<p>UVOD. Bilijarna kalkuloza je najče&scaron;će oboljenje hepatobilijarnog sistema, a holecistektomija predstavlja jedan od najče&scaron;će izvođenih operativnih zahvata. Laparoskopska holecistektomija je danas zlatni standard lečenja holelitijaze. Laparoskopska holecistektomija je pokazala pobolj&scaron;anje u klinički značajnim ishodima kao &scaron;to su skraćenje operativnog vremena, kraća hospitalizacija, smanjenje jačine i trajanja postoperativnog bola i brži povratak dnevnim i radnim aktivnostima. Postoperativna bol i vreme potpunog oporavka ostaju dva glavna problema posle nekomplikovane laparoskopske holecistektomije koje bi trebalo pobolj&scaron;ati. Bol koji je povezan sa laparoskopskom holecistektomijom je kompleksan i multifaktorijalan. On nastaje o&scaron;tećenjem tkiva, disekcijom i uklanjanjem žučne kesice iz svoje lože, stimulacijom periportalnih nerava, iritacijom dijafragme, mehaničkim i hemijskim interakcijama gasa i pneumoperitoneuma, incizijama portova. Istraživanja su označila parijetalni i visceralni bol kao dva glavna mehanizma nastanka bola kod laparoskopske holecistektomije. Bol se ne može meriti nego proceniti jer je subjektivni osećaj. Pokazalo se potrebnim da se na čvr&scaron;ćim naučnim osnovama da odgovor na pitanje da li je moguće blokirati parijetalni i visceralni bol posle laparoskopske holecistektomije u akutnoj fazi. CILJEVI. Cilj studije je da uporedi standardnu analgeziju (ne-opioidnu) (grupa O) sa davanjem parijetalne blokade (grupa P), ili davanjem visceralne blokade (grupa V), ili sa obe date blokade (grupa P+V). Primarni ishodi studije su bolesnikov procenjeni bol pre operacije i posle operacije na 1, 2, 4, 6, 12, 24, 48 sati i 7. dana. Sekundarni ishodi studije su bolesnikova procenjena mučnina na 1,2,4,6,12 sati i bolesnikova procenjena mobilnost 1. 2. i 7. dan. HIPOTEZA. Blokada postoperativnog visceralnog bola i blokada postoperativnog parijetalnog bola posle laparoskopske holecistektomije putem intraperitonealne lokalne infiltracije anestetikom i putem lokalne infiltracije anestetikom pristupnih laparoskopskih portova može značajno smanjiti rani postoperativni bol. MATERIJAL I METODE. Ova prospektivna, randomizirana jednostruko slepa studija je započela septembra 2014. godine i trajala je do januara 2016. godine. Istraživanje je sprovedeno na Klinici za abdominalnu, endokrinu i transplantacionu hirurgiju i Urgentnom centru Kliničkog centra Vojvodine u Novom Sadu kod bolesnika operisanih metodom laparoskopske holecistektomije. Rad je podeljen u nekoliko celina. 1. Procena veličine uzorka; 2. Procena podobnosti za studiju; 3. Anketiranje i uključivanje u studiju; 4. Razvrstavanje u grupe i operativni rad; 5. Period postoperativnog praćenja; 6. Statistička obrada i pisanje rada.<br />1. Procena veličine uzorka. Studija je realizovana podelom bolesnika u 4 grupe. Neophodni broj bolesnika je izračunat uzimajući podatke iz pilot istraživanja slične studije iz 2012. godine. Veličina uzorka je računata za primarni ishod studije&nbsp; (bolesnikov procenjen bol sa NAS) na pretpostavci da treba biti 20% smanjenja bola u prvom postoperativnom satu, uz verovatnoću Tip 1 gre&scaron;ke &alpha;=0.05 i Tipa 2 gre&scaron;ke &beta;=0.10 da postigne adekvatnu statističku snagu oko 80% i da otkrije 20% razlike u srednjoj vrednosti procenjenog bola jedan sat nakon laparoskopske&nbsp; holecistektomije. Procenjeni broj ispitanika po grupama prema zadatim kriterijumima je bio (P+V=65; P=68; V=68; O=65). Studija je započela uključivanjem prvog bolesnika u studiju a zavr&scaron;ena ispunjenim periodom praćenja sve dok poslednji bolesnik nije doneo upitnike o bolu, mučnini i kretanju. 2. Procena podobnosti za studiju. U periodu studije ukupan broj holecistektomiranih bolesnika je bio 1024 (440 klasično i 584 laparoskopski). Samo pogodni bolesnici su anketirani (584) i pročitali su informacioni list o istraživanju. Uključivanje ili procena podobnosti bolesnika za studiju sprovedena je na osnovu uključnih i isključnih kriterijuma. U studiju nije uključeno ukupno 226 bolesnika. Od tog broja 82 bolesnika je odbilo učestvovati u studiji a 144 bolesnika nije ispunilo uključne postavljene kriterijume. Svojim potpisom potvrdilo je uče&scaron;će u studiji 358 bolesnika. 3. Anketiranje i uključivanje u studiju. Nakon prijema bolesnika u bolnicu ispitivači su uzimali anamnezu i bolesnicima je ponuđen informacioni list i informisani pristanak. Nakon čitanja informacije, potpisivanja informisanog pristanka i zadovoljavanja&nbsp; uključnih i isključnih kriterijuma 358 bolesnika je uključeno u studiju. Obavljena je preoperativna priprema i ispitivači su popunili deo podataka u individualnom listu. 4. Razvrstavanje u grupe i operativni rad. Neposredno preoperativno od strane nezavisne osobe neuključene u studiju napravljena je randomizacija izabranih (n=358) u studijske grupe tablicama slučajnog izbora, tako da bolesnici nisu znali kojoj grupi pripadaju, dok su operater i osoblje to znali na početku operacije (jednostruko slepa studija). Nakon randomizacije i operacije bolesnici pripadaju jednoj od sledeće 4 grupe: Kontrolna grupa O=89, u kojoj su bolesnici sa urađenom laparoskopskom&nbsp; holecistektomijom bez visceralne blokade anestetikom i bez parijetalne blokade anestetikom. Eksperimentalna grupa P=88, u kojoj su bolesnici sa urađenom laparoskopskom holecistektomijom bez visceralne blokade anestetikom i sa parijetalnom blokadom anestetikom. Eksperimentalna grupa V=92, u kojoj su bolesnici sa urađenom laparoskopskom holecistektomijom sa visceralnom blokadom anestetikom i bez parijetalne blokade anestetikom. Eksperimentalna grupa P+V=89, u kojoj će biti bolesnici sa urađenom laparoskopskom holecistektomijom sa visceralnom blokadom anestetikom i sa parijetalnom blokadom anestetikom. Primenjivan je uobičajni, standardni protokol anestezije za laparoskopske operacije kod svih ispitanika. Svim bolesnicima plasirana je orogastrična sonda koja se nakon operacije odstranjivala. Kod&nbsp; bolesnika kod kojih je primenjivan lokalni anestetik neposredno pre početka operacije pravio se rastvor lokalnog anestetika (Marcaine&reg; 0,25%). Bolesnici su otpu&scaron;teni sa bolničkog lečenja prvog postoperativnog dana, pod uslovom da nisu imali komplikacija. 5. Postoperativno praćenje i ispunjavanje upitnika. Po dolasku na odeljenje&nbsp; bolesnicima je odmah uključivana ista analgezija. Tokom ispunjavanja informisanog pristanka, bolesnici su dobili upitnik na kojoj će sami procenjivati nivo bola, mučnine i kretanja tokom ležanja u bolnici i vremena praćenja od 7 dana kući. Bolesnici su dolazili na unapred zakazane postoperativne kontrole 7 do 10 dana posle operacije i donosili ispunjene upitnike. Otpu&scaron;teno je i za praćenje ostalo n=302 laparoskopski operisanih bolesnika a isključeno iz studije n=20 bolesnika. 