Regulatory Effects of 5-Day Oral and Intraperitoneal Administration of a Thienopyrimidine Derivative on the Thyroid Status in Rats.

In experiments on rats, we studied the effect of 5-day intraperitoneal (15 mg/kg/day) and oral (40 mg/kg/day) administration of compound TPY3m, a stimulator of the production of thyroid hormones by the thyroid gland developed by us, on the blood levels of thyroxine, triiodothyronine, and thyroid-stimulating hormone and on morphology of the thyroid gland. With both routes of administration, TPY3m caused a sustained moderate elevation of thyroid hormones, mainly thyroxine, with little effect on the level of thyroid-stimulating hormone. TPY3m did not reduce the stimulating effect of thyroliberin on the levels of thyroid hormones and had no damaging effect on the thyroid gland.

Comparison of Steroidogenic and Ovulation-Inducing Effects of Orthosteric and Allosteric Agonists of Luteinizing Hormone/Chorionic Gonadotropin Receptor in Immature Female Rats.

Gonadotropins, including human chorionic gonadotropin (hCG), are used to induce ovulation, but they have a number of side effects, including ovarian hyperstimulation syndrome (OHSS). A possible alternative is allosteric luteinizing hormone (LH)/hCG receptor agonists, including the compound TP4/2 we developed, which remains active when administered orally. The aim was to study the effectiveness of TP4/2 (orally, 40 mg/kg) as an ovulation inducer in FSH-stimulated immature female rats, compared with hCG (s.

Dual PTP1B/TC-PTP Inhibitors: Biological Evaluation of 3-(Hydroxymethyl)cinnoline-4()-Ones.

Dual inhibitors of protein phosphotyrosine phosphatase 1B (PTP1B)/T-cell protein phosphotyrosine phosphatase (TC-PTP) based on the 3-(hydroxymethyl)-4-oxo-1,4-dihydrocinnoline scaffold have been identified. Their dual affinity to both enzymes has been thoroughly corroborated by in silico modeling experiments. The compounds have been profiled in vivo for their effects on body weight and food intake in obese rats.

Stimulation of Ovulation in Immature Female Rats Using Orthosteric and Allosteric Luteinizing Hormone Receptor Agonists.

Human chorionic gonadotropin (hCG) and luteinizing hormone (LH) are widely used for the treatment of reproductive disorders and for controlled ovulation induction, but their use is limited by side effects. Allosteric agonists of the LH/hCG receptor, including thieno[2,3-d]thienopyrimidine TP03 developed by us, can become an alternative. TP03 (50 mg/rat, i.

[Characterization and biological activity of new 4-oxo-1,4-dihydrocinnoline-based inhibitors of the tyrosine phosphatase PTP1B and TCPTP].

Functional disorders in obesity are largely due to a decrease in tissue sensitivity to insulin and leptin. One of the ways to restore it is inhibition of protein phosphotyrosine phosphatase 1B (PTP1B) and T-cell protein phosphotyrosine phosphatase (TCPTP), negative regulators of the insulin and leptin signaling. Despite progress in the development of inhibitors of these phosphatases, commercial preparations based on them have not been developed yet, and the mechanisms of action are poorly understood.

Development of Low-Molecular-Weight Allosteric Agonist of Thyroid-Stimulating Hormone Receptor with Thyroidogenic Activity.

To normalize the thyroid status in hypothyroidism caused by resistance to thyroid-stimulating hormone (TSH), low-molecular-weight allosteric agonists of TSH receptor can be used. A new compound ethyl-2-(4-(4-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]-pyrimidine-4-yl)phenyl)-1H-1,2,3-triazol-1-yl) acetate (TPY3m), which stimulated the production of thyroxine when administered to rats (25 mg/kg, i.p.

The Study of Biological Activity of a New Thieno[2,3-D]-Pyrimidine-Based Neutral Antagonist of Thyrotropin Receptor.

