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Clinical and Experimental Pharmacology & Physiology

Yi Zhu, Xiaochen Zhang, Xiaoe Lou, Min Chen, Peihua Luo, Qiaojun He
With the use of multikinase inhibitors (MKIs) having emerged in recent years, skin toxicities such as hand-foot skin reaction (HFSR) are primary side effects, and they lack effective prediction methods. Here, we updated a previous systematic review by establishing a meta-analysis of the risk of developing HFSR among patients receiving multikinase inhibitors (MKIs) and antivascular endothelial growth factor antibody. Publications from PubMed and abstracts presented at the American Society of Clinical Oncology Annual Meeting up to February 5, 2015 were searched to identify relevant studies, and a total of 236 patients with metastatic tumors in nine trials were included for analysis...
March 15, 2018: Clinical and Experimental Pharmacology & Physiology
Nengyi Hou, Zhiyi Guo, Gaoping Zhao, Guiqing Jia, Bin Luo, Xiaogang Shen, Yifeng Bai
MicroRNA-21-3p (miR-21-3p), the passenger strand of pre-mir-21, has been found to be high-expressing in various cancers and to be associated with tumor malignancy, which is proposed as a novel focus in malignant tumors. Colorectal cancer (CRC), currently known as one of the most prevalent malignancy, is a leading cause of cancer death. This study aimed to investigate the key role of miR-21-3p in CRC by inhibiting its expression using transfection with miR-21-3p inhibitors into human CRC HCT116 cells. Results showed that the expression of miR-21-3p was higher than other CRC cells used in the study including Lovo, HT29, Colo320 and SW480 cells, inhibition of which suppressed the proliferation and induced cell cycle arrest in HCT116 cells...
March 14, 2018: Clinical and Experimental Pharmacology & Physiology
Jovana Jeremic, Tamara Nikolic Turnic, Vladimir Zivkovic, Nevena Jeremic, Isidora Milosavljevic, Ivan Srejovic, Radmila Obrenovic, Snezana Jancic, Milena Rakocevic, Stevan Matic, Dragan Djuric, Vladimir Jakovljevic
This research is designed to test the hypothesis that elevated homocysteine (Hcy) levels in vivo, caused by a deficit in vitamin B complex, promote changes in cardiac function and redox status that lead to heart failure. In order to conduct the study, we used adult male Wistar albino rats (n=30; 4 weeks old; 100±15 g body weight). Hyperhomocysteinemia (HHcy) in these animals was achieved by dietary manipulation. For 4 weeks, the animals were fed with a standard rodent chow (control - CF), a diet enriched in methionine with no deficiency in B vitamins (i...
March 6, 2018: Clinical and Experimental Pharmacology & Physiology
Cing-Yu Chen, Wen-Chuan Lin, Kar-Lok Wong, Ka-Shun Cheng, Yuk-Man Leung, Shu-Er Yang
Gossypol, a polyphenolic dialdehyde toxin isolated from cotton seed, has anti-cancer activities and has recently shown some success to treat glioma. Its effects on brain neurons and blood vessels are poorly understood. In this work we examined the effects of gossypol on cytosolic Ca2+ concentration ([Ca2+ ]i ) of mouse brain bEND.3 endothelial cells. Cell viability tests revealed that after 3-h and 18-h exposures, 10 μM gossypol caused 23 and 65% cell death, respectively; 3 μM gossypol caused no and 21% death, respectively...