6. Statistička obrada i pisanje rada. Ukupno je analizirano 274 listića operisanih bolesnika: u Grupi P+V =67; u Grupi P =70; u Grupi V =70 i u Grupi O =67. Od osnovnih deskriptivnih statističkih parametara za kvalitativnu i kvantitativnu procenu dobijenih rezultata su kori&scaron;ćeni apsolutni brojevi, relativni brojevi, mediana, mod, aritmetička sredina i standardna devijacija (SD). Obrada podataka se vr&scaron;ila&nbsp; osnovnim i naprednim statističkim metodama i programima. Rezultati su prikazani tabelarno i grafički. REZULTATI. Demografski podaci. Ukupno je bilo 188 žena i 86 mu&scaron;karaca, u odnosu 2,2 : 1. Prosečna starost cele grupe je bila 52,1 &plusmn; 15,72 godine. Ukupno je bilo 179 zaposlenih i 95 nezaposlenih. Ukupno je bilo 45 ispitanika sa osnovnim obrazovanjem, 153 ispitanika sa srednjim obrazovanjem i 76 ispitanika sa visokim obrazovanjem. Ukupno je bilo 186 nepu&scaron;ača i 88 pu&scaron;ača. Prosečna vrednost BMI cele grupe je bila 27,24 &plusmn; 4,21 kg/m2. Prosečna vrednost ASA u celoj grupi je bila 2,03 (mediana=2, mod=2). Ne postoji statistički značajna razlika između posmatranih grupa u odnosu na posmatrane parametre. Laboratorijski podaci. Postoji statistički značajna razlika u vrednosti leukocita između posmatranih grupa (p=0,039), u vrednosti uree između posmatranih grupa (p=0,040). Ne postoji statistički značajna razlika u vrednosti eritrocita, trombocita, hemoglobina, &Scaron;UK-a, kreatinina i bilirubina posmatranih grupa. Operativni i postoperativni podaci. Ne postoji statistički značajna razlika u količini upotrebljenog Fentanila između posmatranih grupa. Postoji statistički značajna razlika u dužini trajanja operacije između posmatranih grupa (p=0,003), u trajanju postavljenog abdominalnog drena između posmatranih grupa (p=0,024), u trajanju hospitalizacije između posmatranih grupa (p=0,027), u broju dana do povratka uobičajenim aktivnostima između posmatranih grupa (p=0,000), u broju uzetih tableta između posmatranih grupa (p=0,000). Prosečna ocena zadovoljstva bolesnika posle operacije u celoj grupi je bila 8,80 (mediana=9; mod=10). Najbolju ocenu zadovoljstva bolesnika posle operacije je imala grupa P+V. Procena bola, mučnine i kretanja. Postoji statistički značajna razlika između posmatranih grupa u proceni jačine bola pre operacije (p=0,003). Postoji statistički značajna razlika između posmatranih grupa u proceni jačine bola 1h posle operacije (najbolju procenu bola je imala grupa P+V); u proceni jačine bola 2h posle operacije (najbolju procenu bola je imala grupa P+V); u proceni jačine bola 4h posle operacije (najbolju procenu bola je imala grupa P); u proceni jačine bola 6h posle operacije (najbolju procenu bola je imala grupa P+V); u proceni jačine bola 12h posle operacije (najbolju procenu bola je imala grupa P+V); u proceni jačine bola 24h posle operacije (najbolju procenu bola je imala grupa P+V); u proceni jačine bola 48h posle operacije (najbolju procenu bola je imala grupa P) i u proceni jačine bola 7 dana posle operacije (najbolju procenu bola je imala grupa P). Procenjena bol se pojačava otprilike 2,5 sata posle operacije sa vrhom 3 sata posle operacije, a smanjuje se na istu vrednost kao 2. sata posle operacije, otprilike 5. sata posle operacije. U vremenskim intervalima 1, 2. i 7. postoperativni dan postoji značajno pobolj&scaron;anje u postoperativnoj mobilnosti bolesnika. U vremenskim intervalima 1, 2, 4, 6 i 12 sati postoji značajno pobolj&scaron;anje u procenjenoj vrednosti mučnine bolesnika. Korelacije. Statistički značajna pozitivna korelacija ocene bola posle 1. sata, posle 2. sata, posle 6. sata, posle 12. sata je utvrđena sa brojem uzetih tableta (p=0,000), kao i procene mučnine (p=0,000). Statistički značajna pozitivna korelacija procene bola posle 4. sata je utvrđena sa brojem uzetih tableta (p=0,006), kao i aktivnosti (p=0,014). Statistički značajna korelacija procene bola posle 24. sata je utvrđena sa brojem uzetih tableta (p=0,000; pozitivna) i trajanjem operacije (p=0,028; negativna). Statistički značajna pozitivna korelacija procene bola posle 48. sata i posle 7 dana je utvrđena sa brojem uzetih tableta (p=0,000). ZAKLJUČCI: Primena lokalnog anestetika datog na bilo koji način značajno smanjuje bol posle laparoskopske holecistektomije. Primena lokalnog anestetika datog i&nbsp; portalno i visceralno (P+V) značajno smanjuje bol u odnosu na samo portalnu (P) ili visceralnu (V) primenu u vremenskim intervalima 2, 6, 12 sat posle laparoskopske holecistektomije. Portalna (P) primena sa ili bez visceralne (V) primene lokalnog anestetika značajno smanjuje bol u vremenskim intervalima 1, 4, 24, 48 sati i 7 dana posle laparoskopske holecistektomije. Najbolje kretanje je bilo u grupi P+V posle laparoskopske holecistektomije. Najbolje smanjenje procenjene mučnine je bilo u grupi P posle laparoskopske holecistektomije. Najraniji povratak uobičajenim aktivnostima zabeležen je u grupi P+V. Najbolja ocena zadovoljstva bolesnika hirur&scaron;kim lečenjem bila je u grupi P+V. Postoperativna bol ima najznačajniju pozitivnu korelaciju sa procenjenom mučninom i brojem tableta uzetih od momenta otpusta do prve kontrole bolesnika.</p> / <p>INTRODUCTION: Biliary calculosis is the most frequent disease of the hepatobiliary system, and cholecystectomy is one of the most frequently performed surgical procedures. Today laparoscopic cholecystectomy represents the golden standard in treating cholelithiasis. Laparoscopic cholecystectomy showed improvement in the clinically significant outcomes, such as: reducing the duration of the surgery, shorter hospital stay, reducing the intensity and duration of postoperative pain and faster return to normal daily and working activities. Postoperative pain and the time of full recovery remain the two major problems after a non-complicated laparoscopic cholecystectomy and they should be improved. The pain related to laparoscopic cholecystectomy is complex and multi-factorial in origin. The pain occurs due to damaged tissues, dissection and removal of gallbladder from its cavity, stimulation of periportal nerves, irritation of the diaphragm, mechanical and chemical interaction of gases and pneumoperitoneum and port incisions. Researches have denoted parietal and visceral pains as two major mechanisms in occurrence of pain in laparoscopic cholecystectomy. Pain cannot be measured, but estimated, as it is a subjective feeling. It was considered necessary to find the answer, based on solid scientific evidence, if it was possible to block parietal and visceral pain after laparoscopic cholecystectomy in its acute phase. OBJECTIVES: The aim of this study is to compare standard, non-opioid, analgesia (group O) with applying parietal blockade (group P), or visceral blockade (group V), or compare with both applied blockades (group P+V). The primary outcomes of the study are the patient&acute;s estimated pain before surgery and 1, 2, 4, 6, 12, 24, 48 hours and 7th day after the surgery. The secondary outcomes of this study are the patient&acute;s estimated nausea level during 1, 2, 4, 6, 12 hours, along with the patient&acute;s estimated mobility 1st, 2nd and 7th day, postoperatively. HYPOTHESIS. Blockade of postoperative visceral pain and blockade of postoperative parietal pain following laparoscopic cholecystectomy, applying intraperitoneal local infiltration with anesthetic and also by local infiltration with anesthetic through accessible laparoscopic ports, can significantly reduce early postoperative pain. MATERIAL AND METHODS: This prospectively randomized single-blinded study started in September 2014 and lasted up to January 2016. The research was carried out at the Clinic for Abdominal, Endocrine and Transplantation Surgery and Emergency Center, Clinical Center of Vojvodina in Novi Sad and it involved patients who underwent laparoscopic cholecystectomy. This study has been divided into several units. 1. Assessment of sample size; 2. Assessment of eligibility for the study; 3. Survey and inclusion in the study; 4. Group formation and operational work; 5. Period of postoperative follow-up; 6. Statistical processing and writing the paper.1. Assessment of sample size. The study was realized by dividing the patients into 4 groups. The number of patients necessary was determined based on the data taken as pilot study from a similar study from 2012. Sample size was calculated for the primary outcome of the study (patient&acute;s estimated pain with NAS) based on the assumption that a pain reduction of 20% should occur during the first postoperative hour, with the probability of Type 1 error &alpha;=0.05 and Type 2 error &beta;=0.10 to reach the adequate statistical power of about 80%, and to reveal 20% difference in the average value of the estimated pain one hour after the laparoscopic cholecystectomy. The assessed number of respondents in groups according to the set criteria was (P+V =65;P =68;V =68; O =65). The study started when the first patient was included and it ended with the complete follow-up period when the last patient handed in the survey about pain, nausea and mobility. 