Chronic hypoparathyroidism in adults: clinical features, diagnosis, management and treatment

Hypoparathyroidism is a rare сalcium and phosphate metabolic disorder. Most often it develops after neck surgery. The recent studies show increased morbidity in thyroid and parathyroid pathology wich are the most common causes of hypoparathyroidism. Thus makes this problem more relevant and urgent. Management of a patient with chronic hypoparathyroidism is based on personalized treatment regimen, disease monitoring and prevention of therapy adverse events

Obtaining Cell Cultures of Medicinal Plants

In vitro propagation of medicinal plants has been incorporated into producing healthy plants that are beneficial to humanity. Some basic principles and factors tend to influence the cultivation process, thus, causing this method of plant propagation to be adapted owing to the importance and benefits surrounding this method. The main objective of this research work was to obtain cell cultures of medicinal plants of Cichorium intybus, Stevia rebaudiana Bertoni, Monarda citriodora, and Rhodiola krylovii. In obtaining the cell cultures of these medicinal plants, some steps need to be followed. In this research, the effect of different methods of sterilisation/cultivation of plant seeds and explants were evaluated using two different media compositions, observable differences between sterile and non-sterile plant seedlings of C. intybus, Monarda citriodora, and Rhodiola krylovii. The effect of growth regulator (Kinetin) and non-growth regulator (Kinetin) on the cell cultures was observed in solid and liquid media; the dry and wet weight was determined for a callus of Chicory grown in cell suspension culture. All results were presented on tables and charts

Double-flow focused liquid injector for efficient serial femtosecond crystallography

Serial femtosecond crystallography requires reliable and efficient delivery of fresh crystals across the beam of an X-ray free-electron laser over the course of an experiment. We introduce a double-flow focusing nozzle to meet this challenge, with significantly reduced sample consumption, while improving jet stability over previous generations of nozzles. We demonstrate its use to determine the first room-temperature structure of RNA polymerase II at high resolution, revealing new structural details. Moreover, the double flow- focusing nozzles were successfully tested with three other protein samples and the first room temperature structure of an extradiol ring-cleaving dioxygenase was solved by utilizing the improved operation and characteristics of these devices

Influence of deficiency or insufficiency of vitamin D on the circadian rhythm of serum calcium level

Background: mild hypocalcemia is a common laboratory finding that is not accompanied by the clinical symptoms. The most common causes of hypocalcemia are inadequate calcium intake and vitamin D deficiency. Given the high prevalence of vitamin D deficiency (insufficiency), it seems relevant to determine the daily variability of serum calcium levels before and after its supplementation.Aims: to assess the effect of 25(OH) vitamin D level on the daily profile of serum calcium and 24-hour urinary calcium levels. MATERIALS AND METHODS: the interventional, prospective, comparative study of 10 healthy volunteers (women/men - 9/1) was performed. We have analyzed the daily profiles of serum calcium and 24-hour urinary calcium levels. Summary duration of this study was 8 months and consisted two hospitalizations. Statistical analysis was done on August 2020. The descriptive statistics are represented by medians and the first and third quartiles in Me (Q1; Q3), average, maximum, and minimum values M (min; max) and by absolute and relative frequencies.Results: Me serum calcium levels (Catotaland Cacorr.) and 24-hour urinary calcium levels did not differ before and after vitamin D supplementation. However, the number of reference calcium values increased as 25 (OH) vitamin D level was reached more than 30 ng/ml from 90.8% to 100% for Catotal and from 94.2% to 97.5% for Cacorr. Episodes of hypocalcemia were registered in patients with low vitamin D levels: in 3.33% of cases according to Catotal and 5.8% for Cacorr. The frequency of hypocalcemia decreased for Catotal (to 0%) and for Cacorr. (to 2.5%) after treatment with cholecalciferol. Analysis of Catotal and Cacorr. deviations during the day showed a less variability of the calcium profile after treatment, This study also revealed circadian character of daily serum calcium profile with the presence of maximum (09:40-17:40) and minimum (23:40-07:40) values during the day.Conclusions: Our study demonstrated the improvement of daily serum calcium profile after vitamin D supplementation. We confirmed the increased number of reference calcium values, decreased variability of serum calcium levels during the day and decreased frequency of hypocalcemia

