1,443,673 results match your criteria Drugs in R&D[Journal]


Effects of systematic bisphosphonate use in patients under orthodontic treatment: a systematic review.

Eur J Orthod 2019 Apr 23. Epub 2019 Apr 23.

Department of Orthodontics, School of Health Sciences, Faculty of Dentistry, Aristotle University of Thessaloniki, Greece.

Background: Bisphosphonates are a class of drugs prescribed for several osseous related disorders owing to their ability to regulate bone turnover, which could in turn affect orthodontic treatment outcomes.

Objective: To examine the effect of bisphosphonate (BP) use on orthodontic patients through clinical and radiographic measurements.

Search Methods: Systematic and unrestricted search of 17 databases complemented with additional hand-searches were performed up to March 2019. Read More

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http://dx.doi.org/10.1093/ejo/cjz021DOI Listing

Antibacterial activity study of 1,2,4-triazole derivatives.

Eur J Med Chem 2019 Apr 16;173:274-281. Epub 2019 Apr 16.

Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, PR China. Electronic address:

Antibiotics are commonly used to fight against bacterial infections, but bacteria have already been resistant to almost all antibiotics due to abuse of antibiotics. 1,2,4-Triazole derived compounds possess chemotherapeutic effects including potential antibacterial activities against drug-sensitive as well as drug-resistant pathogens. Hybridization displays a high potential to develop novel drugs with the capacity to overcome drug resistance, reduce toxicity and improve pharmacokinetic profiles. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.043DOI Listing

Multitarget PPARγ agonists as innovative modulators of the metabolic syndrome.

Eur J Med Chem 2019 Apr 13;173:261-273. Epub 2019 Apr 13.

Department of Pharmacy, University of Chieti "G. d.Annunzio", Via Dei Vestini, 31, 66100, Chieti, Italy.

A multitarget pharmacologic approach could be advantageous for the therapy of metabolic multiple diseases, such as the metabolic syndrome, which is characterized by metabolic abnormalities associated with diabetes, obesity, hypertension, and increased cardiovascular risk. PPAR receptors play a critical role in metabolic disorders, affecting glucose and lipid metabolism. Drugs simultaneously targeting PPAR and other validated metabolic targets, represent a promising multitarget approach to combine antihyperglycemic, antihyperlipidemic, and antihypertensive effects. Read More

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http://dx.doi.org/10.1016/j.ejmech.2019.04.030DOI Listing

Development and validation of a multiplexed drug level assay in support of combination biologics therapy clinical studies.

J Pharm Biomed Anal 2019 Apr 13;171:204-211. Epub 2019 Apr 13.

Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Inc., 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA.

Clinical development of biotherapeutics for combination therapy requires monitoring the concentrations of both drugs in biological samples. Traditionally, two assays are required to measure drug levels one at a time, which poses challenges in sample management, data reporting, and cost. The Meso Scale Discovery (MSD®) U-PLEX platform provides a simple and flexible way to create custom multiplex ligand binding assays (LBAs). Read More

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http://dx.doi.org/10.1016/j.jpba.2019.04.021DOI Listing

Multi-class determination of steroid hormones and antibiotics in fatty hotpot ingredients by pressurized liquid extraction and liquid chromatography-tandem mass spectrometry.

J Pharm Biomed Anal 2019 Apr 15;171:193-203. Epub 2019 Apr 15.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road Shenhe District, 110016, Shenyang, Liaoning Province, PR China. Electronic address:

Due to the misuse of hormones and antibiotics resulting in drug residues in meat products, serious concerns have arisen regarding to the potential risks for human health. In this paper, a simple and efficient method was developed to simultaneously quantify six steroid hormones and six antibiotics in fatty foods by combining pressurized liquid extraction (PLE) with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Adsorbents, extraction temperature, extraction time, recycle time and several other parameters were optimized in current investigation. Read More

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http://dx.doi.org/10.1016/j.jpba.2019.04.019DOI Listing

A systemic combined nontargeted and targeted LC-MS based metabolomic strategy of plasma and liver on pathology exploration of alpha-naphthylisothiocyanate induced cholestatic liver injury in mice.

J Pharm Biomed Anal 2019 Apr 8;171:180-192. Epub 2019 Apr 8.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address:

The pathology of cholestatic liver injury (CLI) was complicated, which has limited the development of anti-cholestatic drugs for a long period. Metabolomic researches focused on global and dynamic changes of the organism could shed some light on mechanism investigation. In order to characterize and validate metabolite alterations of alpha-naphthylisothiocyanate (ANIT) induced CLI in C57BL/6 mice, a systemic metabolomic approach combining nontargeted HPLC-ESI-QTOF-MS and targeted UFLC-ESI-MS/MS technologies were developed innovatively. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S07317085183291
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http://dx.doi.org/10.1016/j.jpba.2019.04.009DOI Listing
April 2019
1 Read

Inhibitory effects of sildenafil and tadalafil on inflammation, oxidative stress and nitrosative stress in animal model of bronchial asthma.

