Anthropometric Indices of Obesity and Hypertension in Different Age and Gender Groups of Croatian Population

The aim of this study was to investigate the association of hypertension with the obesity indices – body mass index and waist circumference. The study was based on the data from the Croatian Adult Health Survey 2003, which is a cross-sectional study on the representative sample of 9,070 Croatian adults. The results showed that in both men and women aged 18–64 years and 65 years and older increased BMI and waist circumference were associated with higher odds of hypertension. Odds of hypertension for obese (BMI ł 30) and persons with abdominal obesity (waist circumference ł 102 cm for men, ł 88cm for women) was higher among young and middle aged than among elderly persons. No differences in odds of hypertension were recorded between persons with increased BMI and persons with increased waist circumference. Both BMI and waist circumference exhibited equally strong association with hypertension in Croatian population, in both men and women, and in those who are below or over 65 years of age

Optimization of hot-melt coating in a fluidized-bed apparatus: preparation and characterization of modified release paracetamol granules

Oblaganje topljenjem je proces u kom se supstanca za oblaganje nanosi na supstrat u rastopljenom obliku i najčešće se sprovodi u uređaju tipa fluidizirajućeg sistema. Zbog velikog broja procesnih parametara i kompleksnosti procesa, optimizacija postupka oblaganja topljenjem u ovakvim uređajima predstavlja poseban izazov. Cilj ovog rada je ispitivanje uticaja procesnih parametara na karakteristike granula obloženih topljenjem i optimizacija postupka oblaganja topljenjem u uređaju tipa fluidizirajućeg sistema laboratorijskog kapaciteta. Na osnovu rezultata ispitivanja dobijenih primenom eksperimentalnog dizajna, uočene su dve oblasti koje definišu optimalne uslove procesa oblaganja topljenjem, odnosno, definisan je prostor za dizajn.Komprimovanjem granula obloženih topljenjem mogu se izraditi tablete sa produženim oslobađanjem lekovite supstance. Ispitivanje tabletabilnih karakteristika materijala obloženog topljenjem do sada nije opisano u literaturi. Dobijeni rezultati su pokazali da obložene granule poseduju zadovoljavajuće karakteristike u smislu kompaktibilnosti i pogodnosti za proizvodnju, a da farmaceutsko-tehnološke karakteristike izrađenih tableta odgovaraju zahtevima Ph. Eur. 10.0. Takođe, ispitivanja su pokazala da je brzina rastvaranja paracetamola iz tableta izrađenih od obloženih granula nezavisna do pritiska kompresije primenjenog u postupku izrade tableta.Granule obložene topljenjem i tablete izrađene od obloženih granula predstavljaju pogodne farmaceutske oblike lekova za pedijatrijske pacijente, pre svega zbog primene bezbednih pomoćnih supstanci za oblaganje i mogućnosti maskiranja ukusa, a smanjena učestalost doziranja zbog produženog oslobađanjа lekovite supstance može dodatno povećati komplijansu pacijenata. Rezultati in silico modelovanja i simulacija pokazali su da se primenom obloženih granula paracetamola i tableta izrađenih od obloženih granula, kod dece različitog uzrasta, može postići odgovarajuća sistemska raspoloživost uz istovremeno smanjenje učestalosti uzimanja leka.Hot-melt coating is a process in which the coating excipient is applied on a substrate in a molten state. Generally, fluidized-bed systems are preferred for hot-melt coating. Optimization of hot-met coating in a fluidized-bed apparatus is often a challenge due to the numerous process parameters and the process complexity. The aim of this study was to evaluate the effects of process parameters on the coated granules characteristics and to optimize the hot-melt coating process in the laboratory-scale fluidized-bed apparatus. Based on the experimental design results, two discrete areas defining optimal values of the process parameters were observed i.e., design space was established.Hot-melt coated granules can be compressed to yield prolonged-release tablets. Evaluation of hot-melt coated material tableting properties has not been described in literature so far. The results obtained in this study revealed that hot-melt coated paracetamol granules have suitable tableting properties, in terms of compactibility and manufacturability. In addition, pharmaceutical-technical properties of the tablets made of hot-melt coated granules are within the limits described in the Ph. Eur. 10.0. Dissolution testing showed that the applied range of compression loads during tableting process did not influence the drug dissolution rate from tablets made of hot-melt coated paracetamol granules.Hot-melt coated granules and tablets made of hot-melt coated granules can be a suitable dosage forms for paediatric patients because the presence of the coat can provide taste masking, the coating excipients are generally recognized as safe, and prolonged drug release can reduce the dosing frequency, and consequently, improve patients compliance. In silico modelling and simulation results indicated that administration of hot-melt coated paracetamol granules or tablets made of hot-melt coated granules in different paediatric subgroups can provide suitable drug systemic availability with reduced daily dosing

