Search results for " Blocking"

Antagonization of IL-17A Attenuates Skin Inflammation and Vascular Dysfunction in Mouse Models of Psoriasis

2019

Besides skin inflammation, patients with severe psoriasis suffer from an increased risk of cardiovascular mortality. IL-17A plays a central role in the development of psoriasis and might connect skin and vascular disease. The aim of this study was to clarify whether anti-IL-17A therapy could also ameliorate the vascular dysfunction associated with severe psoriasis. We analyzed three murine models with varying severities of psoriasis-like skin disease concerning their vascular function and inflammation: (i) K14-IL-17A(ind/+) mice with keratinocyte-specific IL-17A overexpression and an early-onset severe psoriasis-like phenotype; (ii) homozygous CD11c-IL-17A(ind/ind) and heterozygous CD11c-IL…

Antibody–Fc/FcR Interaction on Macrophages as a Mechanism for Hyperprogressive Disease in Non–small Cell Lung Cancer Subsequent to PD-1/PD-L1 Blockade

2019

Abstract Purpose: Hyperprogression (HP), a paradoxical boost in tumor growth, was described in a subset of patients treated with immune checkpoint inhibitors (ICI). Neither clinicopathologic features nor biological mechanisms associated with HP have been identified. Experimental Design: Among 187 patients with non–small cell lung cancer (NSCLC) treated with ICI at our institute, cases with HP were identified according to clinical and radiologic criteria. Baseline histologic samples from patients treated with ICI were evaluated by IHC for myeloid and lymphoid markers. T-cell–deficient mice, injected with human lung cancer cells and patient-derived xenografts (PDX) belonging to specific mutat…

Antibody-mediated inhibition of FXIIa blocks downstream bradykinin generation.

2018

IL-1β at the crossroad between rheumatoid arthritis and type 2 diabetes: may we kill two birds with one stone?

2016

ABSTRACT: Although in the past the prevention of joint destruction in rheumatoid arthritis (RA) was strongly emphasized, now a great interest is focused on associated comorbidities in these patients. Multiple data suggest that a large percentage of RA patients are affected by Type 2 Diabetes (T2D), whose incidence has reached epidemic levels in recent years, thus increasing the health care costs. A better knowledge about the pathogenesis of these diseases as well as the mechanisms of action of drugs may allow both policy designers and physicians to choose the most effective treatments, thus lowering the costs. This review will focus on the role of Interleukin (IL)-1β in the pathogenesis of …

Hacia la ley europea del clima: las evaluaciones científicas y el futuro papel de las respuestas jurídicas de los estados miembros

2021

Los problemas climáticos son temas persistentes y omnipresentes dentro de las políticas y legislaciones contemporáneas, que exigen un enfoque interdisciplinario para promover soluciones jurídicas adecuadas para la complejidad del tema. Paradójicamente, las propagandas negacionistas, lejos de bloquear las acciones climáticas, las han propiciado, lo que ha llevado al establecimiento de un organismo científico super partes que reconociese las cuestiones climáticas a través de informes científicos avanzados: el Grupo Intergubernamental de Expertos sobre el Cambio Climático de la ONU (IPCC). Desde entonces, muchos países han usado los hallazgos del IPCC como base científica para desarrollar polí…

Perioperative nonspecific histamine release : a new classification by aetiological mechanisms and evaluation of their clinical relevance

1993

As a consequence of the performance of a randomized controlled clinical trial on perioperative histamine release and cardiovascular and respiratory disturbances, several types of increases in plasma histamine had to be distinguished instead of only two which existed at the beginning of the study: drug-induced allergic and pseudoallergic reactions. First of all, the new classification by aetiology (clinical epidemiology) was derived from a meta-analysis (secondary analysis) of the most recent literature. According to that histamine release in the perioperative period has several, different causes and is involved in several, different disease manifestations. A clear distinction (classificatio…

Prospective Trial of Functional Thyrotropin Receptor Antibodies in Graves Disease

2019

Abstract Context Scarce data exist regarding the relevance of stimulatory (TSAb) and blocking (TBAb) thyrotropin receptor antibodies in the management of Graves disease (GD). Objective To evaluate the clinical utility and predictive value of TSAb/TBAb. Design Prospective 2-year trial. Setting Academic tertiary referral center. Patients One hundred consecutive, untreated, hyperthyroid GD patients. Methods TSAb was reported as percentage of specimen-to-reference ratio (SRR) (cutoff SRR < 140%). Blocking activity was defined as percent inhibition of luciferase expression relative to induction with bovine thyrotropin (TSH, thyroid stimulating hormone) alone (cutoff > 40% inhibitio…

Repeated sugammadex reversal of muscle relaxation during lumbar spine surgery with intraoperative neurophysiological multimodal monitoring

2016

Intraoperative neurophysiological monitoring during spine surgery is usually acomplished avoiding muscle relaxants. A case of intraoperative sugammadex partial reversal of the neuromuscular blockade allowing adequate monitoring during spine surgery is presented. A 38 year-old man was scheduled for discectomy and vertebral arthrodesis throughout anterior and posterior approaches. Anesthesia consisted of total intravenous anesthesia plus rocuronium. Intraoperatively monitoring was needed, and the muscle relaxant reverted twice with low dose sugammadex in order to obtain adequate responses. The doses of sugammadex used were conservatively selected (0.1 mg/kg boluses increases, total dose neede…

Beta-adrenergic blocking activity and haemodynamic effects in man of K� 1313, a new beta-adrenergic antagonist

1971

The beta-adrenergic blocking activity and haemodynamic effects of o-[2-hydroxy-3-(isopropylamino)-propoxy]-benzonitril (Ko 1313) have been studied in 22 patients. Antagonism of isoproterenol-induced tachycardia was used as a measure of the beta-adrenergic blocking activity. Ko 1313 1.0 mg had its maximum beta-adrenoceptor blocking effect 5–30 min after intravenous injection. Ko 1313 10.0 mg produced maximum betablockade 1–4 h after oral administration. 1.0 mg Ko 1313 injected intravenously had approximately the same beta-adrenergic blocking effect as 1.0 mg propranolol also given intravenously. After intravenous administration Ko 1313 was 3–4 times as potent as the same dose given orally. A…

Interruption of CD28-mediated costimulation during allergen challenge protects mice from allergic airway disease

2012

Background Allergic asthma is a T H 2-promoted hyperreactivity with an immediate, IgE, and mast cell–dependent response followed by eosinophil-dominated inflammation and airway obstruction. Objective Because costimulation by CD28 is essential for T H 2 but not T H 1 responses, we investigated the effect of selective interference with this pathway in mice using the models of ovalbumin and house dust mite–induced airway inflammation. Methods To study the role of CD28 in the effector phase of allergic airway inflammation, we developed an inducibly CD28-deleting mouse strain or alternatively used a CD28 ligand-binding site–specific mouse anti-mouse mAb blocking CD28 engagement. Results We show …