Inhibitory effect of propafenone derivatives on pseudomonas aeruginosa biofilm and pyocyanin production

Introduction/Objective Biofilm and pyocyanin production are essential components of Pseudomonas aeruginosa virulence and antibiotic resistance.Our objective was to examine inhibitory effect of synthetized propafenone derivatives 3-(2-Fluoro-phenyl)-1-(2- (2-hydroxy-3-propylamino-propoxy)-phenyl)-propan-1-one hydrochloride (5OF) and3-(2-Trifluoromethyl-phenyl)-1-(2-(2-hydroxy-3-propylamino-propoxy)-phenyl)-propan-1-one hydrochloride (5CF3) on biofilm and pyocyanin in Pseudomonas aeruginosa clinical strains.Methods Effects were tested on nine clinical isolates and one control laboratory strain of P. aeruginosa. In vitro analysis of biofilm growing was performed by incubating bacteria (0.5 McFarland) with 5OF and 5CF3 (500–31.2 μg/ml) and measuring optical density (OD) at 570 nm. Bacteria in medium without com-pounds were positive control. Blank medium (an uninoculated medium without test compounds) was used as negative control. Pyocyanin production was estimated by OD at 520 nm, after bacteria incubated with 5CF3 and 5OF (250 and 500 μg/ml), treated with chloroform, and chloroform layer mixed with HCl. Results A total of 500 μg/ml of 5OF and 5CF3 completely inhibited biofilm formation in 10/10 and 4/10 strains, respectively. A total of 250 μg/ml of 5OF and 5CF3 strongly inhibited biofilm formation in 7/10 strains, while inhibition with 125 μg/ml of 5OF and 5CF3 was moderate. Lower concentrations had almost no effect on biofilm production. Pyocyanin production was reduced to less than 40% of the control value in 6/9, and less than 50% of the control in 7/9 strains with 500 μg/ml of 5OF and 5CF3, respectively. At 250 μg/ml 5OF and 5CF3, most strains had pyocyanin production above 50% of the control value.Conclusion Synthetized propafenone derivatives, 5OF and 5CF3, inhibited biofilms and pyocyanin produc-tion of Pseudomonas aeruginosa clinical strains. Presented results suggest that propafenone derivatives are potential lead-compounds for synthesis of novel antipseudomonal drugs.Увод/Циљ Производња биофилма и пиоцијанина je важан фактор вируленције и антибиотске резистенције бактерије Pseudomonas aeruginosa. Циљ рада је био да се испита инхибиторни ефекат синте-тисаних пропафенонских деривата, 3-(2-флуоро-фенил)-1-[2-(2-хидрокси-3-пропиламино-пропокси)-фенил]-про-пан-1-он-хидрохлорид) (5OF) и 3-(2-трифлуорометилфенил)-1-[2-(2-хидрокси-3-пропиламино-пропокси)-фенил]-про-пан-1-он-хидрохлорид) (5CF3), на продукцију биофилма и пиоцијанина код клиничких изолата бактерије Pseudomonas aeruginosa.Методе Ефекат пропафенонских деривата испитан је на девет клиничких изолата и једном стандардном соју бакте-рије P. aeruginosa. Утицај на продукцију биофилма испитан је in vitro, инкубацијом бактерија (0,5 по Макфарланду) са 5OF и 5CF3 (500–31,2 μg/ml), и мерењем оптичке густине на 570 nm. Бактерије у медијуму без испитиваних једињења су биле позитивна контрола, а сам медијум негативна контро-ла. Производени пиоцијанин, који је одређиван мерењем оптичке густине на 520 nm, на коинкубације бактерија са 5CF3 или 5OF (250 и 500 μg/ml), третиран је хлороформом и мешањем хлороформског слојa са HCl.Резултати При концентрацији од 500 μg/ml 5OF је довео до потпуне инхибиције продукције биофилма код свих испи-тиваних сојева (10/10). Инхибиција биофилма са 500 μg/ml5CF3 била је потпуна код 4/10 сојева. При концентрацији 5OF и 5CF3 од 250 μg/ml продукција биофилма код већине испитаних изолата била је слаба, док је при концентрацији 125 μg/ml 5OF односно 5CF3 продукција била умерена. Ниже концентрације 5OF и 5CF3 нису имале инхибиторни ефекат на формирање биофилма. У присуству 500 μg/ml 5OF у 6/10 испитиваних сојева продукција пиоцијанина пала је на мање од 40% у односу на контролну вредност. Иста концентрација (500 μg/ml) 5CF3 снизила је продукцију пиоцијанина на мање од 50% од контроле у 7/9 сојева. При концентрацији 250 μg/ml 5OF или 5CF3 већина сојева продуковала је пиоцијанин изнад 50% у односу на позитивну контролу.Закључак Синтетисани пропафенонски деривати, 5OF и 5CF3, инхибирају продукцију биофилма и пиоцијанина код клиничких сојева бактерије Pseudomonas aeruginosa. До-бијени резултати указују на то да пропафенонски деривати представљају могућа полазна једињења за синтезу нових антипсеудомонасних агенаса.This work is a part of Jasmina Bašić’s PhD thesis “Ex-amination of correlation between chemical structure, physicochemical properties and retention parameters and antimicrobial activity of newly synthesized derivatives of propiophenone,“ defended at the Department of Phar-maceutical Chemistry, Faculty of Pharmacy, University of Belgrade on September 19, 2016

