apolipoprotein E Knockout Mice.
Abstract The fungal 13-membered cyclodepsipeptides, beauveriolides I and III, were previously reported to be atheroprotective activity in mouse models via inhibiting sterol O-acyltransferase (SOAT) activity. A total of 149 beauveriolide derivatives (BVDs) synthesized combinatorially were evaluated in in silico absorption, distribution, metabolism and excretion (ADME) analysis and inhibitory activity toward the two SOAT isozymes, SOAT1 and SOAT2. Hence, only 11 BVDs exhibited SOAT2-selective inhibition. Among these, we chose BVD327, which had the highest ADME score, for further evaluation. BVD327 administration (50...
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Ohshiro T, Imuta S, Hijikuro I, Yagyu H, Takahashi T, Doi T, Ishibashi S, Tomoda H Tags: Biol Pharm Bull Source Type: research

Characterization and Immunological Activities of Polysaccharides from Polygonatum sibiricum.
In this study, we investigated the physicochemical properties and composition of monosaccharidex from Polygonatum sibiricum. Simultaneously, we explored the in vivo and in vitro immunomodulatory activity and mechanism of Polygonatum sibiricum polysaccharide (PSP) activity by monitoring changes in immune organs, immune cells, and cytokines. The average molecular weight (Mw) of PSP was 9.514 × 104 Da. The monosaccharide components of PSP were galactose, rhamnose, arabinose, mannose, and glucose at a molar ratio of 11.72 : 1.78 : 4.15 : 1.00 : 2.48. P...
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Chen Z, Liu J, Kong X, Li H Tags: Biol Pharm Bull Source Type: research

Potential Mechanisms Underlying the Hepatic-Protective Effects of Danshensu on Iron Overload Mice.
Abstract The purpose of the present study was to investigate the protective effects and the underlying mechanisms of Danshensu on liver injury induced by iron overload. The mouse model was induced by injection of iron dextran intraperitoneally for 14 d. Danshensu significantly ameliorated liver injury by decreasing iron accumulation in the liver, possibly by down-regulating the expression of iron uptake-related proteins: divalent metal ion transporters-1 (DMT-1), transferrin receptor (TfR), and L-type calcium channel α1C subunit. Furthermore, Danshensu alleviated oxidative stress injury through potent...
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Zhang Y, Zhang G, Liang Y, Wang H, Wang Q, Zhang Y, Zhang X, Zhang J, Chu L Tags: Biol Pharm Bull Source Type: research

Dehydrocholic Acid Ameliorates Sodium Taurocholate-Induced Acute Biliary Pancreatitis in Mice.
In conclusion, our study proposes a potential therapy strategy for the incurable ABP. PMID: 32475920 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Zhang X, Xin G, Li S, Wei Z, Ming Y, Yuan J, Wen E, Xing Z, Yu K, Li Y, Zhang J, Zhang B, Niu H, Huang W Tags: Biol Pharm Bull Source Type: research

Inhibitory Effect of the Traditional Chinese Medicine Ephedra sinica granules on Streptococcus pneumoniae Pneumolysin.
In this study, we found that ESG treatment significantly inhibited the oligomerization of PLY and then reduced the activity of PLY without affecting S. pneumoniae growth and PLY production. In a PLY and A549 cell co-incubation system, the addition of ESG resulted in significant protection against PLY-mediated cell injury. Furthermore, S. pneumoniae-infected mice showed decreased mortality, and alleviated tissue damage and inflammatory reactions following treatment with ESG. Our results indicate that ESG is a potential candidate treatment for S. pneumoniae infection that targets PLY. This finding partially elucidates the me...
Source: Biological and Pharmaceutical Bulletin - June 3, 2020 Category: Drugs & Pharmacology Authors: Xu Y, Wei L, Wang Y, Ding L, Guo Y, Sun X, Kong Y, Guo L, Guo T, Sun L Tags: Biol Pharm Bull Source Type: research

