Consumption of antimicrobial preparations in pacients with COVID-19 in the Republic of Moldova

INTRODUCERE Pandemia SARS-CoV-2 domină în prezent fiecare aspect al îngrijirilor medicale de pe glob, umbrind alte probleme de sănătate publică pe termen mai lung - inclusiv creşterea constantă a rezistenţei antimicrobiene, datorită utilizării necorespunzătoare a antibioticelor. În pofida faptului că antibioticele nu tratează și nu previn infecţiile virale precum COVID-19, rezultatele cercetărilor de perspectivă comportamentală efectuate în 9 ţări și zone ale regiunii europene au arătat că utilizarea antibioticelor crește pe tot parcursul pandemiei, împreună cu creşterea cazurilor de infectare cu SARS-CoV-2. SCOPUL LUCRĂRII Evaluarea consumului de preparate antibacteriene din cadrul instituţiilor medicosanitare publice din Republica Moldova pe perioada pandemiei cu SARS-CoV-2, pentru anii 2019-2020, folosind doza zilnică definită (DDD) ca unitate de măsură sunt recomandate de OMS pentru studii de utilizare a medicamentelor MATERIAL ȘI METODE Datele statistice, rezultatele achiziţiilor publice centralizate pentru 370-380 instituţii medicosantitare publice din Republica Moldova au fost analizate, conform Centrului pentru Achiziţii Publice Centralizate în Sănătate, utilizînd unitatea de măsură doza zilnică definită (DDD). REZULTATE Ca urmare a sistematizării datelor se atestă o creștere considerabilă pentru următoarele grupe de preparate antibacteriene: Glicopeptide, DDD sumar pentru anul 2020 constituie 213823.25 (> 2522.37 % comparative cu anul 2019, Macrolide, DDD sumar pentru anul 2020 constituie 287882.19 (> 785.26 % comparativ cu anul 2019, o creștere semnificativă se atestă și pentru Carbapeneme ( > 217.30 %), Sulfamide (> 434.39 % ) și Polipeptide (> 197,86 %). Unele grupe cum ar fi: Cefalosporinele (> 4.32), Amefnicoli (> 25.70 %) au cresct nesemnificativ. Totodată, de menţionat este că a scăzut utilizarea preparatelor cu conţinut de Chinolone (<18 %), Lincosamide (<29,54 %), Peniciline (4,70 %), Chimioterapice (<41.07 %). Concluzii. Pe perioada pandemiei cu SARS-CoV-2 a crescut excesiv utilizarea în sectorul spitalicesc a grupelor de preparate antibacteriene (Glicopeptide, Macrolide, Carbapeneme, Polipeptide), ceea ce poate provoca o creștere a rezistenţei la antibacteriene pe termen lung și creșterea infecţiilor nasocomiale.BACKGROUND The SARS-CoV-2 pandemic is currently dominating every aspect of health care across the globe, putting other longer-term public health issues—including the steady rise of antimicrobial resistance—in the shade, due to the misuse of antibiotics. Despite the fact that antibiotics do not treat or prevent viral infections like COVID-19, the results of behavioural insight research conducted in 9 countries and areas of the European Region showed antibiotic use increasing throughout the pandemic along with cases. OBJECTIVE OF THE STUDY The evaluation of the consumption of antibacterial preparations within the public medical institutions of the Republic of Moldova during the pandemic with SARS-CoV-2, for the years 2019-2020 using the defined daily dose (DDD) as a unit of measurement recommended by the WHO for studies on the use of medicines. MATERIAL AND METHODS Statistical data, results of centralized public procurement for 370-380 public medical institutions in the Republic of Moldova was analyzed according to the Center for Centralized Public Procurement in Health, using the unit of measurement of the defined daily dose (DDD). RESULTS As a result of the systematization of the data, there is a considerable increase for the following groups of antibacterial preparations: Glycopeptides, summary DDD for 2020 is 213823.25 (> 2522.37% compared to 2019), Macrolides, summary DDD for 2020 is 287882.19 (> 785.26% compared to 2019), there is also a significant increase for Carbapenems (> 217.30%), Sulfamides (> 434.39%) and Polypeptides (> 197.86%). Some groups such as: Cephalosporins (> 4.32), Amefnicoli (> 25.70%) increased insignificantly. At the same time, it should be mentioned that the use of preparations containing Chinolone (<18%), Lincosamide (<29.54%), Penicillins (4.70%), Chemotherapeutics (<41.07%) decreased. CONCLUSION During the pandemic with SARS-CoV-2, the use of groups of antibacterial preparations (Glycopeptides, Macrolides, Carbapenems, Polypeptides) in the hospital sector increased excessively, which may cause an increase in long-term antibacterial resistance and an increase in nasocomial infections

