Background And Objective: Icodec is a once-weekly insulin being developed to provide basal insulin coverage in diabetes mellitus. This study evaluated the effects of renal or hepatic impairment on icodec pharmacokinetics.
Methods: Two open-label, parallel-group, single-dose (1.
Background: The NLRP3 inflammasome drives release of pro-inflammatory cytokines including interleukin (IL)-1β and IL-18 and is a potential target for ulcerative colitis (UC). Selnoflast (RO7486967) is an orally active, potent, selective and reversible small molecule NLRP3 inhibitor. We conducted a randomized, placebo-controlled Phase 1b study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of selnoflast.
View Article and Find Full Text PDFPolycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and insulin resistance. The dual sodium-glucose co-transporter 1/2 inhibitor (SGLT1/2i) licogliflozin (LIK066) ameliorates hyperinsulinism in patients with diabetes and obesity. This study examines the effect of licogliflozin on androgens in women with PCOS.
View Article and Find Full Text PDFIndacaterol (IND), is co-formulated with glycopyrronium (GLY), and mometasone furoate (MF) as a once-daily (o.d.) inhaled fixed-dose combination (IND/GLY/MF) delivered via the Breezhaler® device for maintenance treatment of asthma.
View Article and Find Full Text PDFObjective: The objective of this study was to characterize the effects of risankizumab on the in vivo activity of cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A in psoriasis patients using a cocktail approach.
Methods: Patients with moderate to severe chronic plaque psoriasis (n = 21) received single oral doses of sensitive probe substrates for CYP1A2 (caffeine 100 mg), CYP2C9 (warfarin 10 mg), CYP2C19 (omeprazole 20 mg), CYP2D6 (metoprolol 50 mg), and CYP3A (midazolam 2 mg) on day 1, followed by 12 weeks of subcutaneous risankizumab treatment of 150 mg once every 4 weeks from day 8 to day 92, and again the same cocktail of substrates on day 98. Serial blood samples were collected for determination of the CYP probe drugs and metabolites with and without risankizumab.
Objective The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) may contribute to the pathogenesis of systemic lupus erythematosus. The safety, tolerability, and pharmacodynamics of the selective Bcl-2 inhibitor venetoclax (ABT-199) were assessed in women with systemic lupus erythematosus. Methods A phase 1, double-blind, randomized, placebo controlled study evaluated single ascending doses (10, 30, 90, 180, 300, and 500 mg) and multiple ascending doses (2 cycles; 30, 60, 120, 240, 400, and 600 mg for 1 week, and then 3 weeks off per cycle) of orally administered venetoclax.
View Article and Find Full Text PDFInt J Clin Pharmacol Ther
April 2016
Objective: This first-in-human, randomized, double-blind, placebo-controlled trial assessed the safety of NNC0114-0005, a human recombinant anti interleukin (IL)-21 monoclonal antibody, for the treatment of rheumatoid arthritis (RA).
Methods And Materials: Healthy male subjects (HS (n = 44)) and patients with active RA treated with methotrexate (n = 20) were randomized 3 : 1 to single IV or SC doses of NNC0114-0005 (0.0025 - 25 mg/kg) or placebo.
We studied a new method of treatment of amyotrophic lateral sclerosis with autologous mesenchymal stem cells. Autologous mesenchymal stem cells were injected intravenously (intact cells) or via lumbar puncture (cells committed to neuronal differentiation). Evaluation of the results of cell therapy after 12-month follow-up revealed slowing down of the disease progression in 10 patients in comparison with the control group consisting of 15 patients.
View Article and Find Full Text PDFBackground: The most prevalent phenotype of asthma is characterized by eosinophil-dominated inflammation that is driven by a type 2 helper T cell (Th2). Therapeutic targeting of GATA3, an important transcription factor of the Th2 pathway, may be beneficial. We evaluated the safety and efficacy of SB010, a novel DNA enzyme (DNAzyme) that is able to cleave and inactivate GATA3 messenger RNA (mRNA).