Pharmacol Rep 2019 Feb 15;71(3):517-521. Epub 2019 Feb 15.

Vallabhbhai Patel Chest Institute, New Delhi, India.

Background: Cyclic neucleotides are involved in many cellular functions including smooth muscle relaxation, inflammation, and signal transduction. Sildenafil and tadalafil are phosphodiesterase-5 (PDE-5) inhibitors which prevent the degradation of cyclic neucleotide i.e. Read More

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http://dx.doi.org/10.1016/j.pharep.2019.02.008DOI Listing
February 2019

Vielanin P enhances the cytotoxicity of doxorubicin via the inhibition of PI3K/Nrf2-stimulated MRP1 expression in MCF-7 and K562 DOX-resistant cell lines.

Phytomedicine 2019 Mar 11;58:152885. Epub 2019 Mar 11.

Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.

Background: Cancer cells that are resistant to structurally and mechanically unrelated anticancer drugs are said to have multidrug resistance (MDR). The overexpression of the ATP-binding cassette (ABC) transporter is one of the most important mechanisms of MDR. Vielanin P (VP), a dimeric guaiane from the leaves of Xylopia vielana, has the potential to reverse multidrug resistance. Read More

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http://dx.doi.org/10.1016/j.phymed.2019.152885DOI Listing

Development and validation of a method for analysing of duloxetine, venlafaxine and amitriptyline in human bone.

Forensic Sci Int 2019 Apr 8;299:154-160. Epub 2019 Apr 8.

National Centre on Drug Addiction and Doping, Istituto Superiore di Sanità, Rome, Italy.

A method based on gas chromatography-mass spectrometry (GC-MS) is described for the determination of venlafaxine, amitriptyline and duloxetine in human bone. Pulverized samples were incubated in methanol for 1 h under ultrasonication, after the addition of sertraline as internal standard. The samples were centrifuged, and the supernatants were evaporated. Read More

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http://dx.doi.org/10.1016/j.forsciint.2019.04.001DOI Listing

In vitro susceptibility of Plasmodium falciparum isolates from the China-Myanmar border area to artemisinins and correlation with K13 mutations.

Int J Parasitol Drugs Drug Resist 2019 Apr 10;10:20-27. Epub 2019 Apr 10.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, Yunnan Province, 650500, China. Electronic address:

Mutations in the Kelch domain of the K13 gene (PF3D7_1343700) were previously associated with artemisinin resistance in Plasmodium falciparum. This study followed the dynamics of the K13 polymorphisms in P. falciparum parasites from the China-Myanmar border area obtained in 2007-2016, and their in vitro sensitivities to artesunate (AS) and dihydroartemisinin (DHA). Read More

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http://dx.doi.org/10.1016/j.ijpddr.2019.04.002DOI Listing

CRAC channels and disease - From human CRAC channelopathies and animal models to novel drugs.

Authors:
Stefan Feske

Cell Calcium 2019 Mar 11;80:112-116. Epub 2019 Mar 11.

Department of Pathology, New York University School of Medicine, New York, NY, 10016, USA. Electronic address:

Ca release-activated Ca (CRAC) channels are intimately linked with health and disease. The gene encoding the CRAC channel, ORAI1, was discovered in part by genetic analysis of patients with abolished CRAC channel function. And patients with autosomal recessive loss-of-function (LOF) mutations in ORAI1 and its activator stromal interaction molecule 1 (STIM1) that abolish CRAC channel function and store-operated Ca entry (SOCE) define essential functions of CRAC channels in health and disease. Read More

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http://dx.doi.org/10.1016/j.ceca.2019.03.004DOI Listing

Risk of deterioration of geriatric traumatic brain injury in patients treated with antithrombotic drugs.

World Neurosurg 2019 Apr 19. Epub 2019 Apr 19.

The Japan Neurotrauma Data Bank Committee, The Japan Society of Neurotraumatology, Tokyo, Japan.

Objective: Developed countries have rapidly aging populations, and use of antithrombotic drugs is increasing. We investigated the effects of antithrombotic drugs and reversal of these drugs in geriatric traumatic brain injury (TBI) patients.

Methods: Age, gender, mechanism of injury, Glasgow Coma Scale on admission, head CT findings, antithrombotic therapy, acute exacerbation, and outcomes at discharge were examined in 711 patients with geriatric TBI complicated with traumatic intracranial hemorrhage using data from the Japan Neurotrauma Data Bank Project 2015 (JNTDB P2015). Read More

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http://dx.doi.org/10.1016/j.wneu.2019.04.108DOI Listing

A sub-chronic Xysmalobium undulatum hepatotoxicity investigation in HepG2/C3A spheroid cultures compared to an in vivo model.