2. Assessment of eligibility for the study. During the study the number of patients undergoing surgery applying the method of cholecystectomy was 1024 (440 classical and 584 laparoscopic). Only the suitable patients were surveyed (584) and given to read the information leaflet about the study. Inclusion and assessment of patients&acute; eligibility was performed on the basis of inclusion and exclusion criteria. A total of 226 patients was not included in the study. Out of that number 82 patients refused to participate in the study and 144 did not fulfill the inclusive criteria set. By signing 358 patients confirmed their participation in the study. 3. Survey and inclusion in the study. After admitting the patients to hospital the surveyors took their anamnesis and the patients were offered an information leaflet and informed consent. Following the reading of the information leaflet, signing the informed consent and satisfying the criteria for inclusion and exclusion, 358 patients were included in the study. Preoperative preparations were performed and the surveyors filled in some of the data on the individual list. 4. Group formation and operational work. Prior to the surgery an independent person not included in the study carried out the randomisation of the patients chosen (n=358) into study groups by random selection tables. The patients did not know which group they belonged to, while it became known to the surgeon and the operation stuff at the beginning of the surgery (singleblinded study). After randomization and surgery the patients belonged to one of the following groups: Control group O=89 of patients with performed laparoscopic cholecystectomy without visceral blockade by anesthetic and without parietal blockade by anesthetic. Experimental group P=88 of patients with performed laparoscopic cholecystectomy without visceral blockade by anesthetic but with parietal blockade by anesthetic. Experimental group V=92 of patients with performed laparoscopic cholecystectomy with visceral blockade by anesthetic but without parietal blockade by anesthetic. Experimental group P+V=89 of patients with performed laparoscopic cholecystectomy with visceral blockade by anesthetic and with parietal blockade by anesthetic. The standard protocol of anesthesia for laparoscopic cholecystectomy was applied to all patients. An orogastric tube used during the surgery, was removed after it. In patients with applied local anesthetic immediately before surgery a solution of local anesthetic was made (Marcaine&reg; 0,25%). The patients were discharged from hospital the first postoperative day, provided that no complications occurred. 5. Postoperative follow-up and completing the questionnaire. When admitted to the ward the patients were given the same kind of analgesia. While completing the informed consent the patients were given a questionnaire for estimating their pain level, nausea and mobility during their stay in hospital and during the 7-day follow-up period at home. The patients were required to come for 7 and 10-day postoperative check-ups by appointment and then they handed in the questionnaires. n=302 patients with performed laparoscopic cholecystectomy were released and designated for follow-up, and n=20 patients were excluded from the study. 6. Statistical processing and writing the paper. In total 274 operated patients&acute; slips were analysed, by groups as follows: in Group P+V =67; in Group P =70; in Group V =70 and in Group O =67. From the basic descriptive statistical parametres for qualitative and quantitative assessment of results obtained, absolute numbers, relative numbers, the median, mode, arithmetic mean and standard deviation (SD) were used. Data processing was carried out using basic and advanced statistical methods and programmes. The results are presented in tabular and graphical manner. RESULTS. Demographic data. In total there were 188 women and 86 men, in proportion 2,2 : 1. The average age of the whole group was 52,1 &plusmn; 15,72 years. In total there were 179 employed and 95 unemployed persons. In total there were 45 surveyed patients with primary education, 153 surveyed patients with secondary education and 76 surveyed patients with higher education. In total there were 186 nonsmokers and 88 smokers. The mean BMI value of the whole group was 27,24 &plusmn; 4,21 kg/m2. The mean value of ASA of the whole group was 2,03 (the median=2, mode=2). There is no significant difference among the groups observed considering the observed parametres. Laboratory data. There is a statistically significant difference in the value of leukocytes among the observed groups (p=0,039), and in the value of urea among the observed groups (p=0,040). There is no statistically significant difference in the value of the erythrocyte, platelets, hemoglobin, blood glucose, creatinine and bilirubin of the&nbsp; observed groups. Operative and postoperative data. There is no statistically significant difference in the amount of Fentanyl&reg; applied among the observed groups. There is statistically significant difference in the length of the surgery among the observed groups (p=0,003), in the duration of the positioning of abdominal drainage among the observed groups (p=0,024), in the duration of hospital stay among the observed groups (p=0,027), in the number of days until getting back to regular activities among the observed groups&nbsp; (p=0,000), in the number of taken pills among the observed groups (p=0,000). The patients&acute; average satisfaction grade after surgery in the whole group was 8,80 (the median=9; mode=10). Group P+V had the best patient&lsquo;s satisfaction grade after the surgery. Assessment of pain, nausea and mobility. There is statistically significant difference in the estimation of pain intensity before surgery among the observed groups (p=0,003). There is statistically significant difference in the estimation of pain intensity 1 hour after surgery among the observed groups (P+V having the best estimated pain); in the estimation of pain intensity 2 hours after&nbsp; surgery (P+V having the best estimated pain); in the estimation of pain intensity 4 hours after surgery (P having the best estimated pain); in the estimation of pain intensity 6 hours after surgery (P+V having the best estimated pain); in the estimation of pain intensity 12 hours after surgery (P+V having the best estimated pain); in the estimation of pain intensity 24 hours after surgery (P+V having the best estimated pain); in the estimation of pain intensity 48 hours after surgery (P having the best estimated pain) also in the estimation of pain intensity 7 days after surgery (P having the best estimated pain). The estimated pain intensifies at about 2,5 hours after surgery and peaks 3 hours after surgery, and decreases to the same level as it was during 2nd hour after surgery approximately during 5th hour after surgery. There is considerable improvement in mobility of patients in the time interval 1st, 2nd and 7th postoperative days. There is considerable improvement in estimated