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controlled drug screening tests

Eugen Widmeier, Weizhen Tan, Merlin Airik, Friedhelm Hildebrandt
INTRODUCTION: Steroid-resistant nephrotic syndrome (SRNS) inevitably progresses to end-stage kidney disease, requiring dialysis or transplantation for survival. However, treatment modalities and drug discovery remain limited. Mutations in over 30 genes have been discovered as monogenic causes of SRNS. Most of these genes are predominantly expressed in the glomerular epithelial cell, the podocyte, placing it at the center of the pathogenesis of SRNS. Podocyte migration rate (PMR) represents a relevant intermediate phenotype of disease in monogenic causes of SRNS...
October 19, 2016: American Journal of Physiology. Renal Physiology
Milton Luiz Gorzoni, Sueli Luciano Pires, Lilian de Fátima Costa Faria, Márcia Regina Valadares Aguado, Miriam Carmen Santana
CONTEXT AND OBJECTIVE: A search in the SciELO and PubMed databases showed few studies on human immunodeficiency virus (HIV) positive individuals in long-term care institutions (LTCIs), thus prompting the present study. The aim of this study was to ascertain whether there were any HIV-positive individuals in LTCIs for the elderly. DESIGN AND SETTING: Cross-sectional study in which the Hospital Infection Control Committee (HICC) of a 405-bed LTCI was consulted. METHODS: The medical records of 405 individuals interned in the LTCI who had been tested for HIV infection were requested for analysis of the following variables: [1] age and gender; [2] length of stay at LTCI (months); [3] causes and diagnoses on admission to LTCI according to International Classification of Diseases, 10th edition; [4] date of HIV diagnosis; [5] seropositivity for syphilis and hepatitis B and C viruses; [6] medications used at last prescription in medical file; and [7] mean CD4 lymphocyte count based on: total lymphocyte count/6 and total lymphocyte count x 0...
October 13, 2016: São Paulo Medical Journal, Revista Paulista de Medicina
Sanjay Kumar Dey, Pankaj Prabhakar, Manisha Saini, Toyanji Joseph, B K Thelma, Subir K Maulik, Suman Kundu
OBJECTIVE: To identify novel inhibitors of dopamine beta hydroxylase (DBH) and evaluate their antihypertensive properties in L-NAME induced hypertensive rat model. DESIGN AND METHOD: An experimentally validated computational model for hDBH, built in our lab, was used for structure-based, rational drug-design. The three-dimensional model was used for virtual-screening against small molecule databases from NCI, USA and elsewhere. Identified top hits were then tested in vitro against DBH with known inhibitors nepicastat and disulfiram as controls...
September 2016: Journal of Hypertension
Gian Paolo Rossi
Primary aldosteronism (PA) involves more than 11% of patients referred to specialized hypertension centers and, therefore, is much more common than commonly held. Moreover, it causes a damage to the heart, blood vessels and kidneys, which translates into a high rate of cardiovascular events, in excess to the degree of blood pressure raise. Along with the notion that a timely diagnosis entails a fundamental step for the choice of an appropriate therapy, which can correct the arterial hypertension and the hypokalemia, this justifies efforts to search for PA in the majority of the patients with hypertension...
September 2016: Journal of Hypertension
Susanne Hafner, Sabine Haubensak, Tanusree Paul, Oliver Zolk
Background | Differences (polymorphisms) in genes encoding drug targets, drug transport proteins, or drug metabolizing enzymes may be responsible, among other factors, for the observed variation in patients' responses to medications. The field of pharmacogenetics aims to identify patients at higher genetically-determined risk of adverse effects or poor response to medication. This information would allow for modification of dosage or substitution with alternative therapy. However, there is a lack of awareness of pharmacogenetic clinical practise guidelines...
October 2016: Deutsche Medizinische Wochenschrift
Caroline Anne Mitchell, Alice Pitt, Joe Hulin, Rod Lawson, Fleur Ashby, Ivan Appelqvist, Brigitte Delaney
OBJECTIVES: Increased rates of illicit drug inhalation are thought to expose opiate misusers (OMUs) to an enhanced risk of respiratory health problems. This pilot study aimed to determine the feasibility of undertaking respiratory screening of OMUs in a community clinic. SETTING: Single-centre UK community substance misuse clinic. PARTICIPANTS: All clinic attendees receiving treatment for opiate misuse were eligible to participate. 36 participants (mean age=37) were recruited over a 5-week period...
