INFLUENCE OF THE TREATMENT AND PREVENTIVE MEASURES ON THE PHYSICAL INDICATORS OF ORAL LIQUID IN CHILDREN WITH CHRONIC CATARRHIC GINGIVITIS AND DIABETES MELLITUS

The aim of our study was to find out the effect of our proposed treatment and prevention complex, which included oral administration of «Kvertulin» complex drug, «Imupret» drops, «Pikovit» multivitamin drug and «Exodent» local irrigation of the oral cavity with a solution of tooth elixir that influence on the rate of salivation and viscosity of oral fluid in children with chronic catarrhal gingivitis and diabetes mellitus.The treatment and prophylactic measures had positive effect on the homeostasis of the oral cavity, which assisted to reduce the viscosity of the oral fluid, increase the rate of salivation, as evidenced by observation of patients for 6 months. The treatment and prevention complex are recommended to use 2 times a year, as the studied indicators deteriorate over time.

Algorithm for the diagnosis and treatment of primary placental dysfunction in pregnant women of risk groups

Research objective: to evaluate the effectiveness of diagnosis and complex therapy of placental dysfunction (PD) in early stages of gestation.Materials and methods. We examined 110 pregnant women with risk for the primary PD. Exclusion criteria were multiple pregnancies, anomalies of fetal development and internal genital organs of the mother, pregnancy resulting from assisted reproductive technologies.The diagnosis of PD was established in 56 women (group I) based on the assessing the state of extraembryonic structures and blood flow in the spiral and uterine arteries at 12–13 weeks of gestation. The rest of the patients (54 women) entered the control group without PD (group II).Results. All pregnant women with verified PD at 12–13 weeks were prescribed complex drug treatment, which included micronized progesterone, venotonic Normoven, Magnicum, and Artihol. As a result of treatment, already at 22–24 weeks of gestation, the average value of blood flow (resistance index) in the uterine and spiral arteries did not differ significantly in the groups. There was no significant difference in fetometry and placentometry indices at 35–36 weeks of gestation. Complications of the gestational period in patients in the study groups were also almost the same.Conclusions. History of hormonal disorders and miscarriage, clinical signs of miscarriage in early gestation, abnormal embryo placement, extragenital pathology, and genital tract infections are risk factors for PD. Determination of the state of extraembryonic structures at 7–8 weeks of pregnancy (ovum volume, blood flow in the corpus luteum) and at 12–13 weeks (chorion volume, vascularization index, blood flow in the spiral and uterine arteries) can serve as a verification criterion for the PD development. Complex drug therapy, which began from the early stages of gestation (micronized progesterone, Normoven, Magnicum, Artihol) has established itself as an effective method of treating primary PD in pregnant of risk groups.

Molecular mechanism of proton-coupled ligand translocation by the bacterial efflux pump EmrE

The current surge in bacterial multi-drug resistance (MDR) is one of the largest challenges to public health, threatening to render ineffective many therapies we rely on for treatment of serious infections. Understanding different factors that contribute to MDR is hence crucial from the global “one health” perspective. In this contribution, we focus on the prototypical broad-selectivity proton-coupled antiporter EmrE, one of the smallest known ligand transporters that confers resistance to aromatic cations in a number of clinically relevant species. As an asymmetric homodimer undergoing an “alternating access” protomer-swap conformational change, it serves as a model for the mechanistic understanding of more complex drug transporters. Here, we present a free energy and solvent accessibility analysis that indicates the presence of two complementary ligand translocation pathways that remain operative in a broad range of conditions. Our simulations show a previously undescribed desolvated apo state and anticorrelated accessibility in the ligand-bound state, explaining on a structural level why EmrE does not disrupt the pH gradient through futile proton transfer. By comparing the behavior of a number of model charged and/or aromatic ligands, we also explain the origin of selectivity of EmrE towards a broad class of aromatic cations. Finally, we explore unbiased pathways of ligand entry and exit to identify correlated structural changes implicated in ligand binding and release, as well as characterize key intermediates of occupancy changes.

Direct C-H-Sulfonylation of 6-Membered Nitrogen-Heteroaromatics

Heterocyclic sulfones and sulfonamides represent important structural motives in medicinal chemistry and drug development. Therefore, efficient and reliable methods for their construction from simple building blocks are in high demand. Herein we report a novel approach for the direct C-H-sulfonylation of N heteroaromatics via N-activation with triflic anhydride (Tf2O), base-mediated addition of a sulfinate salt and subsequent rearomatization through trifluoromethanesulfinate elimination. This operationally simple one-pot protocol enables direct access to various sulfonylated 6-ring N-heterocycles. It is applicable to the late-stage functionalization of complex, drug-like molecules. The direct incorporation of sulfur dioxide with organometallic reagents as well as the utilization of a rongalite-based sulfonylation reagent provide opportunities for a highly modular synthesis of N-heterocyclic sulfones and sulfonamides from three different building blocks.