J Ethnopharmacol 2019 Apr 19:111897. Epub 2019 Apr 19.

Pharmacen™, Centre of Excellence for Pharmaceutical Sciences, North-West University, Private Bag X6001, Potchefstroom, 2520, South Africa; Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230, Odense M, Denmark; Celvivo IVS, Blommenslyst, Denmark. Electronic address:

Ethnopharmacology Relevance: Traditional herbal medicines are utilized by 27 million South Africans. Xysmalobium undulatum (Uzara) is one of the most widely used traditional medicinal plants in Southern Africa. A false belief in the safety of herbal medicine may result in liver injury. Read More

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http://dx.doi.org/10.1016/j.jep.2019.111897DOI Listing

Differential effects of psychoactive substances on human wildtype and polymorphic T356M dopamine transporters (DAT).

Toxicology 2019 Apr 19. Epub 2019 Apr 19.

Neurotoxicology Research Group, Division Toxicology, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands. Electronic address:

Many psychoactive substances affect the human dopamine (DA) reuptake transporter (hDAT). Polymorphisms in the encoding gene could affect the functionality of the transporter and consequently alter effects of psychotropic and recreational drugs. Recently, a T356 M single nucleotide polymorphism in the human SLC6A3 gene was described, which resulted in functional impairments of DA uptake. Read More

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http://dx.doi.org/10.1016/j.tox.2019.04.012DOI Listing

Dual actions of norathyriol as a new candidate hypouricaemic agent: uricosuric effects and xanthine oxidase inhibition.

Eur J Pharmacol 2019 Apr 19. Epub 2019 Apr 19.

Biomedical Engineering Research Center, Kunming Medical University, Kunming, 650500, China. Electronic address:

Hyperuricaemia, which results from the overproduction and underexcretion of uric acid, has been linked with chronic renal dysfunction, cardiovascular diseases, diabetes and metabolic syndrome. However, available clinical drugs cannot simultaneously target the production and excretion of uric acid. Norathyriol, a natural xanthone, was expected to have the dual actions. Read More

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http://dx.doi.org/10.1016/j.ejphar.2019.04.034DOI Listing

Synergistic effects of 7-O-geranylquercetin and siRNAs on the treatment of human breast cancer.

Life Sci 2019 Apr 19. Epub 2019 Apr 19.

College of Pharmacy, Dalian Medical University, Dalian 116044, China. Electronic address:

Aims: To investigate the antitumor effect of 7-O-geranylquercetin (GQ) combining with survivin siRNA (siSuvi) or IL-10 siRNA (siIL-10) to breast cancer.

Main Methods: Xenograft tumor model was established by subcutaneously inoculating human breast cancer MCF-7 cells in BALB/c nude mice. Transfection efficiency of siRNA mediated by cationic liposome CDO14 in MCF-7 cells and tumor bearing mice was measured by flow cytometer and living imaging sysytem, respectively. Read More

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http://dx.doi.org/10.1016/j.lfs.2019.04.047DOI Listing

Involvement of miR-770-5p in trastuzumab response in HER2 positive breast cancer cells.

PLoS One 2019 22;14(4):e0215894. Epub 2019 Apr 22.

Biotechnology Institute, Ankara University, Ankara, Turkey.

miRNAs may play effective roles in breast cancer so modulating their expression levels could have therapeutic benefits. Recent studies have found the combination of miRNA-based therapeutics with conventional drugs as promising. This study aimed to find drug-responsive miRNAs, and explore their anticancer activities in HER2+ breast cancer cells and regulatory role in the trastuzumab response. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215894PLOS

Dust or disease? Perceptions of influenza in rural Southern Malawi.

PLoS One 2019 22;14(4):e0208155. Epub 2019 Apr 22.

Malawi Liverpool Welcome Trust Clinical Research Programme, Chichiri, Blantyre 3, Malawi.

Influenza virus infections cause between 291 243 and 645 832 deaths annually, with the highest burden in low-income settings. Research in high-income countries has examined public understanding of influenza, but there is little information on views and behaviours about influenza in low-income countries. We explored communities' ideas about the severity, causes, prevention and treatment of influenza in Chikwawa district, Malawi. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208155PLOS

A highly expressed intestinal cysteine protease of Ancylostoma ceylanicum protects vaccinated hamsters from hookworm infection.

PLoS Negl Trop Dis 2019 Apr 22;13(4):e0007345. Epub 2019 Apr 22.

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.

