In silico drug repurposing of anticancer drug 5-FU and analogues against SARS-CoV-2 main protease

The pressing need to find effective drugs against the current deadly COVID-19 disease has recently motivated numerous studies using different approaches to address the problem. One time-saving and less costly strategy is the drug repurposing, which consists in finding new therapeutic uses for approved drugs. Following the same trend, this study has investigated the potential inhibitory activity of 5-FU and its analogues against the SARS-CoV-2 main protease as well as their profile of druggability using molecular docking and ADMET methods. From the calculations performed, four candidates showed promising results with respect to the binding affinity to the target protease, 3CLpro, the therapeutic profile of druggability and safety. Further in-vitro and in-vivo investigations are needed that may clarify their possible mechanism of the pharmacological action to combat COVID-19.

The viral myocarditis with cardiac аrrhythmia as complication of COVID-19 in the practice of family doctor of the tuberculosis dispensary

BACKGROUND: About 70% of TB dispensary patients have chronic somatic diseases which not only prevent effective treatment of TB but also take progressive course themselves. AIMS: To timely detect and treat acute and chronic somatic disease combined with TB. MATERIALS AND METHODS: since 2020 the algorithm of patient complex investigation by specialists of therapeutic profile was developed in the Tuberculosis Dispensary No. 5, among them the general practitioner was the coordinator of the patients medical route. This became especially relevant during the COVID-19 pandemic. RESULTS: In accordance with the developed algorithms of diagnostic search the patient was comprehensively examined. There were no signs of tuberculosis were in him, however the general practitioner involving to specialists team could diagnose signs of complex cardiac arrhythmia the probable cause which was a new coronavirus infection that he had had six weeks before. CONCLUSIONS: The organization of a new form of medical service for phthisiatric patients allowed general practitioner to reveal serious cardiac pathology directly at the TB dispensary, to refer the patient for consultation to the cardiologist-arrhythmologist, to follow the patient and perform recommended cardiologic treatment simultaneously with measures or medical supervision over persons contacting with tuberculosis.

EPIDEMIOLOGICAL, CLINICAL AND THERAPEUTIC PROFILE OF CUTANEOUS LEISHMANIASIS IN THE PROVINCE OF ESSAOUIRA-MOROCCO

Leishmaniasis is a group of parasitic, tropical diseases caused by flagellate protozoa belonging to the genus Leishmania. These parasites affect several mammalian species, including man, to which they are transmitted by the bite of an insect vector, the sandfly. They are widespread in many countries, including the countries of the Mediterranean region. In Morocco, it is a persistent public health problem despite the development and implementation of a control program. Our work is a retroprospective study of leishmaniasis cases observed in the Essaouira province over a period of 5 years (from 01/10/2016 to 31/12/2020). The objective of this study is to develop the epidemiological, clinical and therapeutic profile of this disease with an analytical comparison with other works and researches. 598 cases of cutaneous leishmaniasis were collected and no cases of visceral leishmaniasis. The age group most affected by cutaneous leishmaniasis is the one between 0-5 years old with 147 cases (25.00%) with an average age of 22.70 years. Similarly, a predominance of the female sex was observed with 58.19% of females versus 41.80% of males. The majority of cases were recorded in rural areas. The commune most affected is El-hanchan with a total of 149 cases, or 24.92% of the total cases observed. The epidemiological profile of leishmaniasis in Morocco seems to be gradually reached that of Mediterranean countries characterized by an increase in the number of cases and the emergence of new homes so far free of the parasite. Hence, the need for actions to combat well codified and adapted to different types of leishmaniasis. The measures undertaken in the framework of control program established in Morocco, have been evaluated on a permanent basis in order to develop and adapt them to the evolution of leishmaniasis in the province.

The synthetic triterpenoids CDDO-TFEA and CDDO-Me, but not CDDO, are potent BACH1 inhibitors

The transcription factor BACH1 is a potential target against a variety of chronic conditions linked to oxidative stress and inflammation, and formation of cancer metastasis. However, only a few BACH1 degraders/inhibitors have been described. BACH1 is a transcriptional repressor of heme oxygenase 1 (HMOX1), which is positively regulated by transcription factor NRF2 and is highly inducible by derivatives of the synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO). Most of the therapeutic activities of these compounds are due to their anti-inflammatory and antioxidant properties, which are widely attributed to their ability to activate NRF2. However, with such a broad range of action, these drugs may have other molecular targets that have not been fully identified and could also be of importance for their therapeutic profile. Herein we identified BACH1 as a target of CDDO-derivatives, but not CDDO. While both CDDO and CDDO-derivatives activate NRF2 similarly, only CDDO-derivatives inhibit BACH1, which explains the much higher potency of CDDO-derivatives as HMOX1 inducers compared with unmodified CDDO. Notably, we demonstrate that CDDO-derivatives inhibit BACH1 via a novel mechanism that reduces BACH1 nuclear levels while accumulating its cytoplasmic form. Altogether, our study identifies CDDO-derivatives as dual KEAP1/BACH1 inhibitors, providing a rationale for further therapeutic uses of these drugs

Rheumatoid arthritis in the practice of a nurse of therapeutic profile

The article discusses various aspects of rheumatic diseases that are most common in therapeutic practice. The most detailed information is provided on rheumatoid arthritis (etiology, pathogenesis), clinical symptoms and the basics of laboratory diagnostics are described in detail. The key issues of the significance of osteoporosis as one of the most serious complications of rheumatoid arthritis are discussed separately.

