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Experimental therapeutics

Aline Iannone, Antonio Pedro de Mello Cruz, Joaquim Pereira Brasil-Neto, Raphael Boechat-Barros
Transcranial magnetic stimulation (TMS) has recently been investigated as a possible adjuvant treatment for many neuropsychiatric disorders, and has already been approved for the treatment of drug-resistant depression in the United States and in Brazil, among other countries. Although its use in other neuropsychiatric disorders is still largely experimental, many physicians have been using it as an off-label add-on therapy for various disorders. More recently, another technique, transcranial direct current stimulation (tDCS), has also become available as a much cheaper and portable alternative to TMS, although its mechanisms of action are different from those of TMS...
October 2016: Arquivos de Neuro-psiquiatria
Davide Croci, Edin Nevzati, Hiroki Danura, Salome Schöpf, Javier Fandino, Serge Marbacher, Carl Muroi
BACKGROUND: In subarachnoid hemorrhage (SAH), occurrence of cerebral vasospasm (CVS) mediated by endothelin (ET)-1 might be a result of a compartmental inflammatory response with interleukin (IL)-6 release. We aim to investigate the relationship between ET-1 and IL-6 in association of CVS. METHODS: A total of 24 New Zealand white rabbits where randomly allocated into 3 groups: SAH (n=10), IL-6 (n=10), and sham (n=4). SAH was induced by a closed cranium extracranial-intracranial shunt model...
October 19, 2016: Journal of Neurosurgical Sciences
Ruijie D Teo, Jae Youn Hwang, John Termini, Zeev Gross, Harry B Gray
Corroles are exceptionally promising platforms for the development of agents for simultaneous cancer-targeting imaging and therapy. Depending on the element chelated by the corrole, these theranostic agents may be tuned primarily for diagnostic or therapeutic function. Versatile synthetic methodologies allow for the preparation of amphipolar derivatives, which form stable noncovalent conjugates with targeting biomolecules. These conjugates can be engineered for imaging and targeting as well as therapeutic function within one theranostic assembly...
October 19, 2016: Chemical Reviews
Mariana Angoa-Pérez, John H Anneken, Donald M Kuhn
The present review briefly explores the neurotoxic properties of methcathinone, mephedrone, methylone, and methylenedioxypyrovalerone (MDPV), four synthetic cathinones most commonly found in "bath salts." Cathinones are β-keto analogs of the commonly abused amphetamines and display pharmacological effects resembling cocaine and amphetamines, but despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce unique effects. Among the similarities of synthetic cathinones with their non-keto analogs are their targeting of monoamine systems, the release of neurotransmitters, and their stimulant properties...
October 18, 2016: Current Topics in Behavioral Neurosciences
Malleswarapu Mahesh, Munugala Bharathi, Mooli Raja Gopal Reddy, Manchiryala Sravan Kumar, Uday Kumar Putcha, Ayyalasomayajula Vajreswari, Shanmugam M Jeyakumar
Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases associated with an altered lifestyle, besides genetic factors. The control and management of NAFLD mostly depend on lifestyle modifications, due to the lack of a specific therapeutic approach. In this context, we assessed the effect of carrot juice on the development of high fructose-induced hepatic steatosis. For this purpose, male weanling Wistar rats were divided into 4 groups, fed either a control (Con) or high fructose (HFr) diet of AIN93G composition, with or without carrot juice (CJ) for 8 weeks...
September 2016: Preventive Nutrition and Food Science
Angel R de Lera, A Ganesan
The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders...
2016: Clinical Epigenetics
Roman N Rodionov, Elisa Oppici, Jens Martens-Lobenhoffer, Natalia Jarzebska, Silke Brilloff, Dmitrii Burdin, Anton Demyanov, Anne Kolouschek, James Leiper, Renke Maas, Barbara Cellini, Norbert Weiss, Stefanie M Bode-Böger
Low plasma concentrations of L-homoarginine are associated with an increased risk of cardiovascular events, while homoarginine supplementation is protective in animal models of metabolic syndrome and stroke. Catabolism of homoarginine is still poorly understood. Based on the recent findings from a Genome Wide Association Study we hypothesized that homoarginine can be metabolized by alanine:glyoxylate aminotransferase 2 (AGXT2). We purified human AGXT2 from tissues of AGXT2 transgenic mice and demonstrated its ability to metabolize homoarginine to 6-guanidino-2-oxocaproic acid (GOCA)...
