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Clinical and Experimental Pharmacology & Physiology

Sung Kyoung Kim, Seung Joon Rho, Seung Hoon Kim, Shin Young Kim, So Hyang Song, Jin Young Yoo, Chi Hong Kim, Sang Haak Lee
NADPH oxidase (NOX) plays an important role in inflammatory response by producing reactive oxygen species (ROS). The inhibition of NOX has been shown to induce anti-inflammatory effects in a few experimental models. The aim of this study was to investigate the effects of diphenyleneiodonium (DPI), a NOX inhibitor, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a rat model. Sprague-Dawley rats were intraperitoneally administered by DPI (5 mg/kg) 30 min after intratracheal instillation of LPS (3 mg/kg)...
November 7, 2018: Clinical and Experimental Pharmacology & Physiology
Jussara Maria Gonçalves, Carolina Amália Barcellos Silva, Elena Riet Correa Rivero, Mabel Mariela Rodríguez Cordeiro
Over the past years, studies have described that users of antipsychotics are less likely to develop cancer than the population in general due to cytotoxic properties of this class of drugs on cancer cells. For this reason, Pimozide has been widely studied as a potential anticancer treatment, and satisfactory results in Melanoma, Central Nervous System Tumors, Osteosarcoma, Neuroblastoma, Myeloproliferative Neoplasms, Breast, Lung, Prostate, Ovarian, Colorectal, Pancreatic, and Hepatocellular Carcinoma have been showed...
November 1, 2018: Clinical and Experimental Pharmacology & Physiology
Xiao Zhong, Xiaoqian Qian, Guangping Chen, Xiang Song
Galectin-3, a β-galactoside-binding lectin, is a new important player in the progression of heart failure (HF) and is also linked to poor outcome in patients with cardiovascular disease. Genetic or pharmacological inhibition of galectin-3 slows down the progression of myocardial inflammation, reduces collagen production, attenuates cardiac remodelling, and ameliorates cardiac function. In this review, we summarize recent progress in research on galectin-3 as a regulatory molecule involved in cardiovascular fibrosis in HF and its potential role in the diagnosis, risk assessment and treatment of cardiovascular diseases...
October 29, 2018: Clinical and Experimental Pharmacology & Physiology
Feng Guo, Yongjian Gao, Guoqing Sui, Dan Jiao, Lina Sun, Qingfeng Fu, Chunxiang Jin
YWHAZ (14-3-3ζ) plays crucial roles in regulating proliferation, apoptosis, migration, and invasion of gastric cancer (GC) cells. However, its extensive roles and potential mechanisms in GC cells remain unknown, which need to be researched deeply. In this study, we focused on the role of miR-375/YWHAZ axis in migration, invasion and epithelial-to-mesenchymal transition (EMT) of GC cells. YWHAZ level was assessed by western blot and qPCR assays in GC cells. Scratch and transwell assays were used to determine the migration and invasion of GC cells...
October 24, 2018: Clinical and Experimental Pharmacology & Physiology
Seyhan Sahan-Firat, Meryem Temiz-Resitoglu, Demet Sinem Guden, Sefika Pinar Senol, Ayse Nihal Sari, Meltem Cil, Demet Unsal, Belma Korkmaz, Bahar Tunctan, Kafait U Malik, Cuneyt Kemal Buharalioglu
We have previously demonstrated that the activation of the spleen tyrosine kinase (Syk)/inhibitory-κB (IκB)-α/nuclear factor-κB (NF-κB) p65 signalling pathway contributes to hypotension and inflammatory response in a rat models of zymosan (ZYM)-induced non-septic shock. The purpose of this study was to further examine the possible mechanism underlying the effect of inhibition of Syk by BAY61-3606 via NF-κB activity at the level of nuclear translocation regarding the production of vasodilator and proinflammatory mediators in lipopolysaccharide (LPS) (septic)- and ZYM (non-septic)-induced shock...