Nanoencapsulation of Polyphenols as Drugs and Supplements for Enhancing Therapeutic Profile - A Review

: Polyphenolic phytoconstituents have been widely in use worldwide since ages and are categorised as secondary metabolites of plants. The application of polyphenols such as quercetin, resveratrol. curcumin as nutritional supplement has been researched widely. The use of polyphenols, and specifically quercetin for improving the memory and mental endurance have shown significant effects among rats. Even though similar results has not been resonated among human but encouraging preclinical results have encouraged researchers to explore other polyphenols to study the effects as supplements among athletes. The phytopharmacological research has elucidated the use of natural polyphenols to prevent and treat various physiological and metabolic disorders owing to its free radical scavenging properties, anti-inflammatory, anti-cancer and immunomodulatory effects. In spite of the tremendous pharmacological profile, one of the most dominant problem regarding the use of polyphenolic compounds is their low bioavailability. Nanonization is considered as one of the most prominent approaches among many. This article aims to review and discuss the molecular mechanisms of recently developed nanocarrier-based drug delivery systems for polyphenols and its application as drugs and supplements. Nanoformulations of natural polyphenols are bioactive agents, such as quercetin, kaempferol, fisetin, rutin, hesperetin, and naringenin epigalloccatechin-3-gallate, genistein, ellagic acid, gallic acid, chlorogenic acid, ferulic acid, curcuminoids and stilbenes is expected to have better efficacy. These delivery systems are expected to provide higher penetrability of polyphenols at cellular levels and exhibit a controlled release of the drugs. It is widely accepted that natural polyphenols do demonstrate significant therapeutic effect. However, the hindrances in their absorption, specificity and bioavailability can be overcome using nanotechnology.

Remote Assessment of Professional Competencies Using Simulation Technologies in the Context of COVID-19

Due to the spread of the COVID-19 pandemic, face-to-face educational events and classes were transferred to a distance format, so the traditional II All-Russian Olympiad with international participation in therapy was also held in absentia on April 26-28, 2021. This format provided the opportunity for 759 students and residents to participate in it from 82 educational and scientific organizations in Russia, Kazakhstan, Uzbekistan, Tajikistan and Belarus. This article analyzes the Olympiad held in order to study the possibility of assessing professional competencies using distance technologies among students of 4-6 courses and residents of a therapeutic profile. As tools for assessing the formation of competencies, we used: testing knowledge using an electronic platform for remote testing and assessing practical skills using a computer screen simulator Body Interact. The analysis of the results showed that the bank of test tasks and clinical cases is valid, reliable, and can be used to assess the professional competencies of students in specialty and residency programs of a therapeutic profile.

Synthesis of Platinum(II) N-Heterocyclic Carbenes Based on Adenosine

Organometallic derivatization of nucleosides is a highly promising strategy for the improvement of the therapeutic profile of nucleosides. Herein, a methodology for the synthesis of metalated adenosine with a deprotected ribose moiety is described. Platinum(II) N-heterocyclic carbene complexes based on adenosine were synthesized, namely N-heterocyclic carbenes bearing a protected and unprotected ribose ring. Reaction of the 8-bromo-2′,3′,5′-tri-O-acetyladenosine with Pt(PPh3)4 by C8−Br oxidative addition yielded complex 1, with a PtII centre bonded to C-8 and an unprotonated N7. Complex 1 reacted at N7 with HBF4 or methyl iodide, yielding protic carbene 2 or methyl carbene 3, respectively. Deprotection of 1 to yield 4 was achieved with NH4OH. Deprotected compound 4 reacted at N7 with HCl solutions to yield protic NHC 5 or with methyl iodide yielding methyl carbene 6. Protic N-heterocyclic carbene 5 is not stable in DMSO solutions leading to the formation of compound 7, in which a bromide was replaced by chloride. The cis-influence of complexes 1–7 was examined by 31P{1H} and 195Pt NMR. Complexes 2, 3, 5, 6 and 7 induce a decrease of 1JPt,P of more than 300 Hz, as result of the higher cis-influence of the N-heterocyclic carbene when compared to the azolato ligand in 1 and 4.

A review of chemistry and pharmacology of Piperidine alkaloids of Pinus and related genera

Background: Pinus and other related conifers belonging to family pinaceae are most commonly used medicinal plants in Indian North-western Himalayas. Various parts of these plants including needles are source of several well known alkaloids. Of all the alkaloids, piperidine group is one of important component and hold considerable medicinal importance. Methods: The group of alkaloids was initially identified from genus Piper through which a large variety of piperidine molecules have been extracted. The planar structure of this heterocyclic nucleus enables acetamide groups to be added at various ring configurations. Results: In the area of drug research, the piperidine heterocycle has gained considerable interest. To produce a new therapeutic profile, the broad range of its therapeutic application paved the way for researchers to implant the nucleus from time to time in diversified pharmacophores. Discussion: However, biological functions of piperidine metabolites have been mostly examined on a limited scale and that most of the findings are thus preliminary. We have tried to present different clinical applications of piperidine alkaloids in this study that researchers have already attempted to demystify from time to time. Conclusion: Given the importance of the piperidine nucleus, the study will enable the researcher to produce scaffolds of the highest therapeutic efficacy. We have also illustrated different types of piperidine, its sources in different member of family pinaceae with special emphasis on Pinus.