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Xiaoyan Cui, Zhenqiang Fu, Menghan Wang, Xiaofei Nan, Boai Zhang
OBJECTIVES: Along with their lipid-lowering effect, statins have been reported to have neuroprotective function in both in vivo and in vitro models of neurodegenerative diseases. We conducted this study in order to uncover the he neuroprotective effect of the lipophilic statin pitavastatin (PTV) and investigate the underlying molecular mechanisms using primary cultured cerebral neurons exposed to oxygen-glucose deprivation (OGD). METHODS: The primary cultured cerebral neurons were randomly assigned into four groups: the control group, the pitavastatin treatment group, the OGD group and the OGD + pitavastatin treatment group...
March 16, 2018: Neurological Research
A J McFarland, A K Davey, C M McDermott, G D Grant, J Lewohl, S Anoopkumar-Dukie
3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been associated with conflicting effects within the central nervous system (CNS), with underlying mechanisms remaining unclear. Although differences between individual statins' CNS effects have been reported clinically, few studies to date have compared multiple statins' neuroprotective effects. This study aimed to compare six statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin; 0-100 μM) using an in vitro model of lipopolysaccharide (LPS)-induced neuroinflammation and subsequent neurodegeneration...
March 6, 2018: Toxicology and Applied Pharmacology
Chee Hae Kim, Shuang Wang, Jun-Bean Park, Keun-Hwa Jung, Yeonyee E Yoon, Seung-Pyo Lee, Hyung-Kwan Kim, Yong-Jin Kim, Goo-Yeong Cho, Dae-Won Sohn
AIM: Speckle-tracking imaging has been introduced for the precise assessment of vessel mechanics. However, there are no data on the role of this imaging tool in assessing the changes in vasculature with statin therapy, which is known to enhance vascular elasticity. METHODS: This study was a prospective study including 48 statin-naïve patients (age, 58.2±8.4 years; 29.2% male) with hypercholesterolemia. Circumferential carotid artery strain (CAS) and stiffness index (β2 ) were measured using speckle-tracking imaging before and after 3 months of high-dose pitavastatin treatment (4 mg daily)...
March 7, 2018: Journal of Atherosclerosis and Thrombosis
Katsumi Miyauchi, Takeshi Kimura, Hiroaki Shimokawa, Hiroyuki Daida, Satoshi Iimuro, Hiroshi Iwata, Yukio Ozaki, Ichiro Sakuma, Yoshihisa Nakagawa, Kiyoshi Hibi, Takafumi Hiro, Yoshihiro Fukumoto, Seiji Hokimoto, Yasuo Ohashi, Hiroshi Ohtsu, Yasushi Saito, Masunori Matsuzaki, Ryozo Nagai
Large-scale clinical trials in patients in Western countries with coronary artery disease (CAD) have found that aggressive lipid-lowering therapy using high-dose statins reduces cardiovascular (CV) events further than low-dose statins. However, such evidence has not yet been fully established in Asian populations, including in Japan. The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study addresses whether intensification of statin therapy improves clinical outcomes in Japanese patients with CAD...
March 5, 2018: International Heart Journal
James Harrison, Tom De Bruyn, Adam S Darwich, J Brian Houston
Hepatocyte drug depletion-time assays are well established for the determination of metabolic clearance in vitro. The present study focuses on the refinement and evaluation of a "media loss" assay, an adaptation of the conventional depletion assay involving centrifugation of hepatocytes prior to sampling, allowing estimation of uptake in addition to metabolism. Using experimental procedures consistent with a high throughput, a selection of 12 compounds with a range of uptake and metabolism characteristics (atorvastatin, cerivastatin, clarithromycin, erythromycin, indinavir, pitavastatin, repaglinide, rosuvastatin, saquinavir and valsartan, together with two control compounds - midazolam and tolbutamide) were investigated in the presence and absence of the cytochrome P450 inhibitor 1-aminobenzotriazole and organic anion transporter protein inhibitor rifamycin SV...
February 8, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Elizabeth De Wolf, Christopher De Wolf, Alan Richardson
There is considerable interest in redeploying drugs for use in combination with other oncology therapeutics. The single-agent activity of statins in ovarian cancer has been widely reported, however the drug concentration required to cause cell death is considerably higher than that achieved in patients receiving statin treatment for hypercholesterolemia. Unfortunately, statins can cause myopathy when administered in high doses. One solution to this is to identify drugs that could be used in combination with statins to reduce the dose required and those that may potentially reduce the incidence of adverse side effects...
