7,775 results match your criteria occurred dose-dependent

A phase 1b/2a study of soticlestat as adjunctive therapy in participants with developmental and/or epileptic encephalopathies.

Epilepsy Res 2021 Apr 22;174:106646. Epub 2021 Apr 22.

New York University Langone, New York, NY, USA.

Objective: To evaluate the safety, tolerability, and pharmacokinetics of soticlestat, a first-in-class cholesterol 24-hydroxylase inhibitor, in adults with developmental and/or epileptic encephalopathies (DEE).

Methods: The study comprised a 30-day, randomized, double-blind, placebo-controlled phase (Part A), followed by a 55-day open-label phase (Part B) (ClinicalTrials.gov ID: NCT03166215) . Read More

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Synthesis of dihydrotestosterone derivatives modified in the A-ring with (hetero)arylidene, pyrazolo[1,5-a]pyrimidine and triazolo[1,5-a]pyrimidine moieties and their targeting of the androgen receptor in prostate cancer.

J Steroid Biochem Mol Biol 2021 Apr 29:105904. Epub 2021 Apr 29.

Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720, Szeged, Hungary. Electronic address:

One of the main directions of steroid research is the preparation of modified derivatives in which, in addition to changes in physicochemical properties, receptor binding is significantly altered, thus a bioactivity different from that of the parent compound predominates. In the frame of this work, 2-arylidene derivatives were first synthesized by regioselective modification of the A-ring of natural sex hormone, 5α-dihydrotestosterone (DHT). After Claisen-Schmidt condensations of DHT with (hetero)aromatic aldehydes in alkaline EtOH, heterocyclizations of the α,β-enones were performed with 3-amino-1,2,4-triazole, 3-aminopyrazole and 3-amino-5-methylpyrazole in the presence of t-BuOK in DMF to afford 7'-epimeric mixtures of A-ring-fused azolo-dihydropyrimidines, respectively. Read More

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The familial risk of infection-related hospitalization in children: A population-based sibling study.

PLoS One 2021 28;16(4):e0250181. Epub 2021 Apr 28.

Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.

Objective: To assess the risk of severe childhood infections within families, we conducted a sibling analysis in a population-based cohort study with genealogical linkage. We investigated the sibling risk of hospitalization with common infections, a marker of severity. We hypothesized that having siblings hospitalized for infection would increase the proband's risk of admission with infection. Read More

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Association Between Incident Delirium Treatment With Haloperidol and Mortality in Critically Ill Adults.

Crit Care Med 2021 Apr 5. Epub 2021 Apr 5.

1 Department of Pharmacy and Health Systems Sciences, Bouve College of Health Sciences, Northeastern University, Boston, MA. 2 Department of Intensive Care, Radboud Institute for Health Science, Radboud University Medical Center, Nijmegen, NL. 3 Department of Health Sciences, Bouve College of Health Sciences, Northeastern University, Boston, MA.

Objectives: Haloperidol is commonly administered in the ICU to reduce the burden of delirium and its related symptoms despite no clear evidence showing haloperidol helps to resolve delirium or improve survival. We evaluated the association between haloperidol, when used to treat incident ICU delirium and its symptoms, and mortality.

Design: Post hoc cohort analysis of a randomized, double-blind, placebo-controlled, delirium prevention trial. Read More

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A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors.

Invest New Drugs 2021 Apr 14. Epub 2021 Apr 14.

Eli Lilly and Company, Indianapolis, IN, USA.

Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. Read More

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A study of Pb induced unfolding and aggregation of arginine kinase from : kinetics and computational simulation integrating study.

J Biomol Struct Dyn 2021 Apr 13:1-10. Epub 2021 Apr 13.

College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, P.R. China.

Arginine kinase is a crucial phosphagen kinase in invertebrates, which is associated to the environmental stress response, plays a key role in cellular energy metabolism. In this study, we investigated the Pb-induced inhibition and aggregation of arginine kinase (ESAK) and found that significantly inactivated ESAK in a dose-dependent manner (50 = 0.058 ± 0. Read More

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Y90 Radioembolization to the Prostate Gland: Proof of Concept in a Canine Model and Clinical Translation.

J Vasc Interv Radiol 2021 Apr 8. Epub 2021 Apr 8.

Purpose: The feasibility, safety and absorbed dose distribution of prostate artery (PA) radioembolization (RE) was investigated in a canine model.