The development of low-molecular-weight antagonists of thyroid-stimulating hormone (TSH) receptor is a promising trend in the treatment of autoimmune hyperthyroidism. We studied the effect of thieno[2,3-d]-pyrimidine derivative TPY1 on TSH-stimulated synthesis of thyroid hormones in the culture of FRTL-5 thyrocytes and on thyroliberin-stimulated production of thyroid hormones in rat blood. Preincubation of FRTL-5 cells with TPY1 suppressed the stimulatory effect of TSH on the synthesis of thyroxine and triiodothyronine.

[COMPASS study results as a foundation for new treatment approach for neurological patients. Opinion of the expert council of december 18, 2021].

The resolution of the Council of Experts devoted to the discussion of the effectiveness of the use of a combination of rivaroxaban 2.5 mg 2 times a day and acetylsalicylic acid 100 mg per day to prevent recurrent non-coronary ischemic stroke results of the COMPASS study is presented. The advantages of this combination and the safety of its use are considered.

The Effects of Separate and Combined Treatment of Male Rats with Type 2 Diabetes with Metformin and Orthosteric and Allosteric Agonists of Luteinizing Hormone Receptor on Steroidogenesis and Spermatogenesis.

In men with type 2 diabetes mellitus (T2DM), steroidogenesis and spermatogenesis are impaired. Metformin and the agonists of luteinizing hormone/human chorionic gonadotropin(hCG)-receptor (LH/hCG-R) (hCG, low-molecular-weight allosteric LH/hCG-R-agonists) can be used to restore them. The aim was to study effectiveness of separate and combined administration of metformin, hCG and 5-amino--butyl-2-(methylsulfanyl)-4-(3-(nicotinamido)phenyl)thieno[2,3-]pyrimidine-6-carboxamide (TP3) on steroidogenesis and spermatogenesis in male rats with T2DM.

The Effect of Low-Molecular-Weight Allosteric Agonist of Luteinizing Hormone Receptor on Functional State of the Testes in Aging and Diabetic Rats.

Human chorionic gonadotropin that is widely used for improving spermatogenesis. The effect of chorionic gonadotropin is mediated through luteinizing hormone receptor. Treatment with gonadotropin is associated with undesirable effects due to hyperactivation of testosterone production and luteinizing hormone receptor desensitization.

Comparative Study of the Steroidogenic Effects of Human Chorionic Gonadotropin and Thieno[2,3-D]pyrimidine-Based Allosteric Agonist of Luteinizing Hormone Receptor in Young Adult, Aging and Diabetic Male Rats.

Low-molecular-weight agonists of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (LHCGR), which interact with LHCGR transmembrane allosteric site and, in comparison with gonadotropins, more selectively activate intracellular effectors, are currently being developed. Meanwhile, their effects on testicular steroidogenesis have not been studied. The purpose of this work is to perform a comparative study of the effects of 5-amino---butyl-4-(3-(1-methylpyrazole-4-carboxamido)phenyl)-2-(methylthio)thieno[2,3-] pyrimidine-6-carboxamide (TP4/2), a LHCGR allosteric agonist developed by us, and hCG on adenylyl cyclase activity in rat testicular membranes, testosterone levels, testicular steroidogenesis and spermatogenesis in young (four-month-old), aging (18-month-old) and diabetic male Wistar rats.

New Thieno-[2,3-d]pyrimidine-Based Functional Antagonist for the Receptor of Thyroid Stimulating Hormone.

Thyroid stimulating hormone (TSH) receptor antagonists are required for the treatment of TSH-dependent tumors and Graves disease. We developed the compound 5-amino-N-(tert-butyl)-4-(4-iodophenyl)-2-(methylthio)thieno[2,3-d]pyrimidine-6-carboxamide (TP48) and showed that it reduces the TSH-stimulated adenylate cyclase activity in rat thyroid membranes. Pretreatment of rats with compound TP48 (ip, 40 mg/kg) reduced the increase in the levels of total and free thyroxin in blood and the increase in the expression of thyroglobulin and D2 deiodinase genes in the thyroid gland, which are responsible for the synthesis of thyroid hormones, which were caused by intranasal administration of thyroliberin to animals (300 μg/kg).

