Primjena lijekova kod odabranih vulnerabilnih skupina: stare osobe u kliničkim ispitivanjima

“Vulnerabilna osoba je osoba koja ima veći rizik od ispitivača u kliničkoj studiji nego od samog oboljenja. Primjeri vulnerabilnih osoba uključuju bolesnike s vrlo ozbiljnim oboljenjima koji imaju velika pozitivna očekivanja od primjene novog lijeka, osobe koje imaju profesionalni odnos s istraživačima (npr. studenti medicine, medicinske sestre, zaposleni u farmaceutskim kompanijama i sl.).” Klinički istraživači u prošlosti su štitili vulnerabilne osobe isključujući ih iz istraživanja, ali taj pristup nije više moralno prihvatljiv. Istraživače se potiče da dizajniraju kliničke studije koje bi uključile vulnerabilne subjekte. Da bi postigli moralno valjane rezultate, klinički ispitivači moraju biti svjesni i prihvatiti smjernice i zahtjeve lokalnih etičkih odbora. Nije nerazumno zahtijevati od vulnerabilne osobe da prihvati razumni stupanj rizika u cilju dobrobiti budućih bolesnika

Self-assembly of carbon based nanoparticles films by Langmuir-Blodgett method

Carbon nanoparticles are a class of materials with extraordinary properties. In the past three decades, four major types of carbon nanoparticles were synthesized and investigated: fullerenes, carbon nanotubes, graphene and carbon quantum dots. One of the main properties of such materials is their hydrophobic nature. At the same time, Langmuir–Blodgett (LB) method the for deposition of thin films of hydrophobic materials provides the possibility to design thin films of different carbon-based nanoparticles with special architectures and features enabling their usage in various fields, particularly in electronics and biomedicine. In this review, the state of art of LB thin films of four types of carbon-based nanoparticles and their application in electronics and biomedicine are presented. The breakthrough in this field was finally achieved by application of carbon quantum dots soluble in solvents optimized for LB deposition

Phloroglucinol-Based Carbon Quantum Dots/Polyurethane Composite Films: How Structure of Carbon Quantum Dots Affects Antibacterial and Antibiofouling Efficiency of Composite Films

Nowadays, bacteria resistance to many antibiotics is a huge problem, especially in clinics and other parts of the healthcare system. This critical health issue requires a dynamic approach to produce new types of antibacterial coatings to combat various pathogen microbes. In this research, we prepared a new type of carbon quantum dots based on phloroglucinol using the bottom-up method. Polyurethane composite films were produced using the swell–encapsulation–shrink method. Detailed electrostatic force and viscoelastic microscopy of carbon quantum dots revealed inhomogeneous structure characterized by electron-rich/soft and electron-poor/hard regions. The uncommon photoluminescence spectrum of carbon quantum dots core had a multipeak structure. Several tests confirmed that carbon quantum dots and composite films produced singlet oxygen. Antibacterial and antibiofouling efficiency of composite films was tested on eight bacteria strains and three bacteria biofilms

Pretkoncentracija mikroelemenata iz vode koristeći 4-morfolin ditiokarbamat

The optimum conditions were found for the preconcentration of trace metals in natural waters and model samples with standard metals concentrations by using 4-morpholine dithiocarbamate. The formed complexes were extracted with chloroform. Different methods for recovering the metals from the organic solvent were studied and compared before AAS metal analysis. The developed preconcentration method was successfully applied to the determination of trace metals concentrations in water samples from the "Barje" lake (Leskovac. Yugoslavia).Nađeni su optimalni uslovi za pretkoncentraciju mikroelemenata iz vode koristeći 4-morfolin ditiokarbamat kao kompleksirajući agens. Nagrađeni kompleksi su ekstrahovani hloroformom. Upoređeni su različiti načini ekstrakcije metalnih jona iz organskog rastvarača pre analize atomskom apsorpcionom spektrofotometrijom. Razvijena metoda za pretkoncentraciju uspešno je primenjena za analizu uzoraka vode jezera Barje (Leskovac Jugoslavija)

Uticaj ekstrakta rizoma i korena kukureka (Helleborus odorus W. et K.) na parametre bele krvne slike i stepen fagocitoze kod wistar pacova