February 2018: Oncology Letters
Hong Shen, Rui Li, Rong Yan, Xia Zhou, Xia Feng, Mengjie Zhao, Hong Xiao
There are some conflicting results regarding the benefit of adjunctive therapy with statins for severity of negative symptoms in schizophrenia. This study aimed to verify whether statins use for adjunctive therapy was indeed beneficial to improve psychiatric symptoms in schizophrenia. The data were from CENTRAL, PubMed, Embase and MEDLINE. The Boolean search term used for the electronic database search was (statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR mevastatin OR pitavastatin OR pravastatin OR rosuvastatin OR cerivastatin) and (schizophrenia OR schizoaffective disorder OR psychosis)...
February 5, 2018: Psychiatry Research
Minh-Son To, Shivesh Prakash, Santosh I Poonnoose, Shailesh Bihari
OBJECTIVE: The study utilizes meta-regression analysis to quantify the dose-dependent effects of statin pharmacotherapy on vasospasm, delayed ischemic neurologic deficits (DINDs) and mortality in aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Prospective, retrospective observational studies and randomized controlled trials (RCTs) were retrieved by a systematic database search. Summary estimates were expressed as absolute risk (AR) for a given statin dose or control (placebo)...
February 6, 2018: World Neurosurgery
Umar J Pandit, Gowhar A Naikoo, Mehraj Ud Din Sheikh, Gulzar A Khan, K K Raj, S N Limaye
An electrochemically pretreated silver macroporous (Ag MP) multiwalled carbon nanotube modified glassy carbon electrode (PAN-Ag MP-MWCNT-GCE) was fabricated for the selective determination of an anti-hyperlipidimic drug, pitavastatin (PST). The fabricated electrochemical sensor was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The fabricated electrode was employed in quantifying and determining PST through differential pulse adsorptive stripping voltammetry (DPAdSV) and CV...
August 2017: Journal of Pharmaceutical Analysis
Tsung-Kun Lin, Yi-Sheng Liou, Ching-Heng Lin, Pesus Chou, Gwo-Ping Jong
Background: Statins have been linked to new-onset osteoporotic fractures (NOFs), and different statins may alter the risk for the development of NOFs. Aim: In this study, we investigated the association between different statins and the development of NOFs. Patients and methods: This was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance, including case patients with NOFs from January 2004 to December 2013 and non-NOF subjects...
2018: Clinical Epidemiology
Zhen-Peng Kai, Yue Yin, Zhi-Ruo Zhang, Juan Huang, Stephen S Tobe, Shan-Shan Chen
A method for rapid quantitation of insect juvenile hormones (JH) and intermediates in the biosynthetic pathway, both in vitro and in vivo (hemolymph and whole body), has been developed using GC-MS/MS. This method is as simple as the radiochemical assay (RCA), the most commonly used method for measurement of JH biosynthesis in vitro, without need for further purification and derivatization, or radioactive precursors or ligands. It shows high sensitivity, accuracy and reproducibility. Linear responses were obtained the range of 1-800 ng/mL (approximately 4-3000 nM)...
January 17, 2018: Journal of Chromatography. A
Abeer Al-Qatati, Saeb Aliwaini
Melanoma is an aggressive skin cancer and its incidence is increasing faster than any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy for metastatic melanoma, it has limited success. Statins, including pitavastatin, have been demonstrated to have a range of anti-cancer effects in a number of human cancer cell lines. The present study therefore explored the anti-cancer activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma cells. Cell survival assays demonstrated that combined DTIC and pitavastatin treatment resulted in synergistic cell death...
December 2017: Oncology Letters
Niki Katsiki, Željko Reiner, Eugenia Tedeschi Reiner, Khalid Al-Rasadi, Matteo Pirro, Dimitri P Mikhailidis, Amirhossein Sahebkar
OBJECTIVE: Dyslipidemia is commonly associated with endothelial dysfunction and increased cardiovascular risk. Pitavastatin has been shown to reduce total and low-density lipoprotein cholesterol, to increase high-density lipoprotein (HDL)-cholesterol and improve HDL function. Furthermore, several trials explored its effects on flow-mediated dilation (FMD), as an index of endothelial function. The authors evaluated the effect of pitavastatin therapy on FMD. METHODS: The authors performed a systematic review and meta-analysis of all clinical trials exploring the impact of pitavastatin on FMD...
January 15, 2018: Expert Opinion on Pharmacotherapy
Seiji Miyauchi, Masayuki Masuda, Soo-Jin Kim, Yuudai Tanaka, Kyeong Ryoon Lee, Shouko Iwakado, Momoko Nemoto, Shotaro Sasaki, Kazumi Shimono, Yoshio Tanaka, Yuichi Sugiyama
The effects of bovine serum albumin (BSA) and human serum albumin (HSA) on the unbound hepatic uptake clearance (PSu,inf) of the organic anion transporting polypeptide (Oatp/OATP) substrates 1-anilino-8-naphthalene sulfonate (ANS) and pitavastatin (PTV) were determined using primary cultured hepatocytes of rat and isolated hepatocytes of human, respectively. The PSu,inf value of hepatocytes was estimated by dividing the initial uptake rate of these anions by their unbound concentrations. The PSu,inf values for ANS and PTV were enhanced in the presence of albumin, thereby demonstrating the phenomenon of "albumin-mediated" hepatic uptake...