Edaravone improves intermittent hypoxia-induced cognitive impairment and hippocampal damage in rats.
This study investigated the effects of edaravone, a potent free radical scavenger, on intermittent hypoxia (IH)-induced oxidative damage and cognition impairment in a young rat model of IH. IH rats were treated with edaravone for 4 weeks. Behavioral testing was performed using the Morris water maze, and hippocampal tissues were harvested for further analyses. Edaravone attenuated IH-induced cognitive impairment, reduced morphological and structural abnormalities, and increased the number of mitochondria in the IH rats. Furthermore, edaravone significantly increased the inhibition of hydroxyl free radicals; reduced expressi...
Source: Biological and Pharmaceutical Bulletin - May 30, 2020 Category: Drugs & Pharmacology Authors: Ling J, Yu Q, Li Y, Yuan X, Wang X, Liu W, Guo T, Duan Y, Li L Tags: Biol Pharm Bull Source Type: research

Adenosine A2A Receptor Agonist PSB-0777 Modulates Synaptic Proteins and AMPA Receptor Expression in A Dose- and Time-Dependent Manner in Rat Primary Cortical Neurons.
In this study, we systematically investigated the regulatory effects of a novel A2A receptor agonist, PSB-0777, on the expression of synaptic proteins and AMPA receptors at the cellular level in a time- and dose-dependent manner. After 30 minutes of high-dose PSB-0777 stimulation, the expression of Syn-1, PSD95, and AMPA receptors and the number of synapses were rapidly and significantly increased in rat primary cortical neurons compared with the control. Sustained elevation was found in the low and medium-dose groups after 24 hours and 3 days of treatment. In contrast, after stimulation with PSB-0777 for 3 consecutive day...
Source: Biological and Pharmaceutical Bulletin - May 23, 2020 Category: Drugs & Pharmacology Authors: Luo S, Hou Y, Zhang Y, Ma T, Shao W, Xiao C Tags: Biol Pharm Bull Source Type: research

Risk Factors for Febrile Neutropenia Induced by Docetaxel Chemotherapy in Patients with Non-small Cell Lung Cancer.
Abstract We retrospectively obtained data of patient background and pretreatment characteristics from medical records and identified the predictive factors of febrile neutropenia (FN) in patients with non-small cell lung cancer (NSCLC) treated with docetaxel alone or in combination with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab.Patients were eligible for inclusion in the study if they were 20 years or older, diagnosed with NSCLC, and received docetaxel monotherapy alone or in combination with bevacizumab at the Department of Respiratory Medicine, Kobe City Medical Center General Hospi...
Source: Biological and Pharmaceutical Bulletin - May 21, 2020 Category: Drugs & Pharmacology Authors: Uchida M, Yamaguchi Y, Hosomi S, Ikesue H, Mori Y, Maegawa N, Takano A, Sato Y, Hosohata K, Muroi N, Tomii K, Hashida T, Nakamura T Tags: Biol Pharm Bull Source Type: research

Sanguinarine Rapidly Relaxes Rat Airway Smooth Muscle Cells Dependent on TAS2R Signaling.
Abstract Excessive contraction of airway smooth muscle cells (ASMCs) is a hallmark feature of asthma. Intriguing, the activation of bitter taste receptor (TAS2R) in ASMCs can relax ASMCs. However, there is a lack of potent TAS2R agonists that can be used in asthma therapies since those tested agonists cannot relax ASMCs at the dose below a few hundred micromolar. Considering that sanguinarine (SA) is a bitter substance often used in small doses for the treatment of asthma in folk medicine, the present study was to determine the rapid relaxation effect of SA on ASMCs and to reveal the underlying mechanisms associat...
Source: Biological and Pharmaceutical Bulletin - May 13, 2020 Category: Drugs & Pharmacology Authors: Luo M, Yu P, Ni K, Jin Y, Liu L, Li J, Pan Y, Deng L Tags: Biol Pharm Bull Source Type: research

Reduction in the doses of direct oral anticoagulants and risk of ischemic stroke events: A hospital survey.
Abstract Inappropriately reduced doses (IRDs) of direct oral anticoagulants (DOACs) are common in clinical practice. We performed a retrospective review using electronic medical records of St. Marianna University School of Medicine Hospital (a 1200-bed teaching hospital in Japan) to address the prevalence of IRDs and patient-related factors that result in IRDs. We also surveyed DOAC-treated patients who were hospitalized due to a stroke during the 5-year study period to analyze the association between stroke events and IRDs. We found that one in five patients who were newly prescribed a DOAC was treated with IRDs....
Source: Biological and Pharmaceutical Bulletin - May 12, 2020 Category: Drugs & Pharmacology Authors: Ueda A, Toki S, Kitayama C, Akazawa M Tags: Biol Pharm Bull Source Type: research