nausea level of patients in the time interval 1, 2, 4, 6 and 12 hours. Correlations. Statistically significant positive correlation in estimated pain after 1st hour, after 2nd hour, after 6th hour and after 12th hour was determined by the number of tablets taken (p=0,000), just like the estimated nausea level (p=0,000). Statistically significant positive correlation in estimated pain after 4th hour was determined by the number of tablets taken (p=0,006), just like the activities (p=0,014). Statistically significant positive correlation in estimated pain after 24th hour was determined by the number of tablets taken (p=0,000; positive), and by the duration of the surgery (p=0,028; negative). Statistically significant positive correlation in estimated pain after 48th hour and after 7 days was determined by the number of tablets taken (p=0,000). CONCLUSIONS: The application of local anesthetic, regardless of how it was applied, considerably reduces pain after laparoscopic cholecystectomy. The application of local anesthetic by port or viscerally (P+V) considerably reduces pain compared to only by port (P) or only visceral (V) application in the time intervals of 2, 6, and 12 hours after laparoscopic cholecystectomy. The application of local anesthetic by port (P), with or without visceral (V), considerably reduces pain in the time intervals of 1, 4, 24, and 48 hours and 7 days after laparoscopic cholecystectomy. The best mobility was shown by group P+V after laparoscopic cholecystectomy. Estimated nausea was most reduced in group P after laparoscopic cholecystectomy. Group P+V presented the earliest return to regular activities. The best patients&acute; satisfaction grade with surgical treatment was shown by group P+V. Postoperative pain is most considerably positively correlated with the estimated nausea and pills taken, from the moment of patient&acute;s release from hospital to the first check-up.<br />&nbsp;</p>

<p>Poslednjih godina je prisutan trend povratka prirodi i upotrebi biljnih lekova, kako u prevenciji tako i u lecenju razlicitih bolesti. Timijan (Thymus vulgaris L.) se u narodnoj medicini koristio u lecenju respiratornih oboljenja kao &scaron;to su ka&scaron;alj, bronhitis i astma. Rezultati novijih istraživanja pokazuju da timijan poseduje i druga potencijalno korisna farmakolo&scaron;ka svojstva (antimikrobna, antiinflamatorna, antioksidativna, spazmoliticka, antidijabetesna i anksioliticka). Ciljevi ovog istraživanja su bili da se ispitaju farmakodinamske osobine preparata timijana, njihove interakcije sa lekovima koji deluju na centralni nervni sistem, uticaj na funkciju jetre i parametrem oksidativnog stresa kod životinja izloženih ugljentetrahloridu, kao sadržaj karvakrola i timola u sirupu timijna, pri razlicitim uslovima cuvanja. U farmakodinamskim ispitivanjima kao eksperimentalne životinje kori&scaron;ceni su mi&scaron;evi soja NMRI, a u svim drugim ispitivanjima pacovi soja Wistar. Tinktura timijana je primenjena u dozi od 0,4mk/kg, a sirup u dozi od 12,08 ml/kg, na mi&scaron;evima. Primenjene doze na pacovima su bile 0,18 ml/kg za tinkturu i 5,6 ml/kg za sirup timijana. Za ispitivanje analgetickog dejstva kori&scaron;ceni su metod vrele ploce i test sircetne kiseline. Za procenu motorne koordinacije kori&scaron;cen je test rotirajuceg &scaron;tapa, a za procenu hipnotickog delovanja mereno je vreme spavanja. Prilikom ispitivanja uticaja preparata timijana na farmakokinetiku paracetamola, odre_ivana je koncentracija ovog leka HPLC metodom, a nakon toga su odreeni farmakokinetski parametri paracetamola. Antioksidantna aktivnost preparata timijana odre_ivana je pomocu in vitro i in vivo testova. Nakon žrtvovanja životinja ra_ena je histopatolo&scaron;ka analiza jetrenog tkiva, a u serumu su odre_ivani biohemijski parametri, kao i pokazatelji bubrežene i jetrene funkcije. Sadržaj timola i karvakrola i sirupu timijana odre_en je GC/MS metodom. Sirup i tinktura timijana su pokazali analgeticki efekat u testu vrele ploce, kao i smanjenje broja grceva izazvano primenom sircetne kiseline. Sedmodnevna primena preparata timijana smanjila je analgeticko dejstvo kodeina, a pojacala analgeticki efekat paracetamola. Sirup timijana je potencirao diazepamom izazvan poremecaj motorne koordinacije. Ispitivanjem uticaja preparata timijana na hipnoticko delovanje pentobarbitala, postignuti su razliciti rezultati u zavisnosti od dužine trajanja pretremana. Sedmodnevna primena timijana je produžila vreme trajanja spavanja, dok je jednokratna primena timijana skratila vreme trajanja spavanja. Nakon i intravenske i peroralne primene paracetamola, grupe životinja koje su bile pretretirane preparatima timijana imale su krace poluvreme eliminacije i vecu konstantu eliminacije. Upotreba samo preparata timijana nije imala uticaj na biohemijske i histolo&scaron;ke promene jetrene funkcije. S druge strane, upotreba tincture timijana u kombinaciji sa ugljen-tetrahloridom dovela je do porasta vrednosti AST i ALT enzima u serumu, dok je sirup timijana u kombinaciji sa ugljentetrahloridom smanjio aktivnost aminotransferaza. Najvece odstupanje u koncentracijama aktivnih komponenti timola i karavkrola, pokazali su sirupi cuvani na sobnoj temperaturi (20&deg;C), u sekundarnoj ambalaži i na svetlom mestu. Rezultati dobijeni u toku ovog istraživanja ukazuju da preparati timijana uticu na farmakodinamske osobine kodeina, paracetamola, diazepama i pentobarbitala, kao i na farmakokinetiku paracetamola. Upotreba preparata timijana ispoljila je analgeticki efekat i umanjila posledice izloženosti oksidativnom stresu. Uslovi cuvanja sirupa timijana uticali su na njegovu stabilnost.</p> / <p>In recent years is present trend of return to nature and the use of herbal medicines in prevention and treatment of different diseases. Thyme (Thymus vulgaris L.) was used in folk medicine in the treatment of respiratory diseases such as cough, bronchitis and asthma. The new research results have demonstrated that thyme has many others potentially useful pharmacological properties (antimicrobial, antiinflammatory, antioxidant, antispasmodic, antidiabetic and anxiolytic). The aims of this research were to determine the pharmacodynamic properties of thyme preparations and their interactions with central nervous system drugs, influence on liver function and oxidative stress parameters of animals exposed to carbon tetrachloride, as well as concentration of thymol and carvacrol in thyme syrup, at different storage conditions. In pharmacodynamics examination as experimental animals were used NMRI mice, while in all other test were used Wistar rats. Applied dose of thyme tincture was 0.4 ml/kg and of syrup 12.08 ml/kg, for mice. For rats, applied doses of tincture and syrup were 0.18 ml/kg and 5.6 ml/kg, respectively. The analgesic activity was examined by the hot plate test and acetic acid test. The Rotarod test was used to evaluate the motor coordination and to evaluate hypnotic activity sleeping time was mesaured. In order to examine the influence of thyme preparations on pharmacokinetics of paracetamol, the concentracion of this drug was measured by HPLC metods, and after that pharmocokinetic parameters of paracetamol were determined.The antioxidant acivity of thyme preparations was determined by using in vitro and in vivo tests. After animals sacrificing, histopathological analysis of liver tissue were peroformed, in serum were determined biochemical parameters and renal and hepatic function parameters. Quantification of thymol and carvacrol in syrup was carried out by GC/MS method. Thyme syrup and thyme tincture exhibited analgesic activity in hot plate test and reduced the number