October 14, 2016: BMJ Open
Sang-Hyun Kim, Sang-Ho Jo, Sang-Cheol Lee, Sung-Yoon Lee, Myung-Ho Yoon, Hyang-Lim Lee, Nae-Hee Lee, Jong-Won Ha, Nam-Ho Lee, Dong-Woon Kim, Gyu-Rok Han, Min-Su Hyon, Deok-Gyu Cho, Chang-Gyu Park, Young-Dae Kim, Gyu-Hyung Ryu, Cheol-Ho Kim, Kee-Sik Kim, Myung-Ho Chung, Sung-Chul Chae, Ki-Bae Seung, Byung-Hee Oh
PURPOSE: A fixed-dose combination of a stain and an antihypertensive drug may be useful for the treatment of patients with hypertension and hyperlipidemia. It may also improve patient drug compliance to help control risk factors of cardiovascular disease. This study was designed to evaluate the blood pressure-lowering and cholesterol-lowering effect of a fixed-dose combination of irbesartan-atorvastatin compared with monotherapy by either agent over an 8-week treatment period. METHODS: Patients with comorbid hypertension and hypercholesterolemia were screened for this randomized, double-blind, Phase III study...
October 11, 2016: Clinical Therapeutics
Ana Paula Terrasso, Ana Carina Silva, Augusto Filipe, Pedro Pedroso, Ana Lúcia Ferreira, Paula Marques Alves, Catarina Brito
INTRODUCTION: Central nervous system drug development has registered high attrition rates, mainly due to the lack of efficacy of drug candidates, highlighting the low reliability of the models used in early-stage drug development and the need for new in vitro human cell-based models and assays to accurately identify and validate drug candidates. 3D human cell models can include different tissue cell types and represent the spatiotemporal context of the original tissue (co-cultures), allowing the establishment of biologically-relevant cell-cell and cell-extracellular matrix interactions...
October 11, 2016: Journal of Pharmacological and Toxicological Methods
Mi-Young Son, Young-Dae Kim, Binna Seol, Mi-Ok Lee, Hee-Jun Na, Bin Yoo, Jae-Suk Chang, Yee Sook Cho
Behçet's disease (BD) is a chronic inflammatory and multisystemic autoimmune disease of unknown etiology. Due to the lack of a specific test for BD, its diagnosis is very difficult, and therapeutic options are limited. Induced pluripotent stem cell (iPSC) technology, which provides inaccessible disease-relevant cell types, opens a new era for disease treatment. Here, we generated BD iPSCs from patient somatic cells and differentiated them into hematopoietic precursor cells (BD iPSC-HPCs) as BD model cells...
October 12, 2016: Stem Cells and Development
Allison B Chambliss, Molly Resnick, Athena K Petrides, William A Clarke, Mark A Marzinke
BACKGROUND: Current methods for the detection of single nucleotide polymorphisms (SNPs) associated with aberrant drug-metabolizing enzyme function are hindered by long turnaround times and specialized techniques and instrumentation. In this study, we describe the development and validation of a high-resolution melting (HRM) curve assay for the rapid screening of variant genotypes for targeted genetic polymorphisms in the cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP3A5. METHODS: Sequence-specific primers were custom-designed to flank nine SNPs within the genetic regions of aforementioned drug metabolizing enzymes...
October 12, 2016: Clinical Chemistry and Laboratory Medicine: CCLM
Jamil Al-Asri, Gyöngyi Gyémánt, Erika Fazekas, Gábor Lehoczki, Matthias F Melzig, Gerhard Wolber, Jérémie Mortier
Better control of postprandial hyperglycemia can be achieved by delaying the absorption of glucose resulting from carbohydrate digestion. Because α-amylase initiates the hydrolysis of polysaccharides, the design of α-amylase inhibitors can lead to the development of new treatments for metabolic disorders such as type II diabetes and obesity. In this study, a rational computer-aided approach was developed to identify novel α-amylase inhibitors. Three-dimensional pharmacophores were developed based on the binding mode analysis of six different families of compounds that bind to this enzyme...
October 11, 2016: ChemMedChem
Dayse Sanchez Guimarães Paião, Everton Ferreira Lemos, Andrea da Silva Santos Carbone, Renata Viebrantz Enne Sgarbi, Alexandre Laranjeira Junior, Fellipe Matos da Silva, Letícia Marques Brandão, Luciana Squarizi Dos Santos, Vaneli Silva Martins, Simone Simionatto, Ana Rita Coimbra Motta-Castro, Maurício Antônio Pompílio, Juliana Urrego, Albert Icksang Ko, Jason Randolph Andrews, Julio Croda
BACKGROUND: Globally, prison inmates are a high-risk population for tuberculosis (TB), but the specific drivers of disease and impact of mass screening interventions are poorly understood. METHODS: We performed a prospective cohort study to characterize the incidence and risk factors for tuberculosis infection and disease in 12 Brazilian prisons, and to investigate the effect of mass screening on subsequent disease risk. After recruiting a stratified random sample of inmates, we administered a questionnaire to ascertain symptoms and potential risk factors for tuberculosis; performed tuberculin skin testing (TST); collected sera for HIV testing; and obtained two sputum samples for smear microscopy and culture, from participants reporting a cough of any duration...
