Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Criterios de enfermedad de Behcet

Behçet's disease (BE) refers to a multisystemic disorder whose causes are not yet well known, although some experts have suggested immune (and autoimmune), viral or bacterial, and even genetic causes. It is characterized by recurrent oral and genital ulcers, uveitis, mucocutaneous, articular, neurological, vascular, intestinal and pulmonary manifestations. The objective pursued is to refer to the diagnostic criteria of BE, based on the current scientific and academic literature, there-fore, it was chosen to develop a bibliographic design research, within the framework of a review methodology. The results showed some current meanings and description of symptoms (signs), causes (etiology) and diagnostic criteria of BE. In conclusion, EB is a chronic, incurable and difficult to diagnose disease. Furthermore, it is also possible to dare to assure that, although the ISG criteria are still useful, ICBDs are increasingly used in current medical practice.A doença de Behçet (BE) se refere a um distúrbio multissistêmico cujas causas ainda não são bem conhecidas, embo-ra alguns especialistas tenham sugerido causas imunológicas (e autoimunes), virais ou bacterianas e até genéticas. É caracterizada por úlceras orais e genitais recorrentes, uveítes, manifestações mucocutâneas, articulares, neurológicas, vasculares, intestinais e pulmonares. O objetivo prosseguido é fazer referência aos critérios diagnósticos da BE, com base na literatura científica e acadêmica atual, portanto, optou-se por desenvolver uma pesquisa de projeto bibliográfico, no âmbito de uma metodologia de revisão. Os resultados evidenciaram alguns significados e descrições atuais dos sintomas (sinais), causas (etiologia) e critérios diagnósticos de EB. Concluindo, a EB é uma doença crônica, incurável e de difícil diagnóstico. Além disso, também é possível ousar afirmar que, embora os critérios do ISG ainda sejam úteis, os ICBDs são cada vez mais utilizados na prática médica atual.La enfermedad de Behçet (EB) hace referencia a un desorden multisistémico de causas aún no bien conocidas, aunque algunos expertos han sugerido causas inmunitarias (y autoinmunitaria), virales o bacterianas e inclusive genéticas. Se caracteriza por úlceras orales y genitales recurrentes, uveítis, manifestaciones mucocutáneas, articulares, neurológicas, vasculares, intestinales y pulmonares. El objetivo perseguido es el de referir los criterios diagnósticos de la EB, en base a la literatura cientificoacadémica vigente, por ello, se escogió desarrollar una investigación de diseño bibliográfico, en el marco de una metodología de revisión. En los resultados se mostraron algunas acepciones vigentes y descripción de síntomas (signos), causas (etiología) y criterios diagnósticos de la EB. En conclusión, la EB es una patología crónica, incurable y difícil de diagnosticar. Además, también es posible atreverse a asegurar que, si bien los criterios del ISG aún son útiles, en la práctica médica actual cada vez más se usan los ICBD

Trends in Gliosis in Obesity, and the Role of Antioxidants as a Therapeutic Alternative

Obesity remains a global health problem. Chronic low-grade inflammation in this pathology has been related to comorbidities such as cognitive alterations that, in the long term, can lead to neurodegenerative diseases. Neuroinflammation or gliosis in patients with obesity and type 2 diabetes mellitus has been related to the effect of adipokines, high lipid levels and glucose, which increase the production of free radicals. Cerebral gliosis can be a risk factor for developing neurodegenerative diseases, and antioxidants could be an alternative for the prevention and treatment of neural comorbidities in obese patients. Aim: Identify the immunological and oxidative stress mechanisms that produce gliosis in patients with obesity and propose antioxidants as an alternative to reducing neuroinflammation. Method: Advanced searches were performed in scientific databases: PubMed, ProQuest, EBSCO, and the Science Citation index for research on the physiopathology of gliosis in obese patients and for the possible role of antioxidants in its management. Conclusion: Patients with obesity can develop neuroinflammation, conditioned by various adipokines, excess lipids and glucose, which results in an increase in free radicals that must be neutralized with antioxidants to reduce gliosis and the risk of long-term neurodegeneration