View Article and Find Full Text PDFZh Nevrol Psikhiatr Im S S Korsakova
January 2015
Depression is a severe and usually recurrent mental disorder which leads to a prominent impairment of physical and social functioning, a reduced quality of life of the patients, implies as well an increased morbidity and mortality. Reducing the social-economic depression burden is possible in the optimization of decision-making process of antidepressant choice (including SSRIs and SNRIs) based on the evidence-based risk/benefit ratio and resource saving potential treatment involving target psychosocial interventions and monitoring of long-term treatment adherence.
View Article and Find Full Text PDFWe studied the effect of platelet releasate on osteogenic differentiation of human mesenchymal BM stem cells. Histological staining and reverse transcription PCR analysis showed that addition of platelet releasate to osteogenic differentiation medium stimulated the formation of calcium ossificates and alkaline phosphatase and increased expression of osteopontin and alkaline phosphatase genes.
View Article and Find Full Text PDFPrikl Biokhim Mikrobiol
October 2011
Peculiarities of synthesis of surface-active substances (SAS) are studied at periodical cultivation of Rhodococcus erythropolis EK-1 in the AK-210 fermenter on medium containing n-hexadecane. Maximum indicators of SAS synthesis (concentration of extra cellular SAS is 7.2 g/l; factor of emulsification of the cultural liquid 50%; SAS yield from the substrate 50%) have been observed at 60-70% concentration of dissolved oxygen from the saturation level with aerial oxygen (pH 8.
View Article and Find Full Text PDFBackground: Hypertension can be controlled adequately with existing drugs such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Nevertheless, treatment success is often restricted by patients not adhering to treatment. Immunisation against angiotensin II could solve this problem.
View Article and Find Full Text PDFBackground: Although bleeding and thromboembolism remain major complications after implantation of ventricular assist devices (VADs), no standard anticoagulation protocols are available. Genetic polymorphism of platelet glycoprotein IIb/IIIa may contribute to the development of complications. The present study demonstrates a relationship between the PlA genotype and postoperative complications in patients implanted with pulsatile and axial flow VADs.
View Article and Find Full Text PDFAim: To examine the course of chronic cardiac failure (CCF), morphofunctional parameters of the heart in correlation with activity of cytokine system; to evaluate effectiveness, tolerance and safety of combined CCF treatment including a cardioselective beta-adrenoblocker bisoprolol in patients with CCF FC I-IV having a high plasm level of tumor necrosis factor alpha (TNF-alpha).
Material And Methods: The concentration of TNF-alpha in plasm of 40 patients with IHD complicated by CCF of FC I-IV and ejection fraction under 45% was measured at enzyme immunoassay. The treatment included combined therapy with diuretics, cardiac glycosides, peripheral vasodilators, ACE inhibitors, bisoprolol (group I) or no bisoprolol (group II).
Vestn Ross Akad Med Nauk
June 2002
Experience with ultrasonic examination (USE) in diagnosis of foreign abdominal bodies in 23 patients is reviewed. Foreign abdominal bodies have specific echosemiotics. It is demonstrated that USE provides maximal information about sizes, structure, location of foreign abdominal bodies, their depth of location and relationship with abdominal organs.
View Article and Find Full Text PDFStudies on the immediate and long-term effects of radiation on the B-system immunity of children who were affected by radiation after the Chernobyl disaster (from 1986-1992) are summarized in this paper. Complete clinical and immunological examination of more than 6000 children have been carried out. The dynamics of the immune system, with ongoing reactions of cell proliferation and differentiation, gene amplification, transcription, translation, biosynthesis and switching production of isotypes and subclasses of immunoglobulins, as well as specific and nonspecific (natural) antibodies, make it highly susceptible to the action of radiation in addition to other ecological factors.
View Article and Find Full Text PDFKhirurgiia (Mosk)
February 1992
Clinico-laboratory studies were conducted in 46 patients with wound infection for the treatment of which carbon-dioxide laser was used, and in 78 patients who were operated on with a metal scalpel (control). It is shown that "excision" and "evaporation" of tissues took 15-45 minutes. Repeated interventions were performed in 15% of cases due to bleeding from vessels measuring 1.
View Article and Find Full Text PDFGrud Serdechnososudistaia Khir
January 1993