October 22, 2018: Clinical and Experimental Pharmacology & Physiology
Barbara E Lingwood, Yvonne A Eiby, S Tracey Bjorkman, Stephanie M Miller, Ian M R Wright
Preterm infants are at higher risk of adverse neurodevelopmental outcomes. Inadequate cerebral oxygen delivery resulting from poor cardiovascular function is likely to be a significant contributor to preterm brain injury. In this context, improved support of cardiovascular function is integral to improving preterm outcomes. Many of the treatments used to support preterm cardiovascular function are based on adult physiology and may not be appropriate for the unique physiology of the preterm infant. The preterm heart is structurally immature with reduced contractility and low cardiac output...
October 22, 2018: Clinical and Experimental Pharmacology & Physiology
Jacek Zachwieja, Magdalena Silska-Dittmar, Aleksandra Żurowska, Magdalena Drożyńska-Duklas, Lidia Hyla-Klekot, Grażyna Kucharska, Roman Stankiewicz, Ilona Olszak-Szot, Dorota Drożdż, Anna Moczulska, Danuta Zwolińska, Anna Medyńska, Przemyslaw Sikora, Bieniaś Beata, Marcin Tkaczyk, Anna Rogowska-Kalisz, Danuta Ostalska-Nowicka
The aim of the study was a multicenter analysis of the efficacy and safety of a non-standard immunosuppressive therapy with rituximab (Rtx) in children with steroid-resistant nephrotic syndrome (SRNS) with particular emphasis on the possibility of permanent discontinuation or dose reduction of other immunosuppressive drugs such as glucocorticoids and cyclosporine A after 6 months of observation. The study group consisted of 30 children with idiopathic nephrotic syndrome, who were unresponsive to standard immunosuppressive treatment, and hospitalized in the years 2010-2017 in 8 pediatric nephrology centers in Poland...
October 22, 2018: Clinical and Experimental Pharmacology & Physiology
Rui Adão, Pedro Mendes-Ferreira, Carolina Maia-Rocha, Diana Santos-Ribeiro, Patrícia Gonçalves Rodrigues, André Vidal-Meireles, Cláudia Monteiro-Pinto, Luís D Pimentel, Inês Falcão-Pires, Gilles W De Keulenaer, Adelino F Leite-Moreira, Carmen Brás-Silva
We have previously shown that treatment with recombinant human neuregulin-1 (rhNRG-1) improves pulmonary arterial hypertension (PAH) in a monocrotaline (MCT)-induced animal model, by decreasing pulmonary arterial remodeling and endothelial dysfunction, as well as by restoring RV function. Additionally, rhNRG-1 treatment showed direct myocardial anti-remodelling effects in a model of pressure loading of the RV without PAH. This work aimed to study the intrinsic cardiac effects of rhNRG-1 on experimental PAH and RV pressure overload, and more specifically on diastolic stiffness, at both the ventricular and cardiomyocyte level...
October 19, 2018: Clinical and Experimental Pharmacology & Physiology
Eran Ni, Lingling Zhao, Na Yao, Xiaofang Zhu, Hong Cao, Shuzhen Sun, Weizhong Zhu
Bcl-2-associated athanogene3(BAG3) protects the heart and cardiomyocytes from ischaemia/reperfusion (I/R) injury. Although theanti-apoptosis effect of BAG3 has been demonstratedin multiple cell types, the structural domain of BAG3,which is responsible for its anti-apoptosis effect, is not well understood. BAG3 protein consists of various characteristic amino acid motifs/regions that permit the interaction of BAG3 with numerous proteins involved in many cellular key pathways.The purpose of this study is to determine whether theproline-rich (PXXP) domain of BAG3 is necessary for its cellular protection againsthypoxia-reoxygenation (H/R) stress by binding to its chaperone,heat shock cognate 71 kDa protein (HSC70)...
