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Amino Acid Therapy

Margrit Hollenz, Jochen Labenz, Ahmed Madisch
OBJECTIVE AND METHOD: The treatment of patients with functional dyspepsia (irritable stomache syndrome) was recorded in a nationwide survey among family doctors. On a questionnaire, the physicians should provide information on the use of a combination preparation of gastric enzyme (pepsin) and amino acids, duration of use, therapy success and patients' contentment. RESULTS: A total of 874 family doctors were contacted, 201 questionnaires were completed and evaluated...
October 2017: MMW Fortschritte der Medizin
Albert Dahan, Rutger van der Schrier, Terry Smith, Leon Aarts, Monique van Velzen, Marieke Niesters
The ventilatory control system is highly vulnerable to exogenous administered opioid analgesics. Particularly respiratory depression is a potentially lethal complication that may occur when opioids are overdosed or consumed in combination with other depressants such as sleep medication or alcohol. Fatalities occur in acute and chronic pain patients on opioid therapy and individuals that abuse prescription or illicit opioids for their hedonistic pleasure. One important strategy to mitigate opioid-induced respiratory depression is cotreatment with nonopioid respiratory stimulants...
March 19, 2018: Anesthesiology
Karla Soares-Weiser, John Rathbone, Yusuke Ogawa, Kiyomi Shinohara, Hanna Bergman
BACKGROUND: Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) - a problem often seen as repetitive involuntary movements around the mouth and face. This review, one in a series examining the treatment of TD, covers miscellaneous treatments not covered elsewhere. OBJECTIVES: To determine whether drugs, hormone-, dietary-, or herb-supplements not covered in other Cochrane reviews on TD treatments, surgical interventions, electroconvulsive therapy, and mind-body therapies were effective and safe for people with antipsychotic-induced TD...
March 19, 2018: Cochrane Database of Systematic Reviews
Harrison C Brown, Philip M Zakas, Stephan N George, Ernest T Parker, H Trent Spencer, Christopher B Doering
Potency is a key optimization parameter for hemophilia A gene therapy product candidates. Optimization strategies include promoter engineering to increase transcription, codon optimization of mRNA to improve translation, and amino-acid substitution to promote secretion. Herein, we describe both rational and empirical design approaches to the development of a minimally sized, highly potent AAV-fVIII vector that incorporates three unique elements: a liver-directed 146-nt transcription regulatory module, a target-cell-specific codon optimization algorithm, and a high-expression bioengineered fVIII variant...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Mery Munoz-Persy, Alfredo J Lucendo
Eosinophilic esophagitis (EoE) is a unique form of non-IgE-mediated food allergy characterized by esophageal eosinophilic infiltration that commonly causes dysphagia and food impaction in children and adolescents. Assessing the efficacy of dietary restrictions or drug therapies to achieve clinical and histologic resolution of EoE through randomized controlled trials and meta-analyses has resulted in new evidence-based guidelines. Avoiding food triggers is the only therapy targeting the cause of the disease...
March 17, 2018: European Journal of Pediatrics
Barbara Bassi, Giacomo Dacarro, Pietro Galinetto, Enrico Giulotto, Nicoletta Marchesi, Piersandro Pallavicini, Alessia Pascale, Stefano Perversi, Angelo Taglietti
The last decade came across an increasing demand of theranostic biocompatible nanodevices, possessing the double ability of diagnosis and therapy. In this work, we report the design, synthesis and step-by-step characterization of rationally coated gold nanostars (GNS) for SERS imaging and photothermal therapy (PTT) of HeLa cancer cells. The nanodevice was realized synthesizing GNS with a seed-growth approach, coating them with a controlled mixture of thiols composed of a Raman reporter and a polyethylenglicol with a terminal amino group, and then reacting these amino groups with Folic Acid (FA), in order to impart selectivity towards cancer cells which overexpress folate receptors on their membranes...
March 16, 2018: Nanotechnology
Guillermo Montalban-Bravo, Courtney D DiNardo
Isocitrate dehydrogenases (IDHs) are enzymes involved in multiple metabolic and epigenetic cellular processes. Mutations in IDH1 or IDH2 are detected in approximately 20% of patients with acute myeloid leukemia (AML) and induce amino acid changes in conserved residues resulting in neomorphic enzymatic function and production of an oncometabolite, 2-hydroxyglutarate (R-2-HG). This leads to DNA hypermethylation, aberrant gene expression, cell proliferation and abnormal differentiation. IDH mutations diversely affect prognosis of patients with AML based on the location of the mutation and other co-occurring genomic abnormalities...