Materials And Methods: 14 male castrated beagles received dihydroandrosterone/estradiol to induce prostatic hyperplasia for the duration of the study. Each dog underwent fluoroscopic PA catheterization. Read More

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Opioid Use Increases the Risk of Delirium in Critically Ill Adults Independently of Pain.

Am J Respir Crit Care Med 2021 Apr 9. Epub 2021 Apr 9.

University Medical Center, Utrecht University, Department of Intensive Care Medicine, Utrecht, Netherlands.

Rationale: It is unclear whether opioid use increases the risk of ICU delirium. Prior studies have not accounted for confounding including daily severity of illness, pain and competing events that may preclude delirium detection.

Objectives: To evaluate the association between ICU opioid exposure, opioid dose, and delirium occurrence. Read More

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Phase I study of tamibarotene monotherapy in pediatric and young adult patients with recurrent/refractory solid tumors.

Cancer Chemother Pharmacol 2021 Apr 7. Epub 2021 Apr 7.

Clinical Research Support Office, National Cancer Center Hospital East, Chiba, Japan.

Purpose: Tamibarotene is a synthetic retinoid that inhibits proliferation and induces differentiation of malignant cells by binding to the retinoic acid receptor α/β. Previous in vitro studies have shown that some pediatric solid tumors with retinoic acid receptors differentiate in response to retinoic acid. We conducted a phase I dose-escalation study to determine the recommended dose of tamibarotene for further study in pediatric and young adult patients with recurrent/refractory solid tumors. Read More

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Cassia Abbreviata Enhances Glucose Uptake and Glucose Transporter 4 Translocation in C2C12 Mouse Skeletal Muscle Cells.

J Evid Based Integr Med 2021 Jan-Dec;26:2515690X211006333

Department of Biomedical Sciences, Tshwane University of Technology, Private Bag Pretoria, South Africa.

Background.: This study aim at assessing aqueous extracts for its potential to exhibit anti-diabetic activity in skeletal muscle cells. In addition to the toxicological and glucose absorption studies, the action of extracts on some major genes involved in the insulin signaling pathway was established. Read More

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Toxicity of the insecticide sulfoxaflor alone and in combination with the fungicide fluxapyroxad in three bee species.

Sci Rep 2021 Mar 25;11(1):6821. Epub 2021 Mar 25.

Dipartimento di Scienze e Tecnologie Agro-Alimentari, Alma Mater Studiorum Università di Bologna, Viale Fanin 42, 40127, Bologna, Italy.

The sulfoximine insecticide sulfoxaflor is regarded as a potential substitute for neonicotinoids that were recently banned in the EU due to their side effects on bees. Like neonicotinoids, sulfoxaflor acts as a competitive modulator of nicotinic acetylcholine receptors. In agricultural environments, bees are commonly exposed to combinations of pesticides, and neonicotinoids are known to interact synergistically with fungicides. Read More

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Xylooligosaccharides induce stomatal closure via salicylic acid signaling-regulated reactive oxygen species and nitric oxide production in Arabidopsis.

Physiol Plant 2021 Mar 23. Epub 2021 Mar 23.

Department of Plant Pathology, College of Plant Protection, Anhui Agricultural University, Key Laboratory of Biology and Sustainable Management of Plant Diseases and Pests of Anhui Higher Education Institutes, Hefei, Anhui, China.

Xylooligosaccharides (XOS) are the major coproducts of biofuel production and the most representative functional sugar enhancing animal physiology. However, little is known regarding the biological relevance of XOS to plants. Here, we found XOS triggered stomatal closure in Arabidopsis in a dose-dependent manner. Read More

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Third-generation cephalosporin resistance in clinical isolates of Enterobacterales collected between 2016-2018 from USA and Europe: genotypic analysis of β-lactamases and comparative in vitro activity of cefepime/enmetazobactam.

J Glob Antimicrob Resist 2021 Mar 18;25:93-101. Epub 2021 Mar 18.

Allecra Therapeutics SAS, St Louis, France.

Objectives: This study aimed to investigate third-generation cephalosporin (3GC) resistance determinants [extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases and OXA-type β-lactamases] in contemporary clinical Enterobacterales isolates and to determine the in vitro activity of β-lactams and β-lactam/β-lactamase inhibitor combinations, including the investigational combination of cefepime and the novel β-lactamase inhibitor enmetazobactam.

