199,814 results match your criteria plasma concentrations

Comprehensive in vitro pro-arrhythmic assays demonstrate that omecamtiv mecarbil has low pro-arrhythmic risk.

Clin Transl Sci 2021 May 5. Epub 2021 May 5.

Amgen Research, Safety Pharmacology and Animal Research Center, Amgen Inc., Thousand Oaks, California, USA.

Omecamtiv mecarbil (OM) is a myosin activator (myotrope), developed as a potential therapeutic agent for heart failure with reduced ejection fraction. To characterize the potential pro-arrhythmic risk of this novel sarcomere activator, we evaluated OM in a series of International Conference on Harmonization S7B core and follow-up assays, including an in silico action potential (AP) model. OM was tested in: (i) hERG, Nav1. Read More

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Bioequivalence Study of Oral Suspension and Intravenous Formulation of Edaravone in Healthy Adult Subjects.

Clin Pharmacol Drug Dev 2021 May 6. Epub 2021 May 6.

Mitsubishi Tanabe Pharma Corporation, Chuo-ku, Tokyo, Japan.

The neuroprotective agent edaravone is an intravenous treatment for amyotrophic lateral sclerosis. As intravenous administration burdens patients, orally administered treatments are needed. This phase 1, open-label, single-dose crossover study in 42 healthy adults evaluated bioequivalence of a 105-mg edaravone oral suspension and intravenous edaravone (60 mg/60 min). Read More

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Simple TLC-spectrodensitometric method for studying lipophilicity and quantitative analysis of hypoglycemic drugs in their binary mixture.

Biomed Chromatogr 2021 May 5:e5154. Epub 2021 May 5.

Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt.

A selective and simple salting out assisted thin layer chromatographic methodology was developed for the simultaneous determination of two oral hypoglycemic drugs; namely dapagliflozin (DAPA) and metformin (MET) in their pure forms, tablets, and spiked human plasma samples. Silica gel 60 F plates were used in the separation of the two drugs using mobile phase consisting of; 0.5 M (NH ) SO and methanol (3: 7, v/v). Read More

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Quantification of Plasma Oxylipins Using Solid-Phase Extraction and Reversed-Phase Liquid Chromatography-Triple Quadrupole Mass Spectrometry.

Methods Mol Biol 2021 ;2306:171-186

Center for Translational Biomedical Research, University of North Carolina at Greensboro, Kannapolis, NC, USA.

Oxylipins are an important class of bioactive lipids derived from polyunsaturated fatty acids. They can be both pro- and anti-inflammatory and function as important mediators in various pathological conditions. However, comprehensive analysis of oxylipins still remains a challenge because of their low abundance in plasma and the dominance of structurally similar isomeric species. Read More

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January 2021

Population pharmacodynamic modeling of intramuscular and oral dexamethasone and betamethasone effects on six biomarkers with circadian complexities in Indian women.

J Pharmacokinet Pharmacodyn 2021 May 5. Epub 2021 May 5.

School of Pharmacy and Pharmaceutical Sciences, State University of New York, University at Buffalo, Buffalo, NY, USA.

Population pharmacokinetic/pharmacodynamic (PK/PD) analysis was performed for extensive data for differing dosage forms and routes for dexamethasone (DEX) and betamethasone (BET) in 48 healthy nonpregnant Indian women in a partial and complex cross-over design. Single doses of 6 mg dexamethasone phosphate (DEX-P), betamethasone phosphate (BET-P), or 1:1 mixture of betamethasone phosphate and acetate (BET-PA) were administered orally (PO) or intramuscularly (IM) where each woman enrolled in a two-period cross-over study. Plasma concentrations collected over 96 h were described with a two-compartment model with differing PO and IM first-order absorption inputs. Read More

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Micro-droplet-based calibration for quantitative elemental bioimaging by LA-ICPMS.

Anal Bioanal Chem 2021 May 5. Epub 2021 May 5.

Institute of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Strasse 38, 1090, Vienna, Austria.

In this work, a novel standardization strategy for quantitative elemental bioimaging is evaluated. More specifically, multi-element quantification by laser ablation-inductively coupled plasma-time-of-flight mass spectrometry (LA-ICP-TOFMS) is performed by multi-point calibration using gelatin-based micro-droplet standards and validated using in-house produced reference materials. Fully automated deposition of micro-droplets by micro-spotting ensured precise standard volumes of 400 ± 5 pL resulting in droplet sizes of around 200 μm in diameter. Read More

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Evaluation of Internal Exposure to Radioactive Aerosol Generated From Plasma Melting System Using the Bidas Code.

