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Cilj ove disertacije je da se ispita uticaj aplikacije niacina na metabolizam lipida u peripartalnom periodu, da se utvrdi dali aplikacija niacina utiče na insulinsku rezistenciju, vezu između metaboličkih parametara i lipolize i ketogeneze i uticaj aplikacije niacina na koncetracije NAD i NADP. NAD i NADP predstavljaju adekvatne pokazatelje statusa niacina kod krava u ranoj laktaciji, a njihova vrednost je značajno viša kod krava koje su primale ovaj vitamin. NED i NADP pokazuju pozitivnu korelaciju. Pored ovoga izvedene vrednosti kao što je NAD:NADP indeks i površina ispod krive koju prave ovi vitameri posle teljnja zavise od aplikacije niacina. Aplikacija niacina dovodi do smanjenja koncentracije NEFA, BHB i MDA, a do povećanja koncentracije triglicerida i holesterola u krvi krava. Aplikacija niacina dovodi do porasta koncentracije insulina i glukoze kod krava posle teljenja. Uticaj niacina na insulinsku rezistenciju se mora dvojako posmatrati. Krave koje primaju niacin imaju nižu vrednost indeksa glukoza:insulin, što znači da se po jedinici insulina neutrališe manje glukoze. Ovakvo stanje nastaje jer sa porastom koncentracije insulina opada njegova efikasnost i životinje ulaze u insulinsku rezustenciju. Međutim, RQUICKIBHB indeks insulinske rezistencije je pokazao da su krave koje su primale niacin mnogo osetljivije na insulin, što se može pripisati povećanoj insulinskoj senzitivnosti masnog tkiva. Kod krava koje su primale niacin nađena je niža koncentracija bilirubina i aktivnost AST, ALP i GGT. Nađena je viša koncentracija albumina i viša koncentracija uree i niža koncentracija fosfora. Rezultati pokazuju da aplikacija niacina pozitivno utiče na status hepatocita, a može uticati i na metabolizam proteina u organizmu zbog promena u vrednosti uree. Promena metaboličkih parametara posle teljenja išla je u istom pravcu u oglednoj i kontrolnog grupu, samo se menjao intenzitet promena u funkciji aplikacije niacina. Parcijalna korelacija pokazuje da vitameri niacina, AB The aim of this dissertation is to examine the effect of niacin on lipid metabolism in perpaturient period, to determine does application of niacin have effects on insulin resistance, relationship between metabolic parameters and lipolysis and ketogenesis and effects of application of niacin on NAD and NADP concentration in plasma. NAD and NADP present the adequate indicator of the status of niacin in cows in early lactation, and concentration of NAD and NADP is significant increase in cows that were treated with niacin. NAD and NADP demonstrate positive correlation. Despite this, the derived values like NAD:NADP ratio and area under the curve depends of the application of niacin. Application of niacin leads to decreased NEFA, BHB and MDA plasma concentration, and increased triglyceride and cholesterol concentration in plasma in cows. Application of niacin leads to increased concentration of insulin and glucose in plasma after partum. The effect of niacin on insulin resistance may have two sides. Cows that received niacin had lower value of glucose:insulin ratio, that means that one unit of insulin metabolized less glucose. This state became because with increased insulin concentration decreased its efficiency and animals obtained insulin resistance. On the other hand index RQUICKIBHB for insulin resistance showed that cows that received niacin were much more sensitive to insulin, and that may be as a result of increased insulin sensitivity in adipose tissue. Cows that have received niacin bilirubin concentration and activity of AST, ALP and GGT were decrease. Albumin concentration was increased, urea and phosphor concentration was decreased in group that had received niacin. Results indicate that application of niacin have positive impact on status hepatocytes, and may have influence on protein metabolism in organism because of alteration on value in urea. In control and niacin group alteration on metabolic parameters after partum went on the same direction

