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Jian Chen, Jian Sun, Julian Jiang, Jie Zhou
Cyanidin is an anthocyanidin extracted from a variety of fruits and vegetables. Cyanidin showed benefits against diabetes, cancer, and atherosclerosis. However, the potential neuroprotective effects of cyanidin against Parkinson's disease (PD) have not been examined. Indicated concentrations of cyanidin (1, 3, 10, and 30 μmol/L) were incubated together with 0.5 mmol/L 1-methyl-4-phenylpyridinium (MPP+) to human neuroblastoma SH-SY5Y cells. We found cyanidin prevented MPP+-induced cell demise in a concentration-dependent manner...
July 6, 2018: Pharmacology
Ali Sigaroudi, Martina Kinzig, Oliver Wahl, Christoph Stelzer, Michael Schroeter, Uwe Fuhr, Ulrike Holzgrabe, Fritz Sörgel
BACKGROUND: A drug must reach the central nervous system (CNS) in order to directly cause CNS adverse effects (AEs). Our current study addressed the pharmacokinetic (PK) background of the assumption that CNS concentrations of hydrochlorothiazide (HCT) and ramiprilate may directly cause CNS AEs such as headache and drowsiness. METHODS: In neurological patients, paired serum and cerebrospinal fluid (CSF) samples were withdrawn simultaneously. Some of them were treated with HCT (n = 15, daily chronic doses 7...
July 6, 2018: Pharmacology
Christian Ellermann, Anja Kohnke, Dirk G Dechering, Simon Kochhäuser, Florian Reinke, Michael Fehr, Lars Eckardt, Gerrit Frommeyer
OBJECTIVES: Levosimendan is a calcium sensitizer that is used as positive inotropic drug in acute decompensated heart failure. An increased incidence of atrial fibrillation after levosimendan-treatment was observed in clinical and experimental studies. Due to the limited range of antiarrhythmic drugs, the aim of the present study was to assess potential antiarrhythmic effects of ranolazine in levosimendan-pretreated isolated rabbit hearts. METHODS: Twelve rabbit hearts were excised and retrogradely perfused employing the Langendorff setup...
July 6, 2018: Pharmacology
Luyao Wang, Haojie Shan, Bin Wang, Nan Wang, Zubin Zhou, Chenhao Pan, Feng Wang
BACKGROUND/AIMS: Osteoarthritis is the most common degenerative joint disease and causes major pain and disability in adults. It has been reported that mitochondrial dysfunction in chondrocytes was associated with osteoarthritis. Puerarin has multiple effects including restoring mitochondrial function. In this study, the potential effects of puerarin on osteoarthritis and osteoarthritis associated mitochondrial dysfunctions were evaluated. METHODS: Osteoarthritis rats were treated with puerarin and the severity of osteoarthritis and cartilage damages was evaluated...
June 29, 2018: Pharmacology
Dietmar Enko, Sophia Harringer, Christian Oberkanins, Helene Pühringer, Gabriele Halwachs-Baumann, Gernot Kriegshäuser
Statin-induced myopathy is reported to be significantly associated with the SCLO1B1 c.521T>C polymorphism. To date, SLCO1B1 c.521T>C epidemiologic data for the Austrian population is still lacking. Therefore, this study aimed at assessing the genotype and allele frequencies of the SLCO1B1 c.521T>C variant in Austria and evaluating the clinical performance of 2 commercial real-time polymerase chain reaction (PCR) assays. Genomic DNA isolated from 181 healthy individuals was analyzed for the SLCO1B1 c...
June 28, 2018: Pharmacology
Min Sung Gee, Sung-Bae Kang, Namkwon Kim, Jiyoon Choi, Nam-Jung Kim, Bum-Joon Kim, Kyung-Soo Inn, Jong Kil Lee
Bardoxolone methyl (CDDO-me) is a synthetic triterpenoid that has been shown to suppress various cancers and inflammation. It has been implicated for the suppression of signal transducer and activator of transcription 3 (STAT3)-mediated signaling, which plays crucial roles in the development and progression of hepatocellular carcinoma (HCC). Previously, we showed that hepatitis B virus (HBV) large surface protein (LHB) variant W4P promotes carcinogenesis and tumor progression through STAT3 activation. Thus, we examined the anti-cancer activity of CDDO-me against HCC using W4P-LHB-expressing NIH3T3 cells and HepG2 and Huh7 HCC cell lines...
June 28, 2018: Pharmacology
Hongshan Ge, Lanlan Chen, Ying Su, Chunyan Jin, Ren-Shan Ge
BACKGROUND: Estradiol, produced by aromatase (CYP19A1), is very important for reproduction. Folpet, captan, and captafol belong to the phthalimide class of fungicides. They are used to protect the leaves of plants or fruits. They could be endocrine disruptors and may disrupt CYP19A1 activity. METHODS: In the present study, we investigated the effects of folpet, captan, and captafol on estradiol production and human CYP19A1 activity in JEG-3 cells. RESULTS: Folpet, captan, and captafol decreased estradiol production in JEG-3 cells in a concentration-dependent manner...