January 3, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Huanyun Liu, Pang Bao, Lufeng Li, Yuqing Wang, Chunxin Xu, Mengyang Deng, Jihang Zhang, Xiaohui Zhao
Endothelial progenitor cells (EPC) participate in vessel recovery and maintenance of normal endothelial function. Therefore, pitavastatin-nanoparticles (NPs)-engineered EPC may be effective in repairing injured vasculature. Pitavastatin-loaded poly(lactic-co-glycolic) acid (PLGA) NPs were obtained via ultrasonic emulsion solvent evaporation with PLGA as the carrier encapsulating pitavastatin. The effects and mechanism of pitavastatin-NPs on EPC proliferation in vitro were evaluated. Then, EPC that internalized pitavastatin-NPs were transplanted into rats after carotid artery injury...
December 22, 2017: Scientific Reports
Kiyoshi Hibi, Shinjo Sonoda, Masanori Kawasaki, Yutaka Otsuji, Toyoaki Murohara, Hideki Ishii, Katsuhiko Sato, Ryoji Koshida, Yukio Ozaki, Masataka Sata, Yoshihiro Morino, Tadashi Miyamoto, Tetsuya Amano, Satoshi Morita, Ken Kozuma, Kazuo Kimura, Hisayoshi Fujiwara
BACKGROUND: The results of previous clinical trials on the effects of ezetimibe-statin combination therapy on atherosclerosis are inconsistent, and the anti-atherosclerotic effect of ezetimibe remains controversial.Methods and Results:We conducted a prospective, randomized open-label study at 10 centers. One hundred and twenty-eight statin-naïve patients with acute coronary syndrome (ACS) undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention were randomized to receive either 2 mg/day pitavastatin plus 10 mg/day ezetimibe, or 2 mg/day pitavastatin...
February 23, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
Mariko Harada-Shiba, John J P Kastelein, G Kees Hovingh, Kausik K Ray, Akira Ohtake, Osamu Arisaka, Takao Ohta, Tomoo Okada, Hideki Suganami, Albert Wiegman
AIM: Children with Familial Hypercholesterolemia (FH) are widely prescribed statins, and it has been suggested that the effects of statins differ among ethnicities. We compared the efficacy and safety of pitavastatin in children and adolescents with FH in clinical trials conducted in Japan and Europe. METHODS: Low-density lipoprotein cholesterol (LDL-C) reductions, adjusted for confounding factors, and safety were compared between the studies in Japan and Europe...
November 29, 2017: Journal of Atherosclerosis and Thrombosis
Miglė Paškevičiūtė, Vilma Petrikaitė
Purpose: To evaluate the anticancer activity of lovastatin (LOVA), mevastatin (MEVA), pitavastatin (PITA), and simvastatin (SIMVA) in 2D and 3D models of three human pancreatic cancer cell lines (BxPC-3, MIA PaCa-2, and PANC-1). Methods: The effect of statins on cell viability was estimated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. The activity of statins in 3D pancreatic cancer cell cultures was examined by measuring the size change of spheroids...
2017: Drug Design, Development and Therapy
Khondoker Alam, Taleah Farasyn, Alexandra Crowe, Kai Ding, Wei Yue
OATP1B1 and OATP1B3 mediate hepatic uptake of many drugs (e.g., statins) and can mediate transporter-mediated drug-drug-interactions (DDIs). Bortezomib is the first-in-class proteasome inhibitor drug approved by the U. S. Food and Drug Administration for the treatment of multiple myeloma. The potential of bortezomib to cause OATP-mediated DDIs has not been assessed. The current study investigated the involvement of the ubiquitin-proteasome system (UPS) in OATP1B1 and OATP1B3 degradation and determined the effects of proteasome inhibitors on OATP1B1- and OATP1B3-mediated transport...
2017: PloS One
Zhimin Zha, Junhong Wang, Shiling Li, Yan Guo
This study aimed to investigate whether pitavastatin protected against injury induced by advanced glycation end products products (AGEs) in neonatal rat cardiomyocytes, and to examine the underlying mechanisms. Cardiomyocytes of neonatal rats were incubated for 48 hours with AGEs (100mg/mL), receptor for advanced glycation end products (RAGE), antibody (1 mg/mL) and pitavastatin (600 ng/mL). The levels of p62 and beclin1 were determined by Western blotting. Mitochondrial membrane potential (DYm) and the generation of reactive oxygen species (ROS) were measured through the JC-1 and DCFH-DA...
November 1, 2017: Journal of Biomedical Research
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