Effect of initiation of medications for opioid use disorder on hospitalization outcomes for endocarditis and osteomyelitis in a large private hospital system in the United States, 2014-18.

Background And Aims: Opioid use disorder (OUD) has led to not only increases in overdose deaths, but also increases in endocarditis and osteomyelitis secondary to injection drug use (IDU). We studied the association between initiation of medications for opioid use disorder (MOUD) and treatment outcomes for people with infectious sequelae of IDU and OUD.

Design And Setting: This is a retrospective cohort study reviewing encounters at 143 HCA Healthcare hospitals across 21 states of the United States from 2014 to 2018.

Novel aspects of the activation of NADPH oxidase in neutrophils of rheumatic patients on biological therapy.

The relationship between inflammation and formation of reactive oxygen species (ROS) is still not completely understood and excessive inflammatory reaction is attributed to increased yet also to reduced ROS formation. To compare ROS formation in severe and low inflammation, neutrophil oxidative burst was analyzed in rheumatic patients before and during therapy with TNFα- or interleukin-6 receptor-neutralizing antibodies. Intracellular and extracellular ROS productions were evaluated on the basis of luminol- and isoluminol-enhanced chemiluminescence in isolated peripheral neutrophils.

Increased intracellular and extracellular oxidant production in phagocytes of rheumatic patients treated with biological therapy - whole blood quantification.

Infectious complications, resulting from reduced activity of immune cells, are the most severe and common adverse effects of biological therapy. This study analyzed the effect of biological therapy on blood phagocytes, focusing on the formation of reactive oxygen species (ROS), an important factor in the defence against invading pathogens. Intra- and extracellular ROS production were recorded separately, on the basis of luminol and isoluminol chemiluminescence in patients treated with antibodies against tumor necrosis factor-α or against interleukin-6 receptor.

Effect of N-Feruloylserotonin and Methotrexate on Severity of Experimental Arthritis and on Messenger RNA Expression of Key Proinflammatory Markers in Liver.

Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX).

Ex Vivo and In Vitro Studies on the Cytotoxicity and Immunomodulative Properties of Poly(2-isopropenyl-2-oxazoline) as a New Type of Biomedical Polymer.

Poly(2-alkenyl-2-oxazoline)s are promising functional polymers for a variety of biomedical applications, such as drug delivery systems, peptide conjugates, or gene delivery. In this study, poly(2-isopropenyl-2-oxazoline) (PIPOx) is prepared through free-radical polymerization initiated with azobisisobutyronitrile. Reactive 2-oxazoline units in the side chain support an addition reaction with different compounds containing a carboxylic group, which facilitates the preparation of polymers labeled with two different fluorescent dyes.

Equol Effectively Inhibits Toxic Activity of Human Neutrophils without Influencing Their Viability.

Equol (7,4'-dihydroxy-isoflavan, or 4',7-isoflavandiol) is a chroman derivative produced by intestinal bacteria in response to soy isoflavone intake in some, but not in all, humans. Equol shows strong anti-oxidant, anti-estrogenic, anti-cancerous and anti-inflammatory properties. The antioxidative capacity of equol has recently received considerable attention, and it has been used for preventing and treating several diseases.

On the pharmacology of oxidative burst of human neutrophils.

The effect of three therapeutically used drugs and five polyphenolic compounds on the mechanism of oxidative burst was compared in whole blood and isolated neutrophils at cellular and molecular level. In 10 microM concentration, the compounds investigated decreased the oxidative burst of whole blood in the rank order of potency: N-feruloylserotonin (N-f-5HT) > curcumin (CUR) > quercetin (QUER) > arbutin (ARB) > resveratrol (RES) > dithiaden (DIT) > carvedilol (CARV) > brompheniramine (BPA). The ratio between the percentage inhibition of extracellular versus intracellular chemiluminescence (CL) followed the rank order QUER > N-f-5HT > RES > CUR > DIT and is indicative of the positive effect of the compounds tested against oxidative burst of neutrophils, demonstrating suppression of reactive oxygen species extracellularly with minimal alteration of intracellular reactive oxygen species (ROS).

Can semi-synthetic flavonoids return old microglia to their youthful state?

A number of studies have indicated that brain inflammation may deteriorate during normal aging and that neuroinflammation is amplified in age-related neurodegenerative diseases. A pivotal role in age-related neuroinflammatory pathologies is attributed to amplified and prolonged activation of microglia. In addition, microglia from the aged brain were reported as senescent displaying many functional impairments.

Arbutin and decrease of potentially toxic substances generated in human blood neutrophils.

Neutrophils, highly motile phagocytic cells, constitute the first line of host defense and simultaneously they are considered to be central cells of chronic inflammation. In combination with standard therapeutic procedures, natural substances are gaining interest as an option for enhancing the effectiveness of treatment of inflammatory diseases. We investigated the effect of arbutin and carvedilol and of their combination on 4β-phorbol-12β-myristate-13α-acetate- stimulated functions of human isolated neutrophils.

Selective inhibition of extracellular oxidants liberated from human neutrophils--A new mechanism potentially involved in the anti-inflammatory activity of hydroxychloroquine.

Hydroxychloroquine is used in the therapy of rheumatoid arthritis or lupus erythematosus. Although these diseases are often accompanied by activation of neutrophils, there are still few data relating to the impact of hydroxychloroquine on these cells. We investigated the effect of orally administered hydroxychloroquine on neutrophil oxidative burst in rats with adjuvant arthritis.

Molecular pharmacology of antihistamines in inhibition of oxidative burst of professional phagocytes.