Optimization of hot-melt coating in a fluidized-bed apparatus: preparation and characterization of modified release paracetamol granules

Oblaganje topljenjem je proces u kom se supstanca za oblaganje nanosi na supstrat u rastopljenom obliku i najčešće se sprovodi u uređaju tipa fluidizirajućeg sistema. Zbog velikog broja procesnih parametara i kompleksnosti procesa, optimizacija postupka oblaganja topljenjem u ovakvim uređajima predstavlja poseban izazov. Cilj ovog rada je ispitivanje uticaja procesnih parametara na karakteristike granula obloženih topljenjem i optimizacija postupka oblaganja topljenjem u uređaju tipa fluidizirajućeg sistema laboratorijskog kapaciteta. Na osnovu rezultata ispitivanja dobijenih primenom eksperimentalnog dizajna, uočene su dve oblasti koje definišu optimalne uslove procesa oblaganja topljenjem, odnosno, definisan je prostor za dizajn. Komprimovanjem granula obloženih topljenjem mogu se izraditi tablete sa produženim oslobađanjem lekovite supstance. Ispitivanje tabletabilnih karakteristika materijala obloženog topljenjem do sada nije opisano u literaturi. Dobijeni rezultati su pokazali da obložene granule poseduju zadovoljavajuće karakteristike u smislu kompaktibilnosti i pogodnosti za proizvodnju, a da farmaceutsko-tehnološke karakteristike izrađenih tableta odgovaraju zahtevima Ph. Eur. 10.0. Takođe, ispitivanja su pokazala da je brzina rastvaranja paracetamola iz tableta izrađenih od obloženih granula nezavisna do pritiska kompresije primenjenog u postupku izrade tableta. Granule obložene topljenjem i tablete izrađene od obloženih granula predstavljaju pogodne farmaceutske oblike lekova za pedijatrijske pacijente, pre svega zbog primene bezbednih pomoćnih supstanci za oblaganje i mogućnosti maskiranja ukusa, a smanjena učestalost doziranja zbog produženog oslobađanjа lekovite supstance može dodatno povećati komplijansu pacijenata. Rezultati in silico modelovanja i simulacija pokazali su da se primenom obloženih granula paracetamola i tableta izrađenih od obloženih granula, kod dece različitog uzrasta, može postići odgovarajuća sistemska raspoloživost uz istovremeno smanjenje učestalosti uzimanja leka.Hot-melt coating is a process in which the coating excipient is applied on a substrate in a molten state. Generally, fluidized-bed systems are preferred for hot-melt coating. Optimization of hot-met coating in a fluidized-bed apparatus is often a challenge due to the numerous process parameters and the process complexity. The aim of this study was to evaluate the effects of process parameters on the coated granules characteristics and to optimize the hot-melt coating process in the laboratory-scale fluidized-bed apparatus. Based on the experimental design results, two discrete areas defining optimal values of the process parameters were observed i.e., design space was established. Hot-melt coated granules can be compressed to yield prolonged-release tablets. Evaluation of hot-melt coated material tableting properties has not been described in literature so far. The results obtained in this study revealed that hot-melt coated paracetamol granules have suitable tableting properties, in terms of compactibility and manufacturability. In addition, pharmaceutical-technical properties of the tablets made of hot-melt coated granules are within the limits described in the Ph. Eur. 10.0. Dissolution testing showed that the applied range of compression loads during tableting process did not influence the drug dissolution rate from tablets made of hot-melt coated paracetamol granules. Hot-melt coated granules and tablets made of hot-melt coated granules can be a suitable dosage forms for paediatric patients because the presence of the coat can provide taste masking, the coating excipients are generally recognized as safe, and prolonged drug release can reduce the dosing frequency, and consequently, improve patients compliance. In silico modelling and simulation results indicated that administration of hot-melt coated paracetamol granules or tablets made of hot-melt coated granules in different paediatric subgroups can provide suitable drug systemic availability with reduced daily dosing