of writhes induced by acetic acid. Seven-day pretreatment with thyme preparations reduced analgesic activity of codeine and increased analgesic effect of paracetamol. Thyme syrup potentiated diazepam induced motor coordination impairment. Examining the impact of thyme preparations on hypnotic effect induced by pentobarbital, different results were achieved depending on the duration of pretreatment. Seven-day pretreatment with thyme had prolonged the sleeping time, while after single dose of thyme the sleeping time was decreased. After intravenous and after oral administration of paracetamol, groups pretreated with thyme preparations had decreased elimination half-life and increased elimination constant rate. Administration of thyme preparations alone did not change biochemical nor histological markers of hepatic function. On the other hand, co-administration of thyme tincture and carbon tetrachloride resulted in exacerbation of AST and ALT values in serum, while thyme syrup in coadministration with carbon tetrachloride managed to reduce activities of aminotransferases. The concentration of major active compounds, thymol and carvacrol, was mostly changed when syrups were stored at room temperature (20&deg;C), in secondary containers and in light place. Results obtained in this study demonstrated that thyme preparations do affect pharmacodynamic properties of codeine, paracetamol, diazepam and pentobarbital and pharmacokinetics of paracetamol. Administration of thyme preparations exhibited analgesic activity and reduced the effects of exposure to oxidative stress. Storage conditions of thyme syrup did affect its stability.</p>

Background Based on the gathered data from the previous pilot study and the results of this study we proceeded to the following study which is being focused on the surveillance of the age group 50 - 64 years in the area of prescribed opioid analgesics. Alongside with this, we explored in what possible combinations the medications can be used by the chronic pain patients in the current moment. Methods The base of the research was the qualitative study which was performed by the half-structured deep interview with the participants from the chronic pain patients. The interviews were carried out during the year 2011. Within the main study were pursued two quantitative substudii during the January and March 2012. The first study was focused on the questionnaire survey about the number of the chronic pain patients in the Czech Republic. The second substudy followed the chronic pain patients and their influence by the environmental conditions with the help of the questionnaire in case of the combinations among the prescribed opioid analgesics with alcohol or non-alcohol addictive drugs. Results Half-structured interviews were carried out with 20 participants and with the help of this tool were gathered data pointing out the increasing trend in non-medical use of opioid analgesics and increasing interest...

Trata-se de um ensaio clínico com três Grupos. Avaliaram-se os efeitos da intervenção \"Treinamento, Avaliação e Registro Sistematizado de Dor\" sobre a intensidade da dor, o consumo suplementar de morfina, o tratamento de efeitos colaterais e a satisfação com a analgesia dos doentes, no pós-operatório de cirurgia cardíaca. Foram estudados 182 doentes, no Grupo I (GI, N=55), Grupo II (GII, N=66) e Grupo III (GIII, N=61). Todos receberam a mesma orientação pré-operatória e submeteram-se ao mesmo protocolo medicamentoso para o controle de dor e dos efeitos colaterais. No GI a equipe de enfermagem não recebeu Treinamento e realizou a avaliação da dor conforme rotina da instituição. Nos GII e GIII toda a equipe de enfermagem participou do Curso de Capacitação Sobre a Dor e Seu Controle (Treinamento). No GII a equipe de enfermagem utilizou a Ficha Sistematizada sobre Dor e seu Controle, a cada duas horas. No GIII a equipe de enfermagem não utilizou esta Ficha. Os doentes dos três Grupos também foram avaliados pela pesquisadora nas primeiras 30 horas, a cada 6 horas (6 Momentos). Os resultados foram analisados pelos testes de Kruskal-Wallis, Dunn, Friedman, Qui-quadrado e Verossimilhança. O nível de significância adotado foi de 5%. Os Grupos foram semelhantes quanto à idade, sexo, escolaridade, tipo de cirurgia, tipo de dreno e estado físico. A dor ao repouso e à tosse foi menos intensa no GII. Ao repouso observou-se diferença no Momento 2 (p=0,012) e à tosse, nos Momentos 2, 3, 4 e 6 (p=0,021, p=0,005, p=0,048 e p=0,001, respectivamente). Na dor à inspiração profunda não houve diferença intergrupos. No GII observou-se maior uso de morfina suplementar (p=0,002), maior número de doentes recebendo morfina (p=0,002) e maior média na relação dose de morfina/doente (p=0,022). O GI foi o que menos recebeu antiemético (p=0,019, Momento 2) mas teve a maior ocorrência de náusea e vômito (p=0,032, Momento 6). Prurido ocorreu somente uma vez e não houve depressão respiratória. A satisfação com a analgesia foi mais elevada no GII nos Momentos 2 e 3 (p=0,001 e p=0,012). O Treinamento associado à Ficha Sistematizada sobre a Dor e seu Controle incitou os enfermeiros a intervirem mais vezes para o ajuste da analgesia, melhorou o controle da dor e a satisfação dos doentes com a analgesia. Mostrou-se a melhor opção para o controle da dor no pós-operatório de cirurgia cardíaca / This paper reports on a clinical trial with three Groups. The effects of the intervention \"Training, Assessment and Registration of Pain\" on pain intensity, supplementary consumption of morphine, treatment of side effects, and satisfaction with analgesia among patients in post-operative cardiac surgery. The sample were studied 182 patients, in Group I (GI, N=55), Group II (GII, N=66) and Group III (GIII, N=61). All received the same pre-operative guidelines and submitted themselves to the same medication protocol for the control of pain and its side effects. In GI, the nursing team did not receive the Training, and carried out the pain assessment according to the routine practice of the institution. In GII and GIII, all the nursing team took part in the Curso de Capacitação Sobre a Dor e Seu Controle (Training Course on Pain and its Control). In GII the nursing team used the Ficha Sistematizada sobre Dor e seu Controle (Systematized Record of Pain and its Control) every two hours. In GIII the nursing team did not use this Record. The patients in the three Groups were assessed by the researcher every 6 hours, for the first 30 hours (6 separate moments). The results were analyzed by the Kruskal-Wallis, Dunn, Friedman, Qui-quadrado and Verossimilhança tests. The level of significance adopted was 5%. The Groups were similar, in terms of age, sex, level of education, type of surgery, type of drainage and physical state. The pain in rest and when coughing were less intense in GII. For pain in rest, a difference was observed in Moment 2 (p=0.012) and when coughing, in Moments 2, 3, 4 and 6 (p=0.021, p=0.005, p=0.048 and p=0.001, respectively). For pain on deep inspiration, there was no difference between the groups. In GII, greater use of supplementary morphine was observed (p=0.002), with a higher number of patients receiving morphine (p=0.002), and a higher average ratio of morphine dose to patient (p=0.022). GI was the group which received the least antiemetic (p=0.019, Moment 2) but had the highest occurrence of nausea and vomiting (p=0,032, Moment 6). Pruritis occurred only once, and there was no respiratory depression. Satisfaction with the analgesia was higher in GII in Moments 2 and 3 (p=0.001 and p=0.012). The Training, together with the Systematized Record of Pain and its Control led the nurses to intervene more often in adjusting the analgesia, which improved the pain control and the satisfaction of the patients with the analgesia. This proved to be the best option for the control of post-operative pain following cardiac surgery