October 16, 2018: Clinical and Experimental Pharmacology & Physiology
Gang Chen, Lina Yu, Hui Dong, Zhihao Liu, Yahong Sun
Upregulated in lung cancer, miRNA-182 was found to be related to cancer proliferation and chemoresistance. However, there is no report on the role of miR-182 in radioresistance, which is a main obstacle of radiotherapy. In this study, we aimed to depict the effect of miR-182 inhibition on cellular sensitivity to ionizing radiation. Our data confirmed that miR-182 was upregulated in lung cancers and tissues and that miR-182 was responsive to irradiation. We also showed that miR-182 knockdown suppressed cell proliferation and increased cell apoptosis after irradiation...
October 11, 2018: Clinical and Experimental Pharmacology & Physiology
Hong Ding, Ying Zhou, Haihua Huang
Hypertensive nephropathy, clinically characterized by progressive renal fibrosis and inflammation, is a severe complication of hypertension. The objectives of this study were to investigate the roles of miR-101a in relieving Angiotensin II (Ang II)-mediated hypertensive nephropathy and uncover the possible underlying mechanisms. Hypertensive mouse model was established via continuous 28-day AngII infusion. Systolic blood pressure (SBP), ratio of urine albumin to creatinine, blood urea nitrogen (BUN), serum creatinine (Scr) and glomerular filtration rate (GFR) were evaluated...
October 10, 2018: Clinical and Experimental Pharmacology & Physiology
Stefanie Stangenberg, Long The Nguyen, Ibrahim Al-Odat, Yik Lung Chan, Amgad Zaky, Carol Pollock, Hui Chen, Sonia Saad
Epidemiological and animal studies showed that L-carnitine (LC) supplementation can ameliorate oxidative stress-induced tissues damage. We have previously shown that maternal cigarette smoke exposure (SE) can increase renal oxidative stress in newborn offspring with postnatal kidney underdevelopment and renal dysfunction in adulthood, which were normalised by LC administration in the SE dams during pregnancy. Exposure to an adverse intrauterine environment may lead to alteration in the epigenome, a mechanism by which adverse prenatal conditions increase the susceptibility to chronic disease later in life...
October 5, 2018: Clinical and Experimental Pharmacology & Physiology
Ibraheem Husain, Sana Khan, Saba Khan, Tushar Madaan, Sanjeev Kumar, Abul Kalam Najmi
Rosuvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitor, and one of the most popular antihyperlipidemic medications has been found to possess pharmacodynamic activities much different from its usual indication. Recent research studies have revealed the efficacy of rosuvastatin in attenuating neuroinflammation, reducing the progression of Alzheimer's disease, providing protection against cerebral ischemia and spinal cord injury as well as ameliorating epilepsy. Mechanisms behind the neuroprotective potential of rosuvastatin can be attributed to its pleiotropic effects, independent of its ability to inhibit HMG-CoA reductase...
October 5, 2018: Clinical and Experimental Pharmacology & Physiology
Ruipeng Zhang, Yang Wang, Longfei Pan, Hongyan Tian
The current study aimed to investigate the effects of sildenafil and N-acetylcysteine (NAC) on the haemodynamics in a rabbit model of APT. We developed an APT model using healthy male China big-ear rabbits (2.7±0.4 kg). The rabbits were divided into five groups subjected to various interventions. We recorded the haemodynamic parameters and assessed the oxidative stress and lipid peroxidation response in the groups. Additionally, we detected apoptosis-associated molecules, FoxO1, Bad and Bcl-2, in the lung tissue...
October 5, 2018: Clinical and Experimental Pharmacology & Physiology
Xiang Xiao, Kaiming Jiang, Yunxiao Xu, Hongling Peng, Zhihua Wang, Sufang Liu, Guangsen Zhang
Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, possesses remarkable chemopreventive and therapeutic potential against various types of cancer, including leukaemia. However, the molecular mechanism involved in chronic myeloid leukaemia (CML), especially imatinib-resistant CML cells, is not completely understood. In the present study, we investigated the effect of EGCG on the growth of Bcr/Abl+ CML cell lines, including imatinib-resistant cell lines and primary CML cells. The results revealed that EGCG could inhibit cell growth and induce apoptosis in CML cells...
