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Monica G Ferrini, Eduardo Garcia, Andrea Abraham, Jorge N Artaza, Sabine Nguyen, Jacob Rajfer
INTRODUCTION: COMP-4 is a natural compound-based dietary supplement consisting of the combination of ginger, Paullinia cupana, muira puama and l-citrulline, which when given long-term has been shown in the aged rat to a) upregulate iNOS in the penile smooth muscle cells (SMC), b) reverse the corporal SMC apoptosis and fibrosis associated with corporal veno-occlusive dysfunction (CVOD), and c) improve resulting erectile function. To elucidate the mechanism of how COMP-4 and its individual components modulate the iNOS-cGMP pathway, an in vitro study was conducted using a rat corporal primary SMC culture to determine its effect on NOS, soluble guanylate cyclase (sGC), cGMP and the phosphodiesterase 5 enzyme (PDE5)...
March 15, 2018: Nitric Oxide: Biology and Chemistry
Konstantinos C Fragkos, Alastair Forbes
Background: Citrulline has been described as a marker of intestinal function or absorption but evidence varies according to clinical settings. Objective: The objective of this article is to examine the evidence of plasma citrulline as a marker of intestinal function and absorption in various clinical settings. Methods: Studies were examined for p values, means and standard deviations, correlation coefficients or other metrics depicting the association of citrulline with intestinal function...
March 2018: United European Gastroenterology Journal
Samyuktha Muralidharan Pillai, Petra Seebeck, Ralph Fingerhut, Ji Huang, Xiu-Fen Ming, Zhihong Yang, François Verrey
BACKGROUND: Uninephrectomy (UNX) is performed for various reasons, including kidney cancer or donation. Kidneys being the main site of l-arginine production in the body, we tested whether UNX mediated kidney mass reduction impacts l-arginine metabolism and thereby nitric oxide production and blood pressure regulation in mice. METHODS AND RESULTS: In a first series of experiments, we observed a significant increase in arterial blood pressure 8 days post-UNX in female and not in male mice...
February 25, 2018: Journal of the American Heart Association
Weifeng Tan, Jingquan He, Junliang Deng, Xinwei Yang, Longjiu Cui, Rongzheng Ran, Guangwei Du, Xiaoqing Jiang
Hepatocellular carcinoma with bile duct tumor thrombus (BDTT) is a malignant disease. The most commonly used diagnosis methods for BDTT are MRCP/ERCP, ultrasonic diagnosis or CT scan. However, BDTT is often misdiagnosed as other bile duct diseases, such as extrahepatic cholangiocarcinoma (EHCC), choledochal cyst (Cyst) and common bile duct stone (Stone). Diagnostic methods, which are more accurate and less destructive, are urgently needed. In this paper, we analyzed the small molecule metabolites in the serum of BDTT, Stone, Cyst and EHCC patients and normal people using untargeted GC-MS, and identified 21 metabolites that show different levels among different samples...
February 19, 2018: Scientific Reports
Carlos Costas-Insua, Javier Merino-Gracia, Clara Aicart-Ramos, Ignacio Rodríguez-Crespo
From a catalytic point of view, the three mammalian nitric oxide synthases (NOSs) function in an almost identical way. The N-terminal oxygenase domain catalyzes the conversion of l-arginine to l-citrulline plus ·NO in two sequential oxidation steps. Once l-arginine binds to the active site positioned above the heme moiety, two consecutive monooxygenation reactions take place. In the first step, l-arginine is hydroxylated to make Nω-hydroxy-l-arginine in a process that requires 1 molecule of NADPH and 1 molecule of O2 per mol of l-arginine reacted...
2018: Advances in Protein Chemistry and Structural Biology
Tomoe Tsuboi, Morihiko Maeda, Toshio Hayashi
L-citrulline and L-arginine supplementation has been shown to have several beneficial effects on the cardiovascular system. Nitric oxide (NO) protects against the progression of atherosclerosis and is synthesized by nitric oxide synthase (NOS), which converts L-arginine (L-Arg) into L-citrulline (L-Cit). Our previous study revealed that chronic administration of a combination of L-Cit and L- Arg has a better therapeutic effect on high cholesterol-induced atherosclerosis in rabbits. We investigated how L-Arg and L-Cit affect endothelial function, aging and atherosclerosis...
2018: PloS One
Josef Finsterer, Sinda Zarrouk-Mahjoub
Headache is a prominent feature in mitochondrial disorders (MIDs) but no comprehensive overview is currently available. This review aims at summarising and discussing findings concerning type, frequency, pathogenesis, and treatment of headache in MIDs. The most frequent headache types in MIDs are migraine and migraine-like headache (MLH). MLH is classified as secondary headache. More rarely, tension-type headache, trigemino-autonomic headache, or different secondary headaches can be found. Migraine or MLH may manifest with or without aura...
