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L. Alagić-Džambić, E. Becic, F. Becic, M. Džambić

Statins exhibit their pharmalogical effects by competitive inhibition trough binding with active sites of enzymes. Rosuvastatin, of all statines, has the most binding interactions with the enzyme, and being the most potent statin, it is presumed that the strength of enzyme binding directly influences its potency. Reduction of derivatives of mevalonic acids results with decreased risk of cardiovascular diseases and very significant pleotropic effect of statins. Rosuvastatin comes in the form of calcium salt. During the clinical trial it has been marked as superstatin with its proven activity in lowering cholesterol levels. Aim of this paper was to examine the antiinflammatory and antioxidant activity

B. Imamović, Zinajda Bešić, E. Becic

Introduction: Considering that the research has shown that homosalate act as endocrine-active substance, it is very important to develop quick and sensitive method for tracking its concentrations in sunscreen products. The aim of this paper is to develop and validate the method for determining homosalate in sunscreen preparations and controlling the content of the products found on the market of Bosnia and Herzegovina. Methods: A high pressure liquid chromatography (HPLC) method for determination homosalate in sunscreen products has been developed and validated. Samples of six different manufacturers have been analyzed. HPLC method is method of choice for this type of investigation. Results: According to the calibration curve it has been found that the proposed analytical method in a given range of concentration is linear and that the correlation coefficient is R2=0.9998. Accuracy of the method is in range 94.26% -121.53%.The results have shown that the homosalate concentration in the tested samples did not exceed the maximally permissible concentration (10%). In the sample AV50 homosalate was not declared as an active ingredient, but it was identified and quantified at a concentration of 0.143%. Conclusion: Results of investigation of cosmetic products that are widely present on the market show the need of developing a sufficiently sensitive, easily accessible, analytical method for controlling the content of organic UV filters since the exceeding of the maximally permissible concentration can have a harmful effect on people who use these kinds of products. The results show that developed method meets conditions and is suitable for wide application.

The increasing use of sun-creams containing organic UV-filters has led to increased concentration of these compounds in aquatic environment. Chlorinated water can convert these chemicals into chlorinated products whose toxic effects are of primary concern. The new compound may be more toxic than the starting primary compound. Many studies have shown that UV filters absorb UV light and decompose under solar irradiation, due to their unstable properties. This may lead to formation of certain by-products with harmful effects. Their decomposition products can cause allergic and toxic reactions to the human skin. This study follows the stability of most commonly used UV filters, homosalate, in conditions that include those existent in swimming pools. Stability of the homosalate in chlorinated water was studied in simulated swimming pool water samples. UV spectroscopy was used to follow the reaction of homosalate in presence of free chlorine. Water samples were filtered, acidified, and extracted by use of solid-phase extraction. Gas chromatography with mass spectrometry was used to identify the major transformation by-products. Under the experimental conditions, homosalate reacted with chlorine following zero order reaction. The chemical transformation of the homosalate in chlorinated water led to formation of chlorinated by-products that was identified as:

Lorazepam is an almost water insoluble substance. This study investigated the solubilization of lorazepam depending on media pH, cosolvents (ethanol, propylene glycol, polyethylene glycol 200 and 400), surfactants (Tween 80, Tween 20, Brij 35, sodium-cholate, sodium-deoxycholate, sodium-taurocholate) and cyclodextrins (α-cyclodextrin, -cyclodextrin and 2-hydroxypropyl-β-cyclodextrin). The main objective was to find the most suitable method for providing good solubility of this drug and thus its formulation in a liquid dosage form. Based on the results, the changes in the pH value of the media do not lead to a greater solubility of lorazepam. Of the cosolvents used, the greatest increase in solubility of lorazepam in water was achieved with ethanol. Of the bile salts used, sodium taurocholate showed the best solubilization ability, while Brij 35 was the best of the non-ionic surfactants. The solubility of lorazepam with the cyclodextrin derivative, 2-hydroxypropyl-β-cyclodextrin was better than natural cyclodextrin. Surfactants have the highest ability of solubilization of lorazepam in water.