March 1, 2018: Clinical and Experimental Pharmacology & Physiology
Ioannis Andrikou, Costas Tsioufis, Kyriakos Dimitriadis, Dimitrios Konstantinidis, Alexandros Kasiakogias, Mairi Kouremeti, Eirini Andrikou, Ioanna Karapati, Theodoros Kalos, Christos Fragoulis, Ioannis Liatakis, Evaggelia Koutra, Konstantinos Kyriazopoulos, Costas Thomopoulos, Dimitrios Tousoulis
The role of serum uric acid (SUA) in cardiovascular risk prediction remains to be further determined. We assessed the predictive value of SUA for the incidence of coronary artery disease (CAD) in 2287essential hypertensive patients who were followed up for a mean period of 8 years. The distribution of SUA levels at baseline was split by the median (5.2 mg/dl) and subjects were classified into those with high and low values. Hypertensives who developed CAD (n=57) compared to those without CAD at follow-up (n=2230) had at baseline higher SUA...
February 28, 2018: Clinical and Experimental Pharmacology & Physiology
Aneta Stachowicz, Rafał Olszanecki, Maciej Suski, Anna Wiśniewska, Katarzyna Kuś, Magdalena Białas, Jacek Jawień, Ryszard Korbut
Endothelial nitric oxide synthase (eNOS) - derived nitric oxide (NO) plays an important role not only in endothelium-dependent vasodilation but also in lipid and glucose homeostasis in the liver and exerts beneficial effects on mitochondrial biogenesis and respiration. Thus, the aim of our study was to used iTRAQ-based quantitative proteomics to investigate the changes in protein expression in the mitochondrial and cytosolic fractions isolated from the liver of the double (apolipoprotein E (apoE) and eNOS) knockout (apoE/eNOS-DKO) mice as compared to apoE KO mice (apoE-/- ) - an animal model of atherosclerosis and hepatic steatosis...
February 27, 2018: Clinical and Experimental Pharmacology & Physiology
Ziteng Zhang, Ming Ma, Ronghang Hu, Baobin Xu, Ling Zong, Haixiang Wei, Yanhong Meng
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide; however, clinical and pathological parameters have limited ability in discriminating between clinically significant and indolent ESCC. Since RasGRP3 transcript levels have prognostic value in discriminating ESCC with different clinical aggressiveness, we decided to investigate its putative oncogenic role in ESCC. We found that RasGRP3 was highly expressed in ESCC cells. Suppression of endogenous RasGRP3 expression in esophageal cell lines reduced Ras-GTP formation as well as AKT phosphorylation...
February 20, 2018: Clinical and Experimental Pharmacology & Physiology
Yuwei Deng, Li Hu, Wei Qiang, Zeneng Cheng, Lei Wang, Xiaoxia Wang
Etanercept (ETN) is a widely used anti- tumor necrosis factor-α (TNF-α) agent, which relieves the symptoms of ankylosing spondylitis (AS) by binding to TNF-α to inhibit its inflammation effects. In this study, the effect of TNF-α level on ETN clearance (CL) was investigated, and the TNF-α concentration was initially set as a correction factor for allometric scaling to improve the predictions of individual ETN CLs. Individual ETN CLs and TNF-α concentrations in healthy volunteers and patients with AS were determined by performing ETN pharmacokinetic studies in the two cohorts...
February 13, 2018: Clinical and Experimental Pharmacology & Physiology
Ji Ruan, Yu-Chen Yang, Fu-Quan Long, Chang Sun
UGT2B10 is an important metabolism enzyme in human body and its substrates include multiple amine-containing compounds, especially nicotine, tamoxifen and multiple antidepressants. Multiple common SNPs have been observed in its promoter region, but their role in expression regulation has never been investigated. In this preliminary study, we identified a novel cis-regulatory SNP, rs294775, for UGT2B10 by plasmid construction, mutagenesis, and luciferase assay, whose mechanism was also investigated. Our work provides a basis for further pharmacogenetics study...