January 26, 2018: Clinical Neurology and Neurosurgery
John Ashley, Youngdeok Kim, Joaquin U Gonzales
Supplementation with L-citrulline (Cit) has been shown to improve muscle oxygenation and oxygen uptake (VO2) kinetics during moderate-to-high intensity cycling in young men. The aim of this study was to test the hypothesis whether Cit would improve VO2 kinetics during walking in older and young adults. In a randomized, double-blind study, 26 (15 women, 11 men) adults between the ages of 20-35y (n = 15) and 64-86y (n = 11) completed 7 day periods of taking placebo and L-citrulline (6 g/day) in a crossover manner...
February 2, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Qianni Liu, Meijuan Xu, Rongzhen Zhang, Meizhou Wang, Xian Zhang, Taowei Yang, Zhiming Rao
Arginine deiminase (ADI) was first high-efficient expressed in Corynebacterium crenatum SYPA 5-5. The ADI was purified by Ni-NTA affinity chromatography and SDS-PAGE analysis showed the molecular weight (MW) was 46.8 kDa. The optimal temperature and pH of ADI were 37 ℃ and 6.5 respectively. The Michaelis constant was 12.18 mmol/L and the maximum velocity was 0.36 μmol/(min·mL). Under optimal conditions, 300 g/L of arginine was transformed and the productivity reach 8 g/(L·h). The recombinant strain was cultivated in a 5-L fermentor and used for whole-cell transformation of 300 g/L arginine, under repeated-batch bioconversion, the cumulative production reached 1 900 g/L...
November 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Shannon M Lange, Melanie C McKell, Stephanie M Schmidt, Austin P Hossfeld, Vandana Chaturvedi, Jeremy M Kinder, Jaclyn W McAlees, Ian P Lewkowich, Sing Sing Way, Joanne Turner, Joseph E Qualls
Activation, recruitment, and effector function of T lymphocytes are essential for control of mycobacterial infection. These processes are tightly regulated in T cells by the availability of l-arginine within the microenvironment. In turn, mycobacterial infection dampens T cell responsiveness through arginase induction in myeloid cells, promoting sequestration of l-arginine within the local milieu. Here, we show T cells can replenish intracellular l-arginine through metabolism of l-citrulline to mediate inflammatory function, allowing anti-mycobacterial T cells to overcome arginase-mediated suppression...
2017: Frontiers in Immunology
Ceren Gokmenoglu, Nurdan Ozmeric, Caglar Sungur, Raziye Sahin Bildik, Imge Erguder, Serenay Elgun
OBJECTIVE: Nitric oxide (NO) is synthesized from the conversion of L-arginine to L-citrulline by NO synthase (NOS). Arginase can compete with NOS for the common substrate L-arginine, and thus inhibit NO production. NO levels and arginase ezyme might affect the bone remodeling cycle around implants. The aim of this studywas to investigate NO and arginase levels in gingival crevicular fluid (GCF), peri-implant sulcular fluid (PISF), and saliva. MATERIALS AND METHODS: Twenty patients with one or more implants (Straumann® ; Institute Straumann AG, Basel, Switzerland) restored with fixed crown prostheses were included in the study...
January 2018: Archives of Oral Biology
Cinzia Papadia, Sylwia Osowska, Luc Cynober, Alastair Forbes
The amino acid L-citrulline (CIT) is safely used from the neonatal period onwards in those with urea cycle defects and carbamyl phosphate synthetase or ornithine transcarbamylase deficiencies, but several lines of enquiry indicate that it might have a much wider therapeutic role. When protein intake is low and there is a catabolic state, endogenous arginine (ARG) synthesis cannot fully be met and its supplementation can prove challenging, particularly in patients with critical and multisystem illness. Supplementary CIT could constitute a safer but still focused means of delivering ARG to endothelial and immune cells as CIT is efficiently recycled into these cells and as kidneys can convert CIT into ARG...
October 16, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Joong Kyong Ahn, Jungyeon Kim, Jiwon Hwang, Juhwan Song, Kyoung Heon Kim, Hoon-Suk Cha
Diagnosing Behcet's disease (BD) is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS). Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC) were assessed using GC/TOF-MS, in conjunction with multivariate statistical analysis...