Background: Human hookworms (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum) are intestinal blood-feeding parasites that infect ~500 million people worldwide and are among the leading causes of iron-deficiency anemia in the developing world. Drugs are useful against hookworm infections, but hookworms rapidly reinfect people, and the parasites can develop drug resistance. Therefore, having a hookworm vaccine would be of tremendous benefit. Read More

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http://dx.doi.org/10.1371/journal.pntd.0007345DOI Listing

Genetic and phenotypic characteristics of SCN1A-related epilepsy in Chinese children.

Neuroreport 2019 Apr 19. Epub 2019 Apr 19.

Department of Neurology, Children's Hospital of Chongqing Medical University.

SCN1A gene mutations are associated with epilepsy and neurodevelopmental disorders. This study aimed to explore the genotype and phenotype spectrum of SCN1A gene related epilepsy. Epileptic patients who were treated in the Children's Hospital of Chongqing Medical University from January 2015 to July 2018 and identified as having SCN1A mutations by targeted next-generation sequencing were included. Read More

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http://dx.doi.org/10.1097/WNR.0000000000001259DOI Listing

Anterior nucleus of paraventricular thalamus mediates chronic mechanical hyperalgesia.

Pain 2019 May;160(5):1208-1223

Taiwan International Graduate Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.

Pain-related diseases are the top leading causes of life disability. Identifying brain regions involved in persistent neuronal changes will provide new insights for developing efficient chronic pain treatment. Here, we showed that anterior nucleus of paraventricular thalamus (PVA) plays an essential role in the development of mechanical hyperalgesia in neuropathic and inflammatory pain models in mice. Read More

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http://dx.doi.org/10.1097/j.pain.0000000000001497DOI Listing

Cyclooxygenase-2 and Cytosolic Phospholipase A2 Are Overexpressed in Mucinous Pancreatic Cysts.

Clin Transl Gastroenterol 2019 Apr 15. Epub 2019 Apr 15.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Objectives: Expression of prostaglandin biosynthetic pathway enzymes in mucinous pancreatic cysts is unknown. Cyclooxygenase-2 (COX-2) inhibition is a potential cancer chemoprevention strategy for these lesions. We evaluated the expression of COX-2, cytosolic phospholipase A2 (cPLA2), and protein kinase B (AKT) in the epithelium of pancreatic cysts and correlated enzyme expression with aspirin (ASA) use and cyst fluid prostaglandin E2 (PGE2) concentration. Read More

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http://dx.doi.org/10.14309/ctg.0000000000000028DOI Listing
April 2019
1 Read

Guidelines for Implementing a Low-Cost Volunteer Desexing Skills Training Program for Veterinary and Veterinary Technology Students.

J Vet Med Educ 2019 Apr 22:1-13. Epub 2019 Apr 22.

Although desexing surgeries are considered a core clinical skill for small animal veterinary practice, it can be challenging for veterinary schools to provide students with adequate training opportunities in the traditional curriculum. At the Massey University School of Veterinary Science, we recently established an innovative extracurricular volunteer program designed to have students teaching other students how to perform different elements of desexing procedures as they progress through their degree. This program includes administrative and assistant roles for first-year students (responsible for client communication, patient restraint, and medical record keeping), physical exam and recovery roles for second-year students (responsible for assessing patient fitness for surgery, drawing up anesthetic drugs, and monitoring patients in recovery), anesthesia and neuter surgeon roles for third-year students (responsible for inducing, preparing, and monitoring spay patients and performing cat neuter surgeries), and spay surgeon roles for fourth- and fifth-year students (responsible for performing cat spay surgeries, discharging patients, and following up with clients to monitor recovery). Read More

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http://dx.doi.org/10.3138/jvme.0418-047r1DOI Listing

Detection and Characterization of spp. in Raw Commingled Bulk Tank Milk from Dairies in Pennsylvania.

Foodborne Pathog Dis 2019 Apr 19. Epub 2019 Apr 19.

1 Pennsylvania Veterinary Laboratory, Harrisburg, Pennsylvania.

A microbiological survey was conducted to determine the presence of spp. in raw commingled bulk tank milk (BTM) collected from the Pennsylvania dairies intended for pasteurization. The survey found 8. Read More

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https://www.liebertpub.com/doi/10.1089/fpd.2018.2552
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http://dx.doi.org/10.1089/fpd.2018.2552DOI Listing
April 2019
1 Read

Curcumin-Synthetic Analogs Library Screening by Docking and Quantitative Structure-Activity Relationship Studies for AXL Tyrosine Kinase Inhibition in Cancers.

J Comput Biol 2019 Apr 22. Epub 2019 Apr 22.

The Biotechnology Lab (MedBiotech), BioInova Research center, Rabat Medical and Pharmacy School, Mohammed V University in Rabat, Rabat, Morocco.