February 12, 2018: Clinical and Experimental Pharmacology & Physiology
Fabiana Angelo Marques, Nayara Cristina Perez Albuquerque, Marília Silveira de Almeida Campos, Priscila Freitas-Lima, André Oliveira Baldoni, Veriano Alexandre Júnior, Américo Ceiki Sakamoto, Anderson Rodrigo Moraes Oliveira, Leonardo Régis Leira Pereira
Topiramate (TPM) is a second-generation antiepileptic drug (AED), acting on drug-resistant epilepsy. The aim of the study was to evaluate the influence of the dose, use of other AEDs on TPM plasma concentration (C p ), and frequency of epileptic seizures. A cross-sectional analytical study was developed with patients aged 18-60 years, for diagnosis of drug-resistant epilepsy, using TPM in monotherapy or associated with other AEDs. The following variables were analyzed: age, frequency of epileptic seizures, pharmacotherapeutic regimen with its respective doses, adherence to medication treatment, and adverse events score...
February 9, 2018: Clinical and Experimental Pharmacology & Physiology
Divanei Zaniqueli, Rafael O Alvim, Marcelo P Baldo, Sara G Luiz, Roberto Sá Cunha, José G Mill
Subendocardial viability ratio (SEVR) is a reliable index of myocardial supply-workload balance. This study sought to investigate whether overweight/obese children and adolescents have altered SEVR and to identify which are the associated factors. This cross-sectional study involved 789 individuals. Central haemodynamic was measured by radial applanation tonometry. Diastolic time was shorter (496 ± 122 vs. 537 ± 140 ms, p= 0.014) and diastolic pressure-time index was lower (2681 ± 412 vs. 2814 ± 423 mmHg x s, p=0...
February 9, 2018: Clinical and Experimental Pharmacology & Physiology
Qian Li, Lin Bai, Guiying Shi, Lianfeng Zhang, Yifan Dai, Pingsheng Liu, Yu-Sheng Cong, Miao Wang
Polymerase I and transcript release factor (Ptrf, also known as Cavin1) is an essential component in the biogenesis and function of caveolae. Ptrf knockout mice or patients with PTRF mutations exhibit numerous pathologies including markedly aberrant fuel metabolism, lipodystrophy and muscular dystrophy. In this study, we generated Ptrf transgenic mice to explore its function in vivo. Compared with WT mice, we found that the Ptrf transgenic mice showed obesity with an increased level of ALT (alanine aminotransferase) and AST (aspartate transaminase)...
January 30, 2018: Clinical and Experimental Pharmacology & Physiology
S Saad, I Al-Odat, Y L Chan, K McGrath, C A Pollock, B G Oliver, H Chen
Sex differences in disease susceptibility due to maternal programming have been reported. We previously observed that maternal smoking induced renal disease and neurological changes are restricted to males, whilst both male and female offspring develop metabolic disorders. We have also found that maternal L-carnitine supplementation during gestation and lactation can significantly improve glucose intolerance and hyperlipidaemia in male offspring. This study aimed to determine whether such beneficial effects can also occur in female offspring...
January 30, 2018: Clinical and Experimental Pharmacology & Physiology
Yunfei Ma, Lianfang Du, Fan Li, Zhengqiu Zhu
We wished to ascertain if atropine is useful for suppressing the pain suffered during four-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy) when assessing infertility in women. A total of 252 patients were divided into two groups to receive or not receive atropine (0.5 mg) injection 30 min before 4D-HyCoSy. Pain was evaluated using a numerical rating scale (NRS): during 4D-HyCoSy; upon two-dimensional transvaginal sonography; before catheter insertion; upon insertion and fixation of the catheter into the uterine cavity; 30 min after 4D-HyCoSy...
January 30, 2018: Clinical and Experimental Pharmacology & Physiology
Martha Rocio Servin-Vences, Jessica Richardson, Gary R Lewin, Kate Poole
Cartilage tissue lines the joints of mammals, helping to lubricate joint movement and distribute mechanical loads. This tissue is comprised of isolated cells known as chondrocytes which are embedded in an extracellular matrix. Chondrocytes produce and maintain the cartilage by sensing and responding to changing mechanical loads. Mechanosensitive ion channels have been implicated in chondrocyte mechanotransduction and recent studies have shown that both PIEZO1 and TRPV4 can be activated by mechanical stimuli in these cells...
