Perspectivele tratamentului inhalatoriu al tuberculozei pulmonare

Background. Non-invasive pulmonary administration provides the benefits of release to the target site and avoids the first hepatic passage, reducing the dose and systemic side effects, improving patient compliance, and reducing drug resistance. Objective of the study. Evaluation of new approaches to inhalation delivery of anti-tuberculosis drugs in the form of micronized dry powders. Material and Methods. Advanced bibliographic study using the databases Medline, Environmental Issues & Policy Index, Environmental Sci & Pollution Mgmt, Scopus (Elsevier), Current Contents, Scirus. Over 100 bibliographic sources were evaluated. Results. Inhalable dry powders are widely used due to their better physicochemical stability compared to liquid or suspension- based formulations. Dry powder inhalers are portable, easy to handle and affordable. Studies to develop inhaled forms are being conducted for common antimycobacterial drugs (Pyrazinamide, Isoniazid, Ethambutol, Rifamycin and its analogues, combinations of antituberculosis drugs) and for new substances at various stages of research, in the form of inhaled powders containing proliposomes, microcarriers, polymeric nanoparticles, phospholipid lipospheres, polymeric microparticles. Conclusion. The results of multiple studies show the benefits of dry powder inhalation formulations for the treatment of tuberculosis, such as improved formulation stability, better absorption by alveolar macrophages, controlled release profile and reduced side effects.Study conducted with the support of the project 20.80009.8007.14 “Complex researches for the elaboration of new local anti-infectious pharmaceutical products for the optimization of pharmacotherapy of dental, oropharyngeal and auricular diseases”, within the State Program (2020-2023), project leader: Valica Vladimir, PhD, univ, prof., contracting authority: National Agency for Research and Development.Introducere. Administrarea neinvazivă a medicamentului pe cale pulmonară oferă avantajele eliberării la locul țintă și evită primul pasaj hepatic, fiind posibilă reducerea dozei și a efectelor adverse sistemice, îmbunătățirea complianței pacienților, precum și reducerea rezistenței la medicamente. Scopul lucrării. Evaluarea abordărilor noi de livrare inhalatorie a medicamentelor antituberculoase sub formă de pulberi uscate micronizate. Material și Metode. Studiu bibliografic avansat cu utilizarea bazelor de date Medline, Environmental Issues & Policy Index, Environmental Sci & Pollution Mgmt, Scopus (Elsevier), Current Contents, Scirus. Au fost evaluate peste 100 de surse bibliografice. Rezultate. Pulberile uscate inhalabile sunt utilizate pe scară largă datorită stabilității sale fizico-chimice mai bune comparativ cu formulările lichide sau pe bază de suspensie. Inhalatoarele cu pulbere uscată sunt portabile, ușor de manevrat și accesibile. Sunt realizate studii de elaborare a formelor inhalatorii atât pentru medicamente uzuale antimicobacteriene (Pirazinamida, Izoniazida, Etambutol, Rifamicina și analogii săi, combinații de antituberculoase), cât și pentru substanțe noi, aflate la diverse etape de cercetare, sub formă de pulberi inhalatorii cu conținut de proliposomi, micropurtători, nanoparticule polimerice, liposfere fosfolipidice, microparticule polimerice. Concluzii. Rezultatele multiplelor studii denotă avantajele formulărilor inhalatoare cu pulbere uscată pentru tratarea tuberculozei, cum ar fi îmbunătățirea stabilității formulării, o absorbție mai bună de către macrofagele alveolare, profil de eliberare controlată și efecte secundare reduse.Studiu realizat cu suportul proiectului 20.80009.8007.14 „Cercetări complexe de elaborare a noilor produse farmaceutice antiinfecțioase autohtone pentru optimizarea farmacoterapiei afecțiunilor stomatologice, orofaringiene și auriculare”, din cadrul Programului de Stat (2020-2023), conducător de proiect: Valica Vladimir, dr. hab. șt. farm., prof. univ., autoritatea contractantă: Agenția Națională pentru Cercetare și Dezvoltare