Stanje oralnog zdravlja dece sa posebnim potrebama

Background/Aim. Due to their primary medical condition, children with special needs often display lower levels of oral hygiene, larger prevalence of caries and other oral diseases. The aim of this study was to estimate the prevalence of dental caries, oral cleanliness and presence of malocclusion in children with disabilities, as well as to evaluate eruption time of the permanent molars. Methods. Case-control study was carried out on a group of 107 children with disabilities at the Faculty of Dental Medicine, University of Belgrade, Serbia. The control group comprised of 104 healthy school children. Results. Children with disabilities had statistically higher mean [decayed missing and filled teeth - dmft for primary DMF for permanent dentition (dmft DMFT)] values in both dentitions than children from the control group (p lt 0.05). Oral cleanliness level was much lower in children with disabilities. A significantly higher percentage of Class II malocclusions and a higher tendency to have a delayed time of eruption of permanent molars were observed in the test group in permanent dentition. Conclusion. Considering poor oral health status and higher tendency for development of malloclusions and delayed eruption, it is necessary to develop preventive dental programmes for children with special needs, as well as improve public awareness about these issues.Uvod/Cilj. Deca sa posebnim potrebama često zbog svoje primarne bolesti, imaju niži nivo oralne higijene i veću prevalencu karijesa i drugih oralnih oboljenja. Cilj rada bio je da se proceni prevalenca karijesa, nivoa oralne higijene i prisustvo malokluzija kod dece sa posebnim potrebama, kao i vreme erupcije stalnih molara. Metode. Ispitivanjem oralnog zdravlja obuhvaćeno je 107 dece sa posebnim potrebama na Klinici za dečju i preventivnu stomatologiju Stomatološkog fakulteta u Beogradu. Kontrolnu grupu je činilo 104 zdrave školske dece. Rezultati. Deca sa posebnim potrebama imala su statistički značajno viši nivo indeksa karijesnih, ekstrahovanih i plombiranih zuba (KEP) u obe denticije, u odnosu na kontrolnu grupu (p lt 0.05). Nivo oralne higijene bio je lošiji kod dece sa posebnim potrebama. Takođe, primećeno je statistički značajno povećanje malokluzija klase II, kao i kasnije vreme erupcije stalnih molara kod dece sa posebnim potrebama u odnosu na kontrolnu grupu. Zaključak. Zbog lošijeg stanja oralnog zdravlja i povećane verovatnoće razvoja malokluzija i odloženog nicanja zuba, neophodno je formirati preventivne stomatološke programe za decu sa posebnim potrebama, kao i poboljšati informisanost javnosti o ovom problemu

