The objective of this study was to analyse cardiovascular medicines utilisation patterns in Republic of Srpska (Bosnia and Herzegovina) over the 2002–2006 period.

Statins, such as simvastatin, lower circulating cholesterol levels and are widely prescribed for the treatment of hypercholesterolaemia. Several studies have shown unexpected effects of statins on inflammation. We studied the anti-inflammatory effect of simvastatin using a standard model of an acute local inflammation, the carrageenan-induced footpad oedema. Experimental groups (n = 6-8) were given simvastatin in a dose range 5-30 mg/kg, indomethacin 1-8 mg/kg and methylcellulose (control) per os. Footpad volume was measured with a plethysmograph and compared with the pre-injection volume of the same paw. Swelling (in microlitres) was then calculated, and in drug-treated animals, per cent inhibition was derived through comparison with the control group. Histopathological examination of the skin biopsies was performed to examine severity of paw skin lesions and to confirm the simvastatin-induced inhibition of acute inflammation. Both simvastatin and indomethacin administered orally, 1 hr before carrageenan injection, significantly reduced the extent of footpad oedema. Indomethacin dose-dependently blocked the swelling; the maximal effect was obtained with 8 mg/kg by 48.3% (P < 0.05). Simvastatin produced a comparable anti-inflammatory activity at a dose of 5 mg/kg (32%), while 10 and 30 mg/kg caused a 47.6% and 51.7% reduction, respectively, with the maximal effect observed at 20 mg/kg by 57.2% (P < 0.05). The comparison of the ED(50) of these agents on molar basis showed equipotent anti-inflammatory activity. Histopathological examination of the footpad skin biopsies revealed that simvastatin, dose-dependently and comparablly to indomethacin, reduced polymorphonuclear leucocyte infiltration. These data support the hypothesis that simvastatin has an acute anti-inflammatory activity.

The effect of simvastatin applied in a short-term pretreatment on proinflammatory cytokines production in acute systemic inflammation induced by endotoxin - lipopolysaccharide (LPS) in rats was investigated. Both LPS and simvastatin doses were established in separate experiments in which increasing doses of both compounds were given to obtain the LD(50) LPS and the maximally protective dose of simvastatin against LD(50) LPS. To determine the anti-inflammatory effect, simvastatin was given orally for 5 days, followed by a single intraperitoneal non-lethal dose of LPS (0.25 LD(50)). Plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 were measured by enzyme-linked immunosorbent assay. The acute i.p. LD(50) LPS amounted to 22.15 mg/kg. Simvastatin of 20 mg/kg p.o. was maximally protective against LD(50) LPS, and this dose was used for studying its effects on LPS-induced cytokines production. Cytokines concentrations were significantly increased upon challenge of non-lethal dose of LPS. The peak levels of TNF-alpha and IL-1beta were significantly suppressed by simvastatin, compared to control rats only treated with dimethylsulfoxide before LPS. In contrast, simvastatin did not affect IL-6 levels at all timepoints. Simvastatin pretreatment given orally produced acute anti-inflammatory effects by inhibiting TNF-alpha and IL-1beta, but no IL-6 production.

Aim To investigate the influence of probiotic pre-treatment on the permeation of the antidiabetic drug gliclazide in healthy and diabetic rats. Methods Wistar rats (age 2–3 months, weight 350 ± 50 g) were randomly allocated into one of 4 groups (N = 16 each group): healthy control, healthy probiotic, diabetic control, and diabetic probiotic. Probiotics (75 mg/kg, equal quantities of Lactobacillus acidophilus, Bifidobacterium lactis, and Lactobacillus rhamnosus) were administered twice a day for three days to the appropriate groups after diabetes had been induced with alloxan i.v. 30 mg/kg. Rats were sacrificed, ileal tissues mounted in Ussing chambers and gliclazide (200 µg/mL) was administered for the measurement of the mucosal to serosal absorption Jss(MtoS) and serosal to mucosal secretion Jss(StoM) of gliclazide. Results Treatment of healthy rats with probiotics reduced Jss(MtoS) of gliclazide from 1.2 ± 0.3 to 0.3 ± 0.1 µg/min/cm2 (P < 0.01) and increased Jss(StoM)from 0.6 ± 0.1 to 1.4 ± 0.3 (P < 0.01) resulting in net secretion while, in diabetic tissues, treatment with probiotics increased both Jss(MtoS) and Jss(StoM)fluxes of gliclazide to the comparable levels of healthy tissues resulting in net absorption. Discussion In healthy rats, the reduction in Jss(MtoS) after probiotics administration could be explained by the production of bacterial metabolites that upregulate the mucosal efflux drug transporters Mrp2 that control gliclazide transport. In diabetic rats, the restored fluxes of gliclazide after probiotic treatment, suggests the normalization of the functionality of the drug transporters resulting in a net absorption. Conclusion Probiotics may alter gliclazide transport across rat ileal tissue studied ex vivo.