Methods: Antibacterial susceptibility of 7168 clinical Enterobacterales isolates obtained between 2016-2018 from North America and Europe was determined according to CLSI guidelines. Phenotypic resistance to the 3GC ceftazidime (MIC ≥ 16 µg/mL) and/or ceftriaxone (MIC ≥ 4 µg/mL) but retaining susceptibility to meropenem (MIC ≤ 1 µg/mL) was determined. Read More

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Inhaled JAK inhibitor GDC-0214 reduces exhaled nitric oxide in patients with mild asthma: A randomized, controlled, proof-of-activity trial.

J Allergy Clin Immunol 2021 Mar 17. Epub 2021 Mar 17.

Genentech, Inc, South San Francisco, Calif.

Background: The Janus kinase (JAK) pathway mediates the activity of many asthma-relevant cytokines, including IL-4 and IL-13. GDC-0214 is a potent, inhaled, small-molecule JAK inhibitor being developed for the treatment of asthma.

Objective: We sought to determine whether GDC-0214 reduces fractional exhaled nitric oxide (Feno), a JAK1-dependent biomarker of airway inflammation, in patients with mild asthma. Read More

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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HBM9161, a novel FcRn inhibitor, in a Phase 1 Study for Healthy Chinese Volunteers.

Clin Transl Sci 2021 Mar 20. Epub 2021 Mar 20.

Harbour Biomed, Inc, Shanghai, China.

Blockade of the binding between Neonatal Fc receptor (FcRn) and IgG-Fc reduces circulating IgG, and thus emerges as a potential therapy for IgG-mediated autoimmune conditions. This was a double blind, randomized, single ascending dose study to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of HBM9161 (a humanized FcR monoclonal antibody) in healthy Chinese volunteers. Subjects were randomized to receive a single SC dose of HBM9161 or placebo in a 3:1 ratio in three dosing cohorts (340 mg, 510 mg, or 680 mg respectively), and then followed up for 85 days. Read More

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Oncolytic herpes simplex virus infects myeloma cells and .

Mol Ther Oncolytics 2021 Mar 18;20:519-531. Epub 2021 Feb 18.

Department of Hematology and Hematopoietic Cell Transplantation, Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, Monrovia, CA 91016, USA.

Because most patients with multiple myeloma (MM) develop resistance to current regimens, novel approaches are needed. Genetically modified, replication-competent oncolytic viruses exhibit high tropism for tumor cells regardless of cancer stage and prior treatment. Receptors of oncolytic herpes simplex virus 1 (oHSV-1), NECTIN-1, and HVEM are expressed on MM cells, prompting us to investigate the use of oHSV-1 against MM. Read More

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Phenotypic and genomic characterization of ITEM 17297 spoiler of fresh vegetables: Focus on biofilm and antibiotic resistance interaction.

Curr Res Food Sci 2021 16;4:74-82. Epub 2021 Feb 16.

Institute of Sciences of Food Production, National Research Council of Italy, V. G. Amendola 122/O, 70126, Bari, Italy.

is widely recognized as a spoiler of fresh foods under cold storage, and recently associated also with infections in clinical settings. The presence of antibiotic resistance genes (ARGs) could be acquired and transmitted by horizontal genetic transfer and further increase the risk associated with its persistence in food and the need to be deeper investigated. Thus, in this work we presented a genomic and phenotypic analysis of the psychrotrophic ITEM 17297 to provide new insight into AR mechanisms by this species until now widely studied only for its spoilage traits. Read More

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February 2021

Chemoprotective effect of atorvastatin against benzo(a)pyrene-induced lung cancer via the inhibition of oxidative stress and inflammatory parameters.

Ann Transl Med 2021 Feb;9(4):355

Department of Respiratory, Affiliated Xi'an Central Hospital, The Medical School of Xi'an Jiaotong University, Xi'an, China.

Background: Lung cancer affects approximately 9% of women and 17% of men worldwide, and has a mortality rate of 17%. Previously published studies have suggested that oxidative stress expansion can lead to lung cancer. The aim of the current study was to analyze the possible inhibitory pathway of atorvastatin against lung cancer cells in an model. Read More

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February 2021

The CD44high Subpopulation of Multifraction Irradiation-Surviving NSCLC Cells Exhibits Partial EMT-Program Activation and DNA Damage Response Depending on Their p53 Status.