Antihistamines of the H₁and H₃/H₄groups interfere with oxidative burst of human professional phagocytes in vitro. In the concentration of 10 μM, H₁antihistamines of the 1st and 2nd generation inhibited oxidative burst of human neutrophils in the rank order of potency: dithiaden > loratadine > brompheniramine > chlorpheniramine > pheniramine. Of the H₁antihistamines, the most effective was dithiaden in suppressing oxidative burst of whole human blood and dose-dependently the chemiluminescence of isolated neutrophils at extra- and intracellular level.

Markers of inflammation and oxidative stress studied in adjuvant-induced arthritis in the rat on systemic and local level affected by pinosylvin and methotrexate and their combination.

Oxidative stress (OS) is important in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and its experimental model--adjuvant arthritis (AA). Antioxidants are scarcely studied in autoimmunity, and future analyses are needed to assess its effects in ameliorating these diseases. Although there are studies about antioxidants effects on the course of RA, their role in combination therapy has not yet been studied in detail, especially on extra-articular manifestations of AA.

N-feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis.

Many of disease-modifying anti-rheumatic drugs often have side effects at high doses and/or during long-term administration. Increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis (RA). The aim of the study was to examine the effect of N-feruloylserotonin (N-f-5HT) and methotrexate (MTX) in monotherapy and in combination therapy on disease progression and inflammation in arthritic rats.

On the molecular pharmacology of resveratrol on oxidative burst inhibition in professional phagocytes.

Resveratrol-3,5,4'-trihydroxystilbene-possesses antioxidant activities in vitro. It dose-dependently inhibited the generation of peroxyl, hydroxyl, peroxides, and lipid peroxidation products in cell free systems. Oxidative burst of whole human blood stimulated with PMA, fMLP, OpZ, and A23187 was inhibited in a concentration-dependent way, indicating suppression of both receptor and nonreceptor activated chemiluminescence by resveratrol.

Role of histamine receptors in the effects of histamine on the production of reactive oxygen species by whole blood phagocytes.

Aims: The diverse physiological functions of histamine are mediated through distinct histamine receptors. In this study we investigated the role of H2R and H4R in the effects of histamine on the production of reactive oxygen species by phagocytes in whole blood.

Main Methods: Changes in reactive oxygen species (ROS) production by whole blood phagocytes after treatment with histamine, H4R agonists (4-methylhistamine, VUF8430), H2R agonist (dimaprit) and their combinations with H4R antagonist (JNJ10191584) and H2R antagonist (ranitidine) were determined using the chemiluminescence (CL) assay.

Study of possible mechanisms involved in the inhibitory effects of coumarin derivatives on neutrophil activity.

To specify the site of action of the synthetic coumarin derivatives 7-hydroxy-3-(4'-hydroxyphenyl) coumarin (HHC) and 7-hydroxy-3-(4'-hydroxyphenyl) dihydrocoumarin (HHDC), we evaluated their effects on extra- and intracellular reactive oxygen species (ROS) formation in phorbol-myristate-13-acetate (PMA) stimulated human neutrophils. We studied also the effects of HHC and HHDC on possible molecular mechanisms which participate in the activation of NADPH oxidase, that is, on PKC activity, on phosphorylation of some PKC isoforms (α, βII, and δ), and on phosphorylation of the NADPH oxidase subunit p40(phox). Without affecting cytotoxicity, both coumarines tested were effective inhibitors/scavengers of ROS produced by neutrophils on extracellular level.

The natural stilbenoid piceatannol decreases activity and accelerates apoptosis of human neutrophils: involvement of protein kinase C.

Neutrophils are able to release cytotoxic substances and inflammatory mediators, which, along with their delayed apoptosis, have a potential to maintain permanent inflammation. Therefore, treatment of diseases associated with chronic inflammation should be focused on neutrophils; formation of reactive oxygen species and apoptosis of these cells represent two promising targets for pharmacological intervention. Piceatannol, a naturally occurring stilbenoid, has the ability to reduce the toxic action of neutrophils.

The effects of pterostilbene on neutrophil activity in experimental model of arthritis.

It has been demonstrated that pterostilbene inhibits reactive oxygen species production in neutrophils in vitro. However, little is known about its effects on neutrophils during inflammation in vivo. In this study, the effect of pterostilbene on neutrophil activity was investigated in experimental arthritis model.

Pharmacological influence on processes of adjuvant arthritis: Effect of the combination of an antioxidant active substance with methotrexate.

Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. A certain correlation was observed between oxidative stress, arthritis and the immune system. Reactive oxygen species produced in the course of cellular oxidative phosphorylation and by activated phagocytic cells during oxidative burst, exceed the physiological buffering capacity and result in oxidative stress.

Quercetin inhibits degranulation and superoxide generation in PMA stimulated neutrophils.

Activated neutrophils represent the main source of myeloperoxidase (MPO), superoxide (SO) and subsequently derived oxygen metabolites. They have important microbicidal activities, however in inflammatory conditions they may secondarily attack surrounding tissues. Overproduction of reactive oxygen species, prolonged or excessive liberation of MPO and other effective yet also toxic substances from neutrophils may participate in disturbed apoptosis, intensify the inflammatory processes and result in serious human diseases.

Involvement of caspase-3 in stilbene derivatives induced apoptosis of human neutrophils in vitro.

Chronic inflammatory diseases, e.g. rheumatoid arthritis or cystic fibrosis, are characterised by neutrophil infiltration in inflamed tissues.

Effect of stilbene derivative on superoxide generation and enzyme release from human neutrophils in vitro.

Neutrophils represent the body's primary line of defense against invading pathogens. They most rapidly reach the site of injury or infection, liberate antimicrobial proteins, proteases and produce reactive oxygen species. Prolonged or excessive liberation of these very effective and toxic substances could intensify the inflammatory process and enhance tissue damage in many diseases, such as allergies, infections and rheumatoid arthritis.