The aim of this study was to investigate the pharmacokinetics and glucose-lowering activity of gliclazide alone and in combination with the bile acid salt, sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC), in a rat model of type I diabetes. Eighty male Wistar rats were divided into eight groups (n=10). Four groups were treated with alloxan (30 mg/kg) to induce diabetes. One group of healthy and one group of diabetic rats were administered gliclazide (20 mg/kg), MKC (4 mg/kg) or a combination of gliclazide (20 mg/kg) and MKC (4 mg/kg). One group of healthy and one group of diabetic rats were used as controls. Blood samples were collected from the tail vein 6 hours post-dose and the plasma was analyzed for glucose concentrations. It was found that gliclazide bioavailability was increased in healthy rats when coadministered with MKC, but there was no difference in glucose levels. Gliclazide bioavailability was much lower in diabetic rats and was not altered by MKC. However, the hypoglycemic effect of the combination of gliclazide and MKC was significantly greater in diabetic rats than that of gliclazide alone. It was demonstrated that the combination of MKC and gliclazide produced a significant hypoglycemic effect in a rat model of Type I diabetes. As gliclazide alone does not have a hypoglycemic effect on Type I diabetic rats, it can be concluded that gliclazide potentiates hypoglycemic effect of MKC in Type I diabetic rats.

Sažetak. Infekcije tmdnice su relativno česte, tako da je često i propisivanje antibiotika и trudnoći. Vrsta antibiotika, doza, trajanje, način i učestalost primjene zavise od uzročnika i težine bolesti. U Sjedinjenim Američkim Državama, prema Upravi za hranu i lijekove (engl., Food and Drug Administration, FDA) svi lijekovi, prema riziku za oštećenje ploda, svrstavaju se и 5 grupa (А, В, C, D, X). Najmanji rizik imaju lijekovi iz grupe A i B, a najveći iz grupe X. Cilj rada je bio da se ispita učestalost primjene antibiotika kod trudnica, koje su najčešće indikacije za njihovu primjenu, koji se antibiotici najčešće koriste i и koju grupu rizika po plod spadaju, te koliko je antibiotska terapija trajala. ® Studija je obuhvatila 694 trudnice. Ispitivanje je provedeno tokom 2004. i 2005. godine. Podaci su prikupljeni modifikovanim upitnikom za trudnice Svjetske zdravstvene organizacije, originalno urađenom na Institutu za farmakološka istraživanja “Mario Negri ”, Milano, ltalija. U toku trudnoće, lijekove je uzimalo 574 (82,71%) žene. U prosjeku, uzimano je 2,84 lijeka po trudnici. Najčešće su korišćeni preparati željeza (69,9%) i vitamini (56,1%), a slijede sistemski antibiotici (33,9%), antimikotici u obliku vaginaleta (22,3%), simpatikomimetici za spriječavanje prijevremenog porođaja (22,0%), polni hormoni (progesteron) (13,9%), te benzodiazepini (12,0%>). Od sistemskih antibiotika najčešće su korišćeni beta laktamski antibiotici (penicilini i cefalosporini, FDA grupa B). Najčešće indikacije za terapiju sistemskim antibioticima su bile: infekcije urinarnog trakta, a zatim respiratornog. Utvrđeno je da su antibiotici primjenjivani i kod virusnih infekcija uz opravdanje da se trudnice zaštite od bakterijske superinfekcije. Oko 3% trudnica bilo je na hroničnoj terapiji, koja je započeta prije i trajala je tokom čitave trudnoće (epilepsija, oboljenja štitne žlijezde, i slično). Antibiotike za sistemsku primjenu je koristila treéina trudnica, a najčešće su korisćeni beta laktamski antibiotici, amoksicilin i cefaleksin. Antibiotici su najčešće korišćeni za liječenje infekcija urinarnog i respiratornog trakta. Kod veéine trudnica, liječenje infekcija bilo je neodgovarajuée.

INTRODUCTION Catheter-associated urinary tract infections (CAUTI) are the most common nosocomial infections. The worldwide data show the increasing resistance to conventional antibiotics among urinary tract pathogens. AIM To evaluate the adequacy of initial antimicrobial therapy in relation to the antimicrobial resistance of pathogens responsible for CAUTI in Clinical Center of Banja Luka. METHODS A retrospective study on major causes of CAUTI, antibiotic resistance and treatment principles was conducted at four departments of the Clinical Center of Banja Luka from January 1st, 2000 to April 1st, 2003. RESULTS The results showed that 265 patients had developed CAUTI. The seven most commonly isolated microorganisms were, in descending order: E. coil (31.0%), Pseudomonas aeruginosa (13.8%), Proteus mirabilis (12.9%), Gr. Klebsiella-Enterobacter (12.3%), Enterococcus spp. (5.2%), Pseudomonas spp. (4.3%), Serratia spp. (4.0%). The most common pathogens were highly resistant to ampicillin (64-100%), gentamycin (63-100%), and trimethoprim-sulfamethoxazole (68-100%), while some bacterias, like Pseudomonas aeruginosa and Serratia spp. showed rates of ciprofloxacin resistance as high as 42.8% and 72.7%, respectively. In 55.5% of the cases, the initial antibiotic therapy was inadequate, and was corrected latter on. There were no standard therapeutic protocols for this type of nosocomial infections. CONCLUSION The results of this study emphasized an urgency of the prevention and introduction of clinical protocols for better management of CAUTI. Treatment principles should better correspond to the antibiotic sensitivity of uropathogens.

