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Daoyan Liu
OBJECTIVE: Increased transient receptor potential canonical type 3 (TRPC3) channels have been observed in essential hypertensive patients and spontaneously hypertensive rats (SHR). Our previous study shows that mitochondrial respiratory dysfunctions of blood mononuclear cells link with cardiac disturbance in patients with early-stage heart failure. Telmisartan has beneficial effect on both hypertension and metabolic syndrome. In the present study we tested the hypothesis that telmisartan administration inhibited mitochondrial respiratory function was associated with decreased TRPC3 function in monocytes from genetic hypertensive rats (SHR)...
September 2016: Journal of Hypertension
Yan Wang, Jin Zhang, Yuesheng Qian, Xiaofeng Tang, Huawei Ling, Kemin Chen, Pingjin Gao, Dingliang Zhu
OBJECTIVE: Intracranial arterial stenosis (ICAS) is a common cause of ischemic stroke in Asians, whereas whites tend to have more extracranial lesions. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been associated with ischemic stroke by a large amount of work. However, there are few studies focusing on the relationship of Lp-PLA2 and asymptomatic ICAS or extracranial arterial stenosis (ECAS). We hereby sought to explore the relationship of Lp-PLA2 and ICAS, ECAS and concurrent stenosis in stroke-free hypertensive patients in Chinese population...
September 2016: Journal of Hypertension
Haiyan Luan, Peng Wu, Mingxiao Wang, Hongyu Sui, Lili Fan, Ruimin Gu
Adenosine is a molecule produced by several organs within the body, including the kidneys, where it acts as an autoregulatory factor. It mediates ion transport in several nephron segments, including the proximal tubule and the thick ascending limb (TAL). Ion transport is dictated in part by anionic chloride channels, which regulate crucial kidney functions, including the reabsorption of Na+ and Cl‑, urine concentration, and establishing and maintaining the corticomedullary osmotic gradient. The present study investigated the effects of adenosine on the mRNA expression of chloride voltage‑gated channel Kb (CLCNKB), a candidate gene involved in hypertension, which encodes for the ClC‑Kb channel...
September 26, 2016: Molecular Medicine Reports
Nicholas T Funderburg, Grace A McComsey, Manjusha Kulkarni, Tammy Bannerman, Jessica Mantini, Bernadette Thornton, Hui C Liu, Yafeng Zhang, Qinghua Song, Liang Fang, Jason Dinoso, Andrew Cheng, Scott McCallister, Marshall W Fordyce, Moupali Das
BACKGROUND: Initiation of antiretroviral therapy (ART) and subsequent virologic suppression reduces immune activation and systemic inflammation. METHODS: We examined longitudinal changes in biomarkers of monocyte activation (sCD14, sCD163), and systemic (IL-6, hsCRP, sTNFR-I and D-dimer) and vascular (Lp-PLA2) inflammation in a subgroup (N=100 per arm) of participants enrolled in a randomized, placebo-controlled trial comparing elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF; TAF) to E/C/F/tenofovir disoproxil fumarate (E/C/F/TDF; TDF) in treatment-naïve adults...
October 11, 2016: EBioMedicine
Ivor B Asztalos, Joi A Gleason, Sakine Sever, Reyhan Gedik, Bela F Asztalos, Katalin V Horvath, Michael L Dansinger, Stefania Lamon-Fava, Ernst J Schaefer
BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the primary omega-3 fatty acids in fish oil, have been shown to reduce cardiovascular disease (CVD) risk. OBJECTIVE: This study aimed to examine the independent effects of EPA and DHA on lipid and apolipoprotein levels, as well as on inflammatory biomarkers of CVD risk, using doses often used in the general population. DESIGN: A blinded, randomized 6-week trial was performed in 121 healthy, normolipidemic subjects who received olive oil placebo 6g/d, EPA 600mg/d, EPA 1800mg/d, or DHA 600mg/d...
