Search results for "ADR"

Iron-loaded transferrin (Tf) is detrimental whereas iron-free Tf confers protection against brain ischemia by modifying blood Tf saturation and subse…

2018

Despite transferrin being the main circulating carrier of iron in body fluids, and iron overload conditions being known to worsen stroke outcome through reactive oxygen species (ROS)-induced damage, the contribution of blood transferrin saturation (TSAT) to stroke brain damage is unknown. The objective of this study was to obtain evidence on whether TSAT determines the impact of experimental ischemic stroke on brain damage and whether iron-free transferrin (apotransferrin, ATf)-induced reduction of TSAT is neuroprotective. We found that experimental ischemic stroke promoted an early extravasation of circulating iron-loaded transferrin (holotransferrin, HTf) to the ischemic brain parenchyma.…

Human Mesenchymal Stem Cells Prevent Neurological Complications of Radiotherapy

2019

Radiotherapy is a highly effective tool for the treatment of brain cancer. However, radiation also causes detrimental effects in the healthy tissue, leading to neurocognitive sequelae that compromise the quality of life of brain cancer patients. Despite the recognition of this serious complication, no satisfactory solutions exist at present. Here we investigated the effects of intranasal administration of human mesenchymal stem cells (hMSCs) as a neuroprotective strategy for cranial radiation in mice. Our results demonstrated that intranasally delivered hMSCs promote radiation-induced brain injury repair, improving neurological function. This intervention confers protection against inflamma…

Pterostilbene Decreases the Antioxidant Defenses of Aggressive Cancer Cells In Vivo: A Physiological Glucocorticoids- and Nrf2-Dependent Mechanism

2016

Abstract Aims: Polyphenolic phytochemicals have anticancer properties. However, in mechanistic studies, lack of correlation with the bioavailable concentrations is a critical issue. Some reports had suggested that these molecules downregulate the stress response, which may affect growth and the antioxidant protection of malignant cells. Initially, we studied this potential underlying mechanism using different human melanomas (with genetic backgrounds correlating with most melanomas), growing in nude mice as xenografts, and pterostilbene (Pter, a natural dimethoxylated analog of resveratrol). Results: Intravenous administration of Pter decreased human melanoma growth in vivo. However, Pter, …

2018

OBJECTIVE The lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC processing between humans and rodents, and little is known about the relative physiological importance of POMC products in the human brain. The aim of this study was to determine which POMC-derived peptides are present in the human brain, to establish their relative concentrations, and to test if their production is dynamically regulated. METHODS We analysed both fresh post-mortem human hypothalamic tissue and hypothalamic neurons derived from …

Glycometabolic Alterations in Secondary Adrenal Insufficiency: Does Replacement Therapy Play a Role?

2018

Secondary adrenal insufficiency (SAI) is a potentially life-threatening endocrine disorder due to an impairment of corticotropin (ACTH) secretion from any process affecting the hypothalamus or pituitary gland. ACTH deficit can be isolated or associated with other pituitary failures (hypopituitarism). An increased mortality due to cardiovascular, metabolic, and infectious diseases has been described in both primary and secondary adrenal insufficiency. However, few studies have provided compelling evidences on the underlying mechanism in SAI, because of the heterogeneity of the condition. Recently, some studies suggested that inappropriate glucocorticoid (GCs) replacement therapy, as for dose…

β2-Adrenoceptors and GRK2 as Potential Biomarkers in Patients With Chronic Pulmonary Regurgitation

2019

Pulmonary regurgitation (PR) is a frequent complication after repair of congenital heart disease. Three different GRK isoforms (GRK2, GRK5, and GRK3) and two β-adrenoceptors (β1-AR and β2-AR) are present in peripheral blood mononuclear cells (PBMC) and their expression changes as a consequence of the hemodynamic and neurohumoral alterations that occur in some cardiovascular diseases. Therefore, they could be useful as biomarkers in PR. A prospective study was conducted to describe the expression (TaqMan Gene Expression Assays) of β-ARs and GRKs in PBMC isolated (Ficoll® gradient) from patients with severe PR before and after pulmonary valve replacement and establish if this expression corre…

Vaccination in multiple sclerosis patients treated with highly effective disease-modifying drugs: an overview with consideration of cladribine tablets

2021

Infectious diseases are an important consideration in autoimmune conditions such as multiple sclerosis. Infective episodes may trigger relapses and significantly deteriorate the course of the disease. Some immunotherapies may cause increased rates of infection-related adverse events. Thus, infection and vaccine-related issues should be included in the individualized patient-specific treatment strategy and counseling before starting therapy and regularly on treatment. Clinical and epidemiological studies as well as pharmacovigilance data repeatedly demonstrated the safety of the great majority of vaccines in multiple sclerosis patients. Moreover, studies have shown that vaccinations with kil…

Cardiac and vascular alpha(1)-adrenoceptors in congestive heart failure: a systematic review

2020

As heart failure (HF) is a devastating health problem worldwide, a better understanding and the development of more effective therapeutic approaches are required. HF is characterized by sympathetic system activation which stimulates α- and β-adrenoceptors (ARs). The exposure of the cardiovascular system to the increased locally released and circulating levels of catecholamines leads to a well-described downregulation and desensitization of β-ARs. However, information on the role of α-AR is limited. We have performed a systematic literature review examining the role of both cardiac and vascular α1-ARs in HF using 5 databases for our search. All three α1-AR subtypes (α1A, α1B and α1D) are exp…

The Role of Adrenoceptors in the Retina

2020

The retina is a part of the central nervous system, a thin multilayer with neuronal lamination, responsible for detecting, preprocessing, and sending visual information to the brain. Many retinal diseases are characterized by hemodynamic perturbations and neurodegeneration leading to vision loss and reduced quality of life. Since catecholamines and respective bindings sites have been characterized in the retina, we systematically reviewed the literature with regard to retinal expression, distribution and function of alpha1 (α1)-, alpha2 (α2)-, and beta (β)-adrenoceptors (ARs). Moreover, we discuss the role of the individual adrenoceptors as targets for the treatment of retinal diseases.

Bilateral ruptures of the extensor mechanism of the knee: A systematic review

2017

Abstract Introduction We conduct a systematic and qualitative review of the current literature to evaluate studies that described bilateral ruptures of the extensor mechanism of the knee. Methods A comprehensive literature search was performed to evaluate all studies included in the literature until September 2016. Results Fourteen studies with a total of 44 patients met the inclusion criteria. There were 14 patients with CRF (61%), 6 patients were affected by diabetes mellitus (14%) while other 6 patients were obese patients (14%). Conclusion CRF represents the most frequent comorbidity in patients with bilateral quadriceps/patellar tendon ruptures.