March 15, 2018: Future Oncology
Michael V Fiandalo, John J Stocking, Elena A Pop, John H Wilton, Krystin M Mantione, Yun Li, Kristopher M Attwood, Gissou Azabdaftari, Yue Wu, David S Watt, Elizabeth M Wilson, James L Mohler
Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues...
February 16, 2018: Oncotarget
Matthew Dankner, April A N Rose, Shivshankari Rajkumar, Peter M Siegel, Ian R Watson
The RAS-RAF-MEK-ERK signaling cascade is among the most frequently mutated pathways in human cancer. Approximately 50% of melanoma patients possess a druggable hotspot V600E/K mutation in the BRAF protein kinase. FDA-approved combination therapies of BRAF and MEK inhibitors are available that provide survival benefits to patients with a BRAF V600 mutation. Non-V600 BRAF mutants are found in many cancers, and are more prevalent than V600 mutations in certain tumor types. For example, between 50-80% of BRAF mutations in non-small cell lung cancer and 22-30% in colorectal cancer encode for non-V600 mutants...
March 15, 2018: Oncogene
Nicla Porciello, Paola Grazioli, Antonio F Campese, Martina Kunkl, Silvana Caristi, Marta Mastrogiovanni, Michela Muscolini, Francesca Spadaro, Cédric Favre, Jacques A Nunès, Aldo Borroto, Balbino Alarcon, Isabella Screpanti, Loretta Tuosto
CD28 superagonistic antibodies (CD28SAb) can preferentially activate and expand immunosuppressive regulatory T cells (Treg) in mice. However, pre-clinical trials assessing CD28SAbs for the therapy of autoimmune diseases reveal severe systemic inflammatory response syndrome in humans, thereby implying the existence of distinct signalling abilities between human and mouse CD28. Here, we show that a single amino acid variant within the C-terminal proline-rich motif of human and mouse CD28 (P212 in human vs. A210 in mouse) regulates CD28-induced NF-κB activation and pro-inflammatory cytokine gene expression...
March 14, 2018: Nature Communications
Tomas Majtan, Erez M Bublil, Insun Park, Erland Arning, Teodoro Bottiglieri, Frank Glavin, Jan P Kraus
AIMS: PEGylated human truncated cystathionine beta-synthase, lacking the C-terminal regulatory domain (PEG-CBS), is a promising preclinical candidate for enzyme replacement therapy in homocystinuria (HCU). It was designed to function as a metabolic sink to decrease the severely elevated plasma and tissue homocysteine concentrations. Here we evaluated pharmacokinetics (PK), pharmacodynamics (PD) and sub-chronic toxicity of PEG-CBS in homocystinuric mice and wild type rats and monkeys to estimate the minimum human efficacious dose for clinical trials...
March 8, 2018: Life Sciences
Yusuf Menda, Mark T Madsen, Thomas M O'Dorisio, John Sunderland, Leonard G Watkins, Joseph S Dillon, Sarah L Mott, Michael King Schultz, Gideon K D Zamba, David L Bushnell, M Sue O'Dorisio
Pre-therapy PET imaging with86 Y-DOTATOC PET is considered the ideal dosimetry protocol for90 Y-DOTATOC therapy; however, its cost, low availability and the need for infusion of amino acids to mimic the therapy administration limit its use in the clinical setting. Objectives: To develop a dosimetric method for90 Y-DOTATOC therapy using90 Y-DOTATOC PET/CT and Bremsstrahlung SPECT/CT imaging and to determine if dosimetry-based administered activities differed significantly from standard administered dosages. Materials and Methods: This is a prospective Phase 2 trial of90 Y-DOTATOC therapy in patients with somatostatin receptor positive tumors...
March 9, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Hernán Gonzalo Villagarcía, María Cecilia Castro, Luisa González Arbelaez, Guillermo Schinella, María Laura Massa, Eduardo Spinedi, Flavio Francini
AIM: Hypothalamic obese rats are characterized by pre-diabetes, dyslipidemia, hyperadiposity, inflammation and, liver dysmetabolism with oxidative stress (OS), among others. We studied endocrine-metabolic dysfunctions and, liver OS and inflammation in both monosodium l-glutamate (MSG)-neonatally damaged and control litter-mate (C) adult male rats, either chronically treated with N-Acetyl-l-Cysteine since weaned (C-NAC and MSG-NAC) or not. METHODOLOGY: We evaluated circulating TBARS, glucose, insulin, triglycerides, uric acid (UA) and, aspartate and alanine amino-transferase; insulin sensitivity markers (HOMA indexes, Liver Index of Insulin Sensitivity -LISI-) were calculated and liver steps of the insulin-signaling pathway were investigated...