Tokom perioda rane laktacije brojni unutrašnji i spoljašnji faktori vrše uticaj na produktivnost i zdravlje mlečnih krava. Najznačajniji unutrašnji faktori na početku laktacije su zapaljenski procesi i metabolički stres. S obzirom da su metaboličke i imunološke promene najčešći okidač za nastanak bolesti, neophodno je bilo ispitati da li postoji mogućnost regulisanja ovih promena pomoću nesterodinih antiinflamatornih lekova. Cilj ove doktorske disertacije je bio da se ispita uticaj parenteralne primene ketoprofena na metabolički status, inflamatorne promene, odnos između metaboličkih i inflamatornih promena kod krava posle teljenja, kao i na proizvodnju mleka kod krava u ranoj laktaciji. Za ogled je odabrano 30 krava. Oglednoj grupi od 15 krava je i.m. aplikovan ketoprofen u terapijskoj dozi (3mg/kg telesne mase) tokom tri uzastopna dana nakon teljenja. Kontrolna grupa od 15 krava je predstavljala negativnu kontrolu. Uzorci krvi za analizu su uzimani iz repne vene (vena coccygea) na dan teljenja, u prvoj i drugoj nedelji posle teljenja. Procena inflamacije je vršena na osnovu određivanja koncentracije proteina akutne faze (haptoglobina i fibrinogena) i proinflamatonih citokina (interleukina-1α, faktora nekroze tumora-alfa i interferona gama), dok je procenametaboličkog statusa vršena na osnovu određivanja vrednosti metaboličkih parametarau svim uzorcima krvnog seruma i u svim nedeljama ogleda. Ketoprofen primenjivan parenteralno kod krava posle teljenja je ublažio metabolički stres, uticao na smanjenje inflamatornih procesa i na smanjnje međusobne povezanosti i uticaja između metaboličkih i inflamatornih promena kod krava posle teljenja u poređenju sa netretiranim kravama, a imao je i pozitivan uticaj na proizvodnju mleka u ranoj laktaciji., During the period of early lactation numerous internal and external factors influence the health and productivity of dairy cows. The most important internal factors at the beginning of lactation are inflammatory processes and metabolic stress. Since the metabolic and immunologic changes are the most common trigger for the disease, it was necessary to examine whether there is a possibility of regulating these changes by using non-steroidal anti-inflammatory drugs. The aim of this doctoral thesis was to investigate the effect of parenteral administration of ketoprofen in the metabolic status, inflammatory changes, the relationship between metabolic and inflammatory changes in cows after calving and milk production in cows in early lactation. This study included 30 cows. Experimental group of 15 cows is treated i.m. ketoprofen administered in a therapeutic dose (3 mg / kg body weight) for three consecutive days after calving. A control group of 15 cows accounted for a negative control. Blood samples for analysis were taken from the tail vein (vena coccygea) on the day of calving, in the first and second week after calving. Evaluation of inflammation was based on the determination of the concentration of acute phase proteins (haptoglobin and fibrinogen) and proinflamatonih cytokines (interleukin-1α,tumor necrosis factor-alpha and interferongamma),and the evaluation of the metabolic status performed on the basis of determining the value of metabolic parameters in a blood sample serum and in all the weeks of the experiment. Ketoprofen administered parenterally in cows after calving eased metabolic stress, had impact on reducing inflammatory processes and the decrease of interconnection and influence between metabolic and inflammatory changes in cows after calving compared with untreated cows, and had a positive impact on milk production in the early lactation.

Diazinon (DZN) is an organophosphate insecticide which exerts its effect through the inhibition of acetyl cholinesterase enzyme (AChE). In this work, we studied the development of tolerance to subchronic p.o. administration of DZN in rats, under both in vivo and in vitro conditions. A group of 20 rats (2 groups, n = 10) was administered p.o. the 1/10 of established LD50 DZN (namely 55.87 mg/kg bw) for 28 days. On the 14th and 28th day of study with isolated diaphragm and ileum, we examined the downregulation of nicotinic and muscarinic receptor function through Electrical Field Stimulation (EFS). Maximum contractility of the diaphragm was recorded on the 14th day of the study (25% higher compared to the non-treated rats), while on the 28th day the contractions almost did not differ from the values found in non-treated rats. EFS of isolated ileum on the 14th day of study caused significantly higher contractions compared to the non treated rats, but after 28 days, ileum contractions decreased approximately to the level of contractions in non-treated rats. On the 14th study day, we also recorded increased amplitude of spontaneous ileum contractions, compared to non-treated rats. The application of increasing ACh concentrations caused dose-dependent ileum contractions, without statistically significant differences of median effective concentration (EC50) values in non-treated and treated rats. Tolerance to subchronic DZN administration develops due to various adaptation mechanisms, including the most important one downregulation of nicotinic and muscarinic receptor function.

