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Anusha Jayaraman, Praveen Kumar, Silvia Marin, Pedro de Atauri, Francesca Mateo, Timothy M Thomson, Josep J Centelles, Stewart F Graham, Marta Cascante
Tumour angiogenesis is an important hallmark of cancer and the study of its metabolic adaptations, downstream to any cellular change, can reveal attractive targets for inhibiting cancer growth. In the tumour microenvironment, endothelial cells (ECs) interact with heterogeneous tumour cell types that drive angiogenesis and metastasis. In this study we aim to characterize the metabolic alterations in ECs influenced by the presence of tumour cells with extreme metastatic abilities. Human umbilical vein endothelial cells (HUVECs) were subjected to different microenvironmental conditions, such as the presence of highly metastatic PC-3M and highly invasive PC-3S prostate cancer cell lines, in addition to the angiogenic activator vascular endothelial growth factor (VEGF), under normoxia...
2018: PloS One
Maha Gamal, Jackline Moawad, Laila Rashid, Mary Attia Morcos, Nivin Sharawy
BACKGROUND AND AIM: Tetrahydrobiopterin (BH4) is an essential co-factor that regulates nitric oxide (NO) and reactive oxygen species (ROS) production by nitric oxidesynthases (NOS). In this study, we evaluated the effects of sepsis on BH 4 level and redox status in the brain by using the rat model of sepsis- induced by cecal ligation and puncture (CLP) and examined whether BH4 and/or acetyl-L-carnitine(ALC) could prevent the neuronal apoptosis and neurological changes induced by sepsis...
February 8, 2018: Brain Research
Tugba Ugurlu, Candan Ozogul, Gulistan Sanem Saribas, Seren Gulsen Gurgen, Seda Nur Akyol, Bahar Kartal
The aim of this study was to investigate the effect of antioxidants on angiogenesis in uterine transplantation. We used 24 female rats equally divided into four groups: Group 1 had the uterus stored in HTK (Histidine-Tryptophan-Ketoglutarate) solution at 4 °C cold storage for 4 h. Group 2 had the uterine tissue stored in HTK solution combined with acetyl L-carnitine (10-8  M) for 4 h at +4 °C. The same procedures with Group 1 and 2 were repeated for 24 h for Groups 3 and 4, respectively. Histological investigation and immunohistochemical analysis were performed...
January 31, 2018: Journal of Obstetrics and Gynaecology: the Journal of the Institute of Obstetrics and Gynaecology
Ashok Agarwal, Pallav Sengupta, Damayanthi Durairajanayagam
BACKGROUND: L-carnitine (LC), and its acetylated form, acetyl L-carnitine (ALC), have immense functional capabilities to regulate the oxidative and metabolic status of the female reproductive system. The vulnerability of this system to free radicals demand for advanced strategies to combat them. For this purpose, the 'quasi vitamins' LC and ALC can be used either individually, or in combination with each other or with other antioxidants. MAIN BODY: This review (a) summarizes the effects of carnitines on female fertility along with the findings from various in vivo and in vitro studies involving human, animal and assisted reproductive technology, and (b) proposes their mechanism of actions in improving female fertility through their integrated actions on reducing cellular stress, maintaining hormonal balance and enhancing energy production...
January 26, 2018: Reproductive Biology and Endocrinology: RB&E
Dawn L Hershman, Joseph M Unger, Katherine D Crew, Cathee Till, Heather Greenlee, Lori M Minasian, Carol M Moinpour, Danika L Lew, Louis Fehrenbacher, James L Wade, Siu-Fun Wong, Michael J Fisch, N Lynn Henry, Kathy S Albain
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling side effect of taxanes. Acetyl-L-carnitine (ALC) was unexpectedly found to increase CIPN in a randomized trial. We investigated the long-term patterns of CIPN among patients in this trial. Methods: S0715 was a randomized, double-blind, multicenter trial comparing ALC (1000 mg three times a day) with placebo for 24 weeks in women undergoing adjuvant taxane-based chemotherapy for breast cancer...
January 18, 2018: Journal of the National Cancer Institute
Victoria A Serhiyenko, Alexandr A Serhiyenko
Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus (DM) that is strongly associated with approximately five-fold increased risk of cardiovascular mortality. CAN manifests in a spectrum of things, ranging from resting tachycardia and fixed heart rate (HR) to development of "silent" myocardial infarction. Clinical correlates or risk markers for CAN are age, DM duration, glycemic control, hypertension, and dyslipidemia (DLP), development of other microvascular complications...