Experimental pharmacological research regarding some newly synthesized benzamides on central nervous system functions

Three newly synthesized benzamides by the Department of Pharmaceutical Chemistry of the Faculty of pharmacy from the University of Medicine and Pharmacy „Carol Davila” Bucharest were tested in order to determine whether these new molecules have similar effects on the central nervous system as those already in therapeutic use belonging to the same chemical group, such as tiapride (neuroleptic) or lidocaine (local anaesthetic). Tests were carried out on NMRI mice which were given new compounds, conventionally named I5C, I14C, and II5C in a dose of 1/20 of the lethal dose 50% (LD50), as previously determined. They received this treatment daily for 21 days. The evasive–investigating capacity of mice was determined using the platform test, and the motor activity using an Activity cage device. The results have shown that compounds I5C and II5C decrease the investigation capacity of the mice; and compound I5C inhibits motor activity, while II5C stimulates it. Thus we concluded that only compounds I5C and II5C have a neuroleptic potential that might be investigated further

Experimental pharmacological research regarding some new quinazolin-4-ones derivatives

A series of new compounds with quinazolin-4-one structure, synthesized by the Pharmaceutical Chemistry Department of the Faculty of Pharmacy of the University of Medicine and Pharmacy “Carol Davila” Bucharest, was studied. Five of them were selected, conventionally named S1, S2, S3, S4, S5, and investigated in terms of their potential influence on the central nervous system (CNS). For this purpose, the antidepressant effect was determined using the forced swimming test; the anxiolytic/ anxiogenic effect was determined using the suspended plus-shaped maze (Ugo Basile); the effect on the motor activity was determined using the Ugo Basile activity cage; and the potential analgesic effect was investigated using the hot plate test (Ugo Basile). Compounds S3 and S5 lowered the motor activity and showed an anxiolytic effect, while S1 and S2 proved to have antidepressant and analgesic effects. A good correlation between antidepressant and analgesic effects was observed, consistent with the fact that analgesic drugs, by increasing norepinephrine and serotonin levels in the pain inhibiting descendent pathways, can be used as co-analgesics in therapy

Experimental pharmacological research regarding the antidepressant effect of associating doxepin and selegiline in normal mice

The severity and complexity of depression can vary widely among individuals, thus making single drug therapy ineffective in some cases. Taking this fact into account and using a mouse model, we set on investigating the possibility of obtaining a synergism of action between a classical tricyclic antidepressant that inhibits noradrenalin and serotonin reuptake (doxepin), and a modern antidepressant that inhibits type-B monoamine oxidase (selegiline). We measured the antidepressant effect using the forced swimming test and the tail suspension test. We determined motor activity using the Activity Cage test. Our results have shown that the antidepressant effect intensifies significantly in the animals treated with both antidepressants simultaneously compared to those treated only with doxepin. Furthermore, we observed that selegiline decreases the sedative effect of doxepin in the Activity Cage test

New Potential Beta-3 Adrenergic Agonists with Beta- Phenylethylamine Structure, Synthesized for the Treatment of Dyslipidemia and Obesity