June 28, 2018: Pharmacology
Jyh-Cheng Chen, Peng-Fang Ma, Yuan-Cheng Lin, Chia-Hung Wu, Yi-Shuan Peng, Hao-Yu Zheng, Mu-Chuan Lin, Ya-Tang Li, Yun-Wei Lin
Etoposide (VP16) is a topoisomerase II inhibitor and has been used for the treatment of non-small cell lung cancer (NSCLC). Xeroderma pigmentosum complementation group C (XPC) protein is a DNA damage recognition factor in nucleotide excision repair and involved in regulating NSCLC cell proliferation and viability. Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone that is responsible for the stabilization and maturation of many oncogenic proteins. In this study, we report whether Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) enhanced etoposide-induced cytotoxicity in NSCLC cells through modulating the XPC expression...
June 28, 2018: Pharmacology
Gabriele Cortellini, Fabio Mascella, Margherita Simoncelli, Domenico Lippolis, Maria Cristina Focherini, Fabio Cortellini, Chiara Cherubini, Barbara Gavioli, Giorgio Ballardini
We present tocilizumab desensitization of a 47-year-old woman affected by rheumatoid arthritis with full body delayed erythematous urticarial reaction. Skin test for tocilizumab gave cutaneous reaction after 6 h at 20 mg/mL. The schedule of desensitization was then adapted for non-immediate reaction. We prepared a desensitization procedure reaching the cumulative dose of 516 mg in 5 weeks. After 6 months, the repetition of skin tests had a negative result, with demonstration of tolerance induction. Today the patient has good control of the disease...
June 28, 2018: Pharmacology
Mohammad Shokrzadeh, Nasrin Ghassemi-Barghi
Etoposide is one of the most effective chemotherapeutic agents used in the treatment of various types of cancers. However, as a Topoisomerase II inhibitor, during clinical use, several side effects may occur. In addition, in several in vivo and in vitro studies, etoposide has been shown to have a range of genotoxic effects including single and double strand breaks. Melatonin is an anti-aging and antioxidant hormone synthesized from the pineal gland. The genoprotective, antioxidant, and free radical scavenger properties of melatonin have been well explained in various studies...
June 25, 2018: Pharmacology
Helena Zivna, Iveta Gradošová, Pavel Zivny, Eva Cermakova, Vladimir Palicka
Spontaneously hypertensive rats (SHR) represent a model of essential hypertension. We studied the effect of amlodipine (AML) on bone markers, bone mineral density (BMD), and biomechanical properties of osteopenic bone induced by orchidectomy in male SHR. Rats were allocated to 3 groups and were sacrificed after 12 weeks: sham-operated control; orchidectomised control; and orchidectomised receiving a diet supplemented with AML. Indicators of bone turnover were assessed in bone homogenate, BMD was measured by dual energy X-ray absorptiometry, and the femurs were subjected to biomechanical testing...
June 13, 2018: Pharmacology
Hongmei Mu, Liyong Wang
BACKGROUND/AIMS: To test the effects of Nimodipine plus Yufeng Ningxin tablets on frequent migraine. METHODS: Two hundred forty-two patients with frequent migraine were divided into the control group with those consuming Flunarizine (120 cases) and the treatment group with those consuming Nimodipine plus Yufeng Ningxin tablets (122 cases). The course of frequent migraine treatment lasted 7 weeks. The number of migraine days, visual analogue scale (VAS) score, and response rate were measured...
June 7, 2018: Pharmacology
Dan Liu, Pengtao You, Yan Luo, Min Yang, Yanwen Liu
AIMS: The study aimed to investigate the molecular mechanism of inhibition of proliferation and apoptosis induction by galangin against MCF-7 human breast cancer cells. METHODS: Cell Counting Kit-8 assay was used to assess cell viability and flow cytometry was used to detect cell apoptosis. The expression level of apoptosis-related proteins (cleaved-caspase-9, cleaved-caspase-8, cleaved-caspase-3, Bad, cleaved-Bid, Bcl-2, Bax, p-phosphatidylinositol 3-kinase [PI3K], and p-Akt) and cell cycle-related proteins (cyclin D3, cyclin B1, cyclin-dependent kinases CDK1, CDK2, CDK4, p21, p27, p53) were evaluated by Western blotting...