PERSPECTIVES OF INHALATIVE TREATMENT OF LUNG TUBERCULOSIS

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica MoldovaIntroducere. Administrarea neinvazivă a medicamentului pe cale pulmonară oferă avantajele eliberării la locul țintă și evită primul pasaj hepatic, fiind posibilă reducerea dozei și a efectelor adverse sistemice, îmbunătățirea complianței pacienților, precum și reducerea rezistenței la medicamente. Scopul lucrării. Evaluarea abordărilor noi de livrare inhalatorie a medicamentelor antituberculoase sub formă de pulberi uscate micronizate. Material și Metode. Studiu bibliografic avansat cu utilizarea bazelor de date Medline, Environmental Issues & Policy Index, Environmental Sci & Pollution Mgmt, Scopus (Elsevier), Current Contents, Scirus. Au fost evaluate peste 100 de surse bibliografice. Rezultate. Pulberile uscate inhalabile sunt utilizate pe scară largă datorită stabilității sale fizico-chimice mai bune comparativ cu formulările lichide sau pe bază de suspensie. Inhalatoarele cu pulbere uscată sunt portabile, ușor de manevrat și accesibile. Sunt realizate studii de elaborare a formelor inhalatorii atât pentru medicamente uzuale antimicobacteriene (Pirazinamida, Izoniazida, Etambutol, Rifamicina și analogii săi, combinații de antituberculoase), cât și pentru substanțe noi, aflate la diverse etape de cercetare, sub formă de pulberi inhalatorii cu conținut de proliposomi, micropurtători, nanoparticule polimerice, liposfere fosfolipidice, microparticule polimerice. Concluzii. Rezultatele multiplelor studii denotă avantajele formulărilor inhalatoare cu pulbere uscată pentru tratarea tuberculozei, cum ar fi îmbunătățirea stabilității formulării, o absorbție mai bună de către macrofagele alveolare, profil de eliberare controlată și efecte secundare reduse.Background. Non-invasive pulmonary administration provides the benefits of release to the target site and avoids the first hepatic passage, reducing the dose and systemic side effects, improving patient compliance, and reducing drug resistance. Objective of the study. Evaluation of new approaches to inhalation delivery of anti-tuberculosis drugs in the form of micronized dry powders. Material and Methods. Advanced bibliographic study using the databases Medline, Environmental Issues & Policy Index, Environmental Sci & Pollution Mgmt, Scopus (Elsevier), Current Contents, Scirus. Over 100 bibliographic sources were evaluated. Results. Inhalable dry powders are widely used due to their better physicochemical stability compared to liquid or suspension-based formulations. Dry powder inhalers are portable, easy to handle and affordable. Studies to develop inhaled forms are being conducted for common antimycobacterial drugs (Pyrazinamide, Isoniazid, Ethambutol, Rifamycin and its analogues, combinations of antituberculosis drugs) and for new substances at various stages of research, in the form of inhaled powders containing proliposomes, microcarriers, polymeric nanoparticles, phospholipid lipospheres, polymeric microparticles. Conclusion. The results of multiple studies show the benefits of dry powder inhalation formulations for the treatment of tuberculosis, such as improved formulation stability, better absorption by alveolar macrophages, controlled release profile and reduced side effects

Riscurile administrării incorecte a dexametazonei

Background. Dexamethasone is a synthetic analogue of glucocorticoids, with a stronger activity than cortisol. Despite the benefits in treating some diseases, the incorrect administration can lead to occurrence of side effects, some of which are severe. Objective of the study. The aim was to enumerate what side effects dexamethasone can cause in case of improper use, such as overdose or taking at a late hour. Material and Methods. The information was selected from bibliographic references, articles and publications about the effects of dexamethasone from databases (PubMed, MedlinePlus etc.). Results. Most frequently, the side effects are caused by overdose. Considering that dexamethasone is a synthetic version of cortisol, those effects are associated with hypersecretion of the hormone: „moon face”, muscular weakness, easy bruising, swollen legs, hetero-sexualisation, hyperglycemia, heart diseases and others. Besides, cortisol is a stress hormone, which means that a high dose of dexamethasone can cause effects at the sympathetic nervous system: anxiety, hypertension, and tachycardia. Taking the medication at a late hour doesn’t affect the organism severely, but the person can suffer from insomnia. Conclusion. Incorrect administration of dexamethasone severely affects the human body. In order to prevent the effects, the patient must follow the drug use regimen. In addition, it is important to consult a specialist regarding the treatment.Introducere. Dexametazona este un analog sintetic al glucocorticoizilor, cu activitate mai puternică decât cea a cortizolului. În ciuda avantajelor în tratarea unor boli, administrarea incorectă poate duce la manifestarea unor efecte adverse, unele fiind severe. Scopul lucrării. Scopul a fost de a enumera ce efecte adverse poate cauza dexametazona în cazul utilizării necorespunzătoare ca, spre exemplu, supradozare sau administrarea la o oră târzie. Material și metode. Informația a fost selectată din referințe bibliografice, articole și publicații despre efectele dexametazonei din baze de date (PubMed, Medline Plus etc.). Rezultate. Reacțiile adverse apar cel mai frecvent în cazul supradozării. Ținând cont că dexametazona este o versiune sintetică a cortizolului, aceste efecte sunt asociate cu cele ale hipersecreției hormonului dat: fața de lună plină, slăbiciune musculară, picioarele umflate, hetero-sexualizare, hiperglicemie, afecțiuni cardiace și altele. Pe lângă asta, cortizol este un hormon al stresului, deci doza mărită de dexametazonă poate cauza efecte la nivelul sistemului nervos simpatic: anxietate, hipertensiune, tahicardie etc. Administrarea la o oră târzie nu afectează destul de sever organismul, însă persoana poate suferi de insomnie. Concluzie. Administrarea incorectă a dexametazonei afectează sever organismul uman. Pentru a evita efectele, pacientul trebuie să respecte regimul de utilizare a acestui medicament. De asemenea, este necesar de consulta medicul specialist cu privire la tratamentul dat