January 15, 2018: World Journal of Diabetes
G M Busetto, A Agarwal, A Virmani, G Antonini, G Ragonesi, F Del Giudice, S Micic, V Gentile, E De Berardinis
Since sperm require high energy levels to perform their specialised function, it is vital that essential nutrients are available for spermatozoa when they develop, capacitate and acquire motility. However, they are vulnerable to a lack of energy and excess amounts of reactive oxygen species, which can impair sperm function, lead to immotility, acrosomal reaction impairment, DNA fragmentation and cell death. This monocentric, randomised, double-blind, placebo-controlled trial investigated the effect of 6 months of supplementation with l-carnitine, acetyl-l-carnitine and other micronutrients on sperm quality in 104 subjects with oligo- and/or astheno- and/or teratozoospermia with or without varicocele...
January 7, 2018: Andrologia
Vida Bodaghi-Namileh, Mohammad Reza Sepand, Ameneh Omidi, Mehdi Aghsami, Seyed Afshin Seyednejad, Sara Kasirzadeh, Omid Sabzevari
Industrial and agricultural developments in recent years have resulted in the excessive discharge of arsenic into the environment, making arsenic toxicity a major worldwide concern. Oxidative stress is considered the primary mechanism for arsenic toxicity. The main objective of this study was to evaluate acetyl-l-carnitine's (ALC) protective ability against the arsenic-induced hepatotoxicity. For this purpose, male Wistar rats were distributed randomly into 5 groups of 8 rats each: control, arsenic (5 mg/kg) and arsenic plus ALC (5 mg/kg; 100, 200, 300 mg/kg)...
December 12, 2017: Environmental Toxicology and Pharmacology
Bonnie L Robinson, Melanie Dumas, Syed F Ali, Merle G Paule, Qiang Gu, Jyotshna Kanungo
Ketamine, a phencyclidine derivative, is an antagonist of the Ca2+ -permeable N-methyl-d-aspartate (NMDA)-type glutamate receptors. It is a pediatric anesthetic and has been implicated in developmental neurotoxicity. Ketamine has also been shown to deplete ATP in mammalian cells. Our previous studies showed that acetyl l-carnitine (ALCAR) prevented ketamine-induced cardiotoxicity and neurotoxicity in zebrafish embryos. Based on our finding that ALCAR's protective effect was blunted by oligomycin A, an inhibitor of ATP synthase, we further investigated the effects of ketamine and ALCAR on ATP levels, mitochondria and ATP synthase in zebrafish embryos...
December 7, 2017: Neurotoxicology and Teratology
Hedieh Keshavarz-Bahaghighat, Mohammad Reza Sepand, Mohammad Hossein Ghahremani, Mehdi Aghsami, Nima Sanadgol, Ameneh Omidi, Vida Bodaghi-Namileh, Omid Sabzevari
Augmentation of mitochondrial oxidative stress through activating a series of deadly events has implicated as the main culprit of arsenic toxicity and therapeutic approaches based on improving mitochondrial function hold a great promise for attenuating the arsenic-induced toxicity. Acetyl-L-carnitine (ALC) through balancing the coenzyme A (CoA)/acyl-CoA ratio plays an important role in mitochondrial metabolism and thereby can help protect hippocampal neurons from oxidative damage. In the present study, we aimed to explore the effect of arsenic interactions on the mitochondrial function in the hippocampus of rats...
November 30, 2017: Biological Trace Element Research
Chuanhua Cao, Haiying Yu, Feng Wu, Huixiong Qi, Jingbo He
The anti-cancer activities of antibiotic anisomycin have been demonstrated in kidney, colon and ovarian cancers whereas its underlying mechanisms are not well elucidated. In this work, we investigated whether anisomycin is effective in sensitizes osteosarcoma cell response to chemotherapy. We show that anisomycin inhibits proliferation via inducing osteosarcoma cell arrest at G2/M phase, accompanied by the increased levels of mitotic marker cyclin B and the decreased levels of Rb and E2F-1. Anisomycin also induces apoptosis in a caspase-dependent manner in osteosarcoma cells...
December 2017: Journal of Bioenergetics and Biomembranes
T Truong, D K Gardner
STUDY QUESTION: What is the effect of a combination of three antioxidants (Acetyl-L-Carnitine, N-Acetyl-L-Cysteine and α-Lipoic Acid), present in IVF medium during mouse oocyte and sperm collection, on fertilization and subsequent IVF embryo development? SUMMARY ANSWER: A combination of antioxidants resulted in faster developmental times from the 2-cell stage through to expanded blastocyst stage, accompanied by a significant increase in blastocyst cell number and a reduction of intracellular hydrogen peroxide (H2O2) levels...