Radiat Prot Dosimetry 2021 May 6. Epub 2021 May 6.

Department of Nuclear Engineering, Chosun University, Pilmundae-ro 309, Dong-gu, Gwangju KS008, Republic of Korea.

The radioactive aerosol generated by the Nuclear Power Plant (NPP) decommissioning process can be inhaled by workers and deposited inside the human body, resulting in internal exposure. Because internal exposure, unlike external exposure, is difficult to measure directly, it is all the more necessary to assess the dose workers receive as a result of internal exposure. Precise assessment of the internal exposure necessitates actual measurements in the work environment such as the workers' respiration rate, kind of nuclide and amount of captured nuclide. Read More

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Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis.

Can J Infect Dis Med Microbiol 2021 12;2021:5497427. Epub 2021 Apr 12.

Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Purpose: Invasive aspergillosis is a prevalent fungal disease, especially in Asian countries with a high mortality rate. Voriconazole (VRZ) is the first choice for invasive aspergillosis treatment. Plasma concentration of this drug is unpredictable and varies among individuals. Read More

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The Architecture of Circulating Immune Cells Is Dysregulated in People Living With HIV on Long Term Antiretroviral Treatment and Relates With Markers of the HIV-1 Reservoir, Cytomegalovirus, and Microbial Translocation.

Front Immunol 2021 19;12:661990. Epub 2021 Apr 19.

Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.

Long-term changes in the immune system of successfully treated people living with HIV (PLHIV) remain incompletely understood. In this study, we assessed 108 white blood cell (WBC) populations in a cohort of 211 PLHIV on stable antiretroviral therapy and in 56 HIV-uninfected controls using flow cytometry. We show that marked differences exist in T cell maturation and differentiation between PLHIV and HIV-uninfected controls: PLHIV had reduced percentages of CD4+ T cells and naïve T cells and increased percentages of CD8+ T cells, effector T cells, and T helper 17 (Th17) cells, together with increased Th17/regulatory T cell (Treg) ratios. Read More

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No Relevant Pharmacokinetic Drug-Drug Interaction Between the Sodium-Glucose Co-Transporter-2 Inhibitor Empagliflozin and Lobeglitazone, a Peroxisome Proliferator-Activated Receptor-γ Agonist, in Healthy Subjects.

Drug Des Devel Ther 2021 28;15:1725-1734. Epub 2021 Apr 28.

Department of Clinical Pharmacology and Therapeutics, Chungbuk National University College of Medicine and Hospital, Cheongju, Republic of Korea.

Purpose: Combination therapy with insulin-independent sodium-glucose cotransporter 2 inhibitors and thiazolidinedione drugs, such as lobeglitazone, has been reported to elicit potential additive efficacy in glycemic control in type 2 diabetes mellitus. This study was conducted to evaluate the pharmacokinetic (PK) drug-drug interactions between empagliflozin and lobeglitazone in healthy subjects.

Subjects And Methods: A randomized, open-label, multiple-dose study was conducted in 30 healthy subjects using a three-treatment, six-sequence, three-way crossover design. Read More

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Metabolic Properties of Lowdensity Lipoprotein (LDL) Triglycerides in Patients with Type 2 Diabetes, Comparison with Small Dense LDL-Cholesterol.

J Atheroscler Thromb 2021 Apr 29. Epub 2021 Apr 29.

R&D Department, Denka Co., Ltd.

Aims: Abnormal compositional changes in low-density lipoprotein (LDL) particles, such as triglyceride (TG) enrichment and size reduction, are common in patients with diabetes. Several cohort studies have demonstrated that LDL-TG and sdLDL-cholesterol (C) are sensitive biomarkers for predicting atherosclerotic cardiovascular diseases beyond LDL-C. Although sdLDL has been extensively studied, little is known about the properties of LDL-TG. Read More

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Pharmacokinetic and Adsorptive Analyses of Administration of Oral Voriconazole Suspension via Enteral Feeding Tube in Intensive Care Unit Patients.

Biol Pharm Bull 2021 ;44(5):737-741

Department of Clinical Pharmacy, Oita University Hospital.