Uncoupling agents and their biomedical roles

Introduction. Uncoupling agents, or uncouplers, are molecules, which are classified as ion transporters, located in the internal membrane of mitochondria. They discharge the proton gradient, which is generated by the respiratory chain, by transporting hydrogen ions. As a result, ATP-synthetase cannot be activated due to the lack of that gradient, thus the oxidative phosphorylation is "uncoupled" from the electron transport chain. Therefore, the energy used for ATP synthesis is dissipated in heat, which explains the main role of thermogenesis. There are 2 types of uncouplers: natural, which are UCPs (short for Uncoupling Proteins) and synthetic, which have an importance in research and not only. Aim of study. Exploring the roles and flaws of the uncoupling agents and the factors which increase their activities Methods and materials. Selected from articles, found in databases (PubMed, NCIB, Google Scholar, etc) according to the keywords "uncoupling", "uncoupling agent", "oxidative phosphorylation". Results. The most known and most studied uncoupling agent at the moment is thermogenin (UCP 1), which is present mostly in the brown adipose tissue in newborns and hibernating mammals. It is also involved in energetic balance due to its involvement in uncoupling oxidative phosphorylation from the respiratory chain. The main stimulating factor of thermogenin is exposure to cold temperatures. Besides thermogenesis, uncoupling agents have significant roles even in other organs. For example, in the nervous system, they stimulate the transport of calcium ions outside mitochondria, thus avoiding neuronal hyperexcitability, which is a key feature in epilepsy. Also, they help the neuronal tissue recover from injuries. Another interesting effect scientists noticed about uncouplers is weight loss. Dinitrophenol, a synthetic uncoupling agent, was used as a miracle pill for losing weight in the 1930s until FDA illegalized it in 1938 due to severe side effects. The increase of an uncoupling protein can inhibit beta cells from endocrine pancreas to synthesize insulin, leading to their dysfunction or even to type 2 diabetes. Another point about the uncouplers is that the main factors that increase their activities are free fatty acids and thyroid hormones. Conclusion. Uncoupling agents are not only molecules that generate heat, but have a major influence towards some processes such as neuronal excitability, insulin synthesis, weight loss and so on. At the moment, the scientists are still studying the recently discovered uncouplers, whose roles are still unknown

The bioethical aspects of the phenomenon of medically assisted reproduction in the Republic of Moldova