The discovery and introduction of antimicrobial drugs in clinical practice has been recorded as one of the greatest achievements in the history of medicine. The application of these drugs, made a big, almost revolutionary upheaval in treatment of many infectious diseases. Its significance for the humanity lies in the fact that hundreds of thousands of people, until then condemned to a certain death, has been saved now. However, it was shown that antimicrobial therapy carries some risk of possible occurrence of undesirable and toxic effects, such as direct toxic effects, development of resistance, the impact on the normal microflora or disorder of micropopulation metabolic functions in digestive tract of ruminants, unwanted interactions with other drugs, damage or necrosis of the tissue at the injection site, residues in foodstuff intended for human consumption, suppression of immune system or defense mechanisms of the body, and damage of fetal or neonatal tissue. All mentioned, directly or indirectly, to a greater or lesser degree can reduce the safety of these drugs., Otkriće i uvođenje antimikrobnih lekova u kliničku praksu zabeleženo je kao jedno od najvećih dostignuća u istoriji razvoja medicine. Primenom ovih lekova, napravljen je veliki, gotovo revolucionarni preokret u lečenju brojnih infektivnih bolesti. Kolikije to značaj za čovečanstvo, najbolje govori podatak da je na stotine hiljada ljudi, do tada osuđeno na sigurnu smrt, sada bilo spašeno. Međutim, s vremenom se pokazalo da antimikrobna terapija nosi sa sobom i određeni rizik od moguće pojave neželjenih i toksičnih efekata, kao što su: direktno toksično delovanje, razvoj rezistencije, uticaj na normalnu mikrofloru ili poremećaj metaboličke funkcije mikropopulacije u digestivnom traktu preživara, neželjene interakcije sa drugim lekovima, oštećenje ili nekroza tkiva na injekcionom mestu, rezidue u namirnicama namenjenim za ishranu ljudi, supresija imunog sistema, odnosno odbrambenih mehanizama organizma, te oštećenje fetalnih ili neonatalnih tkiva. Svi oni na direktan ili indirektan način, u manjem ili većem stepenu mogu da umanje bezbednost primene ovih lekova.

According to the Law on medicines and medicinal devices, veterinary drugs must be of high quality, efficacy and safety to be suitable for use on animals. However, there are numerous factors which can alter the intensity of drugs and their established therapeutic efficacy and safety. These factors may depend on the patients themselves i.e. animals (species, age, sex, physiological state, impaired functions of organs involved in the elimination of drugs, diseases of other organ systems, nutrition, genetic disorders, individual varia­tions, tolerance etc.), veterinary surgeons (use of the drug which is not in accordance with the instructions - 'off-label use', improper selection of a drug or drug combination intended for a certain animal species or pathological condition, inadequate drug administration route, inadequate drug dosage and duration of therapy) and the drug itself (inappropriate formulation, bioavailability, instability of formulation, diminishing drug action due to external factors). Not following the instructions on using a drug and incorrect application may affect the rate and extent of the drug absorption. The route of the administration of a pharmaceutical product is defined in clinical trials, and depends on the physical and chemical properties of the active ingredient, characteristics of the pharmaceutical formulation and the anatomical and physiological characteristics of application sites which enable absorption. An adequate drug administration ensures a predictable level and rate of absorption from the application site, drug concentration at the sites of its action and pharmacological response or therapeutic efficacy. Concomitant use of multiple drugs in the same patient should be avoided because of possible interactions (antagonism or sinergism) which may decrease the activity of a drug and its effectiveness or increase them including appearance of drug toxicity. In addition, mixing drugs in an infusion system or a syringe should be avoided becau, Prema Zakonu o lekovima i medicinskim sredstvima