March 6, 2018: Life Sciences
Leyi Wei, Jijun Tang, Quan Zou
BACKGROUND: Cell-penetrating peptides (CPPs) are short peptides (5-30 amino acids) that can enter almost any cell without significant damage. On account of their high delivery efficiency, CPPs are promising candidates for gene therapy and cancer treatment. Accordingly, techniques that correctly predict CPPs are anticipated to accelerate CPP applications in future therapeutics. Recently, computational methods have been reportedly successful in predicting CPPs. Unfortunately, the predictive performance of existing methods is not satisfactory and reliable so as to accurately identify CPPs...
October 16, 2017: BMC Genomics
Yuichi Uchino, Masafumi Watanabe, Munenori Takata, Eisuke Amiya, Kensuke Tsushima, Takeshi Adachi, Yukio Hiroi, Toshikazu Funazaki, Issei Komuro
BACKGROUND: We conducted a randomized, controlled trial to determine whether supplementation with oral branched-chain amino acids (BCAAs) improves serum albumin and clinical outcomes in heart failure (HF) patients with hypoalbuminemia. METHODS AND RESULTS: We randomly assigned 18 in-hospital HF patients with serum albumin < 3.5 g/dL to receive oral BCAA granules (LIVACT® ) for 28 days during their hospital stay or until discharge (BCAA group; N = 9) or to receive no supplementation (controls; N = 9), in addition to recommended HF therapy...
March 6, 2018: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Junji Itou, Wenzhao Li, Shinji Ito, Sunao Tanaka, Yoshiaki Matsumoto, Fumiaki Sato, Masakazu Toi
Sal-like 4 (SALL4) is a transcription factor that enhances proliferation and migration in breast cancer cells. SALL4 expression therefore has the potential to promote cancer malignancy. However, the regulatory mechanisms involved in SALL4 protein expression have not been thoroughly elucidated. In this study, we observed that treating MCF-7 and SUM159 breast cancer cell lines with a proteasome inhibitor increases SALL4 protein levels, suggesting that SALL4 is degraded by the ubiquitin-proteasome system. Using immunoprecipitation to uncover SALL4-binding proteins, we identified an E3 ubiquitin protein ligase, tripartite motif-containing 21 (TRIM21)...
March 6, 2018: Journal of Biological Chemistry
Noelia Clemente Plaza, Manuel Reig García-Galbis, Rosa María Martínez-Espinosa
This review summarizes recent knowledge about the use of the amino acid l-Cysteine (l-Cys) through diet, nutritional supplements or drugs with the aim to improve human health or treat certain diseases. Three databases (PubMed, Scopus, and Web of Science) and different keywords have been used to create a database of documents published between 1950 and 2017 in scientific journals in English or Spanish. A total of 60,885 primary publications were ultimately selected to compile accurate information about the use of l-Cys in medicine and nutritional therapies and to identify the reported benefits of l-Cys on human health...
March 3, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Liyan Hou, Yuning Che, Fuqiang Sun, Qingshan Wang
Beyond nigrostriatal dopaminergic system, the noradrenergic locus coeruleus (LC/NE) neurons are also degenerated in patients with Parkinson's disease (PD), the second most common neurodegenerative disorder. We previously reported that microglia-mediated neuroinflammation contributes to LC/NE neurodegeneration. The purpose of this study is aimed to test whether taurine, an endogenous amino acid, could be able to protect LC/NE neurons through inhibition of microglial activation using paraquat and maneb-induced mouse PD model...
March 5, 2018: Amino Acids
Takahiro Kamiya, Desmond Wong, Yi Tian Png, Dario Campana
Practical methods are needed to increase the applicability and efficacy of chimeric antigen receptor (CAR) T-cell therapies. Using donor-derived CAR-T cells is attractive, but expression of endogenous T-cell receptors (TCRs) carries the risk for graft-versus-host-disease (GVHD). To remove surface TCRαβ, we combined an antibody-derived single-chain variable fragment specific for CD3ε with 21 different amino acid sequences predicted to retain it intracellularly. After transduction in T cells, several of these protein expression blockers (PEBLs) colocalized intracellularly with CD3ε, blocking surface CD3 and TCRαβ expression...
March 13, 2018: Blood Advances
Abeer K Malkawi, Karem H Alzoubi, Minnie Jacob, Goran Matic, Asmaa Ali, Achraf Al Faraj, Falah Almuhanna, Majed Dasouki, Anas M Abdel Rahman
Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats...
2018: Frontiers in Pharmacology
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