Cardiovascular and metabolic status in patients with primary hyperparathyroidism: a single-center experience

IntroductionCardiovascular diseases (CVD) and metabolic disorders (MD) have retained leading positions in the structure of morbidity and mortality for many years. Primary hyperparathyroidism (PHPT) is also associated with a greater incidence of CVD and MD. The aim of the present study was to describe the prevalence and structure of CVD and MD in hospitalized patients with PHPT and to search for possible associations between these pathologies.Methods838 patients with a verified PHPT were included in the study. The studied cohort was divided into 2 groups according to their age at the time of admission: patients aged 18 to 49 years (group A, n = 150); patients aged 50 years and older (group B, n = 688).ResultsThere were no significant differences between two groups in parameters of calcium-phosphorus metabolism. Obesity was diagnosed in 24.2% of patients in group A and in 35.9% in group B. Type 2 diabetes mellitus was more common in older patients (14.4% in group B vs. 2.6% in group A). Arterial hypertension, ischemic heart disease, chronic heart failure and brachiocephalic arteries atherosclerosis were more frequent in older patients, occurring in 79.1%, 10.8%, 8.4%, and 84% of cases respectively. The cutoff points that increased the risk of CVD detection turned out to be age above 56 years, eGFR below 92 ml/min/1.73m2, BMI above 28.3 kg/m2.DiscussionThe present study demonstrated a high incidence of some CVD, as well as disorders of lipid, carbohydrate and purine metabolism in patients with PHPT

Derivatives of 9-phosphorylated acridine as butyrylcholinesterase inhibitors with antioxidant activity and the ability to inhibit β-amyloid self-aggregation: potential therapeutic agents for Alzheimer’s disease

We investigated the inhibitory activities of novel 9-phosphoryl-9,10-dihydroacridines and 9-phosphorylacridines against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase (CES). We also studied the abilities of the new compounds to interfere with the self-aggregation of β-amyloid (Aβ42) in the thioflavin test as well as their antioxidant activities in the ABTS and FRAP assays. We used molecular docking, molecular dynamics simulations, and quantum-chemical calculations to explain experimental results. All new compounds weakly inhibited AChE and off-target CES. Dihydroacridines with aryl substituents in the phosphoryl moiety inhibited BChE; the most active were the dibenzyloxy derivative 1d and its diphenethyl bioisostere 1e (IC50 = 2.90 ± 0.23 µM and 3.22 ± 0.25 µM, respectively). Only one acridine, 2d, an analog of dihydroacridine, 1d, was an effective BChE inhibitor (IC50 = 6.90 ± 0.55 μM), consistent with docking results. Dihydroacridines inhibited Aβ42 self-aggregation; 1d and 1e were the most active (58.9% ± 4.7% and 46.9% ± 4.2%, respectively). All dihydroacridines 1 demonstrated high ABTS•+-scavenging and iron-reducing activities comparable to Trolox, but acridines 2 were almost inactive. Observed features were well explained by quantum-chemical calculations. ADMET parameters calculated for all compounds predicted favorable intestinal absorption, good blood–brain barrier permeability, and low cardiac toxicity. Overall, the best results were obtained for two dihydroacridine derivatives 1d and 1e with dibenzyloxy and diphenethyl substituents in the phosphoryl moiety. These compounds displayed high inhibition of BChE activity and Aβ42 self-aggregation, high antioxidant activity, and favorable predicted ADMET profiles. Therefore, we consider 1d and 1e as lead compounds for further in-depth studies as potential anti-AD preparations

Применение программного продукта «Яндекс.Сервер» для организации поиска в электронном каталоге библиотеки

