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Raquel Santos-de-Souza, Luzia Monteiro de Castro Côrtes, Karen Dos Santos Charret, Léa Cysne-Finkelstein, Carlos Roberto Alves, Franklin Souza-Silva
Serine proteinases in Leishmania (Viannia) braziliensis promastigotes were assessed in this work. This study included the investigation of the enzymatic activity of subcellular fractions obtained from benzamidine affinity chromatography, reverse transcription polymerase chain reactions, and in silico assays of subcellular localization of subtilisin. Promastigote serine proteinases showed gelatinolytic activity with molecular masses of 43 kDa to 170 kDa in the cytosolic fraction and 67 kDa to 170 kDa in the membranous fraction...
March 15, 2019: International Journal of Molecular Sciences
Renata M Lataro, Marcondes A B Silva, Fabiola L Mestriner, Stefany B A Cau, Rita C A Tostes, Helio C Salgado
BACKGROUND: Acetylcholinesterase inhibition prevents autonomic imbalance, reduces inflammation and attenuates the development of hypertension. Considering that vascular dysfunction is a crucial feature of arterial hypertension, we investigated the effects of chronic administration of acetylcholinesterase inhibitors - pyridostigmine or donepezil - on vascular reactivity of spontaneously hypertensive rats (SHR). METHODS: Endothelium-dependent relaxant responses to acetylcholine and contractile responses induced by electric field stimulation (EFS) and alpha-adrenergic agonist were studied in mesenteric resistance arteries from SHR and Wistar Kyoto rats...
March 15, 2019: American Journal of Hypertension
Peter Senior, Irene Hramiak
Limiting postprandial glucose (PPG) excursions is an important aspect of overall glycemic control. Rapid-acting insulin analogues (RAIAs) aim to mimic the physiologic action of endogenous insulin observed in individuals without diabetes and prevent excessive PPG excursions. However, many people with type 1 diabetes and type 2 diabetes treated with RAIAs do not achieve glycated hemoglobin (A1C) targets, and there is an unmet need for further improvements in PPG control. Current RAIAs have a delayed onset and a longer duration of action compared with endogenous insulin secreted in response to meals...
January 24, 2019: Canadian Journal of Diabetes
Hao Zhang, Along Peng, Shuang Guo, Mengzhi Wang, Juan J Loor, Hongrong Wang
This study explores the roles of l-arginine (Arg) and N-carbamylglutamate (NCG) supplementation in the diet in intestine damage, energy state, as well as the associated protein kinase signaling pathways activated by AMP in intrauterine growth retarded (IUGR) suckling lambs. A total of 48 newborn Hu lambs with a normal birth weight (CON) and those with IUGR were randomly divided into four groups, CON, IUGR, IUGR + 1% Arg, and IUGR + 0.1% NCG, with 12 animals in each group. All animals were fed for 21 days, from day 7-28, following birth...
March 14, 2019: Food & Function
Kensuke Ikenaka, Naoki Atsuta, Yasuhiro Maeda, Yuji Hotta, Ryoichi Nakamura, Kaori Kawai, Daichi Yokoi, Akihiro Hirakawa, Akira Taniguchi, Mitsuya Morita, Kouichi Mizoguchi, Hideki Mochizuki, Kazunori Kimura, Masahisa Katsuno, Gen Sobue
OBJECTIVE: To investigate whether arginine methylation is altered in patients with amyotrophic lateral sclerosis (ALS) and how it affects disease severity, progression, and prognosis. METHODS: We compared the immunoreactivity of protein arginine methyltransferase 1 (PRMT1) and its products, asymmetric dimethylated proteins (ASYM), in postmortem spinal cord. We also measured the concentrations of total l-arginine and methylated arginine residues, including asymmetric dimethyl l-arginine (ADMA), symmetric dimethyl arginine, and monomethyl arginine, in CSF samples from 52 patients with ALS using liquid chromatography-tandem mass spectrometry, and we examined their relationship with the progression and prognosis of ALS...
March 13, 2019: Neurology
Jamila H Siamwala, Pavitra Kumar, Vimal Veeriah, Ajit Muley, Saranya Rajendran, Salini Konikkat, Syamantak Majumder, Krishna Priya Mani, Suvro Chatterjee
Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) plays crucial roles in cardiac homeostasis. Adult cardiomyocyte specific overexpression of eNOS confers protection against myocardial-reperfusion injury. However, the global effects of NO overexpression in developing cardiovascular system is still unclear. We hypothesized that nitric oxide overexpression affects the early migration of cardiac progenitor cells, vasculogenesis and function in a chick embryo. Vehicle or nitric oxide donor DEAN (500 mM) were loaded exogenously through a small window on the broad side of freshly laid egg and embryonic development tracked by live video-microscopy...