November 2016: Metabolism: Clinical and Experimental
Jalees Fatima, Ritu Karoli, Ruchita Sharma, Saumya Gupta, Aman Mor
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Yunwi Heo, Young Chul Kwon, Kyoungsoon Shin, Won Duk Yoon, Chang Hoon Han, Seungshic Yum, Euikyung Kim
We have shown that Nemopilema nomurai jellyfish venom (NnV) contains various kinds of proteolytic enzyme activities, including phospholipase (PLA), metalloproteinase (MP) and hyaluronidase activities. In this study, we reported the full-length cDNA and gene sequences of two PLA2 isoforms: acidic PLA2 PA4 and PLA2 PA3A/PA3B/PA5. The full-length cDNA of acidic PLA2 PA4 contains 483 nucleotides (nt), which encode 160 amino acids (and the stop codon), including a signal peptide, six cysteine residues that form disulfide bonds, and metal-binding and catalytic active sites...
October 6, 2016: Toxicon: Official Journal of the International Society on Toxinology
Mauren Villalta, Andrés Sánchez, María Herrera, Mariángela Vargas, Álvaro Segura, Maykel Cerdas, Ricardo Estrada, Indika Gawarammana, Dan E Keyler, Kimberly McWhorter, Roy Malleappah, Alberto Alape-Girón, Guillermo León, José María Gutiérrez
A new whole IgG, freeze-dried, polyspecific antivenom was prepared from the plasma of horses immunized with the venoms of the snakes Daboia russelii, Echis carinatus, Hypnale hypnale, and Naja naja from Sri Lanka. The preclinical neutralizing ability of this antivenom against several toxic and enzymatic activities of these four venoms was analyzed, and compared with that of a batch of VINS antivenom (India) being currently used in Sri Lanka. The activities tested were: lethality, hemorrhagic, in vitro coagulant, proteinase and phospholipase A2...
October 6, 2016: Toxicon: Official Journal of the International Society on Toxinology
María Emilia Garcia Denegri, Gladys P Teibler, Silvana L Maruñak, David R Hernández, Ofelia C Acosta, Laura C Leiva
Bothrops alternatus snake venom is particularly characterized for inducing a prominent haemorrhage and affecting hemostasis as a consequence of 43.1% of metallo-proteinases and less than 10% of PLA2 (almost all non-myotoxic phospholipases) in its venomics. In addition, myonecrosis is the major local effect in viper envenoming which might lead to permanent sequela. Then, the rebuilding of the microvasculature at the local injured site acquires significance since represents one of the pivotal stages for subsequent skeletal muscle regeneration either at morphological or functional aspects...
October 6, 2016: Toxicon: Official Journal of the International Society on Toxinology
Lourdes Dias, Mariana A P Rodrigues, André L Rennó, Alessandra Stroka, Bruna R Inoue, Patrícia C Panunto, Anibal R Melgarejo, Stephen Hyslop
In this work, we examined the hemodynamic responses to Lachesis muta (South American bushmaster) venom in anesthetized male Wistar rats. Venom (1.5 mg/kg, i.v.) caused immediate hypotension that was followed by a gradual return towards baseline over 60 min; there were no significant changes in heart rate, ECG parameters and respiratory rate. A higher dose (3 mg/kg, i.v.) caused sustained hypotension, variable bradycardia, respiratory depression and fluctuations in ECG; death occurred within 10-60 min. Venom injected intramuscularly (15 mg/kg) produced a smaller decrease in blood pressure that was more persistent than with 1...
October 5, 2016: Toxicon: Official Journal of the International Society on Toxinology
Lourdes Dias, Mariana A P Rodrigues, Bruna R Inoue, Renata L Rodrigues, André L Rennó, Valéria B de Souza, Frank D Torres-Huaco, Norma C Sousa, Alessandra Stroka, Anibal R Melgarejo, Stephen Hyslop
In this work, we examined some mechanisms involved in the hypotension caused by Lachesis muta (South American bushmaster) venom in anesthetized rats. Venom (1.5 mg/kg, i.v.) caused immediate hypotension that was maximal after 5 min and gradually returned to baseline over 60 min. Pretreatment of rats with the non-selective nitric oxide synthase (NOS) inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) did not attenuate the early phase of venom-induced hypotension, but abolished the recovery phase and resulted in rapid death; a similar effect was observed with the soluble guanylate cyclase (sGC) inhibitor ODQ...