Procena unosa fluorida putem vode za piće i paste za zube kod dece uzrasta od tri godine - preliminarni rezultati u Beogradu, Republika Srbija

Background/Aim. Fluoride has beneficial effect on dental caries prevention and enables high hardness of enamel. However, fluoride intake above optimal levels can have adverse effects on teeth and bones, especially in young children during the period of intense growth and teeth development. The aim of this study was to assess fluoride intake from water and toothpaste among 3-year-old children in Belgrade, Serbia, in the municipalities of Vračar and Novi Beograd. Methods. A questionnaire for the parents (n = 40) was used to provide information on the water consumption (tap and/or bottled water) and the brand of toothpaste used by children as well as the frequency of tooth brushing and the amount of toothpaste during brushing. Fluoride concentrations in water and toothpaste samples were determined electrochemically by using fluoride-selective electrode. Fluoride intake was estimated through a mathematical model commonly used by the U.S. Environmental Protection Agency. Results. The obtained results indicate no significant difference in daily fluoride intake through drinking water and toothpaste in 3-year-old children in Vračar (n = 19) compared to Novi Beograd (n = 21) (p > 0.05). However, all estimated fluoride levels (0.089-0.625 mg/day) are significantly lower than the optimal daily intake level for caries protection (0.7 mg/day for children up to 4 years, FNB-USA National Institute of Medicine) and two to six times lower than tolerable upper fluoride level for the children of same age (1.3 mg/day, FNB-USA National Institute of Medicine). Furthermore, calculated daily fluoride intake per kilogram body weight confirm very low fluoride intake by water and toothpaste in children of investigated municipalities in Belgrade, being significantly below the recommended an adequate intake (0.05 mg/kg/day, EFSA). Conclusion. This preliminary study has shown that daily fluoride intake in 3-year-olds is lower than tolerable upper fluoride level, even not sufficient for the prevention of dental caries.Uvod/Cilj. Fluoridi imaju pozitivan efekat na prevenciju karijesa zuba kao i povećanje čvrstine zubnog emajla. Međutim, njihov unos iznad optimalnog može imati štetne efekte na zube i kosti, posebno kod male dece tokom intenzivnog rasta i razvoja zuba. Cilj ovog rada bio je da se proceni unos fluorida putem vode za piće i paste za zube kod dece uzrasta od tri godine u Beogradu, na teritoriji dve opštine, Vračar i Novi Beograd. Metode. Anketnim upitnicima (n = 40) za roditelje dobijeni su podaci o vrsti vode koju deca piju (česmenska i/ili flaširana), proizvodima koje koriste za čišćenje i negu zuba, učestalosti pranja zuba kao i količini paste za zube koja se koristi po jednom pranju. Sadržaj fluorida u vodi za piće i pastama za zube određen je elektrohemijski sa fluoridnom jonselektivnom elektrodom. Unos fluorida procenjen je korišćenjem matematičkog modela datog od strane Američke agencije za zaštitu životne sredine. Rezultati. Dobijeni rezultati pokazuju da nema statistički značajne razlike u dnevnom unosu fluorida putem vode za piće i paste za zube između dece uzrasta od tri godine na Vračaru i Novom Beogradu (p > 0,05). Međutim, sve procenjene vrednosti unosa fluorida (0,089-0,625 mg/dan) značajno su niže od optimalnog dnevnog unosa za prevenciju karijesa (0,7 mg/dan za decu uzrasta do 4 godine, FNB-Nacionalnog instituta medicine, SAD) i dva do šest puta niže od tolerišućeg gornjeg nivoa unosa fluorida za decu istog uzrasta (1,3 mg/dan, FNBNacionalnog instituta medicine, SAD). Štaviše, izračunati dnevni unosi fluorida izraženi po kilogramu telesne mase potvrđuju veoma nizak unos fluorida kod dece ispitivanih opština u Beogradu, čak značajno niže od preporučenog optimalnog unosa (0,05 mg/kg/dan, EFSA). Zaključak. Ovim preliminarnim istraživanjem pokazano je da je dnevni unos fluorida kod trogodišnjaka u Beogradu značajno niži od tolerišućeg gornjeg nivoa unosa fluorida, čak niži od optimalnog unosa za prevenciju karijesa