March 7, 2019: International Journal of Molecular Sciences
Emir Taghikhani, Renke Maas, Martin F Fromm, Jörg König
Elevated plasma concentrations of the uremic toxin asymmetrical dimethylarginine (ADMA) and low plasma concentrations of L-homoarginine are independently associated with cardiovascular events and total mortality. Enzymes degrading ADMA [dimethylaminohydrolase 1 (DDAH1)] and synthesizing L-homoarginine [L-arginine:glycine amidinotransferase (AGAT)] are expressed in human proximal tubule cells. So far, it is not known which transport protein in the basolateral membrane of proximal tubule cells is mediating the uptake of ADMA into the cells for subsequent degradation or the export of intracellularly synthesized L-homoarginine...
2019: PloS One
Ravindra D Yeole, Vipul P Rane, Vinod K Ahirrao, Rajesh P Chavan, Anasuya M Patel, Prasad K Deshpande, Mahesh V Patel, Kiran R Patil
WCK 771 is an L-arginine salt of Levonadifloxacin (LND) being developed as intra-venous dosage form and has recently completed Phase-III trial in India. The pharmacokinetics of WCK 771, a novel anti-MRSA fluoroquinolone, was examined in mice, rats, rabbits, dogs, monkeys and humans after systemic administration during pre-clinical and clinical investigations. Urine and serum were evaluated for identification of metabolites. It is observed that LND mainly follows phase-II biotransformation pathways. All the species showed different array of metabolites...
March 12, 2019: Biomedical Chromatography: BMC
Raed Madhi, Milladur Rahman, Matthias Mörgelin, Henrik Thorlacius
Neutrophil extracellular traps (NETs) are involved in acute pancreatitis (AP) but mechanisms controlling NET expulsion in AP are incompletely understood. Herein, we examined the role of c-Abelson (c-Abl) kinase in NET formation and tissue damage in severe AP. AP was induced by taurocholate infusion into pancreatic duct or intraperitoneal administration of l-arginine in mice. Pancreatic, lung, and blood samples were collected and levels of phosphorylated c-Abl kinase, citrullinated histone 3, DNA-histone complexes, myeloperoxidase, amylase, cytokines, and CXC chemokines were quantified...
March 12, 2019: Journal of Leukocyte Biology
Reza Naserzadeh, Niloofar Abad, Behnam Ghorbanzadeh, Mojtaba Dolatshahi, Mohammad Taghi Mansouri
Simvastatin, one of the lipophilic statins, has been shown to be effective in reducing depression in rodents. The present study aimed to investigate the potential antidepressant-like activity of simvastatin and the possible involvement of NO-cGMP-KATP channels pathway and PPARγ using forced swimming test (FST) in mice. In addition, the interaction between simvastatin and fluoxetine as a reference drug was examined. After assessment of locomotor behavior in the open-field test (OFT), FST was applied for evaluation of depressive behavior in mice...
March 8, 2019: Pharmacology, Biochemistry, and Behavior
Jing Huai, Zi Yang, Yan-Hong Yi, Guang-Jiao Wang
BACKGROUND: Fatty acid oxidation (FAO) disorder is involved in the pathogenesis of some cases of preeclampsia (PE). Several studies show that mammalian target of rapamycin (mTOR) signaling pathway is related to FAO. Pravastatin (Pra) can promote FAO in Nω-nitro-L-arginine methyl ester (L-NAME) PE-like mouse model in our previous study. This study aimed to investigate the effect of mTOR signaling pathway in PE-like model treated with Pra. METHODS: Pregnant mice were randomly injected with L-NAME as PE-like model group or saline as control group respectively, from gestational 7th to 18th day...
March 20, 2019: Chinese Medical Journal
Renata M N Eleutério, Francisco O Nascimento, Tamara G Araújo, Marilena F Castro, Tarcísio P Almeida Filho, Pedro A Maia Filho, José Eleutério, Darcielle B D Elias, Romélia P G Lemes
Background: Sickle cell anaemia (SCA) is the most prevalent monogenic disease in Brazil. In SCA, haemoglobin S (HbS) is formed, which modifies red blood cell morphology. Intravascular haemolysis occurs, in which free Hb and free radicals degrade nitric oxide (NO) and release arginase, which reduces arginine levels. Because arginine is a substrate for NO formation, this decrease leads to reduced NO (vasodilator) synthesis. SCA treatment uses hydroxyurea (HU) to maintain high foetal haemoglobin (HbF) levels and reduces HbS to avoid haemolytic episodes...
2019: Advances in Hematology
James McClory, Gui-Xiang Hu, Jian-Wei Zou, David J Timson, Meilan Huang
In microorganisms and plants, NAGK N-acetyl-L-glutamate kinase (NAGK) catalyses the second step in L-arginine synthesis, the phosphorylation of N-Acetyl-L-glutamate (NAG) to give N-acetyl-L-glutamate-5-phosphate (NAGP). NAGK is only present in microorganisms and plants but absent from mammals, which makes it an attractive target for antimicrobial or biocidal development. Understanding the substrate binding mode and reaction mechanism of NAGK is crucial for targeting the kinase to develop potential therapies...