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https://www.liebertpub.com/doi/10.1089/cmb.2019.0052
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http://dx.doi.org/10.1089/cmb.2019.0052DOI Listing
April 2019
1 Read

Patient Satisfaction and Treatments Offered to Swedish Patients with Suspected Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections.

J Child Adolesc Psychopharmacol 2019 Apr 19. Epub 2019 Apr 19.

1 Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.

Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are subtypes of Obsessive-Compulsive Disorder (OCD) with suggested autoimmune etiology. Immunomodulatory treatments have been introduced as treatment options. A recent systematic review concluded that the evidence for all treatment options for PANS and PANDAS is inconclusive. Read More

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http://dx.doi.org/10.1089/cap.2018.0141DOI Listing

Pharmacological Treatment of Youth Substance Use Disorders.

J Child Adolesc Psychopharmacol 2019 Apr 22. Epub 2019 Apr 22.

Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina.

While the majority of youth who experiment with alcohol and drugs do not develop problematic levels of use, 5% of adolescents and 15% of young adults meet criteria for a substance use disorder (SUD). Pharmacotherapy, in combination with behavioral interventions, has the potential to increase the likelihood of successful treatment for youth struggling with SUD; however, the literature in this area is limited. To date, there are no Food and Drug Administration (FDA)-approved medications for adolescent SUD, other than buprenorphine, which has been approved down to 16 years of age for opioid use disorder. Read More

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http://dx.doi.org/10.1089/cap.2019.0009DOI Listing

Kinetic and Molecular Dynamic Studies of inhibitors of Shikimate dehydrogenase from Methicillin-resistant Staphylococcus aureus.

Chem Biol Drug Des 2019 Apr 22. Epub 2019 Apr 22.

Facultad de Medicina y Nutrición, Universidad Juárez del Estado de Durango, Av. Universidad y Fanny Anitúa S/N, Durango, Durango, C.P, 34000, México.

Due to its resistance to many antibiotics, methicillin resistant Staphylococcus aureus (MRSA) have become a worldwide health problem creating the urgent necessity of developing new drugs against this pathogen. In this sense, one approach is to search for inhibitors of important enzymes in its metabolism. According to this, the shikimate pathway is an important metabolic route in bacteria and its enzymes are considered as great targets for the development of new antibiotic drugs. Read More

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http://dx.doi.org/10.1111/cbdd.13532DOI Listing

Role of cyclin-dependent kinases (CDKs) in hepatocellular carcinoma: therapeutic potential of targeting CDKs signaling pathway.

Hepatol Res 2019 Apr 22. Epub 2019 Apr 22.

Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.

Hepatocellular carcinoma (HCC) is a common malignancy of the liver and is the second leading cause of cancer-related mortalities. Two-thirds of patients have advanced disease when diagnosed, and for these patients, treatment strategies remain limited. In addition, there is a high incidence of tumor recurrence after surgical resection with the current treatment regimens. Read More

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http://dx.doi.org/10.1111/hepr.13353DOI Listing

A Comparative Analysis of the Safety Profile of Direct Oral Anticoagulants Using the FDA Adverse Event Reporting System.

Eur J Haematol 2019 Apr 22. Epub 2019 Apr 22.

Division of Hematology, Oregon Health & Science University, Portland, OR.

Introductio: Direct oral anticoagulants (DOACs) are being increasingly used. However, unlike warfarin, less is known regarding their long-term side effects. To better evaluate the rates of DOAC-related adverse events (AEs) on a population level we examined AEs reported to the FDA for three commonly used DOACs and warfarin. Read More

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http://doi.wiley.com/10.1111/ejh.13240
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http://dx.doi.org/10.1111/ejh.13240DOI Listing
April 2019
4 Reads

Pharmacogenomics guidelines: current status and future development.

Clin Exp Pharmacol Physiol 2019 Apr 22. Epub 2019 Apr 22.

Department of Dermatology, Xiangya Hospital, Central South University and Hunan Key Laboratory of Skin Cancer and psoriasis, Central South University, Changsha, 410008, Hunan, China.

Genetic polymorphisms impact biological responses to drugs. Current pharmacogenomics guidelines formulated by different countries, such as CPIC, DPWG, CPNDS, and RNPGx, play important roles in clinical practices. However, the drafting standards for these guidelines vary, resulting in differences in recommendations. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/1440-1681.13
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http://dx.doi.org/10.1111/1440-1681.13097DOI Listing

Predictive analysis of first Abbreviated New Drug Application submission for new chemical entities based on machine learning methodology.

Clin Pharmacol Ther 2019 Apr 22. Epub 2019 Apr 22.

Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.