Latifolin inhibits oxidative stress-induced senescence via upregulation of SIRT1 in human dermal fibroblasts.
In this study, we selected a model in vitro system, hydrogen peroxide (H2O2)-induced senescence in human dermal fibroblasts (HDFs), to examine the protective effects of latifolin against senescence and the detailed molecular mechanisms involved. Latifolin reversed the senescence-like phenotypes of the oxidant-challenged model, including senescence-associated β-galactosidase (SA-β-gal) staining, cell proliferation, and the expression of senescence-related proteins, such as caveolin-1, ac-p53, p21Cip1/WAF1, p16Ink4α, pRb, and cyclinD1. We also found that latifolin induced the expression of silent information ...
Source: Biological and Pharmaceutical Bulletin - May 12, 2020 Category: Drugs & Pharmacology Authors: Lim SH, Li BS, Zhu RZ, Seo JH, Choi BM Tags: Biol Pharm Bull Source Type: research

Effects of Gentiana delavayi Flower Extract on APP Processing in APP/PS1 CHO Cells.
In this study we investigated the influence of G. delavayi flower extract on amyloid precursor protein (APP) processing at molecular and cellular levels. APP/PS1 Chinese hamster ovary (CHO) cells were treated with chloroform extract of G. delavayi flower in different concentrations for 24 h. Concentrations of amyloid β (Aβ) 40 and Aβ42 in the cell supernatant and activity of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), BACE2, and cathepsin D were determined. The expression of APP and neprilysin (NEP) within the cell were further determined. Compared with the control group, the leve...
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Yang M, Zhou KY, Li FF, Yang HY, Yin M, Zhang LH, Wang FS Tags: Biol Pharm Bull Source Type: research

Morphine Stimulates Migration and Growth and Alleviates the Effects of Chemo Drugs via AMPK-Dependent Induction of Epithelial-Mesenchymal Transition in Esophageal Carcinoma Cells.
Abstract The role of morphine, an opioid analgesic drug, in cancer biology has increasingly garnered attention due to its frequent usage in postoperative period for pain management in cancer patients. In this work, we demonstrated that morphine, at clinically relevant concentrations, stimulated migration and growth, and alleviated chemo drugs' efficacy in esophageal carcinoma cells. Although morphine did not affect survival, it protected esophageal carcinoma cells from chemo drugs-induced apoptosis. Mechanistical studies showed that morphine increased RhoA but not Rac1 activity. In addition, morphine activated AMP...
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Zhang J, Yao N, Tian S Tags: Biol Pharm Bull Source Type: research

Clinical Predictors of the Hypoglycemic Effect of Sodium-Glucose Co-transporter-2 Inhibitors in Hyperuricemic Patients: A Retrospective Descriptive Observational Study.
Abstract Sodium-glucose co-transporter-2 (SGLT2) inhibitors decrease glycated hemoglobin (HbA1c) and prevent the progression of cardiovascular and kidney diseases. Because uric acid and electrolytes are physiologically similar to blood glucose in renal excretion, we assessed predictors for the hypoglycemic effect of SGLT2 inhibitor treatment by focusing on serum uric acid and serum electrolytes. We performed a retrospective descriptive observational study at the Tokyo Women's Medical University, Medical Center East, from June 2015 to July 2018. Patients who received treatment with any type of SGLT2 inhibitor were ...
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Hirai T, Kawagoe Y, Kei M, Ogawa R, Itoh T Tags: Biol Pharm Bull Source Type: research

Acanthopanax senticosus Root Extract Exerts Dual Action on Mouse Ileal Smooth Muscle Function, Leading to Modulation of Gastrointestinal Motility.
Abstract Diarrhea is often caused by changes in lifestyle, stress, or side effects of drugs. Acanthopanax senticosus root extract (ASRE) has long been used as a functional food remedy with anti-fatigue, neuroprotective, and immunomodulatory activities. However, it is unclear whether ASRE has beneficial effects on gastrointestinal (GI) motility. Therefore, we first investigated whether ASRE directly affects contractile functions of the isolated mouse ileum, and then assessed its effects on GI transit of a charcoal meal in normal mice and a carbachol (CCh)-induced diarrhea mouse model. ASRE caused contraction of the...
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Miyauchi-Wakuda S, Kagota S, Maruyama-Fumoto K, Shiokawa Y, Yamada S, Shinozuka K Tags: Biol Pharm Bull Source Type: research