Int J Mol Sci 2021 Feb 27;22(5). Epub 2021 Feb 27.

School of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, Moscow Region, Russia.

Ionizing radiation (IR) is used for patients diagnosed with unresectable non-small cell lung cancer (NSCLC). However, radiotherapy remains largely palliative due to the survival of specific cell subpopulations. In the present study, the sublines of NSCLC cells, A549IR (p53wt) and H1299IR (p53null) survived multifraction X-ray radiation exposure (MFR) at a total dose of 60 Gy were investigated three weeks after the MFR course. Read More

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February 2021

Effects of Doxorubicin on Heme Biosynthesis and Metabolism in Cardiomyocyte.

Arq Bras Cardiol 2021 02;116(2):315-322

Capital Medical University Affiliated Beijing Shijitan Hospital,Beijing - China.

Background: Doxorubicin is associated with cardiotoxicity and late cardiac morbidity. Heme is related to cellular oxidative stress. However, its specific regulation in cardiomyocytes under doxorubicin effects has not yet been documented. Read More

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February 2021

[Preclinical and clinical efficacy of orexin receptor antagonist Lemborexant (Dayvigo) on insomnia patients].

Nihon Yakurigaku Zasshi 2021 ;156(2):114-119

Medical Headquarters, Eisai Co., Ltd.

Orexin receptor antagonists have been approved for insomnia, and the insomnia pharmacotherapy is being greatly progressed. Orexin is a neuropeptide produced in the lateral hypothalamic area, and its physiological role has been suggested to be a key mediator controlling the sleep-wake state. Orexin receptor antagonists are thought to induce physiological sleep by acting specifically on the sleep-wake cycle. Read More

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AQP8 participates in oestrogen-mediated buffalo follicular development by regulating apoptosis of granulosa cells.

Reprod Domest Anim 2021 Feb 27. Epub 2021 Feb 27.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, Guangxi University, Nanning, China.

Aquaporins (AQPs), a family of small membrane-spanning proteins, are involved in fluid transport, cell signalling and reproduction. Regulating AQP8 expression influences apoptosis of granulosa cells (GCs), ovarian folliculogenesis, oogenesis and early embryonic development in mice, but its role has never been investigated in other species. The aim of the present study was to characterize the AQP8 function in buffalo follicular development. Read More

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February 2021

LY3022855, an anti-colony stimulating factor-1 receptor (CSF-1R) monoclonal antibody, in patients with advanced solid tumors refractory to standard therapy: phase 1 dose-escalation trial.

Invest New Drugs 2021 Feb 23. Epub 2021 Feb 23.

Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, 1310D Lincoln Tower, 1800 Cannon Drive, Columbus, OH, 43210, USA.

Background Tumor-associated macrophages (TAMs) promote tumor growth, metastasis, and therapeutic resistance via colony-stimulating factor-1 (CSF-1), acting through CSF-1 receptor (CSF-1R) signaling. This phase 1 study determined the safety, tolerability, pharmacokinetics-pharmacodynamics, immunogenicity, and efficacy of the anti-CSF-1R antibody LY3022855 in solid tumors. Methods Patients with advanced solid tumors refractory to standard therapy were enrolled and treated in 2 dosing cohorts: weight-based (part A) and non-weight-based (part B). Read More

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February 2021

Toxicological evaluation of the ketogenic ester bis hexanoyl (R)-1,3-butanediol: Subchronic toxicity in Sprague Dawley rats.

Food Chem Toxicol 2021 Apr 20;150:112084. Epub 2021 Feb 20.

Buck Institute for Research on Aging, CA, USA; Division of Geriatrics, UCSF, CA, USA.

Bis-hexanoyl (R)-1,3-butanediol (BH-BD) is novel ketone ester undergoing development as a food ingredient to achieve nutritional ketosis in humans. Male and female Crl:CD(SD) rats were administered BH-BD twice daily at 9000, 12,000 or 15,000 mg/kg/day, by oral gavage in a 90-day toxicity study with 28-day recovery period; and an interim 28-day phase. Test substance-related early deaths occurred in four females at 15,000 mg/kg/day. Read More

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Novel method to analyze cell kinetics for the rapid diagnosis and determination of the causative agent in allergy.

PLoS One 2021 19;16(2):e0246125. Epub 2021 Feb 19.

Department of Hospital Pharmacy, Fukuoka University Hospital, Fukuoka, Japan.