December 1, 2017: Human Reproduction
Nicola Veronese, Brendon Stubbs, Marco Solmi, Olesya Ajnakina, Andre F Carvalho, Stefania Maggi
OBJECTIVE: Deficiency of acetyl-L-carnitine (ALC) appears to play a role in the risk of developing depression, indicating dysregulation of fatty acids transport across the inner membrane of mitochondria. However, the data regarding ALC supplementation in humans are limited.. We thus conducted a systematic review and meta-analysis investigating the effect of ALC on depressive symptoms across randomized controlled trials (RCTs). METHODS: A literature search in major databases, without language restriction, was undertaken from inception until 30 December 2016...
October 25, 2017: Psychosomatic Medicine
Mariagrazia Grilli
Adult hippocampal neurogenesis (ahNG) occurs in the human brain. Adult generated neurons have been proposed to functionally contribute to relevant hippocampal functions such as learning and memory, mood regulation, and stress response. Learning, environmental enrichment, and physical exercise exert positive effects on ahNG. In parallel, these proneurogenic stimuli have been shown to ameliorate cognitive performance and/or depressive-like behavior in animal models. Conversely, aging, social isolation, and chronic stress exert negative effects on ahNG...
2017: Journal of Pain Research
Carla Nasca, Benedetta Bigio, Danielle Zelli, Paolo de Angelis, Timothy Lau, Masahiro Okamoto, Hideyo Soya, Jason Ni, Lars Brichta, Paul Greengard, Rachael L Neve, Francis S Lee, Bruce S McEwen
We demonstrate that stress differentially regulates glutamate homeostasis in the dorsal and ventral hippocampus and identify a role for the astroglial xCT in ventral dentate gyrus (vDG) in stress and antidepressant responses. We provide an RNA-seq roadmap for the stress-sensitive vDG. The transcription factor REST binds to xCT promoter in co-occupancy with the epigenetic marker H3K27ac to regulate expression of xCT, which is also reduced in a genetic mouse model of inherent susceptibility to depressive-like behavior...
October 11, 2017: Neuron
Oliver T Phillipson
The motor deficits which characterise the sporadic form of Parkinson's disease arise from age-related loss of a subset of dopamine neurons in the substantia nigra. Although motor symptoms respond to dopamine replacement therapies, the underlying disease process remains. This review details some features of the progressive molecular pathology and proposes deployment of a combination of nutrients: R-lipoic acid, acetyl-l-carnitine, ubiquinol, melatonin (or receptor agonists) and vitamin D3, with the collective potential to slow progression of these features...
November 2017: Ageing Research Reviews
E V Ponomareva
An analysis of literature data on the acetyl-L-carnitine treatment in gerontological practice is performed. This review describes the range of biochemical activity and mechanism of action of the drug. The profile and specificity of acetyl-L-carnitine action and the possibility of combining nicergoline with other drugs is discussed. The results of preclinical and clinical studies on the application of acetyl-L-carnitine in the world medical practice are analyzed. The analysis of the studies demonstrates the high efficacy and a broad spectrum of acetyl-L-carnitine treatment...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Ting-Ting Yang, Li Wang, Xiao-Yang Deng, Gang Yu
BACKGROUND: Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease. Fatigue is the most common symptom of MS patients, affecting >80% subjects. Medical treatment is an important method for managing fatigue. Currently, although many drugs have been tested in treatment of MS fatigue, the efficacy of these drugs remain largely unclear. METHODS: We researched available literatures in PubMed, Embase, Medline, Google Scholar, Cochrane Library (August 31, 2016)...
September 15, 2017: Journal of the Neurological Sciences
V A Bozhedomov, N A Lipatova, G E Bozhedomova, I M Rokhlikov, E V Shcherbakova, R A Komarina
The most common cause of male infertility is idiopathic oligo-, and or astheno-, and /or teratozoospermia. In such cases, anti-estrogens, antioxidants (vitamins and trace elements) or carnitines are used, but the evidence on their effectiveness is inconsistent; there are currently no published studies exploring their concurrent use. AIM: To investigate the efficacy and safety of the L- and acetyl-L-carnitine complex, vitamins A, E, C, selenium, zinc and other antioxidants ("SpermActin" + "More than vitamins") in combination with clomiphene citrate (CC) in managing male idiopathic infertility in the form of oligo, and/or astheno-, and/or teratozoospermia...
July 2017: Urologii︠a︡
S I Gamidov, R I Ovchinnikov, A Yu Popova, A Yu Avakyan, G T Sukhikh
INTRODUCTION: Infertility affects an estimated 15% of couples globally. Male factor infertility accounts for about a half of infertility cases. About 40% of infertile men have varicocele. The aim of this study was to investigate the efficacy and safety of a complex of acetyl-L-carnitine, L-carnitine fumarate and alpha-lipoic acid (SpermActin-forte) (SA) for adjuvant antioxidant therapy after microsurgical varicocelectomy (MVE) in men with varicocele and assess its impact on the level of DNA fragmentation in sperm cells...
June 2017: Urologii︠a︡
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