Parabens are esters of p-hydroxybenzoic acid and belong to group of effective preservatives commonly used in cosmetic products, drugs and food. Their antimicrobial activity increases with increasing carbon number of the ester group. A number of cosmetic products and skincare products are preserved with parabens, as well in Europe as in the United States. Methyl, ethyl and propyl paraben are preservatives commonly used in cosmetic products. Usage of parabens should be under great attention, because some studies mentioned that the increased concentration can cause skin irritation and contact dermatitis.. This paper shows optimization of HPLC method for determination of methyl, ethyl and propyl paraben in sunscreen products. The advantage of this analytic method is that the same stationary phase with different mobile phases is used for determination UV filters and parabens as well in sunscreen products. Determination was performed using reversed stationary phase C8 with wavelength 254 nm. Separation was performed using mobile phase methanol: water (60:40 w/w). Analytic method was validated through specificity, linearity, limit of detection (LOD) and limit of quantification (LOQ). Determined limit of detection and limit of quantification for methyl, ethyl and propyl paraben are respectively: LOD-0.035 μg/ml LOQ-0.116 μg/ml; LOD-0.061 μg/ml LOQ-0.203 μg/ml and LOD0.009 μg/ml LOQ-0.031 μg/ml. Coefficient of quantification for methyl, ethyl and propyl paraben are respectively: R-0.9996; R-0.9988 and R-1. A content of parabens was examined on commercial samples available on market in Bosnia and Herzegovina. Concentration of ethyl, methyl and propyl paraben does not exceed maximal allowed concentrations (0.4% for single ester and 0.8% for mixture of esters) in tested samples.

Purpose – The purpose of this paper is to test absorption characteristics of some newly synthesised 4‐hidroxycoumarins, containing phenyl‐prop‐2‐enoyl group at the 3‐position. Change in spectral characteristics in solvents of different polarity (chloroform and acetonitrile) was followed in regard to the influence of the substitution at the phenyl ring and influence of concentration H+ ions. Effectiveness of tested substances was compared with well‐known UV absorbers such as benzophenone‐3 and butyl methoxydibenzoylmethane (BMDM).Design/methodology/approach – All the tested substances were dissolved in chloroform and acetonitrile, with 10‐3 mmol concentration range. The pH was adjusted using 0.1 mol/l HCl, glacial acetic acid, 0.1 mol/l NaOH (aqueous solution) and 0.1 mol/l NaOH (methanolic solution). Spectrophotometric measurement was recorded in the range of 200‐800 nm, using 1‐cm quartz cells.Findings – The tested 4‐hydroxycoumarin derivatives showed good UV absorption properties in the range 280‐380 nm...

The protection of sun radiation is a problem on global level for all living organisms on Earth. The need of people for the overexposure to the UV radiation led human population towards finding novel ways of protection of this kind of radiation, in form of cosmetic preparations applied on the skin. So far, the high values of protection factors of preparations and total block preparations with sun protection factor of 50+ were achieved. Physical and chemical filters which absorb radiation are constituents of these preparations. European Union has set regulations as which substances and in what amounts could be used as UV absorbers. American FDA (Food and Drug Administration) also gave its list of the most frequently used UV absorbers in the sunscreen products, as well as their declared concentrations. The most frequently used concentrations of UV filters in cosmetics is between 0.1% and 10%. Concentrations of UV filters in sunscreen products have to be monitored in order to ensure that they are not less from the declared levels, on which depends the efficacy and safety of the product.

Experimental studies of burns require the use of different animal models. The aim of this work was to establish experimental model of thermal injuries and to evaluate the effects of topical agents on healing of the burn wounds. Forty female Wistar rats were randomly classified in 4 groups and isolated for 2 weeks before the onset of experiment. Animals were primarily anaesthetized with pentobarbital-sodium and then shaved (skin area of their back with diameters 5 cm x 5 cm). A round metal stamp with contact area of 5 cm2 and total weight of 100 g was heated up to 80 degrees C and then applied without additional pressure on the depilated skin of the back for 14 seconds. This procedure produced a standardized burn wound. Induced burn wounds were immediately drowned in the 4 degrees C- water for 3 s in order to maintain microcirculation. After the inducement of thermal injures, all rats were treated with 1% silver sulfadiazine cream, herbal topical preparations or were not treated at all. Burn wounds were treated twice a day until the healing completion. The result of treatment application was a significant reduction of burn wound diameters. Herbal topical preparations expressed positive therapeutic effects on the parameters of burn wounds. The efficiency of silver sulfadiazine cream in burn wound healing was significantly more expressed in comparison to healing process in control group of animals (p < or = 0,001). We conclude that herbal topical preparations efficiently caused the completion of burn wound healing process without scar formation.