Submitted by Maicon Juliano Schmidt (maicons) on 2015-07-10T18:45:36Z No. of bitstreams: 1 Thiago da Silva.pdf: 1419570 bytes, checksum: 6c6e9d3e986eb659ac40f20394e683f6 (MD5) / Made available in DSpace on 2015-07-10T18:45:36Z (GMT). No. of bitstreams: 1 Thiago da Silva.pdf: 1419570 bytes, checksum: 6c6e9d3e986eb659ac40f20394e683f6 (MD5) Previous issue date: 2014-07-04 / Nenhuma / OBJETIVO: identificar e analisar as melhores evidências cientifica como suporte teórico para a elaboração de um protocolo assistencial para o manejo da dor de pacientes adultos cirúrgicos. METODOLOGIA: trata-se de estudo exploratório, realizado em bases de dados através dos descritores obtidos no MeSH/Decs: Acute pain; chronic pain; General surgery; Analgesics; Clinical protocols; Practice guideline; Pain measurement; Pain; Post-Surgery; Post-Operative. A busca foi realizada nas bases de dados PubMed, LILACS e COCHRANE, utilizando-se o método PICO, compreendendo artigos escritos em inglês ou português, a partir de 2001 e classificados conforme o sistema de classificação de Nível de Evidência do Oxford Center for Evidence Based Medicine e o grau de recomendação e o nível de evidência no enfoque tratamento, prevenção, etiologia e diagnóstico, do Grading of Recommendations Assessment, Development and Evaluation ? GRADE. Todos os direitos autorais foram preservados. RESULTADOS: dos 424 artigos encontrados, 29 foram selecionados. Identificaram-se evidências quanto à classificação da intensidade da dor conforme o tipo de cirurgia, os instrumentos para sua avaliação e os principais agentes farmacológicos para o seu manejo. Os resultados mostraram que a maioria dos artigos são do Brasil e Estados Unidos, sendo a maior produção em 2013 (8 artigos), 2009 (5 artigos) e 2010 (4 artigos). As melhores evidências encontradas foram 16 ensaios clínicos randomizado e seis revisões sistemáticas de ensaios clínicos randomizado. A escala de mensuração da dor mais utilizada é a Escala Visual Analógica. Deve ser classificada conforme sua intensidade e seu manejo deve ser adequado de acordo com a potência do analgésico prescrito. CONCLUSÃO: os estudos identificaram inúmeras fragilidades, não existindo um planejamento farmacológico adequado ao paciente cirúrgico. A criação deste protocolo propiciou um caminho seguro e uma base científica de qualidade para o manejo da dor e vêm ao encontro das diretrizes estabelecidas pela Agência Americana de Pesquisa e Qualidade em Saúde Pública, e a Sociedade Americana da Dor. / OBJECTIVE: to identify and analyze the best scientific evidence and theoretical support for the development of a protocol assistance for pain management of surgical adult patients. METHODOLOGY: this is an exploratory study conducted in databases obtained through the descriptors in MeSH / Decs: Acute pain; chronic pain; General surgery; Analgesics; Clinical protocols; Practice guideline; Pain measurement; Pain; Post-Surgery; Post-Operative. The search was performed in PubMed, LILACS and COCHRANE data, using the PICO method, comprising articles written in English or Portuguese, from 2001 and classified according to the classification system LoE of the Oxford Centre for Evidence Based Medicine and grade of recommendation and level of evidence approach in treatment, prevention, etiology and diagnosis, the Grading of Recommendations Assessment, Development and Evaluation - GRADE. All copyrights are preserved. RESULTS: among the 424 articles found, 29 were selected. We identified evidence for the classification of pain intensity according to the type of surgery, the instruments for their assessment and the main pharmacologic agents for its management. The results showed that most of the articles are from Brazil and the United States, with the largest production in 2013 (8 articles), 2009 (5 items) and 2010 (4 articles). The best evidence found were 16 randomized clinical trials and systematic reviews of six randomized clinical trials. The measurement scale is the most widely used pain Visual Analog Scale. Should be classified according to their intensity and their management should be appropriate according to the prescribed analgesic potency. CONCLUSION: the studies identified numerous weaknesses, with no adequate pharmacological planning to surgical patients. The creation of this protocol provided a safe journey and a scientific basis for quality pain management and come to meet the guidelines established by the American Agency for Research and Quality in Public Health, and the American Pain Society.

Les antalgiques utilisés aujourd’hui sont des produits anciens et plusieurs d’entre eux datent du 19ème siècle. La morphine demeure l’antalgique de référence pour les douleurs dites par excès de nociception, mais elle est à l’origine d’effets indésirables gênants et graves. Il a été démontré que l’effet antalgique de la morphine passait par l’activation des canaux potassiques TREK-1. Les travaux de recherche ont donc comme objectif la recherche d’antalgiques originaux activateurs de TREK-1. Nous avons synthétisé des activateurs de TREK-1 décrits dans la littérature puis nous avons évalué leur activité antalgique in vivo (writhing test) ce qui nous a permis d’identifier le CDC comme molécule « lead ». Nous avons ensuite synthétisé 43 analogues du CDC que nous avons évalué pour leur effet antalgique ainsi que leur capacité à activer les canaux TREK-1 (électrophysiologie). Ces molécules ont été préparées en 3 à 12 étapes avec des rendements de 3 à 72 % en utilisant des réactions telles que : aldolisation, oléfination de Watsworth et Horner, Peterson, estérification …Des résultats très prometteurs ont émergé de cette étude de relation structure-activité avec 8 molécules qui se démarquent avec un très bon effet antalgique (>50% inhibition de la douleur) ainsi qu’une bonne activation des canaux TREK-1 (R>2). Enfin nous avons analysé les résultats de cette étude par modélisation moléculaire (QSAR) ce qui nous a permis d’identifier les caractéristiques structurales essentielles de ces molécules. / Analgesics used today are old products and several of them date from the 19th century. Morphine remains the analgesics of reference for pains called by excess of nociception, but it is at the origin of awkward and serious side effects. It was shown that the analgesic effect of morphine passed by the activation of potassium channels TREK-1. The objective of this work is thus to develop original analgesics, activators of TREK-1. We synthesized activators of TREK-1 described in the literature and we evaluated their analgesic activity in vivo (writhing test) which enabled us to identify CDC as a lead molecule. We then synthesized 43 analogues of CDC which we evaluated for their analgesic effect and their ability to activate TREK-1 channels (electrophysiology). These molecules were prepared in 3 to 12 steps with yields ranging from 3 to 72 % by using reactions such as : aldol reaction, Watsworth and Horner’s olefination, Peterson’s olefination, esterification … Very promising results emerged from this structure-activity relationship study with 8 molecules which display a very good analgesic effect (>50% inhibition of pain) as well as a good activation of TREK-1 channels (R> 2). Finally we analyzed the results of this study by molecular modeling (QSAR) which enabled us to identify the essential structural characteristics of these molecules.