June 7, 2018: Pharmacology
Hande Karahan, Sevda Lüle, Pelin Kelicen-Uğur
BACKGROUND/AIMS: Decreasing levels of aromatase and seladin-1 could be one of the molecular mechanisms of Alzheimer's disease (AD). Aromatase is an enzyme that catalyzes estrogen biosynthesis from androgen precursors, and seladin-1 is an enzyme that converts desmosterol to cholesterol, which is the precursor of all hormones. Verifying the potential relationship between these proteins and accordingly determining new therapeutic targets constitute the aims of this study. METHODS: Changes in protein levels were compared in vitro in aromatase and seladin-1 inhibitor-administered human neuroblastoma (SH-SY5Y) cells in vivo in intracerebroventricular (icv) aromatase or seladin-1 inhibitor-administered rats, as well as in transgenic AD mice in which the genes encoding these proteins were knocked out...
May 29, 2018: Pharmacology
Jian-Rong Zhou, Tetsuya Shirasaki, Fumio Soeda, Kazumi Yokomizo, Kazuo Takahama
In this study, we investigated the effect of histamine on capsaicin-induced current and its influence by suplatast in rat trigeminal ganglia neurons using a patch-clamp technique. We found that histamine directly potentiated capsaicin-induced currents in rat sensory neurons, and suplatast had little effect on this potentiation. Since it has been known that suplatast suppresses histamine release from mast cells, it is possible that suplatast inhibits the activation of nociceptive fibers in the pathological condition via prevention of histamine-induced potentiation of the transient receptor potential vanilloid 1 receptor-mediated currents...
May 16, 2018: Pharmacology
Ayami Sato, Haruka Ueno, Momoka Fusegi, Saki Kaneko, Kakeru Kohno, Nantiga Virgona, Akira Ando, Yuko Sekine, Tomohiro Yano
BACKGROUND: Wnt signaling plays an essential role in tumor cell growth, including the development of malignant mesothelioma (MM). Epigenetic silencing of negative Wnt regulators leading to constitutive Wnt signaling has been observed in various cancers and warrants further attention. We have reported that a succinate ether derivative of α-tocotrienol (T3E) has potent cytotoxic effects in MM cells. Thus, in this study, we investigated whether the anti-MM effect of T3E could be mediated via the epigenetic alteration of the Wnt antagonist gene, Dickkopf-1 (DKK1)...
May 15, 2018: Pharmacology
Sandra D Nkandeu, Iman van den Bout, Marianne J Cronjé, Dirk H van Papendorp, Anna M Joubert
BACKGROUND: 2-Methoxyestradiol (2ME2) is an endogenous metabolite of 17-β-estradiol with anti-proliferative and anti-angiogenic properties. Due to 2ME2's rapid metabolism and low oral bioavailability in in vivo settings, 2ME2 analogues have been designed to alleviate these issues. One of these compounds is 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16). A previous work alluded to the ability of ESE-16 to induce autophagic cell death. Therefore, we investigated the mode of action of ESE-16 by studying its effects on autophagy, vesicle formation, and lysosomal organisation...
April 19, 2018: Pharmacology
Jingsong Liu, Lin Zhou, Liyu He, Ying Zhong, Xiaobai Zhang, Bofei Xiao, Guoyong Liu
BACKGROUND: Periplaneta americana is one of the ancient insect groups with the strongest vitality. Periplaneta americana extract (PAE) has been explored as an alternative remedy for many diseases. Although much progress has been made in the study about PAE, the role of the drug in renal disease is rarely reported, especially in renal fibrosis. This study was designed to evaluate the renoprotective effect of PAE treatment to renal fibrosis. METHOD: An in vivo, unilateral ureteral obstruction (UUO) mouse model was built...
April 17, 2018: Pharmacology
Briohny H Spencer, Catherine M McDermott, Russ Chess-Williams, David Christie, Shailendra Anoopkumar-Dukie
BACKGROUND/AIMS: Docetaxel is currently the first-line chemotherapeutic agent available for the treatment of patients with advanced prostate cancer (PCa). While docetaxel has been shown to modestly improve survival times for patients; they also experience significant docetaxel-induced toxicities. If treatment failure occurs, there are currently limited alternatives that show survival benefits for patients and therefore there is an urgent need for adjunct therapies. Some quinazoline-based alpha1-adrenoceptor (ADR) antagonists have previously been shown to have cytotoxic actions in PCa cells, but there is no research into their effects on docetaxel-induced toxicity...
April 17, 2018: Pharmacology
Josef Donnerer, Ingrid Liebmann
This study aimed at investigating whether the synthetic cannabinoid receptor agonist (+)-WIN 55212-2 has neurogenic and myogenic relaxant effects on the longitudinal muscle-myenteric plexus (LMMP) strip of the guinea-pig ileum. (+)-WIN 55212-2, 1-1,000 nmol/L, concentration-dependently inhibited both the electrical stimulation-induced cholinergic twitch responses as well as the myogenic smooth muscle contractions in the LMMP preparation. SR-141716A (rimonabant) 1-1,000 nmol/L, the cannabinoid CB1 receptor antagonist, being without effect on its own, antagonized the (+)-WIN 55212-2-induced effects...
2018: Pharmacology
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