Predicting Method for the Human Plasma Concentration-Time Profile of a Monoclonal Antibody from the Half-life of Non-human Primates.
Abstract Efficiency (speed and cost) and animal welfare are important factors in the development of new drugs. A novel method (the half-life method) was developed to predict the human plasma concentration-time profile of a monoclonal antibody (mAb) after intravenous (i.v.) administration using less data compared to the conventional approach; moreover, predicted results were comparable to conventional method. This new method use human geometric means of pharmacokinetics (PK) parameters and the non-human primates (NHP) half-life of each mAb. PK data on mAbs in humans and NHPs were collected from literature focusing ...
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Nakamura G, Ozeki K, Nagayasu M, Nambu T, Nemoto T, Hosoya KI Tags: Biol Pharm Bull Source Type: research

Opuntia ficus indica Fruits Ameliorate Cisplatin-Induced Nephrotoxicity in Mice.
This study aims to determine the potential renal protective effects of Opuntia ficus-indica (L.) Miller (OFI) fruits against cisplatin-induced nephrotoxicity in mice. The antioxidant activity of OFI methanol extract was calculated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) free radical scavenging assays. Furthermore, the LC-mass spectroscopy (MS) analysis of the OFI fruit extract was carried out. Mice were treated with OFI extract (250 mg/kg) for 10 d and injected with a single dose of cisplatin (20 mg/kg) on the 7th day. The blood samples we...
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Okur ME, Ayla Ş, Karadağ AE, Çiçek Polat D, Demirci S, Seçkin İ Tags: Biol Pharm Bull Source Type: research

Abnormal Vascular Phenotypes Associated with the Timing of Interruption of Retinal Vascular Development in Rats.
Abstract Pathological angiogenesis is a leading cause of blindness in several retinal diseases. The key driving factor inducing pathological angiogenesis is the pronounced hypoxia leading to a marked, increased production of vascular endothelial growth factor (VEGF). The aim of this study was to determine whether the abnormal vascular growth occurs in a manner dependent on the degree of the vascular defects. Vascular defects of two different degrees were created in the retina by subcutaneously treating neonatal rats with the VEGF receptor (VEGFR) tyrosine kinase inhibitor KRN633 on postnatal day (P) 4 and P5 (P4/5...
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Kondo R, Nakano A, Asano D, Morita A, Arima S, Mori A, Sakamoto K, Nagamitsu T, Nakahara T Tags: Biol Pharm Bull Source Type: research

Dendrobium officinale Attenuates Myocardial Fibrosis via Inhibiting EMT Signaling Pathway in HFD/STZ-Induced Diabetic Mice.
Abstract Cardiac fibrosis is a major contributor for diabetic cardiomyopathy and Dendrobium officinale possessed therapeutic effects on hyperglycemia and diabetic cardiomyopathy. To further investigate the possible mechanisms of the Dendrobium officinale on diabetic myocardial fibrosis in mice. Water-soluble extracts of Dendrobium officinale (DOE) from dry stem was analyzed by HPLC and phenol-sulfuric acid method. Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ) (30 mg/kg) for 4 consecutive days after intragastric administration of a high-fat diet (HFD) for 2 weeks. The groups...
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Zeng J, Li D, Li Z, Zhang J, Zhao X Tags: Biol Pharm Bull Source Type: research

Cancer Cachexia May Hinder Pain Control When Using Fentanyl Patch.
The objective of this study was to evaluate the influence of cancer cachexia on pain control in cancer patients receiving a transdermal fentanyl patch (FP) and to investigate whether dry skin was a factor related to cancer cachexia and uncontrolled pain. We retrospectively reviewed the medical records of 77 patients receiving FP treatment for the first time, who were classified into cancer cachexia and non-cancer-cachexia groups, according to European Palliative Care Research Collaborative criteria. On day 7 after FP administration, the mean FP dose and morphine equivalent dose (MED) in the cancer cachexia group were signi...
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Chiba T, Takahashi H, Tairabune T, Kimura S, Ueda H, Kudo K Tags: Biol Pharm Bull Source Type: research