Generic drug products are approved by the US Food and Drug Administration (FDA) through Abbreviated New Drug Applications (ANDA). The ANDA review and approval involves multiple offices across the FDA. Forecasting ANDA submissions can critically inform resource allocation and workload management. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/cpt.1479
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http://dx.doi.org/10.1002/cpt.1479DOI Listing
April 2019
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Association Between Longitudinal Plasma Neurofilament Light and Neurodegeneration in Patients With Alzheimer Disease.

JAMA Neurol 2019 Apr 22. Epub 2019 Apr 22.

Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Importance: Plasma neurofilament light (NfL) has been suggested as a noninvasive biomarker to monitor neurodegeneration in Alzheimer disease (AD), but studies are lacking.

Objective: To examine whether longitudinal plasma NfL levels are associated with other hallmarks of AD.

Design, Setting, And Participants: This North American cohort study used data from 1583 individuals in the multicenter Alzheimer's Disease Neuroimaging Initiative study from September 7, 2005, through June 16, 2016. Read More

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http://dx.doi.org/10.1001/jamaneurol.2019.0765DOI Listing

Swimming Induced Paralysis to Assess Dopamine Signaling in Caenorhabditis elegans.

J Vis Exp 2019 Apr 3(146). Epub 2019 Apr 3.

Harriet Wilkes Honors College, Florida Atlantic University, John D MacArthur Campus; Brain Institute, Florida Atlantic University; Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University;

The swimming assay described in this protocol is a valid tool to identify proteins regulating the dopaminergic synapses. Similar to mammals, dopamine (DA) controls several functions in C. elegans including learning and motor activity. Read More

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http://dx.doi.org/10.3791/59243DOI Listing

Remote Laboratory Management: Respiratory Virus Diagnostics.

J Vis Exp 2019 Apr 6(146). Epub 2019 Apr 6.

Baylor Global Health, Baylor College of Medicine; Department of Medicine, Baylor College of Medicine;

An uptick in recent pandemics (Ebola, Zika, MERS, influenza, etc.) underlines the need for a more 'nimble,' coordinated response that addresses a multitude of issues ranging from transportation, access, facilities, equipment, and communication to provider training. To address this need, we have developed an innovative, scalable, logistics-enhanced, mobile, laboratory facility for emergencies and epidemics in resource-constrained global settings. Read More

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http://dx.doi.org/10.3791/59188DOI Listing

Optimizing pediatric dosing recommendations and treatment management of antiretroviral drugs utilizing therapeutic drug monitoring data in children living with HIV.

Ther Drug Monit 2019 Apr 16. Epub 2019 Apr 16.

Department of Pharmacy, Radboud Institute for Health Sciences (RIHS), Radboud university medical centre, Nijmegen, The Netherlands.

Introduction: This review summarises the current dosing recommendations for antiretroviral drugs (ARVs) in the international pediatric guidelines of the World Health Organisation (WHO), US Department of Health and Human Services (DHHS), and Paediatric European Network for Treatment of AIDS (PENTA) and evaluates the research that informed these approaches. We further explore the role of data generated through therapeutic drug monitoring (TDM) in optimizing the dosing of ARVs in children.

Methods: A PubMed search was conducted for literature on ARV dosing published in English. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000637DOI Listing

Development and validation of a sensitive UHPLC-MS/MS-based method for the analysis of folylpolyglutamate synthetase enzymatic activity in peripheral blood mononuclear cells: application in rheumatoid arthritis and leukemia patients.

Ther Drug Monit 2019 Apr 16. Epub 2019 Apr 16.

Department of Clinical Chemistry, Amsterdam University Medical Centers, location VUmc, Amsterdam, The Netherlands.

Background: Folylpolyglutamate synthetase (FPGS) is a crucial enzyme in both cellular folate homeostasis and the intracellular retention of folate analogue drugs like methotrexate (MTX), which is commonly used for the treatment of (pediatric) leukemia and the anchor drug in rheumatoid arthritis (RA) treatment. To date, assessment of FPGS catalytic activity relies on assays utilizing radioactive substrates which are labor-intensive and require relatively large numbers of cells. Here, we describe a non-radioactive, UHPLC-MS/MS-based method allowing sensitive and accurate measurements of FPGS activity in low cell numbers (i. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000638DOI Listing

Progressive sacroiliitis due to accessory sacroiliac joint mimicking ankylosing spondylitis: A case report.

Medicine (Baltimore) 2019 Apr;98(16):e15324

Department of Rheumatology, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, Korea.

Rationale: An accessory sacroiliac (SI) joint usually has little clinical significance. However, severe arthritic changes can cause chronic buttock or low back pain and can be misdiagnosed as another disease presenting with sacroiliitis such as ankylosing spondylitis (AS).