For intensive care unit (ICU) patients, injectable voriconazole (VRCZ) is difficult to use because the patients often develop acute kidney injury. Since many ICU patients have consciousness disturbance, oral ingestion of tablet formulation is also difficult, and administration of a suspension via enteral feeding tube is required when using VRCZ. In this study, we investigated the in vitro adsorption property of oral VRCZ to feeding tube and performed pharmacokinetic analysis of VRCZ prepared by powdering and simple suspension for ICU patients. Read More

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January 2021


Drug Metab Dispos 2021 May 5. Epub 2021 May 5.

Novartis Institute for Biomedical Research, East Hanover, United States, United States.

Tropifexor (NVP-LJN452) is a highly potent, selective, non-steroidal, non-bile acid farnesoid X receptor (FXR) agonist for the treatment of nonalcoholic steatohepatitis (NASH). Its absorption, metabolism, and excretion were studied following a 1-mg oral dose of [C]tropifexor to four healthy male subjects. Mass balance was achieved with ~94% of the administered dose recovered in excreta through 312 hours collection period. Read More

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Development and verification of a linked ᵪB;-THC/11-OH-THC physiologically-based pharmacokinetic (PBPK) model in healthy, non-pregnant population and extrapolation to pregnant women.

Drug Metab Dispos 2021 May 5. Epub 2021 May 5.

Department of Pharmaceutics, University of Washington, United States

Conducting clinical trials to understand the exposure-risk/benefit relationship of cannabis use is not always feasible. Alternatively, physiologically-based pharmacokinetic (PBPK) models can be used to predict exposure of the psychoactive cannabinoid, THC, and its active metabolite 11-OH-THC. Here, we first extrapolated in vitro mechanistic PK information previously quantified to build a linked THC/11-OH-THC PBPK model, and verified the model with observed data after intravenous and inhalation administration of THC in a healthy, non-pregnant population. Read More

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A Phase 1 Open-Label, Fixed-Sequence Pharmacokinetic Drug Interaction Trial to Investigate the Effect of Cannabidiol on the CYP1A2 Probe Caffeine in Healthy Subjects.

Clin Pharmacol Drug Dev 2021 May 5. Epub 2021 May 5.

GW Research Ltd, Cambridge, UK.

This pharmacokinetic (PK) drug-interaction trial investigated the effects of repeated dosing of a plant-derived pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex in the United States and Epidyolex in Europe; 100 mg/mL oral solution) on caffeine clearance via modulation of cytochrome P450 (CYP) 1A2 activity in healthy adults. In this phase 1 open-label, fixed-sequence trial, all subjects received a single 200 mg caffeine dose and placebo on day 1. Subjects then titrated CBD from 250 mg once daily to 750 mg twice daily between days 3 and 11 and took 750 mg CBD twice daily between days 12 and 27. Read More

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Differential impacts of hemolysis on coagulation parameters of blood samples: A STROBE-compliant article.

Medicine (Baltimore) 2021 May;100(18):e25798

Department of Emergency Medicine, E-Da Hospital.

Abstract: This study aimed at investigating the impact of hemolysis on different coagulation parameters.A total of 216 venous blood samples without visible hemolysis were collected from adult patients at a tertiary referral center over six months. The plasma obtained was quantified for six coagulation parameters including prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, antithrombin III, and protein C. Read More

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Degradation of the Endothelial Glycocalyx Contributes to Metabolic Acidosis in Children Following Cardiopulmonary Bypass Surgery.

Pediatr Crit Care Med 2021 May 4. Epub 2021 May 4.

Paediatric Intensive Care, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. Department of Women and Children's Health, School of Life Course Sciences, King's College London, St Thomas' Hospital, London, United Kingdom. Thrombosis and Vascular Biology Research Group, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. Department of Cardiology, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. Institute of Women and Children's Health, King's College London, St Thomas' Hospital, London, United Kingdom. Department of Infectious Diseases, School of Immunology and Microbial Sciences, King's College London, Guy's Hospital, London, United Kingdom. Department of Intensive Care, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

Objectives: Cardiopulmonary bypass surgery is complicated by metabolic acidosis, microvascular dysfunction, and capillary leak. The glycocalyx-a layer of proteins and sugars lining the vascular endothelium-is degraded during cardiopulmonary bypass. We aimed to describe the kinetics of glycocalyx degradation during and following cardiopulmonary bypass. Read More

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Evaluation of analgesic interaction between morphine, maropitant and dexmedetomidine in dogs undergoing ovariohysterectomy.