Sažetak. U trendu porasta ukupnih troškova za zdravstvo, kontinuirano praćenje upotrebe lijekova и zdravstenom sistemu omogućava sagledavanje zdravstvenog stanja stanovništva, farmakoterapijskih navika doktora i trendova и propisivanju, stepena racionalnosti upotrebe lijekova, te upoređivanja istih sa svjetskim kretanjima. Cilj ovog rada je bio da se analizira upotreba lijekova koji se izdaju na teret Fonda zdravstvenog osiguranja Republike Srpske и periodu 2003-2004. godina. Retrospektivnom studijom analizirana je upotreba lijekova sa pozitivne liste Fonda zdravstvenog osiguranja Republike Srpske 2003-2004. godine. Podaci su obrađeni prema ATC/DDD metodologiji, a rezultati izraženi brojem DDD/1.000 osiguranih lica/dan. Prikazana su i materijalna izdvajanja za lijekove sa pozitivne liste, izraženo и milionima konvertibilnih maraka. U 2004. godini je došlo do porasta upotrebe lijekova od 21% izraženo brojem DDD, a materijalna izdvajanja su porasla za 25% и odnosu na prethodnu godinu. Najveéa je upotreba lijekova и grupama za kardiovaskularne bolesti (ACE inhibitori i Ca blokatori), lijekova koji djeluju na sistem za varenje i metabolizam (antidijabetici i antiulkusici), koji djeluju na nervni sistem (antiepileptici i anksiolitici), te sistemski antiinfektivi. U obe godine najveéi su troškovi bili izdvojeni za lijekove и liječenju kardiovaskularnih oboljenja. Porast upotrebe lijekova, kao i povećanje troškova и zdravstvu zahtijeva detaljnu analizu, primjenom farmakoekonomskih metoda koje bi trebalo da pomognu pri donošenju odluka о raspodjeli raspoloživih sredstava. Na osnovu ovakvih podataka država тога kontinuirano da prilagođava zdravstevnu politiku и skladu sa standardnim kliniâkim smjernicama i medicini zasnovanoj na dokazima, kako bi farmakoterapiju učinila racionalnom i dostupnom cjelokupnom stanovništvu.

Using spectrophotometric assay, we have studied the distribution of α-D-mannosidase, β-D-galactosidase, and N-acetyl-β-D-glucosaminidase in hog serum, the aqueous humor, optic nerve, retina, and uvea (iris, ciliary body, choroid). N-acetyl-β-D-glucosaminidase was the most active gycosidase in all tissues that we studied. The highest activity of α-D-mannosidase was found in the extracts prepared from the iris, while β-D-galactosidase and N-acetyl-β-D-glucosaminidase were the most active in the extracts of the choroid and ciliary body, respectively. The aqueous humor and serum had several times lower specific activity of glycosidases than did the extracts of ocular tissues or optic nerve. There was no significant difference between the activity of these enzymes in the aqueous humor and serum. High activity of glycosidases in the optic nerve suggests their role for intrinsic axonal repair. Retinal extracts had the smallest glycosidase activity of all ocular extracts prepared. The physiological role of these findings is discussed.

INTRODUCTION Using the Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) methodology, we analyzed utilization of prescription-only drugs in Banja Luka region in 2000-2001. MATERIAL AND METHODS A retrospective study on drug utilization, according to ATC classification, was conducted on the basis of data received from Central City Pharmacy Banja Luka, and results were presented in terms of DDD/1000 inhabitants/day. RESULTS Pharmaco-epidemiological analysis showed that the list of 20 most frequently prescribed drugs in 2000 included 8 cardiovascular drugs and 6 anti-infective drugs. In 2001, 20 most frequently prescribed drugs, included 9 cardiovascular drugs, and 4 anti-infective drugs. Regarding anti-infective agents, the most frequently prescribed antibiotics were amoxicillin, doxycyline, co-trimoxazole and gentamicin. The most frequently prescribed drug in 2000 was diazepam (5.33 DDD/1000 inhabitants/day). The use of this drug significantly increased in 2001 (7.95 DDD/1000 inhabitants/day). DISCUSSION AND CONCLUSION Based on total analysis, it can be concluded that the positive drug list, defined by the Health Insurance Fund, significantly affected the drug utilization profile, but some drugs are considered to be irrationally prescribed.