October 5, 2016: Toxicon: Official Journal of the International Society on Toxinology
Kai Wu, Jianfeng Xu, Regan Fong, Xiaozhou Yao, Yanmei Xu, William Guiney, Frank Gray, Andrew Lockhart
OBJECTIVE: To evaluate in healthy volunteers the safety, pharmacokinetics (PK), pharmacodynamics (PD), and drug-drug interaction (DDI) potential of GSK2647544, (a selective lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor). METHODS: Study 1 was a single-blind, randomized, placebo-controlled, crossover study with healthy male volunteers randomized to receive single escalating oral doses (0.5 - 750 mg) of GSK2647544. Study 2 was a single-blind, randomized, placebo-controlled study with healthy volunteers randomized to receive repeat doses (80 mg) of GSK2647544...
October 10, 2016: International Journal of Clinical Pharmacology and Therapeutics
Maroula G Kokotou, Dimitris Limnios, Aikaterini Nikolaou, Anastasia Psarra, George Kokotos
The regulation of the catalytic activity of the various phospholipase A2 enzymes is of high importance because these enzymes are involved in various pathological conditions such as arthritis, cardiovascular diseases, neurological diseases, and cancer. Thus, a great effort has been devoted in developing synthetic inhibitors as new agents to treat inflammatory diseases. Some of them have reached clinical trials. Areas covered: This review article discusses the phospholipase A2 inhibitors presented in patent literature from October 2012 to June 2016, their activities in vitro and in vivo as well as the results of clinical trials using synthetic PLA2 inhibitors...
October 8, 2016: Expert Opinion on Therapeutic Patents
Andreas Krebs, Juergen Doerfer, Alexandra Krause, Juergen Grulich-Henn, Martin Holder, Wolfgang Hecker, Kai Lichte, Arno Schmidt-Trucksaess, Karl Winkler, Karl Otfried Schwab
BACKGROUND: The objective of the study was to assess the effect of atorvastatin on inflammation markers and low-density lipoprotein (LDL) subfractions. METHODS: In a prospective, randomized, double-blind pilot study involving 28 adolescents with type 1 diabetes (T1D), lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, high-sensitivity C-reactive protein (hsCRP), and subfractions of LDL were measured at baseline, after 1 year and 2 years of treatment with atorvastatin (10 mg/day) vs...
October 1, 2016: Journal of Pediatric Endocrinology & Metabolism: JPEM
Felipe Roberto Borba Ferreira, Pollyanna Michelle da Silva, Tatiana Soares, Larissa Gonçalves Machado, Larissa Cardoso Corrêa de Araújo, Teresinha Gonçalves da Silva, Gabriela Souto Vieira de Mello, Maira Galdino da Rocha Pitta, Moacyr Jesus Barreto de Melo Rego, Emmanuel Viana Pontual, Russolina Benedeta Zingali, Thiago Henrique Napoleão, Patrícia Maria Guedes Paiva
This study characterized the protein/peptide profile of venom isolated from the spider Lasiodora sp. (Mygalomorphae, Theraphosidae) found in northeastern Brazil and determined its antimicrobial activity, toxicity against human cells, and hemolytic activity. Protein concentration of the Lasiodora sp. venom was 4.53 ± 0.38 mg/mL. SDS-PAGE showed proteins with molecular masses up to 75 kDa, some of which contained disulfide bridges. RP-HPLC analysis separate at least 12 peaks that were identified by mass spectrometry as peptides U1-theraphotoxin-Lp1a (lasiotoxin-1), U1-theraphotoxin-Lp1c (lasiotoxin-3), U3-theraphotoxin-Lsp1a (LTx5), and ω-theraphotoxin-Asp3a as well as the proteins phospholipase A2 (PLA2) and hyaluronidase...