October 3, 2016: BMC Infectious Diseases
A T Chen, S Zou
Arrhythmia caused by drug-induced cardiotoxicity is among the leading reasons for late-stage drug attrition and is therefore a core subject in safety testing of new compounds. Alternative methods such as surface and interface characterization approaches for assessing the drug-mediated cardiotoxicity should be promoted, in order to reduce, refine and replace the use of laboratory animals. Here, we investigate the possibility of using known human Ether-à-go-go-Related Gene (hERG) channel blockers to induce irregular beating patterns in the mouse and human induced pluripotent stem cell-derived (miPSC and hiPSC) cardiomyocyte (CM) model systems...
September 29, 2016: Analyst
James W Kazura
Onchocerciasis is one of the two filarial helminth "neglected tropical diseases" (the other being lymphatic filariasis) that has been targeted for geographically local elimination followed by global eradication. The last known areas of Onchocerca volvulus transmission in the Americas have recently been reported to be eliminated. In contrast, achieving metrics for interruption of O. volvulus transmission in Africa, thus removing the requirement for continued monitoring and mass drug administration (MDA) with ivermectin, has been more challenging...
October 3, 2016: American Journal of Tropical Medicine and Hygiene
Dhiana Efani Dahari, Raifana Mohamad Salleh, Fauze Mahmud, Lee Ping Chin, Noor Embi, Hasidah Mohd Sidek
Exploiting natural resources for bioactive compounds is an attractive drug discovery strategy in search for new anti-malarial drugs with novel modes of action. Initial screening efforts in our laboratory revealed two preparations of soil-derived actinomycetes (H11809 and FH025) with potent anti-malarial activities. Both crude extracts showed glycogen synthase kinase 3β (GSK3β)-inhibitory activities in a yeast-based kinase assay. We have previously shown that the GSK3 inhibitor, lithium chloride (LiCl), was able to suppress parasitaemia development in a rodent model of malarial infection...
August 2016: Tropical Life Sciences Research
Belinda K Mössner, Benjamin Staugaard, Janne Jensen, Søren Thue Lillevang, Peer B Christensen, Dorte Kinggaard Holm
AIM: To detect chronic hepatitis B (CHB), chronic hepatitis C (CHC) and human immunodeficiency virus (HIV) infections in dried blood spot (DBS) and compare these samples to venous blood sampling in real-life. METHODS: We included prospective patients with known viral infections from drug treatment centers, a prison and outpatient clinics and included blood donors as negative controls. Five drops of finger capillary blood were spotted on filter paper, and a venous blood sample was obtained...
September 7, 2016: World Journal of Gastroenterology: WJG
Diana Solari, Francesca Tesi, Matthias Unterhuber, Germano Gaggioli, Andrea Ungar, Marco Tomaino, Michele Brignole
OBJECTIVES: Most elderly patients affected by reflex vasodepressor syncope take one or more hypotensive drugs. The role of these drugs in causing syncope has not yet been established. We hypothesised that recurrence of syncope and presyncope can be reduced by discontinuing/reducing vasoactive therapy without increasing the risk of cardiovascular and neurological events. METHODS: This randomised, parallel, prospective, trial was conducted from January 2014 to March 2016 in four general hospitals...
September 23, 2016: Heart: Official Journal of the British Cardiac Society
L Rayner, A Simpson, F Matcham, S Shetty, O Lahoti, G Groom, M Hotopf
OBJECTIVE: This cross-sectional survey aimed to assess the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD), and drug and alcohol dependence in a limb reconstruction population and examine associations with demographic and functional variables. METHODS: As part of routine clinical care, data were collected from 566 patients attending a tertiary referral centre for limb reconstruction between April 2012 and February 2016. Depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol and drug dependence were measured using standardised self-report screening tools...
October 2016: Journal of Psychosomatic Research
Thomas Piper, Wilhelm Schänzer, Mario Thevis
Testosterone (T) misuse still represents a major problem in sports drug testing. Many strategies have been developed and applied to routine doping controls in recent years to enable both to identify suspicious samples in initial testing procedures and to confirm the exogenous origin of urinary T by means of carbon isotope ratio (CIR) determinations. Depending on the tested individual's genotype of UGT2B17, significantly different amounts of T are glucuronidated and excreted, which results in unaffected T/epitestosterone ratios after T misuse in those subjects with the deletion/deletion polymorphism (del/del)...
September 20, 2016: Drug Testing and Analysis
Malligurki Raghurama Rukmani, Shekhar P Seshadri, Kandavel Thennarasu, Trichur R Raju, Talakad N Sathyaprabha
BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder. Autonomic nervous system plays a vital role in attention, self-regulation, emotional stability and social affiliation, which are affected in ADHD. The prefrontal cortex, which is vital for attention, motor control, emotional regulation and higher order autonomic control, is hypofunctional in ADHD. In addition, catecholamine dysregulation is there. PURPOSE: We hypothesized that there is autonomic dysfunction: reduction in overall heart rate variability (HRV) and sympathovagal imbalance in children with ADHD...
July 2016: Annals of Neurosciences
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