Beta-3 adrenergic receptors have important physiological implications, being expressed in many places in the body, including brown adipose tissue. Of the effects studied in preclinical research on lipid metabolism attributable to stimulation of these receptors, we can mention the increased thermogenesis and metabolic rate in the brown adipose tissue, reduction of body weight in obese diabetic rats, lowering of intra-abdominal and subepithelial fat in nonobese and nondiabetic rats, decrease of triglyceride, and increase of HDL cholesterol levels. Carbohydrate metabolism is also changed by beta-3 adrenergic agonists, the most prevalent effects being blood glucose lowering in diabetic rats, increasing insulin secretion of the pancreas, or increasing glucose tolerance. Metabolic effects of 13 newly synthesized compounds of beta-phenylethylamine structure and reference BRL 37344 were investigated in order to identify a potential affinity for beta-3 adrenergic receptors. The antidiabetic and hypolipemiant effects were investigated on a rat model of alloxan-induced diabetes. The results demonstrated that new beta-phenylethylamine derivatives produced marked biological activity over lipid profile. All compounds have markedly decreased the values of total cholesterol, LDL cholesterol, and triglycerides and also have increased the values of antiatherogenic HDL cholesterol. The effects were significantly more intense than the reference substance BRL 37344

Determination of pyrrolizidine alkaloids in dietary sources using a spectrophotometric method

Pyrrolizidine alkaloids (PAs) are a class of toxic compounds found in the composition of more than 6000 plants. People can be exposed to PAs by consuming phytotherapeutic products, food from crops contaminated with seeds of some species with high content of PAs, and/ or contaminated animal products like bee products. For this reason we developed and validated a method for quantitative determination of PAs, from the most frequently contaminated food sources, honey and flour. Colorimetric Ehrlich reagent method was used with standard addition (1mg/kg senecionine). The extraction solvent was methanol 50% acidified with citric acid to pH 2-3, as this solvent can be used for alkaloids and N-oxides. We found that, in extracting the alkaloid only once from the dietary sources, the percent of recovery is low (52.5% for honey, and 45.75% for flour). Using successive extractions, three times with the same solvent, the senecionine retrieval percentage increased to 86.0% for honey and 76.0% for flour. The method was validated using the following parameters: selectivity, linearity (0,25- 20 mg/ mL senecionine), accuracy (average recovery 93.5 - 107.93%) and precision (RSD 3,26-4.55%.). The calculated limit of quantification (0.174 mg/ mL) makes this method applicable for determining Pas occurring at toxic levels for consumers

Comparative evaluation of the bioavailability for oral medicines with potassium and spironolactone

Scientific Center of Medicine Fellow Nicolae Testemitsanu State University of Medicine and Pharmacy of the Republic of Moldova, Department of Pharmaceutical and Toxicological Chemistry, Nicolae Testemitsanu State University of Medicine and Pharmacy, Chisinau, the Republic of Moldova, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, Bucharest, RomaniaRezumat. Conform studiilor recente, una dintre cele mai răspândite cauzele a hipertensiunii arteriale este un consum ridicat de sare (clorură de sodiu) și un aport scăzut de potasiu (K+). Creșterea aportului de potasiu de 1,64 g poate reduce riscul de accident vascular cerebral cu 21% (p = 0,0007) și a bolilor cardiovasculare. În Republica Moldova există produse medicinale cu diferitele săruri de K+ care pot fi utilizate ca supliment mineral pentru tratarea deficienţei de K+ (hipopotasemie). Astfel, a fost necesar să se stabilească unor parametri pentru a elabora medicamentul cu cea mai înaltă biodisponibilitate. Datele obţinute vor fi utilizate pentru a selecta compoziţia produsului medicamentos combinat cu cea mai mare biodisponibilitate, eficacitate și siguranţă.Summary. According to recent studies, one of the widely-spread causes of the arterial hypertension is a high consumption of salt (sodium chloride) and a low potassium (K+) intake. An increase in potassium intake of 1.64 g may reduce the risk of stroke by 21% (p=0.0007) and cardiovascular disease. There were found the different salts of K+, which can be used as a mineral supplement to treat K+-deficiency (hypopotassemia) in the Republic of Moldova. Thus, it was necessary to establish some parameters in order to find the medicine with the highest bioavailability. The obtained data will be used in order to select the composition to create the fixed-dose drug combination with the highest bioavailability, efficacy and safety

