Population Pharmacokinetic and Pharmacodynamic Modeling of Romiplostim Biosimilar GP40141 and Reference Product in Healthy Volunteers to Evaluate Biosimilarity.

GP40141 is a romiplostim biosimilar. A Phase 1 clinical trial was previously conducted in healthy volunteers to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety of GP40141 compared to the reference romiplostim (NCT05652595). Using noncompartmental analysis, the biosimilarity of PD end points was determined according to the classical criterion (0.

[The use of sodium hyaluronate to treat upper limb disease: A review].

The most common diseases of the upper limb are osteoarthritis (OA) of the joints of the hands, lateral epiconlitis, tendinitis of the shoulder muscles, adhesive capsulitis. OA of the shoulder and acromioclavicular joints is less common. The development of acute and subacute pain in the elbow and shoulder joints in the vast majority of cases is determined by the pathology of soft tissues: muscles, ligamentous apparatus and related synovial bags, making it difficult to diagnose.

Pharmacogenetic aspects of efficacy and safety of methotrexate treatment in pediatric acute lymphoblastic leukemia.

Objectives: To evaluate the role of ABCB1 (C3435T rs1045642, rs1128503, rs2032582, rs4148738), SLCO1B1 T521C rs4149056 genetic polymorphisms in the development of major types of methotrexate (MTX) toxicities and the occurrence of a terminal event (death, relapse) in pediatric АLL.

Methods: The study included 124 patients diagnosed with pediatric ALL. All patients treated according to the protocols of the German BFM group (2002/2009) with high-dose (1,000, 2,000 and 5,000 mg/m) methotrexate.

Changes of Signaling Pathways in Hypothalamic Neurons with Aging.

The hypothalamus is an important regulator of autonomic and endocrine functions also involved in aging regulation. The aging process in the hypothalamus is accompanied by disturbed intracellular signaling including insulin/insulin-like growth factor-1 (IGF-1)/growth hormone (GH), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/the mammalian target of rapamycin (mTOR), mitogen activated protein kinase (MAPK), janus kinase (JAK)/signal transducer and activator of transcription (STAT), AMP-activated protein kinase (AMPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), and nitric oxide (NO). In the current review, I have summarized the current understanding of the changes in the above-mentioned pathways in aging with a focus on hypothalamic alterations.

Prospective multicenter online testing of the carotid endarterectomy risk stratification calculator carotidscore.ru.

Aim: To evaluate the incidence of complications, including fatal outcomes, ischemic strokes, and transient ischemic attacks, associated with carotid endarterectomy (CEA) in patients categorized as low-, medium-, and high-risk based on their CarotidSCORE (carotidscore.ru).

Material And Methods: This prospective, multicenter study was conducted from January 1, 2022, to December 20, 2022, and enrolled 5,496 patients with stenosis of the internal carotid artery (ICA), who were categorized into four groups according to their risk level.

Are the Goals of Therapy Achievable in Patients with Rheumatoid Arthritis Receiving Upadacitinib in Real Clinical Practice?

The aim of the study was to evaluate the effectiveness of UPA in RA patients in real clinical practice after 3 and 6 months of therapy. The study included 63 RA patients with high activity of the disease. Activity was assessed according to the DAS28(ESR), DAS28(CRP), SDAI, CDAI; functional ability to HAQ; quality of life to the EQ-5D; disease activity according to the patient's RAPID-3 index; the level of depression and anxiety to the HADS scale.

[Diagnosis and treatment of early forms of cognitive impairment: possibilities of influencing neuronal energy metabolism. Resolution of the Council of Experts].

Diagnosis and treatment of early forms of cognitive impairment: possibilities of influencing neuronal energy metabolism. Resolution of the Council of Experts.

A randomized, double-blind, comparative study of the pharmacodynamics and pharmacokinetics of GP40141 (romiplostim biosimilar) and reference romiplostim in healthy male volunteers.

Aims: The pharmacodynamic (PD) similarity between GP40141, a proposed romiplostim biosimilar, and reference romiplostim was evaluated. Pharmacokinetics and safety were also assessed.

Methods: In this phase 1, randomized, double-blind, single-dose, crossover comparative study with an adaptive design, 56 healthy male volunteers were randomized 1:1 to receive a 3 ug × kg subcutaneous dose of GP40141 and reference romiplostim.

A Multicentric Study of Different Methods of Open Surgical Cerebral Revascularization for Internal Carotid Artery Orifice Stenosis.

To analyze the long-term results of transposition of the internal carotid artery (ICA) into the lateral wall of the external carotid artery (ECA) in the presence of hemodynamically significant stenosis of the ICA. During the period from 3.10.

[Comparative clinical study of pharmacokinetics and bioequivalence of Relonova and Maxalt].

Objective: Evaluation of the bioequivalence of the tested Relonova, tablets, 10 mg and Maxalt, tablets, 10 mg drugs on an empty stomach in healthy volunteers.

Material And Methods: The pharmacokinetic analysis population included 40 volunteers, the safety analysis population included 40 volunteers. The average age of randomized volunteers (men - 20, women - 20) was 29.

Expression of MicroRNA-200a/b/c in the Mediobasal Hypothalamic Nuclei with Aging.