Palladium(II)-Stabilized Pyridine-2-Diazotates: Synthesis, Structural Characterization, and Cytotoxicity Studies.

Well-defined diazotates are scarce. Here we report the synthesis of unprecedented homoleptic palladium(II) diazotate complexes. The palladium(II)-mediated nitrosylation of 2-aminopyridines with NaNO results in the formation of metal-stabilized diazotates, which were found to be cytotoxic to human ovarian cancer cells.

THE RELATIONSHIP BETWEEN PHYSICAL-CHEMICAL CHARACTERISTICS AND BIOLOGICAL ACTIVITY OF PEPTIDE 562—572 OF LUTEINIZING HORMONE RECEPTOR MODIFIED BY DECANOYL RADICALS AT THE N- AND C-TERMINI.

Lipophilic derivatives of peptides corresponding to the cytoplasmic regions associated with the G-protein coupled receptors (GPCRs) are capable of functioning as an intracellular agonist. Previously, we have shown that peptides corresponding to region 562—572 of luteinizing hormone receptor (LHR) and modified by decanoate and palmitate at the C-terminus activate adenylyl cyclase (AC) in the testes of rats. The stimulating effect of peptide 562—572 modified by decanoates at the N- and C-termini (IV) peaked at a concentration of 10(–5) M and then subsequently decreased with increasing concentration.

[The method of quantitative assessment of rehabilitation in patients with cerebral stroke].

We have designed a new Self-Service scale for assessing patients with cerebral stroke. This scale enables to determine the degree of patients' self-servicing in everyday life, his/her social activity, mobility, memory and speech. It was administered to 59 patients (33 men and 26 women) aged from 35 to 79 years at admission to and discharge from the hospital.

[Aspects of ischemic stroke course in patients with heart-related embolism].

193 patients with acute ischemic hemispheric stroke were examined. We divided them into two groups. Group 1 included patients with cardiac embolism (n = 49), patients without embolisms (n = 144) formed Group 2.

[Efficacy of OSMO-Adalat in patients with arterial hypertension in combination with kinked precerebral arteries].

Aim: To evaluate effectiveness of OSMO-adalat in combination of arterial hypertension (AH) with kinked precerebral arteries (KPA).

Material And Methods: Before and after a 3-month course of OSMO-Adalat in a dose 30 and 60 mg, 28 patients with AH (degree 2-3) and KPA were examined for arterial pressure (AP), dyscirculatory encephalopathy, orthostatic stability, ischemic heart disease, transitory ischemic attacks, side effects of therapy.

Results: A complete normalization of AP was achieved in 9(32.

[Autoantibodies to NMDA-type glutamate receptors in the blood of patients with acute ischemic and hemorrhagic stroke].

The characteristics of accumulation of autoantibodies (aAbs) on NMDA-type glutamate receptors were studied in blood of patients at different stages (1-4 days, 5-7 days, 8-14 days, up to 28 days) of acute period of ischemic or hemorrhagic stroke. The stability of low values (1.29 +/- 0.

[Age-related dynamics of energy metabolism enzymes of neurons and microvessels of the brain in spontaneously hypertensive rats].

The age changes in the activity of some enzymes in neurons and in microvessels, revealed histochemically, as well as the volume of microvessels in spontaneously hypertensive (SH) rats differ from these changes in the controls. At the age of 3 months the activity of these enzymes and the number of active microvessels in SH rats increased. At the age of 6 months the activity of studied enzymes in SH rats decreased, while the number of active microvessels remained constant.

[Study of prevalence and structure of cerebrovascular disorders in different regions of the USSR based on simultaneous epidemiological examinations].

The authors describe the data of the screenings of the representative random samples from the open male population aged 20 to 54 years, carried out in accordance with the common program in 6 cities of this country. The prevalence of definite cases of cerebrovascular diseases (CVD) ranged from 7.7% in Moscow to 12% in Irkutsk.