Introducere. Fenomenul reproducerii medicale asistate este o ramură a medicinei moderne, un subiect important atât la nivel național, cât și internațional. Reproducerea medicală asistată (RMA) oferă soluții și tehnici avansate pentru cuplurile care întâmpină greutăți în a concepe un copil în mod natural. Scopul lucrării. Examinarea și analizarea principalelor aspecte bioetice ce însoțesc practica RMA în contextul specific al Republicii Moldova. Material și metode. Lucrarea se bazează pe o cercetare documentară în baza datelor științifice PubMed și Medline. Au fost studiate articole în detaliu și au fost extrase informații privind reglementarea și supervizarea serviciilor de RMA în Republica Moldova. Rezultate. Lucrările analizate au pus în evidență principalele principii bioetice ce constau în autonomia pacienților, cuplurile și indivizii au libertatea de a decide cu privire la utilizarea tehnicilor de reproducere asistată, confidențialitatea și protecția datelor personale, ceea ce este esențial în respectarea intimității și drepturilor pacienților, accesibilitate și echitate, este important ca toți indivizii și cuplurile să aibă acces egal indiferent de statutul socio-economic sau de alți factori discriminatorii, supervizarea și reglementarea practicilor medicale, acest lucru asigură respectarea standardelor etice și calitate, astfel protejând bunăstarea și sănătatea pacienților implicați. Concluzii. Principiile bioetice reprezintă fundamentul unei practici responsabile a RMA, este necesară o abordare adecvată pentru asigurarea practicii medicale etice în concordanță cu drepturile individului, a părților implicate în procesul de reproducere medical asistată.Background. The phenomenon of medically assisted reproduction (MAR) is a branch of modern medicine, an important topic both nationally and internationally. Medically assisted reproduction offers advanced solutions and techniques for couples who have difficulty conceiving a child naturally. Objective of the study. Examination and analysis of the main bioethical aspects that accompany the practice of MAR in the specific context of the Republic of Moldova. Material and methods. The work is based on documentary research based on PubMed and Medline scientific data. Detailed articles have been studied and information on the regulation and supervision of MAR services in the Republic of Moldova has been extracted. Results. The analyzed works highlighted the main bioethical aspects consisting in the autonomy of patients, couples and individuals have the freedom to decide on the use of assisted reproduction techniques, confidentiality and protection of personal data, which is essential in respecting the privacy and rights of patients, accessibility and equity, it is important that all individuals and couples have equal access regardless of socio-economic status or other factors discriminatory, supervising and regulating medical practices, this ensures compliance with ethical standards and quality, thus protecting the well-being and health of the patients involved. Conclusion. The bioethical aspects are the foundation of a responsible practice of MAR, an adequate approach is needed to ensure ethical medical practice in accordance with the rights of the individual, of the parties involved in the process of medical assisted reproduction

Home-related injuries among children under 18 years old: knowledge, attitudes and practice in the Republic of Moldova

Introduction. Home-related injuries today represent a major medical and social problem, and are constantly growing. According to the WHO 2004, an estimated 424 000 people of all ages died from falls worldwide, approximately 1500 children each year and is the leading cause of death among children aged 5 to 9 years old and 15 to 19 years old. Most injuries among young children occur in the home environment and more than 95% of these deaths occur in low and middle income countries. Every year in the Republic of Moldova more than 40,000 children arrive at the hospital as a result of domestic accidents. Aim of study. To assess the knowledge, attitudes and practices of parents with children aged under 18 years old regarding home related injuries and elaboration of preventive measures. Methods and materials. A cross-sectional study was conducted among parents, grandparents and other caregivers with children aged 0-18 years, during October-December 2021. It was applied a KAP questionnaire (knowledge, attitudes and practices) developed on the basis of a review of the literature, applied and distributed online on social networks. The following variables were analysed: demographics data, level of supervision, perception of the accident risks and risk factors in the household; risk awareness and knowledge of first aid measures in these situations among children. Results. The questionnaire was completed by 423 respondents mostly by parents (77,3%), close relatives (21,7%) and grandparents (1%), mostly aged between 25- 45 years old (82,6%), of which 94,3% female and 5,7% male, mostly from urban (81%). About 45% of respondents mentioned that never left alone their children or without supervision, in 20,5% less than 5 min, 16,7% for 5-30 min, 14,4% for more than 30 min. The most common house-related injuries among children is falling (57,4%), followed by stings with sharp objects (6,8%), burns (4,2%), fractures (2,4%), drowning (1,2%), suffocation (0,2%) and other (27, 6%).The majority consider home a risky environment in which a child could be injured (68,3%), while 15,4% don't know, and 16,3% not risky at all. First aid measures are known in approx. 70%. The general state of health of children after injury is considered mostly as good (79,9%) and acceptable (14,9%). One third of the children (31,4%) who suffered a home-related injury was examined and discharged without treatment, 14,4%- with further observation, while only 4%- hospitalized and treated in hospital only. Conclusion. This study underlines the knowledge and attitude of parents to home-related injury among children in the last year in Moldova. The first step in preventing home-related injuries among children is by raising awareness among parents and caregivers in regard to risks of injuries among children in the home environment, and it is important to implement safety measures for the most in risk group ages