The anti-inflammatory properties of four medicinal plants were investigated. These plant extracts were subjected to screening for their possible effects as antioxidative, analgesic, and anti-inflammatory agents. In the antioxidant activity, the Plantago lancelota extracts resulted in an IC50 value of 0.4 mg/mL compared to the positive control quecertin with IC50 0.04 mg/mL Plantago lanceolata inhibited COX-2 activity with IC50 values of 0.41 mg/mL. However, the COX-1 inhibition indicated an IC50 of 68.99 mg/mL. The lipoxygenase assay indicated that Plantago lanceolata was the most active plant species with an IC50 value of 4.86 mg/mL compared to the positive control (quecertin) with an IC50<2mg/mL. The nitric oxide assay of the plant extracts indicates a dose-dependent activity of our plant extracts. Likewise the cell viability result indicated a good activity at dose 100 mg/mL. / Life and Consumer Sciences / M. Sc. (Life Sciences)

Trata-se de um ensaio clínico com três Grupos. Avaliaram-se os efeitos da intervenção \"Treinamento, Avaliação e Registro Sistematizado de Dor\" sobre a intensidade da dor, o consumo suplementar de morfina, o tratamento de efeitos colaterais e a satisfação com a analgesia dos doentes, no pós-operatório de cirurgia cardíaca. Foram estudados 182 doentes, no Grupo I (GI, N=55), Grupo II (GII, N=66) e Grupo III (GIII, N=61). Todos receberam a mesma orientação pré-operatória e submeteram-se ao mesmo protocolo medicamentoso para o controle de dor e dos efeitos colaterais. No GI a equipe de enfermagem não recebeu Treinamento e realizou a avaliação da dor conforme rotina da instituição. Nos GII e GIII toda a equipe de enfermagem participou do Curso de Capacitação Sobre a Dor e Seu Controle (Treinamento). No GII a equipe de enfermagem utilizou a Ficha Sistematizada sobre Dor e seu Controle, a cada duas horas. No GIII a equipe de enfermagem não utilizou esta Ficha. Os doentes dos três Grupos também foram avaliados pela pesquisadora nas primeiras 30 horas, a cada 6 horas (6 Momentos). Os resultados foram analisados pelos testes de Kruskal-Wallis, Dunn, Friedman, Qui-quadrado e Verossimilhança. O nível de significância adotado foi de 5%. Os Grupos foram semelhantes quanto à idade, sexo, escolaridade, tipo de cirurgia, tipo de dreno e estado físico. A dor ao repouso e à tosse foi menos intensa no GII. Ao repouso observou-se diferença no Momento 2 (p=0,012) e à tosse, nos Momentos 2, 3, 4 e 6 (p=0,021, p=0,005, p=0,048 e p=0,001, respectivamente). Na dor à inspiração profunda não houve diferença intergrupos. No GII observou-se maior uso de morfina suplementar (p=0,002), maior número de doentes recebendo morfina (p=0,002) e maior média na relação dose de morfina/doente (p=0,022). O GI foi o que menos recebeu antiemético (p=0,019, Momento 2) mas teve a maior ocorrência de náusea e vômito (p=0,032, Momento 6). Prurido ocorreu somente uma vez e não houve depressão respiratória. A satisfação com a analgesia foi mais elevada no GII nos Momentos 2 e 3 (p=0,001 e p=0,012). O Treinamento associado à Ficha Sistematizada sobre a Dor e seu Controle incitou os enfermeiros a intervirem mais vezes para o ajuste da analgesia, melhorou o controle da dor e a satisfação dos doentes com a analgesia. Mostrou-se a melhor opção para o controle da dor no pós-operatório de cirurgia cardíaca / This paper reports on a clinical trial with three Groups. The effects of the intervention \"Training, Assessment and Registration of Pain\" on pain intensity, supplementary consumption of morphine, treatment of side effects, and satisfaction with analgesia among patients in post-operative cardiac surgery. The sample were studied 182 patients, in Group I (GI, N=55), Group II (GII, N=66) and Group III (GIII, N=61). All received the same pre-operative guidelines and submitted themselves to the same medication protocol for the control of pain and its side effects. In GI, the nursing team did not receive the Training, and carried out the pain assessment according to the routine practice of the institution. In GII and GIII, all the nursing team took part in the Curso de Capacitação Sobre a Dor e Seu Controle (Training Course on Pain and its Control). In GII the nursing team used the Ficha Sistematizada sobre Dor e seu Controle (Systematized Record of Pain and its Control) every two hours. In GIII the nursing team did not use this Record. The patients in the three Groups were assessed by the researcher every 6 hours, for the first 30 hours (6 separate moments). The results were analyzed by the Kruskal-Wallis, Dunn, Friedman, Qui-quadrado and Verossimilhança tests. The level of significance adopted was 5%. The Groups were similar, in terms of age, sex, level of education, type of surgery, type of drainage and physical state. The pain in rest and when coughing were less intense in GII. For pain in rest, a difference was observed in Moment 2 (p=0.012) and when coughing, in Moments 2, 3, 4 and 6 (p=0.021, p=0.005, p=0.048 and p=0.001, respectively). For pain on deep inspiration, there was no difference between the groups. In GII, greater use of supplementary morphine was observed (p=0.002), with a higher number of patients receiving morphine (p=0.002), and a higher average ratio of morphine dose to patient (p=0.022). GI was the group which received the least antiemetic (p=0.019, Moment 2) but had the highest occurrence of nausea and vomiting (p=0,032, Moment 6). Pruritis occurred only once, and there was no respiratory depression. Satisfaction with the analgesia was higher in GII in Moments 2 and 3 (p=0.001 and p=0.012). The Training, together with the Systematized Record of Pain and its Control led the nurses to intervene more often in adjusting the analgesia, which improved the pain control and the satisfaction of the patients with the analgesia. This proved to be the best option for the control of post-operative pain following cardiac surgery

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A riparina I, alcamida isolada do fruto verde de Aniba riparia, foi avaliada em modelos animais clÃssicos para screening de drogas com atividades antinociceptiva, antiinflamatÃria e antiulcerogÃnica, tais como, contorÃÃes abdominais induzidas por Ãcido acÃtico, teste da formalina, placa quente, edema de pata induzido por carragenina e dextrano, Ãlcera gÃstrica induzida por etanol e indometacina, edema de pata e nocicepÃÃo induzidos por glutamato, como tambÃm em modelos comportamentais que permitam excluir a possibilidade de uma atividade central induzir falsos-positivos nos modelos anteriores, tais como testes do campo aberto, rota rod e tempo de sono induzido por pentobarbital. A riparina I foi administrada de forma aguda em todos os testes, nas doses de 25 e 50 mg/kg, atravÃs das vias oral e intraperitoneal. Os resultados mostraram que esta alcamida nÃo alterou a atividade locomotora no teste do campo aberto, nem diminuiu o nÃmero de quedas no teste do rota rod, descartando a possibilidade de haver sedaÃÃo ou incoordenaÃÃo motora por parte de riparina I, de modo que tais parÃmetros gerassem falsos-positivos nos testes de nocicepÃÃo e inflamaÃÃo. A avaliaÃÃo sedativa/hipnÃtica da riparina I, no teste do tempo de sono induzido por pentobarbital, mostrou uma potencializaÃÃo do sono, que parece estar envolvido com processos farmacocinÃticos ou com mecanismos de regulaÃÃo do sono, jà que o efeito