Water quality assessment of the Borska Reka river using the WPI (Water Pollution Index) method

The Borska Reka river (47 km long, 373 km2 of basin area) is located in eastern Serbia and it is the biggest tributary of the river Veliki Timok. It is also one of the most polluted watercourses in Serbia. Using the data of the Republic Hydrometeorological Service of Serbia, the paper analyzes water pollution using the combined physical-chemical WPI index (water pollution index) over two periods: 1993-1996 and 2006-2009. The analysis of parameters showed significantly increased values of heavy metals (especially iron and manganese) which are indicators of inorganic pollution (primarily because of mining), but also increased values of organic pollution indicators (Biological Oxygen Demand-BOD5, ammonium, coliform germs), as the result of uncontrolled domestic wastewater discharge

SUBSTITUENT EFFECT ON THE BINDING MODE AND TOXICITY OF SELECTED 1,4-BENZODIAZEPIN-2-ONE

Extended abstract: 1,4-benzodiazepin-2-ones (BZ) are effective in the treatment of depression, anxiety, epilepsy, insomnia, etc [1]. The structural modifications of 1,4-benzodiazepin-2-ones allow new areas of application due to the change in reactivity, potential binding modes, and stability. A series of eight BZs (Figure 1) has been selected to examine the effect of substituents on the binding energy towards µ-opioid receptor, Lipinski’s rules, and toxicity. Out of many available structures, the selected BZs have four positions in which the substituents were changed [2]. In position R1 an electron-withdrawing (NO2, CN) and electron-donating groups (Cl) are present [2]. The positions R2 and R3 contain H, OH, and CH3 groups. Only bromazepam, a commonly used drug, has nitrogen atom in the second aromatic ring. The structures of selected benzodiazepines were optimized in the Gaussian Program Package at the M06-2X/6-311++G(d,p) level of theory. The molecular docking studies were performed on the µ-opioid receptor (PDB: 4DKL) in AutoDOCK 4.0. The binding site of protein was determined by the presence of morphinan antagonist in the crystal structure. For the toxicity evaluation, the ProTox-II was used. All of the investigated compounds meet Lipinski’s rules of five: the molecular weight below 500 Da, the logP lower than 5, the number of H-bond donors lower than five, and H-bond acceptors lower than 10. When the toxicity is concerned, the selected BZs fall within several categories. Nordiazepam and diazepam have the lowest predicted LD50 dose of 48 mgkg-1, and they belong to the class II compounds which are fatal if swallowed. 7-cyano-1,4-benzodiazepin-2-one has lower toxicity with an LD50 value of 290 mgkg-1 (class III compounds: toxic if swallowed). The ciano group in structure is probably responsible for the hydrogen bond formation with the neighboring amino acids, as examined below. The rest of the compounds belong to the class IV: harmful if swallowed, with LC50 values ranging from 550 (nitrazepam) to 2000 (clonazepam) mgkg-1. The substituent effect on the toxicity is very complex, as all of the investigated compounds have several active positions. The values of binding energies range from -29.3 (bromazepam) to -22.8 (nordiazepam) kJmol-1. Due to the similarity in structure, all of the investigated compounds have similar values of the binding energies and in all cases, this is a favorable process. The presence of an N atom in the second ring structure is an important structural moiety as this is the only feature that differentiates bromazepam from other compounds. The importance of electronegative groups in position R1 is proven in the case of 7-cyano-1,4-benzodiazepin-2-one and nitrazepam. In general, compounds with two electronegative substituents (Cl, NO2, and OH) have higher binding energies. Further research is needed to obtain a detailed structure-activity relationship model that will correlate the substituent properties with toxicity/protein binding affinity.This work was supported by the Ministry of Science and Technological Development of the Republic of Serbia (Contract Nos. 451-03-9/2021-14/200378 and 451-03-9/2021-14/200146)Publishe