January 23, 2018: Clinical and Experimental Pharmacology & Physiology
Jie Li, Bing Xu, Zhi Chen, Chanjuan Zhou, Li Liao, Yinghua Qin, Chuangchuang Yang, Xiaodong Zhang, Zicheng Hu, Lin Sun, Dan Zhu, Peng Xie
Numerous studies have reported that inflammation is involved in the pathophysiology of depression. Pioglitazone, a PPAR-γ agonist, has potential anti-inflammatory and antidepressive effects. However, the underlying molecular mechanisms of the antidepressant-like effect of pioglitazone on an inflammation-related mouse model of depression remain to be fully elucidated. Herein, we aimed to explore the effects of pioglitazone on depressive-like behaviours of mice exposed to lipopolysaccharides (LPS), and elucidate the underlying mechanisms...
January 23, 2018: Clinical and Experimental Pharmacology & Physiology
Karthigesh Sree Raman, Gaetano Nucifora, Joseph B Selvanayagam
Cardiovascular Magnetic Resonance Imaging (CMR) permits accurate phenotyping of many cardiac diseases. CMR's inherent advantages are its non-invasive nature, lack of ionizing radiation and high accuracy and reproducibility. Furthermore, it is able to assess many aspects of cardiac anatomy, structure and function. Specifically, it can characterize myocardial tissue, myocardial function, myocardial mass, myocardial blood flow/perfusion, irreversible and reversible injury, all with a high degree of accuracy and reproducibility...
January 19, 2018: Clinical and Experimental Pharmacology & Physiology
Erkan Kilinc, Yasar Dagistan, Aysel Kukner, Bayram Yilmaz, Sami Agus, Gizem Soyler, Fatma Tore
The exact mechanism of migraine pathophysiology still remains unclear due to the complex nature of migraine pain. Salmon calcitonin (SC) exhibits antinociceptive effects in the treatment of various pain conditions. In this study, we explored the mechanisms underlying the analgesic effect of salmon calcitonin on migrane pain using glyceryltrinitrate(GTN)-induced model of migraine and ex-vivo meningeal preparations in rats. Rats were administered intraperitoneally saline, GTN(10mg/kg), vehicle, saline+GTN, SC(50μg/kg)+GTN, and SC alone...
January 18, 2018: Clinical and Experimental Pharmacology & Physiology
Jeong-Seok Kim, Seon-Hwa Jeong, Sin-Hee Han, Ho-Keun Yi
Gomisin A from the fruit of Schisandra chinensis has many pharmacological properties, including hepato-protective, anti-diabetic, and anti-oxidative stress. However, the potential benefit of gomisin A is still not well understood, especially in aging progression. Therefore, the aim of this study was to clarify whether the promotion of mitochondrial biogenesis and autophagy of gomisin A affects anti-aging progression, and its mechanism. Intermediate (PD32) Human diploid fibroblast (HDF) cells were brought to stress-induced premature senescence (SIPS) using hydrogen peroxide (H2 O2 )...
January 10, 2018: Clinical and Experimental Pharmacology & Physiology
Yali Zhu, Miaomiao Du, Lisha Yi, Zhihong Liu, Guifang Gong, Xiang Tang
Endometrial polyps (EPs) are localized benign overgrowths at the endometrium, with currently unknown etiology and pathogenesis. Although symptoms of EP can be alleviated or resolved by hysteroscopic polypectomy, a significant fraction of individuals develop recurrent EPs after initial EP removal. And in rare cases, EPs may undergo malignant transformation. In depth understanding of the mechanisms that are involved in EP development is urgently needed. Recent works indicate that dysregulations in the immune system participate in the development of a variety of symptoms, such as aging, obesity and hypertension, many of which are EP risk factors...
January 2, 2018: Clinical and Experimental Pharmacology & Physiology
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