The objective of this research was to study the effects that the extract of rhizome and root of Helleborus odorus W. et K. (Ranunculaceae) can have on modifications in the parameter values of white blood cells count and degree of phagocytosis by peritoneal macrophages and neutrophil granulocytes in Wistar rats. The trial was conducted on 28 rats divided into 4 groups with 7 animals in each group. To the control group of rats sterile physiological solution in the quantity of 0.25 mL/100 g BW was applied intramuscularly. For the purpose of monitoring the effect of the extract of rhizome and root of hellebore (HE) during a time period, the HE was applied intramuscularly to rats in a dose of 10 mg/100 g BW, while the blood samples for analysis were taken after 24h, 48h and 72h. The consequence of intramuscular application of HE was an increased count of total leukocytes in all trial groups, the most expressed leukocytosis being registered 24h after application of HE. Statistically significant higher value in the count and percent of neutrophil granulocytes in the blood was recorded 24h after treatment in relation to the control and two other trial groups (p lt 0.001), among which a statistical significance was not established. The extract of hellebore rhizome and root has led to lymphopenia, resulting in the increase of the neutrophil/limphocyte index in the trial groups 24h and 48h after treatment. The application of HE had no significant effect on the count of monocytes in treated animals. The applied extract has caused a significant increase in the degree of phagocytosis by residing peritoneal macrophages and neutrophil granulocytes in blood.Cilj ovog rada je bio da se ispita uticaj ekstrakta rizoma i korena H. odorus W. et K. na promenu vrednosti parametara bele krvne slike i stepen fagocitoze od strane peritonealnih makrofaga i neutrofilnih granulocita kod pacova soja Wistar. Ogled je izveden na 28 pacova podeljenih u 4 grupe po 7 jedinki. Kontrolnoj grupi pacova je intramuskularno aplikovan sterilan fiziološki rastvor u količini od 0,25 ml/100 g TM. U cilju praćenja efekta ekstrakta rizoma i korena kukureka (EK) u toku vremena, pacovima je intramuskularno aplikovan EK u dozi od 10mg/100g TM, a krv za analizu je uzimana posle 24h, 48h i 72h. Intramuskularna aplikacija EK imala je za posledicu povećanje broja ukupnih leukocita u svim oglednim grupama, pri čemu je najizraženija leukocitoza registrovana 24h nakon aplikovanja EK. Statistički značajno veća vrednost broja i procenta neutrofilnih granulocita u krvi zabeležena je 24h posle tretmana u odnosu na kontrolnu i ostale dve ogledne grupe (p lt 0,001), između kojih nije utvrđena statistička značajnost. Ekstrakt rizoma i korena kukureka doveo je do nastanka limfopenije, što je imalo za posledicu povećanje neutrofilno/limfocitnog indeksa u oglednim grupama 24h i 48h nakon tretmana. Aplikacija EK nije značajno uticala na broj monocita kod tretiranih životinja. Upotrebljeni ekstrakt doveo je do značajnog povećanja stepena fagocitoze od strane rezidentnih peritonealnih makrofaga i neutrofilnih granulocita krvi

Antibacterial and Antibiofouling Activities of Carbon Polymerized Dots/Polyurethane and C60/Polyurethane Composite Films

The cost of treatment of antibiotic-resistant pathogens is on the level of tens of billions of dollars at the moment. It is of special interest to reduce or solve this problem using antimicrobial coatings, especially in hospitals or other healthcare facilities. The bacteria can transfer from medical staff or contaminated surfaces to patients. In this paper, we focused our attention on the antibacterial and antibiofouling activities of two types of photodynamic polyurethane composite films doped with carbon polymerized dots (CPDs) and fullerene C60. Detailed atomic force, electrostatic force and viscoelastic microscopy revealed topology, nanoelectrical and nanomechanical properties of used fillers and composites. A relationship between the electronic structure of the nanocarbon fillers and the antibacterial and antibiofouling activities of the composites was established. Thorough spectroscopic analysis of reactive oxygen species (ROS) generation was conducted for both composite films, and it was found that both of them were potent antibacterial agents against nosocomial bacteria (Klebsiela pneumoniae, Proteus mirabilis, Salmonela enterica, Enterococcus faecalis, Enterococcus epidermis and Pseudomonas aeruginosa). Antibiofouling testing of composite films indicated that the CPDs/PU composite films eradicated almost completely the biofilms of Pseudomonas aeruginosa and Staphylococcus aureus and about 50% of Escherichia coli biofilms

Uticaj cimiazol hidrohlorida na mitotsku i proliferativnu aktivnost u kulturama humanih limfocita