September 25, 2018: Clinical and Experimental Pharmacology & Physiology
Raphaëlle Corremans, Rui Adão, Gilles W De Keulenaer, Adelino F Leite-Moreira, Carmen Brás-Silva
Anthracycline chemotherapy has a prominent role in treating many forms of cancer. Unfortunately, cardiotoxic side effects represent a serious limitation to their use, with doxorubicin being the leading drug of the group. Indeed, anthracycline-induced cardiomyopathy is an important public health concern because it may not be detected for many years and remains a lifelong threat. Even after decades of investigation, neither the exact mode of action of anthracyclines nor the pathways leading to their side effect are fully understood...
September 23, 2018: Clinical and Experimental Pharmacology & Physiology
Shuzo Yamamoto, Tatsushi Mutoh, Kazumasu Sasaki, Tomoko Mutoh, Yasuko Tatewaki, Yasuyuki Taki
We aimed to evaluate the feasibility of a noninvasive method of cerebral blood flow (CBF) measurement using high-frequency power Doppler ultrasound imaging in a mouse model of subarachnoid haemorrhage (SAH). The 3-dimensionally (3D) reconstructed blood flow signals (%vascularity) within the brain volume of the middle cerebral artery territory correlated well with reference parameters, baseline carotid artery blood flow (r2 = 0.52, P < 0.0001) and normalized CBF changes (r2 = 0.74 P < 0.0001). These data suggest that the 3D power Doppler analysis may have potential for reflecting real-time CBF changes during the acute phase of experimental SAH, which may be applicable to preclinical studies on early brain injury...
September 21, 2018: Clinical and Experimental Pharmacology & Physiology
Thekkuttuparambil Ananthanarayanan Ajith, Thankamani Gopinathan Jayakumar
Incidence of coronary heart disease (CHD) increases worldwide with varying etiological factors. In addition to the control of risk factors, dietary modification has been recommended to reduce the prevalence. Omega-3 (ω-3) fatty acids (FAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), of fish oil are beneficial for the prevention of CHD. The effect can be ascribed to anti-inflammatory, vasodilating, antiarrhythmic, antihypertensive activities and lowering of triacyl glycerol level. The American Heart Association advises two fish meals per week in subjects without CHD or supplementation of 1 g of EPA plus DHA per day in subjects with CHD...
September 19, 2018: Clinical and Experimental Pharmacology & Physiology
Francisco José Batista-Lima, Felipe Macário Dos Santos Rodrigues, Kalinne Kelly Lima Gadelha, Daniel Maia Nogueira de Oliveira, Emanuella Feitosa Carvalho, Tatyanne Linhares Oliveira, Fernanda Carlos Nóbrega, Teresinha Silva Brito, Pedro Jorge Caldas Magalhães
β-Phenylethylamine (β-PEA) is a trace amine with chemical proximity to biogenic amines and amphetamines. It is an endogenous agonist of trace amine-associated receptors (TAARs) that acts as a neuromodulator of classic neurotransmitters in the central nervous system. At high concentrations, β-PEA contracts smooth muscle, and a role for TAARs in these responses has been postulated. The high dietary intake of trace amines has been associated with such symptoms as hypertension and migraine, especially after the intake of foods containing such compounds...
September 19, 2018: Clinical and Experimental Pharmacology & Physiology
Mehmet Bülbül, Osman Sinen, V Nimet İzgüt-Uysal, Gökhan Akkoyunlu, Saffet Öztürk, Fatma Uysal
Exposure to stress induces gastrointestinal (GI) dysmotility. In rodents, acute restraint stress (ARS) inhibits gastric emptying (GE) and intestinal transit (IT) via central and peripheral corticotropin-releasing factor (CRF)-mediated pathways. Peripherally administered apelin-13 was shown to inhibit GI motor functions; moreover, stress-induced upregulation of gastric apelin content was demonstrated in rats suggesting that peripheral apelin may mediate stress-induced alterations in GI motility. We investigated the role of endogenous peripheral apelin in stress-induced GI dysfunction...
September 17, 2018: Clinical and Experimental Pharmacology & Physiology
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