Application of in vitro Drug Metabolism Studies in Chemical Structure Optimization for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP)

This study demonstrated the importance of metabolite identification for the discovery of novel and safe drug candidates for the treatment of FOP and helped medicinal chemists steer away from potential metabolic liabilities. Introduction Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder involving progressive and widespread postnatal ossification of soft tissues (Buyse et al., 1995). The heterotopic ossification occurs independently from normal bone and progresses in a well-defined spatial pattern. It forms ribbons, sheets and plates of bone that may fuse the joints of the individual. The ectopic calcification may also affect muscles, tendons and ligaments, causing severe pain, impairing mobility and typically leading to premature mortality. It affects approximately 1 in 2 million individuals (Shore and Kaplan, 2008). A congenital disorder, it usually manifests itself after physical trauma, surgery, viral illness or myositis during the first decade of life (Buyse et al., 1995; Yu et al., 2008a; Pignolo et al., 2013). Bearers hold no ethnic, racial, gender, or geographic predisposition (Pignolo et al., 2013). Rarely, genetic inheritance may be involved. When observed, genetic transmission is autosomal dominant and can be inherited from either mother or father. The general cause of the disease is a heterozygous mutation in the ACVR1 gene which encodes the bone morphogenetic protein (BMP) type I receptor ALK2 (Shore et al., 2006; Yu et al., 2008a)....
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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This article reviews implications of cannabis use for defendants' eligibility and participation in problem-solving courts, with a focus on adult drug courts and mental health courts. This article also examines a range of policies, such as abstinence-based, tolerance-based, and adaptive approaches, that problem-solving courts may consider implementing. Further research is needed to characterize existing problem-solving court policies toward cannabis use and to develop evidence-based practices that courts may follow. PMID: 31533992 [PubMed - as supplied by publisher]
Source: Journal of the American Academy of Psychiatry and the Law - Category: Medical Law Tags: J Am Acad Psychiatry Law Source Type: research
Authors: Nakamura H, Utsunomiya A, Ishida Y, Horita T Abstract A 48-year-old man was brought to our emergency room with acute abdominal pain and systemic edema, indicating acute circulatory failure with lactic acidosis. Furosemide treatment paradoxically worsened the systemic edema and induced confusion. He had no drinking history but hardly ate legumes or meats containing thiamine. Administration of fursultiamine dramatically improved the symptoms and subsequently caused pulmonary edema. Thiamine deficiency may occur in nondrinkers with an unbalanced diet. In this condition, diuretic therapy can worsen the symptom...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
We describe the case of a 52-year-old female outpatient who developed OIC while receiving oxycodone for pain due to cancer with multiple bone metastases. Although she did not have brain metastasis, opioid withdrawal syndrome (OWS) developed after taking naldemedine orally. Her Clinical Opiate-Withdrawal Score (COWS) was 19 (moderate symptoms). However, she recovered from OWS on intravenous fentanyl and a continuous infusion of oxycodone. She did not develop OWS thereafter and was discharged two days after recovery. PMID: 31534081 [PubMed - as supplied by publisher]
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
Authors: Hotta T, Okimoto T, Hamaguchi M, Tsubata Y, Isobe T Abstract A 40-year-old Japanese man with advanced pulmonary adenocarcinoma harboring anaplastic lymphoma kinase (ALK)-rearranged was administered the selective ALK inhibitor ceritinib as a third-line treatment and continued treatment for nine months. After fourth-line treatment, we performed rechallenge with ceritinib as a fifth-line treatment. On day 54 after rechallenge, the patient developed acutely deteriorating dyspnea. Chest computed tomography showed extensive ground-glass opacities. We diagnosed him with ceritinib-induced interstitial lung disease...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
Publication date: Available online 19 September 2019Source: Molecular and Biochemical ParasitologyAuthor(s): Fuli Zheng, Claudia Colasante, Frank VonckenAbstractSimilar to higher eukaryotes, the protist parasite T. brucei harbours several iron-containing proteins that regulate DNA and protein processing, oxidative stress defence and mitochondrial respiration. The synthesis of these proteins occurs either in the cytoplasm or within the mitochondrion. For mitochondrial iron cluster protein synthesis, iron needs to be transported across the solute impermeable mitochondrial membrane. In T. brucei we previously identified 24 mi...
Source: Molecular and Biochemical Parasitology - Category: Parasitology Source Type: research
Authors: Kim J, Kim SR, Lee H, Nam DH Abstract Objectives: Acupuncture is often used for relieving symptoms of fibromyalgia syndrome (FMS). Our aim is to ascertain whether verum acupuncture is more effective than sham acupuncture in FMS. Methods: We collected RCTs to investigate the effects of verum acupuncture and sham acupuncture on pain, sleep quality, fatigue, and general status in FMS patients. The databases used for data retrieval were PubMed, Central Cochrane, EMBASE, PsycINFO, CNKI, VIP, OASIS, KoreaMed, and RISS. Selection/exclusion from the retrieved records was performed according to prespecified cri...
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
This study is the first report to investigate current practice patterns and approach of Korean medicine doctors to CDH treatment. This data may be of significance to Korean medicine doctors in drawing clinical guidelines and conducting randomized controlled trials (RCTs) to generate high-level evidence on the effectiveness of nonsurgical integrative medicine treatments for CDH. PMID: 31534461 [PubMed]
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
jo EP Abstract Interleukin-6 (IL-6) is a unique cytokine that can play both pro- and anti-inflammatory roles depending on the anatomical site and conditions under which it has been induced. Specific neurons of the hypothalamus provide important signals to control food intake and energy expenditure. In individuals with obesity, a microglia-dependent inflammatory response damages the neural circuits responsible for maintaining whole-body energy homeostasis, resulting in a positive energy balance. However, little is known about the role of IL-6 in the regulation of hypothalamic microglia. In this systematic review, w...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
Publication date: Available online 19 September 2019Source: Carbohydrate PolymersAuthor(s): Isabel Romo, Lilian Abugoch, Cristian TapiaAbstractThe research aim was to study the nature of intermolecular interactions involved in the formation of soluble complexes between chenopodins (QP) and anionic/cationic polysaccharides, sodium alginate (Alg) and chitosan (CH), above the pI of QP at different protein-polysaccharide ratios; and to evaluate their structural-physicochemical properties. The interactions and properties analysed by electrical conductivity, zeta potential, hydrodynamic particle size, intrinsic and extrinsic flu...
Source: Carbohydrate Polymers - Category: Biomedical Science Source Type: research
Publication date: Available online 19 September 2019Source: Thermochimica ActaAuthor(s): Klaudia Ordon, Monika Szlachta, Piotr Szatkowski, Kinga PielichowskaAbstractNew polyurethane-based materials (PUs) have been fabricated via a two-step bulk polymerization method with starch as a crosslinker, and 1,4-butanediol as a chain extender. Hydroxyapatite (HAp) was used as a bioactive compound. The structure, morphology and thermal properties of the PUs were investigated. The chemical structure of the obtained materials was confirmed by FTIR. The SEM-EDX analysis confirmed the incorporation of starch and HAp into the PU matrix. ...
Source: Thermochimica Acta - Category: Chemistry Source Type: research
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