Development of the Commercial Manufacturing Process for Ipatasertib

Ipatasertib is a potent small molecule Akt kinase inhibitor currently being tested in Phase III clinical trials for the treatment of metastatic castration-resistant prostate cancer and triple negative metastatic breast cancer. In this paper an overview of the development achievements towards the commercial manufacturing process is given. The convergent synthesis consists of ten steps with eight isolated intermediates and utilizes a wide range of chemical techniques and technologies to build-up this complex drug. All three stereocenters are introduced using enzyme or metal catalysis.

Prevention of recurrence of endometrial polyps in women of reproductive age

The objective: the optimization of management of women in reproductive age after removal of endometrial polyps based on the study of the antioxidant status of the organism.Materials and methods. We examined 150 women in reproductive age with endometrial polyps, 65 (43.3%) patients of them were diagnosed with glandular polyp, 85 (56.7%) – with glandular fibrous polyps. 110 patients after polypectomy were divided into three clinical groups: the first group (32 (29.1%) women) did not receive anti-relapse therapy, the second group (36 (32.7%) persons) used dydrogesterone, the third group (42 (38.2%) women) – received complex drug anti-recurrence therapy (thioctic acid preparation, ascorbic acid, α-tocopherol acetate, indole-3-carbinol). In all women, the antioxidant indicators in blood and the presence of recurrent polyps were determined in 12 months after the treatment. Results. Before polypectomy in patients with endometrial polyps, a decrease of indicators of antiradical activity by 28.52%, restored forms of non-protein SH-groups – by 16.46%, protein SH-groups – by 25.31%, ascorbic acid – by 27.04%, α-tocopherol – by 21.62%, the value of the integral indicator of antioxidant protection – by 31.01% were found compared to the persons in the control group, as well as an increase in the concentration of malonic dealdehyde by 37.23%, non-protein SS groups – by 43.48%, protein SS-groups - by 29.43% and oxidized forms of ascorbic acid – by 29.68%.In 12 months after polypectomy, recurrence of the pathology was in 21.9% of patients of the first group, in 16.7% – of the second group, and no recurrence was detected in women in the third group.Conclusions. In patients with endometrial polyps there are a decrease in level of components of antioxidant protection in the organism and the expressed intensification of processes of free radical and peroxide oxidation of lipids. The use of a comprehensive approach that combines the polypectomy with the use of antioxidant drugs in the postoperative period, in such patients allows to prevent a recurrence of the pathology.

Description of medication adherence in hypertensive respondents at Mandalika Mataram elderly social centre

Introduction: Elderly people are at high risk of non-adherence to hypertensive therapy due to changes in body function and ageing processes. Objectives: The purpose of this study is to explore medication adherence among hypertensive respondents at the Mandalika Mataram NTB Elderly Social Centre. Methods: This study is descriptive observational with a purposive sampling technic. The sample consisted of 30 respondents who met the inclusion criteria. Data were collected using the Modified Morisky Adherence Scale (MMAS-8). Results: The results showed that adherence among participants was high (23.3%), moderate (56.1%), and low (20.0%). Respondent adherence was associated with the role of health workers in monitoring drug therapy. Non-adherence was several factors, including side effects of the drug, complex drug regimens, and ageing.

Safer Tripping: Serotonergic Psychedelics and Drug Checking. Submission and Detection Rates, Potential Harms, and Challenges for Drug Analysis

Purpose of Review With the continuous emergence of new psychoactive substances, drug checking (DC) services are challenged by an increasingly complex drug market. Considering the resumed scientific and public interest in serotonergic psychedelics (SPs) like LSD, psilocybin, and 2C-B, we present the results of a literature search investigating the presence and proportion of SPs in DC samples. Recent Findings In 15 identified reports, submission and detection rates of SPs were comparably low, but increasing. Samples contained considerable amounts of adulterations or analogues, mostly novel SPs with unknown toxicological profiles and in some cases potentially life-threatening effects. The detection of SPs, however, requires advanced analysis techniques currently not available to most DC services. Summary Given the substantial proportion of novel SPs in DC samples and the associated risks, DC can be a valuable harm reduction and monitoring tool for SPs if analysis techniques with high sensitivity are employed.