Risks of incorrect administration of dexamethasone

Introduction. Despite the significant benefits of dexamethasone (synthetic analogue of cortisol), incorrect administration can cause serious side effects. Purpose. The aim was to enumerate what side effect can be caused by incorrect use of this drug. Material and methods. The information was selected from articles and publications from databases. Results. One of the most common type of incorrect use is overdose. Besides chronic treatment, the side effects are similar with Cushingoid symptoms. Taking dexamethasone at late hour can cause insomnia, as it inhibits the production of melatonin. Thus, this affects the circadian rhythm of glucocorticoids and melatonin release (Fig 1). Moreover, irregular doses disbalance the hypothalamic-pituitaryadrenal axis, which may be associated with maladaptive stress response. In order to maintain the circadian rhythm, it is necessary to use the drug in the morning. Dexamethasone supresses immune system by inhibiting macrophage and T-cell activity and antibody production. Thus, it is not recommended to take vaccines during drug therapy. Speaking of therapy, some pills like NSAIDs, birth control pills, antibiotics, blood thinners must not combine with dexamethasone because it will make the treatment less effective or increase the risks of side effects. Long-term therapy can lead to memory loss and, sometimes, dementia. It increases glutamate concentration, leading to hippocampus disfunction and brain atrophy. On the other hand, the same increase of glutamate, but in prefrontal cortex (Fig. 2), can cause depression, behaviour issues etc. Conclusions. In order to avoid the side effects of dexamethasone, the patient must follow the use regimen and the doctor's indications. The best hour to take dexamethasone safely is in the morning

Perspectivele tratamentului inhalatoriu al tuberculozei pulmonare

Introducere. Administrarea medicamentului pe cale pulmonară oferă avantajele eliberării la locul ţintă, fiind posibilă reducerea dozei şi sporirea biodisponibilităţii medicamentului. Scopul. Evaluarea abordărilor noi de livrare inhalatorie a medicamentelor antituberculoase sub formă de pulberi uscate micronizate. Materiale și metode. Au fost evaluate peste 100 de surse bibliografice, în baze de date precum Medline, Environmental Issues & Policy Index, Environmental Sci & Pollution Mgmt, etc. Rezultate. Sunt realizate studii de elaborare a formelor inhalatorii atât pentru medicamente uzuale antimicobacteriene cât şi pentru substanţe noi, aflate la diverse etape de cercetare sub formă de pulberi inhalatorii. Concluzii. Rezultatele multiplelor studii denotă avantajele formulărilor inhalatoare cu pulbere uscată pentru tratarea tuberculozei, cum ar fi îmbunătăţirea stabilităţii formulării, o absorbţie mai bună de către macrofagele alveolare, profil de eliberare controlată și efecte secundare reduse

Calcule ab initio a moleculei de oxigen

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chișinău, Republica Moldova, Congresul consacrat aniversării a 75-a de la fondarea Universității de Stat de Medicină și Farmacie „Nicolae Testemițanu” din Republica Moldova, Ziua internațională a științei pentru pace și dezvoltareIntroducere. Oxigenul participă în calitate de catalizator și oxidant în multe procese iar energia de activare mare a reacțiilor se datorează atât energiei legăturii cât și valorii spinului oxigenului. Scopul. Cercetarea structurii moleculei de oxigen prin calcule cuanto-chimice Material și metode. Calcule ab initio MO LCAO Hartree-Fock-Roothaan SCF cu aproximări RHF sau ROHF, baze 6-31G* și TZV, programul GAMESS** Rezultate. Prezența a doi electroni HOMO pe orbitalul molecular degenerat 2 ∗ permite moleculei O2 stări de singlet și triplet. Optimizarea structurii electronice a moleculei de oxigen cu M=1 și M=3 a identificat pentru stările excitate singlet 1 și 1∑ + o reactivitate sporită în comparație cu starea fundamentală paramagnetică 3∑ − (-149,6040 u.a.). Concluzii. Stările excitate singlet au energii mai înalte și distanțe mai mari dintre atomi în molecula O2 în comparație cu starea fundamentală triplet (1,21Å). Reactivitatea sporită a stărilor singlet se caracterizează prin o necesitate de energie de disociere mai mică decât în O2 triplet

Electrocatalytic activity of Au nanoparticles onto TiO2 nanotubular layers in oxygen electroreduction reaction: size and support effects

Electrocatalytic activity of both bare high-ordered TiO2 nanotubes (TNTs) and gold nanoparticles (Au NPs) loaded TNTs toward oxygen reduction reaction (ORR) has been examined by cyclic voltammetry (CV). Cyclic voltammograms for Au NPs-TNT electrodes are characterized by an additional wave observed at less negative potentials which is responsible for oxygen electroreduction on the surface of gold NPs. The overpotential for O-2 reduction on the Au surface grows with increasing the temperature of TNT annealing and the Au NPs size. The nature of the effects observed was explained by peculiarities of the electron transport through Schottky barrier formed at the Au NPs - TiO2 interface. The width of the Schottky barrier, determined by semiconductor doping level and Au NPs size, plays a key role in the mechanism of electron transport through the space charge region. (C) 2016 Elsevier Ltd. All rights reserved