Redoks-status i koncentracije biometala u Wistar štakora nakon subakutnog izlaganja fluoridu i zaštitni učinak selena

This study aimed to investigate the effect of 150 mg/L sodium fluoride (NaF) on redox status parameters and essential metals [copper (Cu), iron (Fe), and zinc (Zn)] in the blood, liver, kidney, brain, and spleen of Wistar rats and to determine the protective potential of selenium (Se) against fluoride (F-) toxicity. Male Wistar rats were randomly distributed in groups of five (n=5) receiving tap water (control) or water with NaF 150 mg/L, NaF 150 mg/L + Se 1.5 mg/L, and Se 1.5 mg/L solutions ad libitum for 28 days. Fluorides caused an imbalance in the redox and biometal (Cu, Fe, and Zn) status, leading to high superoxide anion (O2 .-) and malondialdehyde (MDA) levels in the blood and brain and a drop in superoxide dismutase (SOD1) activity in the liver and its increase in the brain and kidneys. Se given with NaF improved MDA, SOD1, and O2 .- in the blood, brain, and kidneys, while alone it decreased SH group levels in the liver and kidney. Biometals both reduced and increased F- toxicity. Further research is needed before Se should be considered as a promising strategy for mitigating F- toxicity. © 2022 Jelena Radovanović, Biljana Antonijević, Katarina Baralić, Marijana Ćurčić, Danijela Đukić-Ćosić, Zorica Bulat, Dragana Javorac, Aleksandra Buha Đorđević, Jelena Kotur-Stevuljević, Emina Sudar-Milovanović, Evica Antonijević Miljaković, Miloš Beloica, and Zoran Mandinić, published by Sciendo. Cilj ovog istraživanja bio je utvrditi djelovanje 150 mg/L natrijevog fluorida (NaF) na redoks-status i koncentracije esencijalnih elemenata [bakar (Cu), željezo (Fe) i cink (Zn)] u krvi, jetri, bubrezima, mozgu i slezeni Wistar štakora te mogući zaštitni učinak selena (Se) od toksičnosti prouzročene fluoridom (F-). Mužjaci Wistar štakora nasumično su razvrstani u četiri skupine (n=5), nakon čega su 28 dana konzumirali običnu vodu ili vodu s otopinom NaF 150 mg/L, NaF 150 mg/L + Se 1,5 mg/L ili Se 1,5 mg/L. Izloženost fluoridu dovela je do poremećaja redoks-parametara i koncentracija istraživanih biometala. Utvrđene su povišene razine superoksid aniona (O2.-) i malondialdehida (MDA) u krvi i mozgu, smanjena aktivnost superoksid dismutaze (SOD1) u jetri te njezin porast u mozgu i bubrezima. Nadomjesni Se u kombinaciji s NaF pozitivno je utjecao na razine MDA, SOD1 i O2.- u krvi, mozgu i bubrezima, a sâm Se smanjio je razine SH skupina u jetri i bubrezima. Izloženost fluoridu uzrokovala je sniženje, ali i porast koncentracija biometala. Nužna su dodatna istraživanja kako bi se ispitali antioksidacijski učinci Se na toksičnost izazvanu F-.Cilj ovog istraživanja bio je utvrditi djelovanje 150 mg/L natrijevog fluorida (NaF) na redoks-status i koncentracije esencijalnih elemenata [bakar (Cu), željezo (Fe) i cink (Zn)] u krvi, jetri, bubrezima, mozgu i slezeni Wistar štakora te mogući zaštitni učinak selena (Se) od toksičnosti prouzročene fluoridom (F-). Mužjaci Wistar štakora nasumično su razvrstani u četiri skupine (n=5), nakon čega su 28 dana konzumirali običnu vodu ili vodu s otopinom NaF 150 mg/L, NaF 150 mg/L + Se 1,5 mg/L ili Se 1,5 mg/L. Izloženost fluoridu dovela je do poremećaja redoks-parametara i koncentracija istraživanih biometala. Utvrđene su povišene razine superoksid aniona (O2.-) i malondialdehida (MDA) u krvi i mozgu, smanjena aktivnost superoksid dismutaze (SOD1) u jetri te njezin porast u mozgu i bubrezima. Nadomjesni Se u kombinaciji s NaF pozitivno je utjecao na razine MDA, SOD1 i O2.- u krvi, mozgu i bubrezima, a sâm Se smanjio je razine SH skupina u jetri i bubrezima. Izloženost fluoridu uzrokovala je sniženje, ali i porast koncentracija biometala. Nužna su dodatna istraživanja kako bi se ispitali antioksidacijski učinci Se na toksičnost izazvanu F-