sedativo nÃo foi corroborado no campo aberto. No teste das contorÃÃes induzidas por Ãcido acÃtico, riparina I inibiu significativamente o nÃmero de contorÃÃes, sugerindo uma atividade antinociceptiva. Como este teste à inespecÃfico, jà que vÃrias classes de drogas revertem estas contorÃÃes, foram utilizados modelos mais especÃficos para avaliar a atividade antinociceptiva. No teste da formalina, riparina I inibiu significativamente o tempo de lambedura da pata, tanto na fase nociceptiva do teste, como na fase inflamatÃria. No entanto, o papel antinociceptivo de riparina I parece ser devido sua atividade antiinflamatÃria, jà que a naloxona, um antagonista opiÃide, nÃo foi capaz de reverter o efeito antinociceptivo de riparina I, porÃm, a L-arginina, substrato para o mediador inflamatÃrio Ãxido nÃtrico, foi capaz de reverter este efeito. Para melhor avaliar o papel antiinflamatÃrio de riparina I, utilizaram-se outros modelos mais especÃficos. No edema de pata induzido por carragenina, riparina I foi capaz de reverter significativamente o volume de edema, nos tempos estudados, sugerindo que possa estar inibindo a produÃÃo de histamina, bradicinina, serotonina e prostaglandinas, mediadores inflamatÃrios secretados durante o processo. Como a bradicinina à um mediador nociceptivo comum a primeira fase do teste da formalina e ao edema de carragenina, este resultado sugere uma razÃo para a reversÃo significativa no tempo de lambedura de pata na primeira fase do teste da formalina. Riparina I tambÃm foi capaz de reverter, de maneira significativa, o edema de pata induzido por dextrano, sugerindo que esteja inibindo a produÃÃo de histamina e serotonina, mediadores inflamatÃrios secretados no processo. Riparina I inibiu significativamente o percentual de Ãrea ulcerada tanto em Ãlceras induzidas por indometacina como por etanol, ressaltando sua utilidade como antiinflamatÃrio nÃo ulcerogÃnico. Por fim, riparina I tambÃm foi capaz de diminuir tanto a nocicepÃÃo quanto o volume do edema de pata induzidos por glutamato, sugerindo que possa estar atuando como antagonista dos receptores glutamatÃrgicos envolvidos no processo inflamatÃrio. Concluindo, riparina I parece apresentar propriedades antiinflamatÃrias pela inibiÃÃo de mediadores como histamina, serotonina, bradicinina, prostaglandinas, glutamato e Ãxido nÃtrico, descartando o envolvimento do sistema opiÃide neste processo. / Riparin I, an alkamide isolated from unripe fruit of Aniba riparia, was evaluated in animal classical models for screening of drugs with antinociceptive, antiinflammatory and antiulcerogenic effects. These models are acetic acid-induced writhing test, formalin test, hot plate test, carrageenan-induced paw oedema, dextran-induced paw oedema, glutamate-induced nociception and paw oedema, indomethacin- and ethanol-induced gastric ulcer. Some behavioral models were used to evaluate if a central activity of drug were involved in antiinflammatory and antinociceptive properties of riparin I. These models are open field, rota rod and pentobarbital-induced sleeping time. Riparin I was administered with doses of 25 and 50 mg/kg, orally and intraperitoneally. The results show that this alkamide did not have effects neither on open field test nor on the rota rod test, discarding the possibility of sedation or motor incordination have influence in antiinflammatory/antinociceptive effects of riparin I. The sedative/hypnotic evaluation in pentobarbital-induced sleeping time shows an increase in sleeping time, probably due pharmacokynetics or sleeping regulation mechanisms, because the sedative effect was not corroborated in the open field test. The open field test is considered more specific than pentobarbital-induced sleeping time. In acetic acid-induced writhing test, riparin I decrease the number of writhies, suggesting an antinociceptive effect. This test is a non-specific test, because antiinflammatory, antidepressant and opioid drugs can decrease the number of writhies. In formalin test, riparin I decrease pawÂs licking time in both phases of test, suggesting antinociceptive and antiinflammatory effects. The antinociceptive effect of riparin I seems to be due their antiinflamatory properties, since naloxone could not abolish the antinociceptive effect of riparin I, but, L-arginine could. In the carrageenan-induced paw oedema test, riparin I decrease this parameter, suggesting that riparin I acts inhibiting the syntesis of bradykinin, serotonin, hystamin and prostaglandins, mediators involved in this test. This result probably indicates why riparin I decrease the pawÂs licking time in first phase of formalin test, since bradykinin is a common mediator involved in first phase of formalin test and carrageenan-induced paw oedema test. In the dextran-induced paw oedema test, riparin I decrease this parameter, suggesting that riparin I acts inhibiting the syntesis of serotonin and hystamin, mediators involved in this test. Riparin I decreased the ulcerated area induced by indomethacin and ethanol, outstanding your properties like antiinflammatory drug, but not like an ulcerogenic drug. Riparin I could decrease the nociception and the paw oedema, both induced by glutamate, suggesting that riparin I can inhibit the glutamatergic receptors involved in inflammatory processes. In conclusion, riparin I seems act by inhibition of inflammatory mediators like hystamin, serotonin, bradykinin, prostaglandins, glutamate and nitric oxide and seems do not act by opioid system.

Pharmaceuticals are biological active compounds with different functional groups, physico-chemical and biological properties. These chemical compounds are called as “new contaminants” which cumulate in various environmental components. These contaminants input to environment from industrial processes, hospitals and health care institutions or household sources and these pollutants can to negatively interact with environmental components. Pharmaceuticals are separated according to structure and their effects to live organisms. On the basis of drug consumption in Czech Republic the non-steroidal anti-inflammatory drugs are the most using pharmaceuticals, because these drugs can be obtain without prescriptions. The choosing analgesics for study were monitored in waste water from waste waters treatment plant (WWTP Brno – Modřice) and in surface water from two sampling sites of river Kretinka. Pharmaceuticals were monitored in surface waters in Czech Republic, in Scotland (river Thurso) and in Taiwan (river Erren, Agongdian, Yanshuei and canal of Tainan) Solid phase extraction (SPE) is used for extraction of study pharmaceutical from water system. The high performance liquid chromatography (HPLC) with diode array detection or mass spectrometry was used for determination of drugs in surface waters from Czech Republic. The water samples from Scotland and Taiwan were analysed and the high performance liquid chromatography with mass spectrometry (HPLC/MS) was used for determination of pharmaceuticals. The method of HPLC/MS enables the determination of study compounds in the very low range of concentrations (ng ? l-1). All monitored pharmaceuticals were identified and quantified in water samples from river Kretinka in Czech Republic, river Thurso (Scotland) and rivers Erren, Agongdian, Yanshuei and canal of Tainan in Taiwan and the obtained data were compared.