Patient Concerns: A 33-year-old woman was diagnosed with AS due to chronic buttock pain and progressive sacroiliitis on plain X-ray and magnetic resonance imaging (MRI). Read More

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http://dx.doi.org/10.1097/MD.0000000000015324DOI Listing

Endovascular treatment of a ruptured thoracic aortic pseudoaneurysm secondary to Pott disease during a spine surgery: A case report and a literature review.

Medicine (Baltimore) 2019 Apr;98(16):e15306

Department of Orthopedic Surgery.

Rationale: The coexistence of a tuberculous aortic pseudoaneurysm and Pott disease in patients with a history of tuberculosis (TB) is relatively rare, and the treatment strategies remain still controversial.

Patient Concerns: A 57-year-old female patient with a history of primary pulmonary TB presented with symptoms of breathlessness, chest pain, weight loss, and fever. Magnetic resonance imaging (MRI) and computed tomography (CT) showed a thoracic aortic pseudoaneurysm secondary to Pott disease at T11/12 level. Read More

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http://dx.doi.org/10.1097/MD.0000000000015306DOI Listing

Effect of remifentanil and midazolam on ED95 of propofol for loss of consciousness in elderly patients: A randomized, clinical trial.

Medicine (Baltimore) 2019 Apr;98(16):e15132

Department of Anesthesiology and Pain Medicine.

Background: Older people are more vulnerable to hemodynamic instability caused by propofol due to their decreased initial distribution volume and increased sensitivity to propofol. Midazolam or remifentanil can often be coadministered because of their synergistic or additive effects with propofol as well as amnesic properties and the blockade of sympathetic stimulation. However, no study has confirmed the appropriate dose of propofol for loss of consciousness in aged patients when administered with other drugs, including opioids or benzodiazepines. Read More

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http://dx.doi.org/10.1097/MD.0000000000015132DOI Listing

Variant angina induced by carbon monoxide poisoning: A CARE compliant case report.

Medicine (Baltimore) 2019 Apr;98(16):e15056

Department of Emergency.

Rationale: Carbon monoxide (CO) poisoning can cause severe damage to the nervous system, and can also cause serious damage to organs, such as the heart, kidneys, and lungs. CO damage to myocardial cells has been previously reported. This can lead to serious complications, such as myocardial infarction. Read More

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http://dx.doi.org/10.1097/MD.0000000000015056DOI Listing

New approach for investigating neuropathic allodynia by optogenetics.

Authors:
Makoto Tsuda

Pain 2019 May;160 Suppl 1:S53-S58

Department of Life Innovation, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.

Mechanical allodynia is pain caused by normally innocuous mechanical stimuli and is a cardinal and intractable symptom of neuropathic pain. Roles of low-threshold mechanoreceptors (LTMRs), including Aβ fibers, in mechanical allodynia have previously been proposed, but the necessity and sufficiency of LTMRs in allodynia have not been fully determined. Recent technological advances have made it possible to achieve subpopulation-specific ablation, silencing or stimulation, and to dissect and elucidate complex neuronal circuitry. Read More

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http://dx.doi.org/10.1097/j.pain.0000000000001506DOI Listing
May 2019
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Pentazocine, a Kappa-Opioid Agonist, Is Better Than Diclofenac for Analgesia in Acute Pancreatitis: A Randomized Controlled Trial.

Am J Gastroenterol 2019 Apr 16. Epub 2019 Apr 16.

Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.

Objectives: The ideal analgesic is not known for patients with acute pancreatitis (AP). Concerns have been raised about serious adverse effects of opioid analgesics increasing the severity of AP. We hypothesized that nonsteroidal anti-inflammatory drugs might be better analgesics because of their anti-inflammatory effect. Read More

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http://dx.doi.org/10.14309/ajg.0000000000000224DOI Listing

Multicenter retrospective study to evaluate the impact of trabectedin plus pegylated liposomal doxorubicin on the subsequent treatment in women with recurrent, platinum-sensitive ovarian cancer.

Anticancer Drugs 2019 Apr 18. Epub 2019 Apr 18.

Navarra University Clinic Madrid.

Debulking surgery, followed by taxane/platinum-based chemotherapy has traditionally been the first-line treatment for advanced ovarian cancer. However, most patients will experience recurrence afterwards, and receive subsequent lines of therapy. It has been proposed that extending the treatment-free interval of platinum can improve the response to a subsequent platinum-based chemotherapy, and reduce associated toxicities in women with recurrent, platinum-sensitive ovarian cancer. Read More

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http://dx.doi.org/10.1097/CAD.0000000000000794DOI Listing

Postvaccination Fever Response Rates in Children Derived Using the Fever Coach Mobile App: A Retrospective Observational Study.

JMIR Mhealth Uhealth 2019 Apr 22;7(4):e12223. Epub 2019 Apr 22.

Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Postvaccination fever is a mild adverse event that naturally improves without complications, but is highly prevalent and can be accompanied by febrile convulsions in some cases. These adverse effects may cause parents to delay or avoid vaccinating their children.

Objective: This study aimed to identify postvaccination fever patterns and the ability of antipyretics to affect changes in these patterns from data collected from a mobile app named Fever Coach. Read More

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http://dx.doi.org/10.2196/12223DOI Listing

Evidence of fentanyl use is common and frequently missed in a cross-sectional study of emergency department patients in Baltimore, Maryland.

Clin Toxicol (Phila) 2019 Apr 22:1-3. Epub 2019 Apr 22.

b Center for Substance Abuse Research (CESAR) , University of Maryland , College Park , MD , USA.

Objective: Fentanyl-associated deaths have risen in Maryland, but the prevalence of illicit fentanyl use is unknown. Our objective was to measure whether fentanyl is present among emergency department (ED) patients seeking care for a drug overdose.

Design: The prevalence of fentanyl use was determined using a cross-sectional study of a convenience sample of adult ED patients with complaints of apparent opioid overdose, withdrawal from opioids, and/or requesting treatment for their substance use disorder (SUD) between February and April, 2018. Read More

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http://dx.doi.org/10.1080/15563650.2019.1605078DOI Listing

Antiviral Meroterpenoid Rhodatin and Sesquiterpenoids Rhodocoranes A-E from the Wrinkled Peach Mushroom, Rhodotus palmatus.

Org Lett 2019 Apr 22. Epub 2019 Apr 22.

Department of Microbial Drugs , Helmholtz Centre for Infection Research GmbH , Inhoffenstraße 7 , 38124 Braunschweig , Germany.

Rhodatin (1), a meroterpenoid featuring a unique pentacyclic scaffold with both spiro and spiroketal centers, and five unusual acorane-type sesquiterpenoids, named rhodocoranes A-E (2-6, respectively), are the first natural products isolated from the basidiomycete Rhodotus palmatus. Their structures were elucidated by two-dimensional NMR experiments and HRESIMS, while the absolute configuration of the substance family was determined by Mosher's method utilizing 2. Rhodatin strongly inhibited hepatitis C virus, whereas 4 displayed cytotoxicity and selective antifungal activity. Read More

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http://dx.doi.org/10.1021/acs.orglett.9b01017DOI Listing

Simultaneous Relative Quantification of Various Polyglycerophospholipids with Isotope-Labeled Methylation by Nanoflow Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry.

Anal Chem 2019 Apr 22. Epub 2019 Apr 22.

Herein, we introduce a comprehensive analytical method for the separation and relative quantification of poyglycerophos-pholipids (PGPLs), including phosphatidylglycerol (PG), bis(monoacylglycero)phosphate (BMP), bis(diacylglycerol)phosphate (BDP), hemi-BDP, cardiolipin (CL), monolysocardiolipin (MLCL), and dilysocardiolipin (DLCL), using isotope-labeled methylation (ILM) with nanoflow ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (nUHPLC-ESI-MS/MS). Abnormal levels of BMP and CL have been associated with the pathology of lysosomal storage and neurodegenerative diseases. Thus, simultaneous analysis of all PGPLs is important to understand the mechanisms and pathologies of such diseases. Read More

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http://dx.doi.org/10.1021/acs.analchem.9b00800DOI Listing

Trends in substance use and in the attributable burden of disease and mortality in the WHO European Region, 2010-16.

Eur J Public Health 2019 Apr 22. Epub 2019 Apr 22.

WHO European Office for Prevention and Control of Noncommunicable Diseases, World Health Organization, Regional Office for Europe, Moscow, Russian Federation.

Background: This paper examines changes in substance use, and compares the resulting attributable burden of disease in the WHO European Region between 2010 and 2016.

Methods: Data for 2010 and 2016 on the number of deaths, years of life lost (YLL) and disability-adjusted life years (DALYs) lost were obtained by sex and country from the 2016 Global Burden of Disease (GBD) study. Exposure data for all substances except alcohol were obtained from the same study, while alcohol data were obtained from the WHO. Read More

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http://dx.doi.org/10.1093/eurpub/ckz064DOI Listing

Point mutation detection by economic HRM protocol primer design.

Biochem Biophys Rep 2019 Jul 9;18:100628. Epub 2019 Apr 9.

Dept. of Clinical Laboratory Science, Faculty of Pharmacy, University of Kufa, Iraq.

Globally more than 100 million SNPs in populations. These variations approximately 4-5 million SNPs in a people genome, occur almost every 1000 nucleotides on average and present either unique or in many in individuals. They can act as genetic signs, associated with illness and respond to chemicals and drugs. Read More

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http://dx.doi.org/10.1016/j.bbrep.2019.100628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458491PMC
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