Oxidative Formation of Methylglyoxal in Glycerol Preparations during Storage.
In this study, we showed for the first time, that a trace amount of MGO was present as an impurity in glycerol preparations used as external medicines and intravenous infusions, when kept unused. The concentration of MGO in the glycerol solutions, diluted to a concentration of 20%, significantly increased after storage for one month when compared to the MGO concentration immediately after opening. Following storage for 6 months at 25°C, MGO concentration increased by about 300 times (approx. 170 µM), and at 40°C, it increased by about 600 times (approx. 350 µM). In the case of intravenous ...
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Sugiura K, Koike S, Suzuki T, Ogasawara Y Tags: Biol Pharm Bull Source Type: research

Fluorinated Kavalactone Inhibited RANKL-Induced Osteoclast Differentiation of RAW264 Cells.
Abstract Bone loss and bone-related disease are associated with the deregulation of osteoclast function, and therefore agents that affect osteoclastogenesis have attracted attention. The purpose of the present study was to discover modified kavalactone analogs as potential anti-osteoclastogenic agents. We assessed the effect of 26 analogs on osteoclast differentiation in vitro. The most potent compound, (E)-6-(2-fluorostyryl)-4-methoxy-2H-pyran-2-one (22), suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenic differentiation of RAW264 cells with IC50 values of 4.3 ...
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Kumagai M, Nishikawa K, Mishima T, Yoshida I, Ide M, Watanabe A, Fujita K, Morimoto Y Tags: Biol Pharm Bull Source Type: research

Unique Genotyping Protocol of CYP2D6 Allele Frequency Using Real Time Quantitative PCR from Japanese Healthy Women.
This study aimed to investigate the frequencies of CYP2D6 genotypes in a Japanese female subject of 216 healthy volunteers. The volunteers were genotyped for CNV Exon 9 and four CYP2D6 genetic variants (*2, *5, *10, *14, *41) performed by TaqMan® genotyping assays. The CNV allele frequencies were 82.9% for two copies, 11.6% for one copy, 4.6% for three copies and 0.9% for zero copy, respectively. The frequencies of CYP2D6*1, *2, *5, *10, *14, and *41 were 38.7, 16.7, 6.3, 34.7, 0.2, and 1.2%, respectively. CYP2D6*5 and *14 were the major defective alleles. However, this genotyping is labor intensive, time consuming, an...
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Kisoi M, Imai M, Yamamura M, Sakaguchi Y, Murata S, Ichikawa A, Kinoshita K Tags: Biol Pharm Bull Source Type: research

Naloxone Is a Potential Binding Ligand and Activator of the Capsaicin Receptor TRPV1.
In conclusion, our data suggest that besides acting as an opioid receptor antagonist, naloxone may function as a potential TRPV1 agonist. PMID: 32378567 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Authors: Melkes B, Markova V, Hejnova L, Marek A, Novotny J Tags: Biol Pharm Bull Source Type: research

Errata for Biological and Pharmaceutical Bulletin.
Authors: PMID: 32378568 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - May 8, 2020 Category: Drugs & Pharmacology Tags: Biol Pharm Bull Source Type: research

The application of the in-situ hyperthermia emission from acoustic nanodroplets for theranostic dual-imaging and antitumor modalities.
In this study, we have developed a theranostic nanocarrier that can emit heat upon the exposure to ultrasound (US) irradiation as well as the generation of a contrast signal that can be detected with ultrasonography. The prepared acoustic nanodroplets (NDs) made with liquid perfluporopentane (PFPn) had an average size of 197.7 ± 3.6 nm in diameter and were stable in vitro for 60 min. US irradiation at 2 W.cm-2 induced phase change of NDs into bubbles in vitro. On the other hand, the intra-tumor injection of NDs in combination with US irradiation induced thermal emission in situ in B16BL6 melanoma tumor implanted int...
Source: Biological and Pharmaceutical Bulletin - May 2, 2020 Category: Drugs & Pharmacology Authors: Abdalkader R, Unga J, Maruyama K, Yamashita F, Hashida M Tags: Biol Pharm Bull Source Type: research