October 18, 2016: Scientific Reports
Erika Yeh, Lauren A Weiss
Autism spectrum disorder (ASD) has been long known to have substantial genetic etiology. Much research has attempted to identify specific genes contributing to ASD risk with the goal of tying gene function to a molecular pathological explanation for ASD. A unifying molecular pathology would potentially increase understanding of what is going wrong during development, and could lead to diagnostic biomarkers or targeted preventative or therapeutic directions. We review past and current genetic mapping approaches and discuss major results, leading to the hypothesis that global dysregulation of gene or protein expression may be implicated in ASD rather than disturbance of brain-specific functions...
October 14, 2016: Molecular and Cellular Probes
Mansi R Khanna, Jane Kovalevich, Virginia M-Y Lee, John Q Trojanowski, Kurt R Brunden
A group of neurodegenerative diseases referred to as tauopathies are characterized by the presence of brain cells harboring inclusions of pathological species of the tau protein. These disorders include Alzheimer's disease and frontotemporal lobar degeneration due to tau pathology, including progressive supranuclear palsy, corticobasal degeneration, and Pick's disease. Tau is normally a microtubule (MT)-associated protein that appears to play an important role in ensuring proper axonal transport, but in tauopathies tau becomes hyperphosphorylated and disengages from MTs, with consequent misfolding and deposition into inclusions that mainly affect neurons but also glia...
October 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Hyun Sook Hong, Dae Yeon Hwang, Ju Hyeong Park, Suna Kim, Eun Jung Seo, Youngsook Son
Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease (IBD). Thus, regulation of inflammation is regarded as the ultimate therapy for intestinal disease. Substance-P (SP) is known to mediate proliferation, migration, and cellular senescence in a variety of cells. SP was found to mobilize stem cells from bone marrow to the site of injury and to suppress inflammatory responses by inducing regulatory T cells (Tregs) and M2 macrophages...
October 14, 2016: Cytokine
Corinne G Wong, Mehran Taban, Kathryn Osann, Fred N Ross-Cisneros, T C Bruice, Grit Zahn, Timothy You
PURPOSE: Intravitreal vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) produced florid retinal neovascularization and hemorrhage in the rabbit. This study seeks to determine whether sustained subchoroidal release of both VEGF and bFGF can induce robust choroidal neovascularization (CNV) in the rabbit. METHODS: Subchoroidal implantation through the sclera of polymeric pellets containing both 15 μg VEGF and 15 μg bFGF was performed on adult pigmented male Dutch belted rabbits (N = 6) and NZW albinos (N = 8)...
October 17, 2016: Current Eye Research
Wei Zhang, Jianzhou Liu, Jianxin Qiu, Xiaoliang Fu, Qisheng Tang, Fan Yang, Zhiguang Zhao, He Wang
MicroRNAs (miRNAs) have emerged as important regulators in cancer that are implicated in regulation of various cellular processes. miR-382 has been proposed as a tumor suppressor by several recent studies. However, the function of miR-382 in prostate cancer remains unknown. In this study, we aimed to investigate the potential function of miR-382 in prostate cancer. We found that miR-382 was significantly decreased in prostate cancer specimens and cancer cell lines. The overexpression of miR-382 in prostate cancer cells markedly inhibited cell proliferation, migration, and invasion...
October 3, 2016: Oncology Reports
Xiangrong Cui, Xuan Jing, Xueqing Wu, Meiqin Yan
Male infertility is a complex, multifactorial and polygenic disease that contributes to ~50% cases of infertility. Previous studies have demonstrated that excess weight and obesity factors serve an important role in the development of male infertility. An increasing number of studies have reported that resveratrol may regulate the response of cells to specific stimuli that induce cell injury, as well as decrease germ cell apoptosis in mice or rats. In the present study, the semen quality and serum sex hormone levels were evaluated in 324 men, which included 73 underweight, 82 normal weight, 95 overweight and 74 obese men...
October 12, 2016: Molecular Medicine Reports
Amanda Fortes Francisco, Shiromani Jayawardhana, Michael D Lewis, Karen L White, David M Shackleford, Gong Chen, Jessica Saunders, Maria Osuna-Cabello, Kevin D Read, Susan A Charman, Eric Chatelain, John M Kelly
The insect-transmitted protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, and infects 5-8 million people in Latin America. Chagas disease is characterised by an acute phase, which is partially resolved by the immune system, but then develops as a chronic life-long infection. There is a consensus that the front-line drugs benznidazole and nifurtimox are more effective against the acute stage in both clinical and experimental settings. However, confirmative studies have been restricted by difficulties in demonstrating sterile parasitological cure...
