Search results for "harm"

Liraglutide Ameliorates Erectile Dysfunction via Regulating Oxidative Stress, the RhoA/ROCK Pathway and Autophagy in Diabetes Mellitus

2020

Background Erectile dysfunction (ED) occurs more frequently and causes a worse response to the first-line therapies in diabetics compared with nondiabetic men. Corpus cavernosum vascular dysfunction plays a pivotal role in the occurrence of diabetes mellitus ED (DMED). The aim of this study was to investigate the protective effects of glucagon-like peptide-1 (GLP-1) analog liraglutide on ED and explore the underlying mechanisms in vivo and in vitro. Methods Type 1 diabetes was induced in rats by streptozotocin, and the apomorphine test was for screening the DMED model in diabetic rats. Then they were randomly treated with subcutaneous injections of liraglutide (0.3 mg/kg/12 h) for 4 weeks. …

Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA)

2020

The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17. Nonetheless, many patients remain without a conclusive genetic diagnosis, which shows that there must be additional as yet undiscovered NBIA gen…

Perspectives of Pharmacology over the Past 100 Years

2019

It is fitting that the 100th anniversary of the Handbook of Experimental Pharmacology celebrates not only its founding but also the founding of experimental pharmacology as both had their beginnings in Germany. Founded in 1919 by Arthur Heffter (1859–1925) as the “Handbuch der Experimentellen Pharmakologie” and renamed to its current title in 1937, the Handbook has continued to capture the emergence and developments of experimental pharmacology since the initial systematic work of Rudolf Buchheim and his student Oswald Schmiedeberg. Heffter, the first Chairman of the German Society of Pharmacology, was also responsible for isolating mescaline as the active psychedelic component from the pey…

Chronic Myelogenous Leukemia: Approaches to Pharmacological Resistance

2017

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder characterized by the reciprocal t (9:22) chromosomal translocation. This rearrangement produces the socalled Philadelphia chromosome carrying the chimeric Bcr-Abl oncoprotein, p210, responsible of disease progression [1]. Because of its critical role in pathogenesis, the scientific community had focused on targeting Bcr–Abl for treatment of CML. For many years Imatinib (IM), as selective inhibitor of the Tyr-Kinase activity of the oncoprotein, was used to treat CML patients [2]. From 2000 some data relative to IM resistance were available. There are many mechanisms responsible of IM resistance, more often point mutat…

Safety assessment of nanoparticles for drug delivery by means of classic in vitro assays and beyond.

2016

Nanoparticles (NPs) are particularly promising tools for drug delivery and targeting, but to date, only a relatively small number of nanoscale drug delivery systems have been officially approved for drug therapy. Therapeutic NPs are designed for human use and consequently have to withstand critical toxicological analysis, which plays a pivotal role in the decision on the future practical realization of the respective drug-delivery concepts. Nanotoxicology is still a maturing discipline that often lacks profound analysis of non-acute, sub-lethal effects. Areas covered: In this review, a representative selection of current in vitro assays for cell culture-based assessment of nanotoxicity is d…

Effect of Manganese Chloride and of Cotreatment with Cadmium Chloride on the In Vitro Proliferative, Motile, and Invasive Behavior of MDA-MB231 Breas…

2019

We examined the dose&ndash

Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway

2019

Abstract Immune checkpoint blockade therapy has changed prognoses for many melanoma patients. However, immune responses that correlate with clinical progression of the disease are still poorly understood. To identify immune responses correlating with melanoma clinical evolution, we analyzed serum cytokines as well as circulating NK and T-cell subpopulations from melanoma patients. The patients' immune profiles suggested that melanoma progression leads to changes in peripheral blood NK and T-cell subsets. Stage IV melanoma was characterized by an increased frequency of CCR7+CD56bright NK cells as well as high serum concentrations of the CCR7 ligand CCL19. CCR7 expression and CCL19 secretion …

Lycopene and Vascular Health

2018

Lycopene is a lipophilic, unsaturated carotenoid, found in red-colored fruits and vegetables, including tomatoes, watermelon, papaya, red grapefruits, and guava. The present work provides an up to date overview of mechanisms linking lycopene in the human diet and vascular changes, considering epidemiological data, clinical studies, and experimental data. Lycopene may improve vascular function and contributes to the primary and secondary prevention of cardiovascular disorders. The main activity profile of lycopene includes antiatherosclerotic, antioxidant, anti-inflammatory, antihypertensive, antiplatelet, anti-apoptotic, and protective endothelial effects, the ability to improve the metabol…

Translation of Basic Research into Clinics: Killer Immunoglobulin-like Receptors Genes in Autoimmune and Infectious Diseases

2018

Killer immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIRs and HLA loci are highly polymorphic, and some of their combinations have been found to protect against viral infections or to predispose to autoimmune disorders. In particular, some activating KIRs profiles may be detrimental in autoimmune pathogenesis, and specific KIRs may be particularly aggressive in the clearance of different microorganisms, protecting individuals in the control of a given pathogen. So, considering that in the pathogenesis of many autoimmune disorders and infections innate immunity plays a key role, the recent …

2017

Multiple sclerosis (MS) is a chronic autoimmune disease caused by an insufficient suppression of autoreactive T lymphocytes. One reason for the lack of immunological control is the reduced responsiveness of T effector cells (Teff) for the suppressive properties of regulatory T cells (Treg), a process termed Treg resistance. Here we investigated whether the disease-modifying therapy of relapsing-remitting MS (RRMS) with dimethyl fumarate (DMF) influences the sensitivity of T cells in the peripheral blood of patients towards Treg-mediated suppression. We demonstrated that DMF restores responsiveness of Teff to the suppressive function of Treg in vitro, presumably by down-regulation of interle…