The huge amounts of information accumulated by libraries in recent years put before developers a problem of the organization of fast and qualitative search which decision is possible with the use of modern search tools of Web-technology. The author examines one of these tools the software product “Yandex. Server”, allowing to organize optimum search in the electronic library catalog. The software product “Yandex. Server” gives a chance to carry out optimum search taking into account morphology of Russian and English languages, as well as the various logical conditions that provides effective and flexible search in the electronic library catalog.Накопленные библиотеками за последние годы огромные массивы информации ставят перед разработчиками задачу организации быстрого и качественного поиска, решение которой возможно с использованием современных поисковых инструментов веб-технологии. Автор рассматривает один из таких инструментов - программный продукт «Яндекс. Сервер», позволяющий организовать оптимальный поиск в электронном каталоге библиотеки с учетом морфологии русского и английского языков, а также различных логических условий

Structural Basis for the Role of Tyrosine 257 of Homoprotocatechuate 2,3-Dioxygenase in Substrate and Oxygen Activation

Homoprotocatechuate 2,3-dioxygenase (FeHPCD) utilizes an active site Fe^II to activate O₂ in a reaction cycle that ultimately results in aromatic ring cleavage. Here, the roles of the conserved active site residue Tyr257 are investigated by solving the X-ray crystal structures of the Tyr257-to-Phe variant (Y257F) in complex with the substrate homoprotocatechuate (HPCA) and the alternative substrate 4-nitrocatechol (4NC). These are compared with structures of the analogous wild type enzyme complexes. In addition, the oxy intermediate of the reaction cycle of Y257F-4NC + O₂ is formed <i>in crystallo</i> and structurally characterized. It is shown that both substrates adopt a previously unrecognized, slightly nonplanar, strained conformation affecting the geometries of all aromatic ring carbons when bound in the FeHPCD active site. This global deviation from planarity is not observed for the Y257F variant. In the Y257F-4NC-oxy complex, the O₂ is bound side-on to the Fe^II, while the 4NC is chelated in two adjacent sites. The ring of the 4NC in this complex is planar, in contrast to the equivalent FeHPCD intermediate, which exhibits substantial local distortion of the substrate hydroxyl moiety (C2–O^–) that is hydrogen bonded to Tyr257. We propose that Tyr257 induces the global and local distortions of the substrate ring in two different ways. First, van der Waals conflict between the Tyr257-OH substituent and the substrate C2 carbon is relieved by adopting the globally strained structure. Second, Tyr257 stabilizes the localized out-of-plane position of the C2–O^– by forming a stronger hydrogen bond as the distortion increases. Both types of distortions favor transfer of one electron out of the substrate to form a reactive semiquinone radical. Then, the localized distortion at substrate C2 promotes formation of the key alkylperoxo intermediate of the cycle resulting from oxygen attack on the activated substrate at C2, which becomes sp³ hybridized. The inability of Y257F to promote the distorted substrate structure may explain the observed 100-fold decrease in the rates of the O₂ activation and insertion steps of the reaction

Innovative Green Approach for Extraction of Piperine from Black Pepper Based on Response Surface Methodology

Bioactive compounds like piperine (alkaloids) offer a variety of health benefits due to their biological and pharmacological potential. Piperine has been revealed to have anti-inflammatory, anti-aging, anti-diabetes, anti-bacterial, anti-ulcer, and anti-carcinogenic characteristics. Recent research has been conducted to extract piperine using effective and environmentally friendly techniques. In this study, we sought to assess the potential and efficacy of natural deep eutectic solvents to extract piperine from black pepper seeds using an ultrasound-assisted extraction technique. A Box&ndash;Behnken design combined with response surface methodology was used to evaluate the optimum extraction conditions of piperine. Extraction efficiency was evaluated based on the extraction yields of piperine, antioxidant activity, total polyphenols, and total flavonoids. The results showed that the choline chloride-citric acid-1,2-propylene glycol combination (1:2:2 molar ratio) with 25% (v/v) of water was the most effective at extracting piperine from black pepper. It was found that the extraction yield of piperine was significantly influenced by the liquid&ndash;solid ratio and extraction time. The optimal extraction conditions were determined and it was found that antioxidant activities and total polyphenol content in the piperine-rich extracts were remarkably related to the piperine content. The piperine extract purity was found to be 90%. Our results indicate that black pepper could be used as a functional food application