Association of Hypertension with Long-Term Overweight Status and Weight Gain: the CroHort Study

Overweight is associated with hypertension, but longitudinal studies on the effect of weight gain on blood pressure are relatively rare. Aim of this study was to investigate association of long-term overweight status as well as of becoming overweight with hypertension. Odds of hypertension in 2008 were calculated for 1,383 respondents from Croatian Adult Health Cohort Study (CroHort) who had normal blood pressure in 2003. The results showed that for women both long-term overweight status and recently becoming overweight (in the last 5 years) were significantly associated with development of hypertension, while for men this was true only for long-term overweight. Prevention activities aimed at maintenance of normal body weight should be important part of primary prevention of hypertension

Five-year Cumulative Incidence of Obesity in Adults in Croatia: the CroHort Study

The objective of this paper was to evaluate the 5-year incidence of obesity on a sample of 3229 adults and investigate the potential effect of several sociodemographic and lifestyle habits on weight change and obesity incidence in these individuals. The average annual rate of increase in the prevalence of obese adults between 2003 and 2008 was 10.60% for men and 11.08% for women. Analysis showed that development of obesity in 5-year period in women in Croatia is significantly positively associated with frequent consumption of »hidden« fats of animal origin and significantly negative with each higher education level. No significant predictor of obesity has been found in men. Obesity remains a serious health problem for the Croatian population; the alarming rates of excess body weight continue to increase. Preventive measures should urgently be undertaken

Five-year Cumulative Incidence of Obesity in Adults in Croatia: the CroHort Study

The objective of this paper was to evaluate the 5-year incidence of obesity on a sample of 3229 adults and investigate the potential effect of several sociodemographic and lifestyle habits on weight change and obesity incidence in these individuals. The average annual rate of increase in the prevalence of obese adults between 2003 and 2008 was 10.60% for men and 11.08% for women. Analysis showed that development of obesity in 5-year period in women in Croatia is significantly positively associated with frequent consumption of »hidden« fats of animal origin and significantly negative with each higher education level. No significant predictor of obesity has been found in men. Obesity remains a serious health problem for the Croatian population; the alarming rates of excess body weight continue to increase. Preventive measures should urgently be undertaken

Obesity – New Threat to Croatian Longevity

The aim of this study was to examine the association of weight gain and life expectancy at birth in Croatia.Mean body mass index was based on the data from the Croatian Adult Health Survey 2003. Birth rate and mortality data needed for life expectancy calculation were supplied by the Central Bureau of Statistics. The results suggest that the increase in mean body mass index value (1.31 kg m–² for women and 1.41 kg m–² for men) will shorten life expectancy at birth for one year. Obesity, if unchecked, might have a negative effect on life expectancy in Croatia. Despite widespread knowledge about how to reduce the severity of the problem, observed trends in obesity in Croatia continue to worsen. These trends threaten to diminish the health and life expectancy of current and future generations