Beta-asarone alleviates myocardial ischemia-reperfusion injury by inhibiting inflammatory response and NLRP3 inflammasome mediated pyroptosis.
This study used a rat model with 45minutes occlusion and 24hours releasing of proximal segment of left anterior descending coronary artery. The effects of β-Asarone on cardiac histopathology, myocardial infarction size, levels of cardiac troponin T(cTNT) , myeloperoxidase(MPO) and interleukin-1β(IL-1β), protein expressions of apoptosis-associated speck-like protein containing a CARD(ASC), Nod-like receptor protein 3(NLRP3), caspase-1and Gasdermin D(GSDMSD) , and left ventricular performance were studied respectively. Our results showed that administration of β-Asarone significantly improved the heart ou...
Source: Biological and Pharmaceutical Bulletin - April 22, 2020 Category: Drugs & Pharmacology Authors: Xiao B, Huang X, Wang Q, Wu Y Tags: Biol Pharm Bull Source Type: research

Three-Dimensional Culture of Umbilical Cord Mesenchymal Stem Cells Effectively Promotes Platelet Recovery in Immune Thrombocytopenia.
In this study, 2D and 3D cultured MSCs were used to evaluate cytokine secretion, extracellular matrix (ECM) gene expression, immune regulatory activity, and therapeutic effects in a mouse model of ITP. MSCs cultured on scaffolds had higher expression levels of immune regulatory genes, such as IDO1, HLA-G, and PTGS2, and greater inhibitory activity against lymphocyte activation that those of 2D-MSCs. In addition, 3D-MSCs exhibited higher ECM expression and greater protection against interferon-γ (IFN-γ)-induced apoptosis. In a mouse study, ITP was induced by guinea pig anti-mouse platelet serum injections. Based...
Source: Biological and Pharmaceutical Bulletin - April 21, 2020 Category: Drugs & Pharmacology Authors: Gong X, Sun D, Li Z, Shi Q, Li D, Ju X Tags: Biol Pharm Bull Source Type: research

Increased Vancomycin Clearance in Patients with Solid Malignancies.
We examined the pharmacokinetics of VAN retrospectively based on trough concentrations at large scale and identified pharmacokinetic differences between Japanese patients having solid malignancy and non-malignancy patients. Data were analyzed from 162 solid malignancy patients and 261 non-malignancy patients, including the patient's background, VAN dose, and pharmacokinetics of VAN. We failed to detect differences in values for VAN clearance or shorter elimination half-lives between these two groups. In contrast, multiple regression analysis under adjusting for confounding factors by propensity score, showed that VAN clear...
Source: Biological and Pharmaceutical Bulletin - April 14, 2020 Category: Drugs & Pharmacology Authors: Izumisawa T, Wakui N, Kaneko T, Soma M, Imai M, Saito D, Hasegawa H, Horino T, Takahashi N Tags: Biol Pharm Bull Source Type: research

Foreword.
PMID: 32238699 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Ishida T, Kawakami S, Hosoya KI Tags: Biol Pharm Bull Source Type: research

Therapeutic Application of Small Extracellular Vesicles (sEVs): Pharmaceutical and Pharmacokinetic Challenges.
Abstract Small extracellular vesicles (sEVs), including exosomes as typical example, are cell-derived vesicles comprising lipid bilayer with a diameter approximately 100 nm. sEVs are endogenous delivery vehicles that deliver their contents such as nucleic acids and proteins to recipient cells. Because of their potential nature as endogenous delivery vehicles, therapeutic applications of sEVs as delivery systems of various drugs are expected. To develop sEV-based therapeutics, a variety of challenges should be overcome. In this review, we summarize the current status and future perspectives of therapeutic ap...
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Takakura Y, Matsumoto A, Takahashi Y Tags: Biol Pharm Bull Source Type: research

Lipid Nanoparticles for Cell-Specific in Vivo Targeted Delivery of Nucleic Acids.
Abstract The last few years have witnessed a great advance in the development of nonviral systems for in vivo targeted delivery of nucleic acids. Lipid nanoparticles (LNPs) are the most promising carriers for producing clinically approved products in the future. Compared with other systems used for nonviral gene delivery, LNPs provide several advantages including higher stability, low toxicity, and greater efficiency. Additionally, systems based on LNPs can be modified with ligands and devices for controlled biodistribution and internalization into specific cells. Efforts are ongoing to improve the efficiency of l...
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Khalil IA, Younis MA, Kimura S, Harashima H Tags: Biol Pharm Bull Source Type: research