Glimepiride is the oral antidiabetic, second-generation sulfonylurea. It is structurally similar to glyburide. Glimepiride exhibited more potent glucose-lowering effects than glyburide and longer duration of hypoglycemic effect. Glimepiride is useful in the treatment of non-insulin-dependent (type II) diabetes mellitus. Glimepiride is indicated as an adjunct to diet and exercise for non-insulin dependent diabetes mellitus. Glimepiride reduces glucose levels blood by stimulating insulin release from functional pancreatic beta cells in response to glucose. Glimepiride in daily dose 1 to 8 mg is causing a dose-related decrease blood glucose levels and glycosylated hemoglobin fasting state and postprandially. If the maximum dose of glimepiride fails to lower blood glucose sufficiently, metformine or insuline may be added to glimepiride monotherapy. Glimepiride is very safe drug and adverse effects causing by glimepiride are very rare. The risk of hypoglycemia after use of glimepiride is very small, therefore is the therapy with glimepiride is more preferable than the therapy with glibenclamide.

D. Završnik, Faiwa Basic, Fahir Secic, E. Becic, S. Jažić

Background and Purpose: Due to the exceptional reactivity of 4-hydroxycoumarin, as well as the versatile biological activity of coumarin derivatives, the synthesis of 3-substituted derivatives of 4-hydoxycoumarin were carried out, and antibacterial and antifungal activity were tested. We assumed that newly-prepared derivatives might have antifungal and antibacterial activity. Material and Methods: Microbiological activity of compounds was tested by the diffusion method on the species of bacteria Escherihia coli 113-1, Pseudomonas aeruginosa ATCC 9027, Staphylococcus aureus SG 511, and fungi Candida albicans ATCC 10231. For comparison of results, the antibacterial activity of currently used antibiotics to the same species ofbacteria was tested. Results: The synthesis of derivatives of 3-cinammoyl-4-hydroxy-coumarin and azomethines of 4-hydroxycoumarin was carried out. Both groups of compounds showed significant microbiological activity. Conclusion: All synthesized compounds showed antimycotic and antibacterial activity. Derivatives of3-cinnamoyl-4-hydroxycoumarin in relation to azomethines of 4-hydroxycoumarin showed better activity in case of all bacteria and fungi species. The best antibacterial activity was shown by the species which had -Cl or -OCH 3 as substituents, and the best antimycotic activity was shown by the species which contained Cl.

Hexetidine is very safe oral antiseptic with broad antibacterial and antifungal activity in vivo and in vitro. It has local-anesthetics, astringent and deodorant activity. Also, it has very strong antiplac effects. Resistention of microorganisms on hexetidine is short and transient. These characteristics give important therapeutic role in treatment of oral infections.

Background and Purpose: On the basis of structural similarity of newly synthesized compounds and non-steroidal anti-inflammatory drugs, we assumed that these compounds might have analgesic activity. Materials and Methods:Analgesic effects of newly synthesized compounds were analyzed on the albino mice of both genders. The sense of pain was caused by thermal stimulus by the method of hot plate. Individual analgesic effect of newly synthesized compounds was measured 30, 60, 90 and 120 minutes after a single oral administration in a dose of 35 mg/kg. Physiological solution in the same volume was administered to a control group. The surveyed compounds have the following chemical names: A = 1-phenyl-5-(4-acetamido-phenyl)-3-(4-hydroxycoumarin)-Δ 2 -pyrazolin, B = 1-phenyl-5-(3-chlorphenyl)-3-(4-hydroxycoumarin)-Δ 2 -pyrazolin, C = /1/-benzopyrano-(4,3b)-7-methyl-quinoline-6-on, D = 2-(2-hydroxyphenyl)-4-methylqui-noline-3-carbonic acid. Results: Latency period for the compound A was significantly extended (p<0.001) 30 and 60 minutes after application as compared to the control group. However, 90 and 120 minutes after the application, this difference was not statistically significant (p=0,806 and p =0, 773) (t-test). The latency period for the compounds B and C as compared to the control group was significantly extended (p<0.001) in all observed time intervals. Similarly, the latency period for the compound D was extended 30 and 60 minutes after the application and was significant as compared to the control group (p<0.001). Latency was also increased when registered after 90 and 120 minutes (p=0.008 and p=0.026). Conclusions: After oral application, the investigated compounds showed analgesic effects to the sense of pain caused by a thermal stimulus.

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