October 17, 2016: Scientific Reports
Matheus D Baldissera, Carine F Souza, Thirssa H Grando, Geisa S Dolci, Luciana F Cossetin, Karen L S Moreira, Marcelo L DA Veiga, Maria Izabel U M DA Rocha, Aline A Boligon, Marli M A DE Campos, Lenita M Stefani, Aleksandro S DA Silva, Silvia G Monteiro
The aim of this study was to evaluate the effect of nerolidol free (N-F) and nerolidol-loaded in nanospheres (N-NS) on the hepatic antioxidant/oxidant status of mice experimentally infected by Trypanosoma evansi. In the liver it was measured: reactive oxygen species (ROS), thiobarbituric reactive acid substances (TBARS) and non-protein thiols (NPSH), catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST) and performed histopathological examination. In addition, seric levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured...
October 17, 2016: Parasitology
Narges Amel Zabihi, Matteo Pirro, Thomas P Johnston, Amirhossein Sahebkar
Nonalcoholic fatty liver disease (NAFLD) is the most common type of liver disease. NAFLD is considered a multifactorial disease and a clinically relevant hepatic manifestation of metabolic syndrome. NAFLD is often accompanied by a constellation of metabolic and non-metabolic alterations, like dyslipidemia, insulin resistance in the liver and peripheral tissues, inflammation and oxidative stress; therefore, treatment of NAFLD should be directed at correcting all of these disturbances. The natural polyphenol curcumin has been the subject of increasing research for the treatment of NAFLD due to its lipid-modifying, antioxidant, anti-inflammatory, insulin-sensitizing, anti-steatotic, and anti-fibrotic properties...
October 10, 2016: Current Pharmaceutical Design
Maria Vadalà, Julio Cesar Morales-Medina, Annamaria Vallelunga, Beniamino Palmieri, Carmen Laurino, Tommaso Iannitti
Cancer is one of the most common causes of death worldwide. Available treatments are associated with numerous side effects and only a low percentage of patients achieve complete remission. Therefore, there is a strong need for new therapeutic strategies. In this regard, pulsed electromagnetic field (PEMF) therapy presents several potential advantages including non-invasiveness, safety, lack of toxicity for non-cancerous cells, and the possibility of being combined with other available therapies. Indeed, PEMF stimulation has already been used in the context of various cancer types including skin, breast, prostate, hepatocellular, lung, ovarian, pancreatic, bladder, thyroid, and colon cancer in vitro and in vivo...
October 17, 2016: Cancer Medicine
Egidio Iorio, Maria José Caramujo, Serena Cecchetti, Francesca Spadaro, Giulia Carpinelli, Rossella Canese, Franca Podo
Triple-negative breast cancer (TNBC), defined as lack of estrogen and progesterone receptors in the absence of protein overexpression/gene amplification of human epidermal growth factor receptor 2, is still a clinical challenge despite progress in breast cancer care. (1)H magnetic resonance spectroscopy allows identification and non-invasive monitoring of TNBC metabolic aberrations and elucidation of some key mechanisms underlying tumor progression. Thus, it has the potential to improve in vivo diagnosis and follow-up and also to identify new targets for treatment...
2016: Frontiers in Oncology
Karyna M O B de Figueiredo Ribeiro, Lidiane Maria de Brito Macedo Ferreira, Raysa Vanessa de Medeiros Freitas, Camila Nicácio da Silva, Nandini Deshpande, Ricardo Oliveira Guerra
Introduction Benign Paroxysmal Positional Vertigo is the most common cause of dizziness in elderly people. Recent studies have shown that the elderly present higher Benign Paroxysmal Positional Vertigo recurrence and that vertiginous symptomatology remission varies according to comorbidities and the therapeutic techniques applied. Objective To assess the short-term effectiveness of Vestibular Rehabilitation in addition to Canalith Repositioning Maneuver on positive to negative Dix-Hallpike test, on recurrence and number of maneuvers to achieve a negative test in elderly patients with chronic Benign Paroxysmal Positional Vertigo...
October 2016: International Archives of Otorhinolaryngology
Łukasz Mokros, Michał Seweryn Karbownik, Katarzyna Nowakowska-Domagała, Janusz Szemraj, Łukasz Wieteska, Karol Woźniak, Andrzej Witusik, Adam Antczak, Tadeusz Pietras
Background: There is barely any evidence of antipsychotic drugs affecting the molecular clockwork in human, yet it is suggested that clock genes are associated with dopaminergic transmission, i.e. the main target of this therapeutics. We decided to verify if haloperidol and olanzapine affect expression of CLOCK, BMAL1, PER1 and CRY1 in a human central nervous system cell line model. Methods: U-87MG human glioblastoma cell line was used as an experimental model. The cells were incubated with or without haloperidol and olanzapine in the concentration of 5 and 20 μM for 24 h...
November 1, 2016: Biological Rhythm Research
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