Relationship between fluoride intake in Serbian children living in two areas with different natural levels of fluorides and occurrence of dental fluorosis

The amount of fluoride present naturally in drinking water is highly variable, being dependent upon the individual geological environment from which the water is obtained. Chronic exposure to exceeding fluoride doses induces set of toxic effects, i.e. fluorosis. The aim of this study was to examine fluoride content in water and in the most frequently used vegetables, potato and bean, grown in two different Serbian regions. Le. control region (Valjevo) and high naturally occurring fluoride region (Vranjska Banja), and moreover, to correlate estimated daily intake with dental fluorosis occurrence as an adverse effect of fluoride exposure of schoolchildren in Serbia. Study confirmed significant difference in fluoride content in water, potato and bean, consumed by 12-year-old children in two investigated municipalities. Results of the study indicated positive and statistically significant correlation between daily intake of fluoride and dental fluorosis level in the fluorotic municipality of Vranjska Banja (r = 0.61: p = 0.000017). Obtained relationship could be evaluated by means of binary logistic regression analysis, whereas probability for fluorosis occurrence could be predicted using the following equation: fluorosis occurence (%) (34.852 x C-water - 12.644 x C-potato - 9.362 x C-bean - 7.673) x 100 (Chi-square (3) = 33.033; p lt 0.001)

Oral and perioral soft tissue lesions and oral functions in patients with dystrophic epidermolysis bullosa

Background/Aim. Dystrophic epidermolysis bullosa (DEB) is characterized by distinct systemic and skin changes, as well as numerous oral manifestations. The aim of the study was to examine oral and perioral soft tissues and oral functions in DEB patients by monitoring changes over a period of one year. Methods. Twenty-four patients (1 month to 36 years old) were clinically examined initially (T0), after 6 months (T6), and after 12 months (T12). Appearance and localization of perioral and oral bullae and scars, maximum mouth opening, reduced vestibule depth, absence of lingual papillae and palatal rugae, and restricted tongue movement due to scarring were monitored. The values of maximum mouth opening at the initial examination were compared to those measured in the healthy con-trol group of the same age. The age of patients and differences between the dominant and recessive subtypes of DEB were analyzed. Results. The average maximum mouth opening was significantly lower in DEB patients compared to healthy individuals. Oral and perioral bullae and scars, microstomia, and reduced vestibule depth were very common, with no statistically significant difference among T0, T6, and T12. The prevalence of restricted tongue movement due to scarring and the absence of lingual papillae and palatal rugae increased significantly over one year. Patients with microstomia, vestibule depth, and restricted tongue movement due to scarring were significantly older than patients without these characteristics. Lingual papillae and palatal rugae were more frequently absent in recessive than dominant DEB. Conclusion. DEB causes significant changes in oral and perioral soft tissues and oral functions impairment