September 29, 2016: Toxicon: Official Journal of the International Society on Toxinology
Petra Micova, Klara Hahnova, Marketa Hlavackova, Barbara Elsnicova, Anna Chytilova, Kristyna Holzerova, Jitka Zurmanova, Jan Neckar, Frantisek Kolar, Olga Novakova, Jiri Novotny
Cardiac resistance against acute ischemia/reperfusion (I/R) injury can be enhanced by adaptation to chronic intermittent hypoxia (CIH), but the changes at the molecular level associated with this adaptation are still not fully explored. Phospholipase A2 (PLA2) plays an important role in phospholipid metabolism and may contribute to membrane destruction under conditions of energy deprivation during I/R. The aim of this study was to determine the effect of CIH (7000 m, 8 h/day, 5 weeks) on the expression of cytosolic PLA2α (cPLA2α) and its phosphorylated form (p-cPLA2α), as well as other related signaling proteins in the left ventricular myocardium of adult male Wistar rats...
September 30, 2016: Molecular and Cellular Biochemistry
Erik P A van Iperen, Suthesh Sivapalaratnam, Michael V Holmes, G Kees Hovingh, Aeilko H Zwinderman, Folkert W Asselbergs
BACKGROUND AND AIMS: Type 2 diabetes (T2D), low-density lipoprotein-cholesterol (LDL-c), body mass index (BMI), blood pressure and smoking are established risk factors that play a causal role in coronary artery disease (CAD). Numerous common genetic variants associating with these and other risk factors have been identified, but their association with CAD has not been comprehensively examined in a single study. Our goal was to comprehensively evaluate the associations of established and emerging risk factors with CAD using genetic variants identified from Genome-wide Association Studies (GWAS)...
September 13, 2016: Atherosclerosis
Ka Lun Cheung, Rachael Jarrett, Sumithra Subramaniam, Maryam Salimi, Danuta Gutowska-Owsiak, Yi-Ling Chen, Clare Hardman, Luzheng Xue, Vincenzo Cerundolo, Graham Ogg
Psoriasis is a chronic inflammatory skin disease associated with a T helper 17 response. Yet, it has proved challenging to identify relevant peptide-based T cell antigens. Antigen-presenting Langerhans cells show a differential migration phenotype in psoriatic lesions and express constitutively high levels of CD1a, which presents lipid antigens to T cells. In addition, phospholipase A2 (PLA2) is highly expressed in psoriatic lesions and is known to generate neolipid skin antigens for recognition by CD1a-reactive T cells...
September 26, 2016: Journal of Experimental Medicine
Kyung-Hwa Jung, Hyunjung Baek, Dasom Shin, Gihyun Lee, Sangwon Park, Sujin Lee, Dabin Choi, Woojin Kim, Hyunsu Bae
Asthma is a common chronic disease characterized by bronchial inflammation, reversible airway obstruction, and airway hyperresponsiveness (AHR). Current therapeutic options for the management of asthma include inhaled corticosteroids and β2 agonists, which elicit harmful side effects. In the present study, we examined the capacity of phospholipase A2 (PLA2), one of the major components of bee venom (BV), to reduce airway inflammation and improve lung function in an experimental model of asthma. Allergic asthma was induced in female BALB/c mice by intraperitoneal administration of ovalbumin (OVA) on days 0 and 14, followed by intratracheal challenge with 1% OVA six times between days 22 and 30...
2016: Toxins
Davinia Pla, Benjamin W Bande, Ronelle E Welton, Owen K Paiva, Libia Sanz, Álvaro Segura, Christine E Wright, Juan J Calvete, José María Gutiérrez, David J Williams
: The Papuan black snake (Pseudechis papuanus Serpentes: Elapidae) is endemic to Papua New Guinea, Indonesian Papua and Australia's Torres Strait Islands. We have investigated the biological activity and proteomic composition of its venom. The P. papuanus venom proteome is dominated by a variety (n≥18) of PLA2s, which together account for ~90% of the venom proteins, and a set of low relative abundance proteins, including a short-neurotoxic 3FTx (3.1%), 3-4 PIII-SVMPs (2.8%), 3 cysteine-rich secretory proteins (CRISP; 2...
September 17, 2016: Journal of Proteomics
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