November 2, 2017: International Journal of Molecular Sciences
Vishwajit S Chowdhury, Guofeng Han, Mohammad A Bahry, Phuong V Tran, Phong H Do, Hui Yang, Mitsuhiro Furuse
Recently we demonstrated that L-citrulline (L-Cit) causes hypothermia in chicks. However, the question of how L-Cit mediates hypothermia remained elusive. Thus, the objective of this study was to examine some possible factors in the process of L-Cit-mediated hypothermia and to confirm whether L-Cit can also afford thermotolerance in young chicks. Chicks were subjected to oral administration of L-Cit along with intraperitoneal injection of a nitric oxide synthase (NOS) inhibitor, N(G)-nitro-l-arginine methyl ester HCl (L-NAME), to examine the involvement of NO in the process of hypothermia...
October 2017: Journal of Thermal Biology
Kenia P Nunes, Gisele F Bomfim, Haroldo A Toque, Theodora Szasz, R Clinton Webb
AIM: Angiotensin II (AngII), a corpus cavernosum (CC) constrictor peptide, modulates Toll like receptor (TLR) expression, a key element of the innate immune system, contributing to impaired vascular function in pathological conditions. However, it is unknown whether TLR4 is involved in AngII-induced erectile dysfunction. In this study, we investigated whether TLR4 plays a role in cavernosal dysfunction caused by AngII upregulation. MATERIAL AND METHODS: Cavernosal smooth muscle cells (CSMC) from C57/BL6 mice were treated with AngII (0...
December 15, 2017: Life Sciences
Anna Sandqvist, Jörn Schneede, David Kylhammar, Dan Henrohn, Jakob Lundgren, Mikael Hedeland, Ulf Bondesson, Göran Rådegran, Gerhard Wikström
Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from L-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects...
October 3, 2017: Heart and Vessels
Joaquin U Gonzales, Andrea Raymond, John Ashley, Youngdeok Kim
What is the central question of this study? Does short-term supplementation with l-citrulline in order to increase l-arginine improve exercise blood flow and peripheral dilatation responses to exercise in older adults? What is the main finding and its importance? l-Citrulline increased femoral blood flow by 11% and vascular conductance by 14% during lower-limb exercise in older men, whereas no changes were observed in older women. This modest improvement in bulk muscle blood flow in older men has implications for altering muscle metabolism that may result in enhanced exercise tolerance in older adults...
December 1, 2017: Experimental Physiology
Miroslava Majzúnová, Zuzana Pakanová, Peter Kvasnička, Peter Bališ, Soňa Čačányiová, Ima Dovinová
BACKGROUND: The brain stem contains important nuclei that control cardiovascular function via the sympathetic nervous system (SNS), which is strongly influenced by nitric oxide. Its biological activity is also largely determined by oxygen free radicals. Despite many experimental studies, the role of AT1R-NAD(P)H oxidase-superoxide pathway in NO-deficiency is not yet sufficiently clarified. We determined changes in free radical signaling and antioxidant and detoxification response in the brain stem of young and adult Wistar rats during chronic administration of exogenous NO inhibitors...
September 11, 2017: Journal of Biomedical Science
Amir M Khan, Joshua Choi, Richard A Freiberg, Charles J Glueck, Naila Goldenberg, Ping Wang
Mutations in the T786C endothelial nitric oxide synthase gene (eNOS) are associated with osteonecrosis and Prinzmetal's angina. Nitric oxide is necessary for bone health and ameliorates Prinzmetal's angina. This study compared mutations of T786C eNOS in 146 patients with primary osteonecrosis, 114 patients with Prinzmetal's angina, and 83 normal control subjects. Patients with osteonecrosis had more mutant eNOS alleles than control subjects (42% vs 22%, respectively; P<.0001) but had the same number of mutant alleles as patients with Prinzmetal's angina (42% vs 41%, respectively; P=...
September 1, 2017: Orthopedics
Michaela Conrad, Harish Nag Kankipati, Marlies Kimpe, Griet Van Zeebroeck, Zhiqiang Zhang, Johan M Thevelein
Two nutrient-controlled signalling pathways, the PKA and TOR pathway, play a major role in nutrient regulation of growth as well as growth-correlated properties in yeast. The relationship between the two pathways is not well understood. We have used Gap1 and Pho84 transceptor-mediated activation of trehalase and phosphorylation of fragmented Sch9 as a read-out for rapid nutrient activation of PKA or TORC1, respectively. We have identified conditions in which L-citrulline-induced activation of Sch9 phosphorylation is compromised, but not activation of trehalase: addition of the TORC1 inhibitor, rapamycin and low levels of L-citrulline...
August 1, 2017: FEMS Yeast Research
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