N Z Vet J 2021 May 5:1-27. Epub 2021 May 5.

School of Veterinary Science, Massey University, Palmerston North, New Zealand.

Aims: To compare the analgesic effect of morphine combined with maropitant and/or dexmedetomidine to morphine alone given at a higher dose, and to evaluate the pharmacokinetics of the drug combinations, in dogs undergoing ovariohysterectomy (OHE).

Methods: Forty client owned-dogs were randomised into four treatment groups (n=10 per group) each to receive a different analgesic protocol. After premedication with I/M acepromazine anaesthesia was induced with propofol to effect and maintained with isoflurane in 100% oxygen delivered via a circle system. Read More

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Detailed Method for Performing the ExSTA Approach in Quantitative Bottom-Up Plasma Proteomics.

Methods Mol Biol 2021 ;2228:353-384

Gerald Bronfman Department of Oncology, Jewish General Hospital, McGill University, Montreal, QC, Canada.

The use of stable isotope-labeled standards (SIS) is an analytically valid means of quantifying proteins in biological samples. The nature of the labeled standards and their point of insertion in a bottom-up proteomic workflow can vary, with quantification methods utilizing curves in analytically sound practices. A promising quantification strategy for low sample amounts is external standard addition (ExSTA). Read More

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January 2021

Renal dysfunction and podocyturia in pre-eclampsia may be explained by increased urinary VEGF.

Nephrol Dial Transplant 2021 May 5. Epub 2021 May 5.

Complications of Diabetes Unit, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: Preeclampsia has a major impact on renal function as shown by the development of proteinuria and podocyturia. How the systemic, Fms-like tyrosine kinase-1 (sFlt-1)-driven inhibition of vascular endothelial growth factor (VEGF) activity detected in preeclampsia directly affects renal function remains unknown. Aim of the study was to clarify whether a non-canonical, renal centered escape from VEGF inhibition in case of preeclamptic pregnancy might have a direct impact on the renal function. Read More

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Characterising and communicating the potential hazard posed by potentially toxic elements in indoor dusts from schools across Lagos, Nigeria.

Environ Sci Process Impacts 2021 May 4. Epub 2021 May 4.

Department of Geography and Environmental Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, UK.

Ambient and indoor air pollution results in an estimated 7 million premature deaths globally each year, representing a major contemporary public health challenge, but one poorly quantified from a toxicological and source perspective. Indoor exposure represents possibly the greatest potential overall exposure, yet our indoor environments are still poorly understood, modelled and characterized. In rapidly growing cities, such as Lagos, Nigeria, environmental monitoring can play an important role in establishing baseline data, monitoring urban pollution trends and in environmental education. Read More

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Oral bioavailability and pharmacokinetics of esculetin following intravenous and oral administration in rats.

Xenobiotica 2021 May 5:1-24. Epub 2021 May 5.

College of Pharmacy, Kyungsung University, 309, Suyeong-ro, Nam-gu, Busan, 48434, Republic of Korea.

Esculetin is the main active ingredient isolated from (Nakai) Pamp. and L. The present study investigated the oral bioavailability and pharmacokinetics of esculetin in rats, following intravenous and oral administration. Read More

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Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau.

EMBO Mol Med 2021 May 5:e14022. Epub 2021 May 5.

Clinical Memory Research Unit, Faculty of Medicine, Lund University, Lund, Sweden.

Alzheimer's disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer's disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N = 88), both plaque and tangle density contributed independently to higher P-tau217, but P-tau217 was not elevated in patients with non-Alzheimer's disease tauopathies (N = 9). Read More

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Relationship between plasma rabbit anti-thymocyte globulin concentration and immunosuppressive therapy response in patients with severe aplastic anemia.

Eur J Haematol 2021 May 4. Epub 2021 May 4.

Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Objectives: Patients with acquired aplastic anemia (AA) without HLA-matched sibling donors or aged >40 years receive immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG). We investigated the relationship between plasma rabbit ATG (r-ATG) concentration and IST response.

Methods: From May 2012 to October 2017, 81 patients with severe AA who required initial IST were included. Read More

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Evaluation of the Pharmacokinetic Interaction and Safety of Atogepant Co-Administered with Acetaminophen or Naproxen in Healthy Participants: A Randomized Trial.