Potential of Lipoprotein-Based Nanoparticulate Formulations for the Treatment of Eye Diseases.
Abstract Lipoproteins are naturally occurring nanoparticles and their main physiological function is the promotion of lipid metabolism. They can be prepared in vitro for use as drug carriers, and these reconstituted lipoproteins show similar biological activity to their natural counterparts. Some lipoproteins can cross the blood-retinal barrier and are involved in intraocular lipid metabolism. Drug-loaded lipoproteins can be delivered to the retina for the treatment of posterior eye diseases. In this review, we have discussed the therapeutic applications of lipoproteins for eye diseases and introduced the emerging...
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Fukuda R, Murakami T Tags: Biol Pharm Bull Source Type: research

Generation of Human Induced Pluripotent Stem Cell-Derived Hepatocyte-Like Cells for Cellular Medicine.
Abstract Liver transplantation and hepatocyte transplantation are effective treatments for severe liver injuries, but the donor shortage is a serious problem. Therefore, hepatocyte-like cells generated from human induced pluripotent stem (iPS) cells with unlimited proliferative ability are expected to be a promising new transplantation resource. The technology for hepatic differentiation from human iPS cells has made great progress in this decade. The efficiency of hepatic differentiation now exceeds 90%, making it possible to produce nearly homogeneous hepatocyte-like cells from human iPS cells. Because there is ...
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Deguchi S, Takayama K, Mizuguchi H Tags: Biol Pharm Bull Source Type: research

Reduced Serum Cholesterol and Triglyceride Levels in a Choline-Deficient L-Amino Acid-Defined High-Fat Diet (CDAHFD)-Induced Mouse Model of Non-alcoholic Steatohepatitis (NASH).
In this study, we have revealed that mice fed CDAHFD showed significantly lowerd serum total cholesterol and triglyceride (TG) levels, in addition to reduced body weight (BW). Furthermore, hepatic microsomal triglyceride transfer protein (MTP) expression was significantly downregulated in CDAHFD-fed mice. Thus, the current CDAHFD-fed mouse model has points that are distinct from human NAFLD/NASH, in general, which is based upon abdominal obesity. PMID: 32238704 [PubMed - in process] (Source: Biological and Pharmaceutical Bulletin)
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Yasuda D, Torii H, Shimizu R, Hiraoka Y, Kume N Tags: Biol Pharm Bull Source Type: research

Increased Expression of Sema3C Indicates a Poor Prognosis and Is Regulated by miR-142-5p in Glioma.
Abstract Sema3C has been reported to promote glioma stem cells self-renewal and glioblastoma growth. However, the prognostic value and the regulatory mechanism for its abnormal expression in glioma remain poorly understood. In the current study, the immunohistochemistry results demonstrated that Sema3C was overexpressed in 169 of 216 (78.2%) interpretable glioma patients compared with 3 of 15 (20.0%) interpretable non-neoplastic brain cases (p = 0.0001). Sema3C overexpression was significantly associated with histologic type (p = 0.008), high Ki67 labeling index (p = 0.02)...
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Zhang H, Ma H, Zhang W, Duan D, Zhu G, Cao W, Liu B Tags: Biol Pharm Bull Source Type: research

Induced Prostanoid Synthesis Regulates the Balance between Th1- and Th2-Producing Inflammatory Cytokines in the Thymus of Diet-Restricted Mice.
Abstract Multiple external and internal factors have been reported to induce thymic involution. Involution involves dramatic reduction in size and function of the thymus, leading to various immunodeficiency-related disorders. Therefore, clarifying and manipulating molecular mechanisms governing thymic involution are clinically important, although only a few studies have dealt with this issue. In the present study, we investigated the molecular mechanisms underlying thymic involution using a murine acute diet-restriction model. Gene expression analyses indicated that the expression of T helper 1 (Th1)-producing cyt...
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Razali N, Hohjoh H, Inazumi T, Maharjan BD, Nakagawa K, Konishi M, Sugimoto Y, Hasegawa H Tags: Biol Pharm Bull Source Type: research