veterinarski lekovi moraju da budu kvalitetni, dovoljno efikasni i bezbedni za primenu na životinjama. Međutim, brojni su faktori koji mogu da menjaju jačinu dejstva leka, ustanovljenu terapijsku efikasnost i bezbednost. Ovi faktori mogu da potiču od samog pacijenta - životinje (vrsta, uzrast, pol, fiziološko stanje, poremećena funkcija organa za eliminaciju lekova, oboljenja drugih organskih sistema, ishrana, genetski poremećaji, individualne varijacije, tolerancija itd.), veterinara (upotreba leka koja nije u skladu sa uputstvom - 'off label use', nepravilan izbor leka ili kombinacije lekova za vrstu životinje ili patološko stanje, neadekvatan način aplikacije leka, neodgovarajuća doza leka i dužina primene, inkompatibilnost i interakcija) i samog leka (neodgovarajuća formulacija, niska biološka raspoloživost, nestabilnost formulacija, slabljenje dejstva leka pod uticajem spoljašnjih faktora). Nepridržavanje preporučenog uputstva o načinu aplikacije leka, kao i nepravilna aplikacija može da utiče na brzinu i stepen apsorpcije leka. Sam način aplikacije gotovog leka definisan je tokom njegovog kliničkog ispitivanja, i zavisi od fizičko-hemijskih osobina lekovite supstance, karakteristika farmaceutske formulacije i anatomskih i fizioloških osobina mesta aplikacije koja obezbeđuju apsorpciju. Primena leka na preporučen način omogućava predvidljiv stepen i brzinu apsorpcije sa mesta primene, koncentraciju leka na mestu delovanja i farmakološki odgovor, odnosno terapijsku efikasnost. Treba da se izbegava istovremena primena više lekova kod istog pacijenta zbog moguće interakcije (antagonizam ili sinergizam) koja smanjuje aktivnost leka i njegovu efikasnost ili mu, pak, pojačava efekat uključujući i pojavu toksičnosti. Takođe, treba da se izbegava mešanje lekova u infuzionom sistemu ili brizgalici, jer odsustvo vidljivih reakcija ne znači da je mešavina lekova kompatibilna.

Maintaining bird health, regarding diseases or agents acting on the gastrointestinal tract, is crucial in broiler production, since this is the entry route of nutrients for bird development. Also, it is well known that broiler production is impossible without antibiotics, which are used as growth promoters and in order to suppress overgrowth of pathogenic microflora in the gastrointestinal tract. Taking into account this, we investigated the growth promoting and beneficial effects of three phytoadditives (Ocimum basilicum, Thymus vulgaris and Pimpinella anisum) on growth performances (body weight, total feed intake, feed conversion ratio and carcass yield), concentrations of glucose, total proteins, albumin, total bilirubin, triglycerides and activity of creatine kinase enzyme, in broiler chicks at 56 days of age. On the day of hatching 150 broiler chicks, were divided into five equally groups (n=30). The control group (1st group) of broilers received a basal diet (BD) without any feed additive. The second, third and fourth groups of chicks were fed BD enriched with 1% of Ocimum basilicum pulverised herba, 0.5% of Ocimum basilicum and 0.5% of Thymus vulgaris pulverised herba and 0.5% of Thymus vulgaris herba and 2% of Pimpinella anisum pulverised fructus, respectively. The fifth group was fed with BD mixed with Salinomycin (60 ppm). The results indicated that feeding the diets enriched with selected herbal supplement failed to affect the growth performance of chickens at 56 days of age. In addition, this supplementation had no influence on glucose metabolism, but we observed beneficial effects on some parameters of protein metabolism. The concentration of total proteins was significantly higher in chicks fed with phytoadditives; 41.71±1.08 vs 35.88±1.04 g/L; p<0.01. Albumin concentration was also significantly higher in experimental groups (28.29±1.32 vs 19.73±0.51 g/L; p<0.001). Creatine kinase activity and total bilirubin concentration were significantly reduced i

