ObjectiveJAK inhibitors have shown efficacy in rheumatoid arthritis (RA). We undertook this study to test our hypothesis that selective inhibition of JAK‐1 would combine good efficacy with a better safety profile compared with less selective JAK inhibitors.MethodsIn two 4‐week exploratory, double‐blind, placebo‐controlled phase IIa trials, 127 RA patients with an insufficient response to methotrexate (MTX) received filgotinib (GLPG0634, GS‐6034) oral capsules (100 mg twice daily or 30, 75, 150, 200, or 300 mg once daily) or placebo, added onto a stable regimen of MTX, to evaluate safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of filgotinib. The primary efficacy end point was the number and percentage of patients in each treatment group meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 4.ResultsTreatment with filgotinib at 75–300 mg met the primary end point and showed early onset of efficacy. ACR20 response rates progressively increased to week 4, and the Disease Activity Score in 28 joints using the C‐reactive protein (CRP) level decreased. Marked and sustained improvements were observed in serum CRP level and other PD markers. The PK of filgotinib and its major metabolite was dose proportional over the 30–300 mg range. Early side effects seen with other less selective JAK inhibitors were not observed (e.g., there was no worsening of anemia [JAK‐2 inhibition related], no effects on liver transaminases, and no increase in low‐density lipoprotein or total cholesterol). A limited decrease in neutrophils without neutropenia was consistent with immunomodulatory effects through JAK‐1 inhibition. There were no infections. Overall, filgotinib was well tolerated. Events related to study drug were mild or moderate and transient during therapy, and the most common such event was nausea.ConclusionSelective inhibition of JAK‐1 with filgotinib shows initial efficacy in RA with an encouraging safety profile in these exploratory studies.
Aim of the study: Among the key genes involved in the development of non-alcoholic fatty liver disease (NAFLD) are genes encoding the synthesis of glutathione S-transferase (GST). Material and methods: Deletion polymorphism of GSTT1 and GSTM1 genes was investigated in 104 NAFLD patients and 45 healthy individuals. Biochemical blood analysis, tumor necrosis factor-α (TNF-α), interleukin-10, leptin and adiponectin plasma levels were studied. Results: The distribution of deletion vs. non-deletion genotypes of the GSTT1 gene in NAFLD patients was 18 (17.3%) vs. 86 (82.7%) patients and in healthy people it was 6 (13.3%) vs. 39 (86.7%) individuals. The genotype distribution of the GSTM1 gene was as follows: 52 (50.0%) NAFLD patients had null genotype vs. 52 patients (50.0%) with non-deletion genotype; in the control group-23 (51.1%) vs. 22 (48.9%) individuals. Deletion of the GSTT1 gene in NAFLD patients was associated with twice as high (p = 0.01) TNF-α level in the blood as compared to patients with normal genotype. Higher concentration of leptin in blood by 37.1% (p = 0.04) was observed in patients with null genotype of the GSTM1 gene, as compared to those with normal genotype. Conclusions: Deletion polymorphism of GSTT1 and GSTM1 genes distribution among NAFLD patients did not differ as compared to healthy individuals. Null-genotype GSTT1 gene carriers were characterized by higher TNF-α concentration and null-genotype GSTM1 gene carriers were characterized by elevated leptin level as compared to normal genotype carriers.
Actuality. The rapid growth of morbidity, age-related poly- and comorbidity complicate and increase the cost of the treatment process of such patients, leading to the search for prophylactic and therapeutic agents of multisystem and diverse metabolic action. Aim of the Research. Coverage of modern scientific advances in the studies of therapeutic and prophylactic properties of ginger as a spice and source of drugs, as well as justification for its wider use under different conditions of the human body. Materials and Methods. Information search in printed and electronic publications, search databases; methods of analysis, comparison and generalization of data. Results. The healing properties of ginger have been proven on the basis of historical and modern data. Thus, it posesses hypolipidemic, antisclerous, disaggregating, hypoglycemic, antioxidant, anti-inflammatory, analgesic, vasodilating properties, and the ability to regulate secretory and motor disorders of the digestive system. Gastro-, hepato-, cardio-, neuro-, arthroprotective features of ginger products are indisputable, as well as the effectiveness of their application for the diseases of the digestive, cardiovascular, bronchopulmonary systems, musculoskeletal system and prospects for their use for endocrine diseases, in neurology, oncology , immunology. Conclusions. Ginger as a universal spice and a source of drugs of prophylactic and therapeutic action with multisystem and diverse metabolic properties should be used more widely in patients with age related poly-and comorbidity, which can improve their rehabilitation outcomes and increase economic efficiency. Key Words: ginger, properties, poly- and comorbidity, application, prophylaxis.
Резюме. У контексті глобального зростання хвороб щитоподібної залози та необхідності пошуку причин цієї тенденції у статті наведена інформація щодо найбільш поширених хімічних забруднювачів довкілля та їх негативного впливу на функцію і структуру щитоподібної залози, можливих механізмів такої дії. Наведено також власні дослідження з ураження щитоподібної залози у хворих на остеоартроз, які проживали чи працювали в зонах екологічного неблагополуччя. Звернута увага на пріоритетність подібних досліджень з огляду на тенденції до прогресуючого погіршення довкілля.
Relevance. Post COVID syndrome (PCS) is a common occurrence in patients who have experienced an acute stage of coronavirus infection. Methods of rehabilitation of such patients are insufficiently developed, especially with the use of health nutrition. The objective is to increase the effectiveness of rehabilitation of patients with moderate manifestations of PCS through the additional use of health foods using fruits, vegetables and spices with special prophylactic properties. Materials and Methods. In 64 patients with moderate manifestations of PCS aged 28-65 years, clinical observations were conducted at the outpatient stage according to the developed program and the use of informational and educational guidelines, remote counseling. Results. In patients with mild manifestations of PCS, the application of the developed program of health nutrition with minimal manifestations of comorbidities for proper recovery of functional status and manifestations of PCS compliance with the recommendations requires 1.5-2.0 months. With moderate manifestations of PCS in patients treated in the acute period inpatient and had a significant age-related polymorbid background to achieve the desired effect, the need for such an approach required 3-3.5 months of use. Conclusion. Patients who have suffered an acute stage of covid infection with the subsequent development of PCS as a variant of comprehensive rehabilitation, it is advisable to use a diet using ingredients with high health properties (spices, berries, fruits, vegetables, etc.). Key Words: post COVID syndrome, rehabilitation, health nutrition, spices.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.