Cymiazole hydrochloride is the active ingredient of a synthetic systemically acting acaricide used in beekeeping (Apitol®, Apichem®). Considering that residues of cymiazole hydrochloride were detected in all bee products being used for human nutrition and as alternative medications in human and veterinary medicine, the objective of this study was to evaluate the effects of cymiazole hydrochloride on mitotic activity of cultured human lymphocytes. The mitotic and proliferation indices in phytohaemagglutinin-activated human peripheral blood lymphocytes were determined using three experimental concentrations of cymiazole hydrochloride (0.01; 0.1; 1mg/ml). All experimental concentrations of cymiazole hydrochloride increased mitotic index values (MI) by a statistically highly significant amount (p lt 0.001). Moreover, proliferation index (PI) was also changed very significantly (p lt 0.001) after each experimental cymiazole hydrochloride treatment. The dose dependent increase in proliferation index values clearly demonstrates the ability of cymiazole hydrochloride to induce significant alterations of cell cycle kinetics having an influence on G0 state and arousing cell division. This indicates a risk from consuming bee products with cymiazole hydrochloride residues particularly in those predisposed to malignant diseases. Strict respect to the withrawal time while using cymiazole hydrochloride (Apitol®, Apichem®) is of great importance because residue levels higher than the permitted one can easily occur in honey and other bee products from treated honey bee colonies.Cimiazol hidrohlorid predstavlja aktivnu supstancu sintetičkih akaricida sa sistemskim dejstvom koji se koriste u pčelarstvu (Apitol®, Apichem®). Obzirom da su rezidue cimiazol hidrohlorida detektovane u svim pčelinjim proizvodima, koji se koriste u ishrani i kao alternativni lekovi u humanoj i veterinarskoj medicini, cilj ovog rada bio je ispitivanje efekata cimiazol hidrohlorida na mitotsku i proliferativnu aktivnost humanih limfocita u kulturi. Analizirani su mitotski i proliferativni indeksi humanih limfocita aktiviranih fitohemaglutininom pri čemu su koršćene tri eksperimentalne koncentracije cimiazol hidrohlorida u opsegu od 0.001 mg/ml do 1 mg/ml. Sve tri eksperimentalne koncentracije cimiazol hidrohlorida izazvale su vrlo visoko signifikantno (p lt 0.001) povećanje vrednosti mitotskog indeksa (MI) humanih limfocita. Takođe, vrednosti proliferativnog indeksa (PI) su vrlo visoko signifikantno (p lt 0.001) povećane nakon svakog eksperimentalnog tretmana cimiazol hidrohloridom. Dozno zavisno povećanje vrednosti proliferativnog indeksa jasno pokazuje sposobnost cimiazol hidrohlorida da izazove značajne promene u kinetici ćelijskog ciklusa utičući na G0 tačku i podstičući ćelijsku deobu, što ukazuje na rizik prilikom konzumiranja pčelinjih proizvoda sa reziduama cimiazol hidrohlorida, posebno kod jedinki sklonih malignitetima. Izuzetno je značajno strogo poštovanje karence prilikom upotrebe cimiazol hidrohlorida (Apitol®, Apichem®) jer rezidue, u količini većoj od dozvoljene, mogu veoma lako dospeti u med i druge pčelinje proizvode dobijene od tretiranih pčelinjih društava

Bioetička pitanja u vezi sa sigurnošću lijekova kod vulnerabilnih skupina

U cilju procjene stavova studenata medicine u odnosu na sudjelovanje vulnerabilnih subjekata u kliničkim ispitivanjima, proveli smo studiju presjeka (N = 174, studenti dodiplomskih studija Medicinskog fakulteta, Univerziteta u Beogradu). Studija presjeka provedena je tijekom jednog dana, na slučajno odabranim uzorcima studenata 3. godine (95/493 studenata) i 6. godine (79/510 studenata). Ukupno je odgovoreno na 83 % postavljenih pitanja. Rezultati studije pokazali su da studenti našeg fakulteta uglavnom nisu voljni sudjelovati kao dobrovoljci u kliničkim ispitivanjima, niti raditi u nehigijenskim romskim naseljima. Studenti su naglasili važnost dobivanja pristanka i djeteta i roditelja za sudjelovanje u kliničkom ispitivanju. Kada su u pitanju ispitivanja novih lijekova na populaciji starijih dementnih bolesnika, većina ispitanika smatra da informirani pristanak treba biti sličan pristanku za bilo koju drugu populaciju. U zaključku, tekući medicinski kurikulum treba biti više usmjeren na procjenu sigurnosti lijekova u vulnerabilnim skupinama. Posebno je potrebno unaprijediti rad s pripadnicima marginaliziranih skupina (npr. dodatna edukacija, posjeti nehigijenskim romskim naseljima i zajednički projekti)