March 8, 2019: Journal of Physical Chemistry. B
Izumi Suzuki, Keishoku Sakuraba, Takumi Horiike, Takafumi Kishi, Junya Yabe, Takashi Suzuki, Masahiko Morita, Akihito Nishimura, Yoshio Suzuki
PURPOSE: Oral L-citrulline (Cit) increases plasma L-arginine (Arg) concentration and the production of nitric oxide (NO). NO dilates blood vessels and potentially improves sports performance. The combination of oral Arg and Cit (Arg + Cit) immediately and synergistically increases plasma Arg and nitrite/nitrate (NOx) concentrations more than either Cit or Arg alone. This prompted us to assess the effects of oral Arg + Cit on 10-min cycling performance in a double-blind, randomized, placebo-controlled crossover trial...
February 16, 2019: European Journal of Applied Physiology
Ali Abbaszadeh-Kasbi, Nazgol-Sadat Haddadi, Amir Dehdashtian, Khashayar Afshari, Seyedeh Zarifeh Jazaeri, Naser Khodaei, Majid Momeni, Ahmad-Reza Dehpour
BACKGROUND: Recent reports have identified angiogenic, anti-inflammatory, and antioxidant properties of acute treatment with nicotine via activation of nicotinic acetylcholine receptors (nAChRs). In addition, the nitric oxide (NO) pathway is involved in ischemic reperfusion injuries. OBJECTIVES: We investigated the effects of acute pretreatment with nicotine in a rat model of random-pattern skin flap and the potential role of the NO pathway. METHODS: The Sprague-Dawley rats received increasing doses of (-)-nicotine (0...
March 6, 2019: Annals of Plastic Surgery
Reem T Atawia, Katharine L Bunch, Haroldo A Toque, Ruth B Caldwell, Robert W Caldwell
Obesity has reached epidemic proportions and its prevalence is climbing. Obesity is characterized by hypertrophied adipocytes with a dysregulated adipokine secretion profile, increased recruitment of inflammatory cells, and impaired metabolic homeostasis that eventually results in the development of systemic insulin resistance, a phenotype of type 2 diabetes. Nitric oxide synthase (NOS) is an enzyme that converts L-arginine to nitric oxide (NO), which functions to maintain vascular and adipocyte homeostasis...
March 1, 2019: Frontiers in Bioscience (Landmark Edition)
S Benito, A Sánchez-Ortega, N Unceta, M A Goicolea, R J Barrio
Pediatric chronic kidney disease (CKD) is currently assessed using glomerular filtration rate (GFR), which is calculated from different equations based on serum creatinine concentration. However, serum creatinine is affected by several factors and is not reliable enough for the diagnosis of CKD, especially at early stages. Recent targeted and untargeted metabolomics studies found 7 new potential biomarkers that could be useful for early pediatric chronic kidney disease diagnosis. Thus, a new LC-QQQ-MS analytical method has been developed and validated aimed at routine analysis of these 7 potential biomarkers: NG,NG'-dimethyl-l-arginine di(p-hydroxyazobenzene-p'-sulfonate) (SDMA), S-adenosyl-l-methionine (SAM), n-butyryl-l-carnitine (nC4), iso-butyryl-l-carnitine (iC4), citrulline (CIT), creatinine (CNN) and d-erytro-sphingosine-1-phosphate (S1P), in addition to creatinine, the classical biomarker for CKD diagnosis...
February 27, 2019: Journal of Pharmaceutical and Biomedical Analysis
A W Olusanya, A P Arikawe, I C Udenze, J A Odoka, J O Leigh
Cognitive impairment is a common adverse effect associated with carbamazepine use. One of the proposedmechanisms for cognitive impairment may be attributed to the pro-oxidant properties of carbamazepine. This studyinvestigated the effects of L-Arginine supplementation with carbamazepine on cognition in adult male non-epileptic rats.Adult male Sprague-Dawley rats with average weight 200g to 220g were divided into 4 groups; (1) Control group treatedwith distilled water, (2) L-Arginine group treated with L-Arginine (100mg/kg BW) in distilled water, (3) Carbamazepinegroup treated with carbamazepine (25mg/kg BW twice daily) in distilled water, and (4) Carbamazepine + L-Arginine grouptreated with Carbamazepine and L-Arginine as above for two weeks to assess the acute changes in cognition and oxidativestress markers...
December 30, 2018: Nigerian Journal of Physiological Sciences: Official Publication of the Physiological Society of Nigeria
Nadège Gouignard, Floriane Cherrier, Emma Brito-Fravallo, Adrien Pain, Natalia Marta Zmarlak, Katia Cailliau, Corinne Genève, Kenneth D Vernick, Colette Dissous, Christian Mitri
Vector-borne diseases and especially malaria are responsible for more than half million deaths annually. The increase of insecticide resistance in wild populations of Anopheles malaria vectors emphasises the need for novel vector control strategies as well as for identifying novel vector targets. Venus kinase receptors (VKRs) constitute a Receptor Tyrosine Kinase (RTK) family only found in invertebrates. In this study we functionally characterized Anopheles VKR in the Gambiae complex member, Anopheles coluzzii...
March 5, 2019: Scientific Reports
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