Effects of Diluent Volume and Administration Time on the Incidence of Anaphylaxis Following Docetaxel Therapy in Breast Cancer.
In this study, we retrospectively analyzed the risk factors for developing anaphylaxis in 182 female breast cancer patients treated with docetaxel. We found that 6.6% of all patients (n = 12) experienced anaphylaxis. Multivariate analyses indicated that concentration of docetaxel higher than 0.275 mg/m2/mL, docetaxel dose rate higher than 1.15 mg/m2/min, and white blood cell count less than 4290 cells/mL are risk factors for developing docetaxel-related anaphylaxis. In particular, concentrations of docetaxel or doses per administration time were associated with a high odds ratio (11.88 or 11.60)...
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Ishida S, Masuguchi K, Kawashiri T, Tsuji T, Watanabe H, Akiyoshi S, Kubo M, Masuda S, Egashira N Tags: Biol Pharm Bull Source Type: research

Kosen-cha, a Polymerized Catechin-Rich Green Tea, as a Potential Functional Beverage for the Reduction of Body Weight and Cardiovascular Risk Factors: A Pilot Study in Obese Patients.
In this study, we prepared kosen-cha from green tea using high pressure extraction, to reduce the astringent taste of the green tea. We identified a large quantity of polymerized GTCs in kosen-cha. To investigate the effects of kosen-cha containing polymerized GTCs in obese Japanese patients, we designed an open-label pilot study in which 6 obese subjects (body mass index (BMI)>25 kg/m2) were administered kosen-cha (5 g/L/d) for 12 weeks. Body composition, serum lipids, insulin resistance, vascular functions, and cardiac hypertrophy were measured before and 12 weeks after kosen-cha administration. Kosen-ch...
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Katanasaka Y, Miyazaki Y, Sunagawa Y, Funamoto M, Shimizu K, Shimizu S, Sari N, Shimizu Y, Wada H, Hasegawa K, Morimoto T Tags: Biol Pharm Bull Source Type: research

Examination of Aggregate Formation upon Simultaneous Dissolution of Methacrylic Acid Copolymer LD Enteric Coating Agent, Pharmaceutical Additives, and Zwitterionic Ingredients.
In this study, we have clarified the factors causing aggregate formation, focusing on the role of pharmaceutical additives and electrostatic interaction. Co-suspension of enteric-coated proton pump inhibitor (PPI) esomeprazole magnesium hydrate with levofloxacin resulted in aggregate formation, whereas the non-enteric-coated PPI vonoprazan fumarate did not. A comparison of pharmaceutical additive in the two PPIs highlighted polysorbate 80 and methacrylic acid copolymer LD as candidates causing aggregation. When these pharmaceutical additives were added to levofloxacin, only methacrylic acid copolymer LD induced aggregate f...
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Nakagawa Y, Suzuki T, Suga Y, Shimada T, Sai Y Tags: Biol Pharm Bull Source Type: research

In Vitro Inhibitory Effects of Sesamin on CYP4F2 Activity.
In this study, the effects of sesamin on catalytic activity of CYP4F2 were investigated in vitro. Sesamin inhibited luciferin-4F2/3 O-dealkylase activity of recombinant human CYP4F2 with an IC50 value of 0.381 µM. When preincubated in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) for 20 min, sesamin potentiated the inhibition of CYP4F2 activity. Moreover, kinetic analysis of the inactivation revealed that sesamin showed a preincubation time- and concentration-dependent inhibition of CYP4F2 activity yielding a maximal inactivation rate constant (kinact) value of 0.354&thinsp...
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Watanabe H, Yamaori S, Kamijo S, Aikawa K, Ohmori S Tags: Biol Pharm Bull Source Type: research

The Trend for Antibiotic Use for Clostridioides (Clostridium) difficile Infection in Japan.
Abstract In Japan, there is no national surveillance study of Clostridioides (Clostridium) difficile infection (CDI), and details about the epidemiology and treatment status of CDI are unknown. Additionally, clinical practice guidelines (CPGs) for CDI are published by four different institutions. All CPGs recommend that the antimicrobials, vancomycin (VCM) and metronidazole (MNZ), should be selected according to disease severity. However, the trends for VCM and MNZ use in Japan remain unclear. Therefore, this study was aimed at clarifying the secular trends for VCM and MNZ use based on sales data from 2006 to 2015...
Source: Biological and Pharmaceutical Bulletin - April 4, 2020 Category: Drugs & Pharmacology Authors: Ishii S, Muraki Y, Kusama Y, Yagi T, Goto R, Ebisui A, Kawabe A, Inose R, Ohmagari N Tags: Biol Pharm Bull Source Type: research