Clin Drug Investig 2021 May 5. Epub 2021 May 5.

Global Patient Safety & Epidemiology, AbbVie, Madison, NJ, USA.

Background: Atogepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist in development for preventive treatment of migraine.

Objective: To evaluate potential pharmacokinetic drug-drug interactions (DDIs), safety and tolerability of atogepant co-administered with acetaminophen or naproxen in healthy participants.

Methods: This open-label, randomized, five-way crossover, single-center, phase 1 DDI trial randomized healthy adult participants to one of ten intervention sequences to receive single-dose 60 mg atogepant, 1000 mg acetaminophen, 500 mg naproxen, or co-administrations of atogepant with acetaminophen or naproxen, with 7-day washout periods between interventions. Read More

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Serum C-Reactive Protein Is Negatively Associated With Olfactory Identification Ability in Older Adults.

Iperception 2021 Mar-Apr;12(2):20416695211009928. Epub 2021 Apr 14.

Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden; Stockholm Gerontology Research Center, Stockholm, Sweden.

Importance: Olfactory deficits are common in aging and associated with several conditions linked to inflammation. A few studies suggest that increased concentration of pro-inflammatory biomarkers may be related to olfactory deficits, but these associations are understudied in population-based samples.

Objective: To investigate the association between serum concentrations of C-reactive protein (CRP) and olfactory identification level as well as rate of change in aging. Read More

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Cerium and gallium containing mesoporous bioactive glass nanoparticles for bone regeneration: Bioactivity, biocompatibility and antibacterial activity.

Mater Sci Eng C Mater Biol Appl 2021 May 24;124:112050. Epub 2021 Mar 24.

Institute of Biomaterials, Department of Material Science and Engineering, University of Erlangen-Nuremberg, 91058 Erlangen, Germany. Electronic address:

In recent years, mesoporous bioactive glass nanoparticles (MBGNPs) have generated great attention in biomedical applications. In this study, cerium and gallium doped MBGNPs were prepared by microemulsion assisted sol-gel method in the binary SiO-CaO system. MBGNPs with spheroidal and pineal shaped morphology were obtained. Read More

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Genetically-determined variations of are associated with antioxidant, muscular, and lipid biomarkers in response to Brazil nut consumption by patients using statins.

Br J Nutr 2021 May 5:1-21. Epub 2021 May 5.

Department of Health Sciences, Division of Nutrition and Metabolism, Ribeirão Preto Medical School, University of São Paulo - FMRP/USP, Brazil.

Several single nucleotide polymorphisms (SNPs) could indirectly, as well directly, influence metabolic parameters related to health effects in response to selenium (Se) supplementation. This study aimed to investigate whether the selenoprotein SNPs were associated with the response of Se status biomarkers to the Brazil nut consumption in patients using statins, and if the variation in Se homeostasis could affect antioxidant protection, lipid profile, muscle homeostasis, and selenoproteins mRNA. The study was performed in the Ribeirão Preto Medical School University Hospital. Read More

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Gut microbiota contributes to the development of endometrial glands in gilts during the ovary-dependent period.

J Anim Sci Biotechnol 2021 May 5;12(1):57. Epub 2021 May 5.

State Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, Hubei, China.

Background: The hyper-prolificacy Meishan gilts achieved a superior endometrial gland development (EGD) than white crossbred gilts during the ovary-independent period (before 60 d of age). Then, the EGD continues under the management of ovary-derived steroid hormones that regulated by gut microbiota (after 60 d of age). However, whether Meishan gilts' superiority in EGD lasting to the ovary-dependent period (after 60 d of age) and the role of gut microbiota in this period both remain unclear. Read More

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Plasma markers in pulmonary hypertension subgroups correlate with patient survival.

Respir Res 2021 May 4;22(1):137. Epub 2021 May 4.

Department of Pulmonary Medicine, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.

Background: Recent studies have provided evidence for an important contribution of the immune system in the pathophysiology of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we investigated whether the inflammatory profile of pulmonary hypertension patients changes over time and correlates with patient WHO subgroups or survival.

Methods: 50 PAH patients (16 idiopathic (I)PAH, 24 Connective Tissue Disease (CTD)-PAH and 10 Congenital Heart Disease (CHD)-PAH), 37 CTEPH patients and 18 healthy controls (HCs) were included in the study. Read More

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