TFEB; Beyond Its Role as an Autophagy and Lysosomes Regulator

Transcription factor EB (TFEB) is considered the master transcriptional regulator of autophagy and lysosomal biogenesis, which regulates target gene expression through binding to CLEAR motifs. TFEB dysregulation has been linked to the development of numerous pathological conditions; however, several other lines of evidence show that TFEB might be a point of convergence of diverse signaling pathways and might therefore modulate other important biological processes such as cellular senescence, DNA repair, ER stress, carbohydrates, and lipid metabolism and WNT signaling-related processes. The regulation of TFEB occurs predominantly at the post-translational level, including phosphorylation, acetylation, SUMOylating, PARsylation, and glycosylation. It is noteworthy that TFEB activation is context-dependent; therefore, its regulation is subjected to coordinated mechanisms that respond not only to nutrient fluctuations but also to stress cell programs to ensure proper cell homeostasis and organismal health. In this review, we provide updated insights into novel post-translational modifications that regulate TFEB activity and give an overview of TFEB beyond its widely known role in autophagy and the lysosomal pathway, thus opening the possibility of considering TFEB as a potential therapeutic target

Antiangiogenic Effect of Dopamine and Dopaminergic Agonists as an Adjuvant Therapeutic Option in the Treatment of Cancer, Endometriosis, and Osteoarthritis

Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies

Therapeutic Potential of Dopamine and Related Drugs as Anti-Inflammatories and Antioxidants in Neuronal and Non-Neuronal Pathologies

Dopamine (DA), its derivatives, and dopaminergic drugs are compounds widely used in the management of diseases related to the nervous system. However, DA receptors have been identified in nonneuronal tissues, which has been related to their therapeutic potential in pathologies such as sepsis or septic shock, blood pressure, renal failure, diabetes, and obesity, among others. In addition, DA and dopaminergic drugs have shown anti-inflammatory and antioxidant properties in different kinds of cells. Aim: To compile the mechanism of action of DA and the main dopaminergic drugs and show the findings that support the therapeutic potential of these molecules for the treatment of neurological and non-neurological diseases considering their antioxidant and anti-inflammatory actions. Method: We performed a review article. An exhaustive search for information was carried out in specialized databases such as PubMed, PubChem, ProQuest, EBSCO, Scopus, Science Direct, Web of Science, Bookshelf, DrugBank, Livertox, and Clinical Trials. Results: We showed that DA and dopaminergic drugs have emerged for the management of neuronal and nonneuronal diseases with important therapeutic potential as anti-inflammatories and antioxidants. Conclusions: DA and DA derivatives can be an attractive treatment strategy and a promising approach to slowing the progression of disorders through repositioning

Exposure to Sub-Lethal Doses of Permethrin Is Associated with Neurotoxicity: Changes in Bioenergetics, Redox Markers, Neuroinflammation and Morphology

Permethrin (PERM) is a member of the class I family of synthetic pyrethroids. Human use has shown that it affects different systems, with wide health dysfunctions. Our aim was to determine bioenergetics, neuroinflammation and morphology changes, as redox markers after subacute exposure to PERM in rats. We used MDA determination, protein carbonyl assay, mitochondrial O2 consumption, expression of pro-inflammatory cytokines and a deep histopathological analysis of the hippocampus. PERM (150 mg/kg and 300 mg/kg body weight/day, o.v.) increased lipoperoxidation and carbonylated proteins in a dose-dependent manner in the brain regions. The activities of antioxidant enzymes glutathione peroxidase, reductase, S-transferase, catalase, and superoxide dismutase showed an increase in all the different brain areas, with dose-dependent effects in the cerebellum. Cytokine profiles (IL-1β, IL-6 and TNF-α) increased in a dose-dependent manner in different brain tissues. Exposure to 150 mg/kg of permethrin induced degenerated and/or dead neurons in the rat hippocampus and induced mitochondrial uncoupling and reduction of oxidative phosphorylation and significantly decreased the respiratory parameters state 3-associated respiration in complex I and II. PERM exposure at low doses induces reactive oxygen species production and imbalance in the enzymatic antioxidant system, increases gene expression of pro-inflammatory interleukins, and could lead to cell damage mediated by mitochondrial functional impairment

Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry

International audienc

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

International audienc