Drug-induced allergy (DIA), an unexpectedly triggered side effect of drugs used for therapeutic purposes, is a serious clinical issue that needs to be resolved because it interrupts the treatment of the primary disease. Since conventional allergy testing is insufficient to accurately predict the occurrence of DIA or to determine the drugs causing it, the development of diagnostic and predictive tools for allergic reactions is important. We demonstrated a novel method, termed high-sensitive allergy test (HiSAT), for the rapid diagnosis of allergy (within 1 hr; with true-positive diagnosis rates of 89% and 9% for patients with and without allergy-like symptoms, respectively). Read More

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February 2021

Unfermented Freeze-Dried Leaf Extract of ( Jack.) Induced Cytotoxicity and Apoptosis in MDA-MB-231 and MCF-7 Breast Cancer Cell Lines.

Evid Based Complement Alternat Med 2021 30;2021:8811236. Epub 2021 Jan 30.

Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Jalan UMS, Kota Kinabalu, Sabah 88400, Malaysia.

The present study was conducted to determine the cytotoxicity effect of (Jack.) leaf extracts and also its possible anticancer mechanism of action against breast cancer cell lines: non-hormone-dependent MDA-MB-231 and hormone-dependent MCF-7. The leaves of were processed into unfermented and fermented batches before drying using freeze and microwave-oven drying techniques. Read More

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January 2021

Biocompatibility of self-adhesive resin cement with fibroblast cells.

J Prosthet Dent 2021 Apr 15;125(4):705.e1-705.e7. Epub 2021 Feb 15.

Professor, Centro de Investigação interdisciplinar Egas Moniz (CiiEM), Instituto Universitário Egas Moniz, Caparica, Portugal. Electronic address:

Statement Of Problem: Dental cements that release monomers that negatively impact adjacent oral soft tissues may adversely affect clinical outcomes. However, in vitro studies evaluating the cytotoxic and genotoxic potential of substances released from dental cements are lacking.

Purpose: The purpose of this in vitro study was to define and compare the cytotoxicity and genotoxicity of the eluates of a self-adhesive resin cement (RelyX Unicem 2 Automix) autopolymerized and light polymerized with 2 other types of luting cements: a glass ionomer cement (Ketac Cem Easymix) and a resin-modified glass ionomer cement (Ketac Cem Plus). Read More

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Relation between coffee consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy.

Epilepsia 2021 Mar 14;62(3):765-777. Epub 2021 Feb 14.

Department of Functional Neurology and Epileptology, Hospices Civils de Lyon and University of Lyon, Lyon, France.

Objective: Caffeine is an antagonist of the adenosine pathway, which is involved in regulation of breathing. Extracellular concentrations of adenosine are increased in the immediate aftermath of a seizure. Seizure-related overstimulation of adenosine receptors might promote peri-ictal apnea. Read More

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A randomized single and multiple ascending dose study in healthy volunteers of LTI-291, a centrally penetrant glucocerebrosidase activator.

Br J Clin Pharmacol 2021 Feb 11. Epub 2021 Feb 11.

Centre for Human Drug Research, Leiden, The Netherlands.

Aims: A mutation in the GBA1 gene is the most common genetic risk factor for developing Parkinson's disease. GBA1 encodes the lysosomal enzyme glucosylceramidase beta (glucocerebrosidase, GCase) and mutations decrease enzyme activity. LTI-291 is an allosteric modulator of GCase, enhancing its activity. Read More

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February 2021

Nanomolar melatonin influences insulin synthesis and secretion in rat insulinoma INS-1E cells.

J Physiol Pharmacol 2020 Oct 8;71(5). Epub 2021 Feb 8.

East Coast Life Sciences institute, College of Life Science, Gangneung-Wonju National University, Gangneung, Gangwon-do, Republic of Korea.

Pancreatic beta-cell dysfunction results in reductions of insulin synthesis/secretion, cell survival, and insulin sensitivity thereby inducing diabetes mellitus. In this study, how nanomolar melatonin regulates insulin synthesis and secretion in rat insulinoma INS-1E cells was investigated. At melatonin concentrations of 10 - 100 nM for 48 hours, melatonin significantly increased the insulin protein level in INS-1E cells above the level in control cells without melatonin or glucose treatments and decreased the insulin level in media with glucose: increases in insulin synthesis and decreases in insulin secretion occurred in dose-dependent manners. Read More

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October 2020