Determination of pyrrolizidine alkaloids in dietary sources using a spectrophotometric method

Pyrrolizidine alkaloids (PAs) are a class of toxic compounds found in the composition of more than 6000 plants. People can be exposed to PAs by consuming phytotherapeutic products, food from crops contaminated with seeds of some species with high content of PAs, and/ or contaminated animal products like bee products. For this reason we developed and validated a method for quantitative determination of PAs, from the most frequently contaminated food sources, honey and flour. Colorimetric Ehrlich reagent method was used with standard addition (1mg/kg senecionine). The extraction solvent was methanol 50% acidified with citric acid to pH 2-3, as this solvent can be used for alkaloids and N-oxides. We found that, in extracting the alkaloid only once from the dietary sources, the percent of recovery is low (52.5% for honey, and 45.75% for flour). Using successive extractions, three times with the same solvent, the senecionine retrieval percentage increased to 86.0% for honey and 76.0% for flour. The method was validated using the following parameters: selectivity, linearity (0,25- 20 mg/ mL senecionine), accuracy (average recovery 93.5 - 107.93%) and precision (RSD 3,26-4.55%.). The calculated limit of quantification (0.174 mg/ mL) makes this method applicable for determining Pas occurring at toxic levels for consumers

Very Fast RP–UHPLC–PDA Method for Identification and Quantification of the Cannabinoids from Hemp Oil

In recent years, hemp oils have become ubiquitous in health products on the European market. As the trend continues to grow and more cannabinoids are researched for their therapeutic benefits, more academic and industrial interests are drawn to this direction. Cannabidiol, Δ9-tetrahydrocannabinol, and their acidic forms remain the most examined cannabinoids in hemp and cannabis oils, in the case of cannabidiol due to its proven health implications in numerous articles, and in the case of Δ9-tetrahydrocannabinol, due to the legislation in the European area. These oils sold on the internet contain a wide range of cannabinoids that could demonstrate their effects and benefits. As a result of these claims, we developed a robust and rapid method that can identify and quantify 10 of the most common cannabinoids found in hemp oils: cannabivarin, cannabidiolic acid, cannabigerolic acid, cannabigerol, cannabidiol, cannabinol, Δ9-tetrahydrocannabinol, Δ8-tetrahydrocannabinol, cannabichromene, and tetrahydrocannabinolic acid in less than 11 min, with reverse-phase–high-performance liquid chromatography–photodiode matrix system (RP–UHPLC–PDA) equipped with C18 column, eluting in a gradient using water and acetonitrile with formic acid as mobile phases. The quantification of 9 sample products presented in different matrixes was performed using a calibration curve obtained by analyzing standard solutions from a 10-cannabinoid-mix-certified reference standard. The developed method demonstrated the ability to identify and quantify the main cannabinoids in hemp oil and is a useful tool for pharmaceutical professionals

Understanding the Molecular Mechanisms Underlying the Analgesic Effect of Ginger

Chronic pain has a high prevalence and a profound impact on patients and society, and its treatment is a real challenge in clinical practice. Ginger is emerging as a promising analgesic&mdash;effective against various types of pain and well-tolerated by patients. However, we are just beginning to understand its complex mechanism of action. A good understanding of its mechanism would allow us to fully utilize the therapeutical potential of this herbal medicine as well as to identify a better strategy for treating chronic pain. To provide this information, we searched PubMed, SCOPUS, and Web of Science for in vitro studies or animal experiments investigating the analgesic effect of ginger extract or its components. The analysis of data was carried out in the form of a narrative review. Our research indicates that ginger extract, through its various active ingredients, suppresses the transmission of nociceptive signals while activating the descendent inhibitory pathways of pain