Background: MicroRNAs (miRNAs) belong to small non-coding RNAs that coordinate the expression of cellular genes at the post-transcriptional level. The hypothalamus is a key regulator of homeostasis, biological rhythms and adaptation to different environmental factors. It also participates in the aging regulation.

Validity and reliability of the Russian version of the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).

Objective: The aim of this study is to elaborate a valid and reliable Russian version of the ALSFRS-R.

Methods: Russian adaptation of the ALSFRS-R was applied twice in 50 ALS patients followed by the test-retest analysis with a 7-day interval between applications and internal consistency analysis.

Results: Test-retest analysis showed very strong correlation for all of the ALSFRS-R variables.

Predictive modeling of adverse drug reactions to tamoxifen therapy for breast cancer on base of pharmacogenomic testing.

Objectives: The present study investigated the analysis of adverse drug reactions (ADRs) to tamoxifen (TAM) in breast cancer patients in relation to the carriage of genetic polymorphisms of genes encoding enzymes of CYP system and transporters of P-glycoprotein (Pg) and predictive models based on it.

Methods: A total of 120 women with breast cancer taking adjuvant TAM were examined for the gene polymorphisms such as , , , , , and (). Allelic variants were determined using the real-time polymerase chain reaction method.

Pharmacological Properties of Sulfonamide Derivatives, New Inhibitors of Carbonic Anhydrase.

Selective blocking of individual isoforms of carbonic anhydrase (CA) is now one of the main directions in the development of its inhibitors. The new 1,2,4-oxadiazole-containing sulfonamides B12 and B13 predominantly block CA II and CA IX. The study of acute toxicity of B12 and B13 showed their safety.

[Functional morphology of the bladder and its vascular system in relation to age changes and evolution of BPH].

Introduction: The increase in the proportion of people with various urinary disorders, which are based on anatomical and functional bladder remodeling due to aging, is currently un-deniable. This problem becomes more relevant due to the elevation in life expectancy. At the same time, the features of bladder remodeling, in particular, the structural changes of its vascular bed, are still practically not described in the literature.

Chondroitin sulfate and glucosamine combination in patients with knee and hip osteoarthritis: A long-term observational study in Russia.

Background: Oral treatment of glucosamine (GA) combined with chondroitin sulfate (CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clinical trials. While the effectiveness of GA and CS on both clinical and radiological findings has been demonstrated, only a few high-quality trials exist. Therefore, controversy regarding their effectiveness in real-world clinical practice remains.

Comparability of biosimilar romiplostim with originator: Protein characterization, animal pharmacodynamics and pharmacokinetics.

The results of preclinical studies of romiplostim analogue GP40141 are presented. The effect of a cell proliferation, phosphorylation of the TPO receptor and JAK2 phosphorylation were studied in the presence of romiplostim and in the presence of GP40141 in a cell line of mice (Mus musculus) lymphoblasts with stable expression of human TPO receptor 32D-hTPOR clone 63. Binding to the TPO receptor and to the neonatal Fc receptor (FcRn) was examined for both romiplostim and the developed analogue.

A comparative analysis of lecturers' satisfaction with Anatomage and Pirogov virtual dissection tables during clinical and topographic anatomy courses in Russian universities.

Anatomy is increasingly taught using computer-assisted learning tools, including electronic interactive anatomy dissection tables. Anatomage was he first virtual anatomy dissection table introduced in Russian medical universities and gained popularity among lecturers and students. The Pirogov interactive anatomy table was recently released, but the strengths and weakness of each platform is currently unknown.

Ontogenetic Changes in the Expression of the Lin28 Protein in the Rat Hypothalamic Tuberal Nuclei.

The hypothalamus is a primary regulator of homeostasis, biological rhythms and adaptation to different environment factors. It also participates in the aging regulation. The expression of neurons containing Lin28 was studied by immunohistochemistry in male rats aged 2, 6, 12, and 24 months in the tuberal region of the rat hypothalamus.

[Hyaluronic acid in the treatment of osteoarthritis of various localization: A review].

The article discusses the treatment of osteoarthritis (OA), the prevalence of which is high, and according to some forecasts it will increase by 50% in the next 20 years. The authors emphasize the high comorbidity among patients suffering from OA and high cardiovascular and gastrointestinal risks with frequent use of NSAIDs, the volume of consumption of which is constantly increasing. Discussing recommendations for the treatment of patients with OA, the article focuses on the use of hyaluronic acid (HA) preparations in the treatment of OA.

[Empagliflozin and heart failure: position paper of the experts on the results of the online meeting and discussion of the EMPEROR-Preserved Trial].

At an international online expert meeting held on September 16, 2021, the results of the empagliflozin research program EMPA-REG Outcome, EMPEROR-Reduced and EMPEROR-Preserved were reviewed. We analyzed cardiovascular and renal outcomes during the treatment with empagliflozin in patients with chronic heart failure, regardless of the presence of type 2 diabetes mellitus. The positive results of the EMPEROR-Preserved study are updated and their significance for clinical practice is discussed.

[Approaches to vaccine prevention in multiple sclerosis].

The article presents an overview of modern approaches to vaccine prevention in multiple sclerosis (MS). Compared with the general population, patients with MS have been shown to have an increased risk of morbidity, a tendency to have a more severe course, and a greater mortality from vaccine-preventable infections. At the same time, in Russia, until recently, traditionally adhered to a conservative tactic of limiting vaccination in patients with autoimmune diseases, including MS.