Prema Zakonu o lekovima i medicinskim sredstvima veterinarski lekovi moraju da budu kvalitetni, dovoljno efikasni i bezbedni za primenu na životinjama. Međutim, brojni su faktori koji mogu da menjaju jačinu dejstva leka, ustanovljenu terapijsku efikasnost i bezbednost. Ovi faktori mogu da potiču od samog pacijenta - životinje (vrsta, uzrast, pol, fiziološko stanje, poremećena funkcija organa za eliminaciju lekova, oboljenja drugih organskih sistema, ishrana, genetski poremećaji, individualne varijacije, tolerancija itd.), veterinara (upotreba leka koja nije u skladu sa uputstvom - 'off label use', nepravilan izbor leka ili kombinacije lekova za vrstu životinje ili patološko stanje, neadekvatan način aplikacije leka, neodgovarajuća doza leka i dužina primene, inkompatibilnost i interakcija) i samog leka (neodgovarajuća formulacija, niska biološka raspoloživost, nestabilnost formulacija, slabljenje dejstva leka pod uticajem spoljašnjih faktora). Nepridržavanje preporučenog uputstva o načinu aplikacije leka, kao i nepravilna aplikacija može da utiče na brzinu i stepen apsorpcije leka. Sam način aplikacije gotovog leka definisan je tokom njegovog kliničkog ispitivanja, i zavisi od fizičko-hemijskih osobina lekovite supstance, karakteristika farmaceutske formulacije i anatomskih i fizioloških osobina mesta aplikacije koja obezbeđuju apsorpciju. Primena leka na preporučen način omogućava predvidljiv stepen i brzinu apsorpcije sa mesta primene, koncentraciju leka na mestu delovanja i farmakološki odgovor, odnosno terapijsku efikasnost. Treba da se izbegava istovremena primena više lekova kod istog pacijenta zbog moguće interakcije (antagonizam ili sinergizam) koja smanjuje aktivnost leka i njegovu efikasnost ili mu, pak, pojačava efekat uključujući i pojavu toksičnosti. Takođe, treba da se izbegava mešanje lekova u infuzionom sistemu ili brizgalici, jer odsustvo vidljivih reakcija ne znači da je mešavina lekova kompatibilna., According to the Law on medicines and medicinal devices, veterinary drugs must be of high quality, efficacy and safety to be suitable for use on animals. However, there are numerous factors which can alter the intensity of drugs and their established therapeutic efficacy and safety. These factors may depend on the patients themselves i.e. animals (species, age, sex, physiological state, impaired functions of organs involved in the elimination of drugs, diseases of other organ systems, nutrition, genetic disorders, individual varia­tions, tolerance etc.), veterinary surgeons (use of the drug which is not in accordance with the instructions - 'off-label use', improper selection of a drug or drug combination intended for a certain animal species or pathological condition, inadequate drug administration route, inadequate drug dosage and duration of therapy) and the drug itself (inappropriate formulation, bioavailability, instability of formulation, diminishing drug action due to external factors). Not following the instructions on using a drug and incorrect application may affect the rate and extent of the drug absorption. The route of the administration of a pharmaceutical product is defined in clinical trials, and depends on the physical and chemical properties of the active ingredient, characteristics of the pharmaceutical formulation and the anatomical and physiological characteristics of application sites which enable absorption. An adequate drug administration ensures a predictable level and rate of absorption from the application site, drug concentration at the sites of its action and pharmacological response or therapeutic efficacy. Concomitant use of multiple drugs in the same patient should be avoided because of possible interactions (antagonism or sinergism) which may decrease the activity of a drug and its effectiveness or increase them including appearance of drug toxicity. In addition, mixing drugs in an infusion system or a syringe should be avoided becau

Cilj ovog rada je da se ispitaju određeni biohemijski parametri u krvi ovaca u uslovima različitog intenziteta parazitske infekcije sa Strongyloides papillosus, kao i nakon terapije albendazolom. Istraživanje je izvedeno na ovcama virtemberg rase (n = 30) kod kojih je utvrđen niski, srednji i visoki intenzitet parazitske infekcije sa S. papillosus. Kontrolnu grupu (n = 10) činile su ovce negativne na prisustvo parazitske infekcije. Stepen i vrsta promene praćeni su određivanjem koncentracije glukoze, ukupnih proteina, albumina, Albumin/Globulin odnosa, AST, uree, ukupnog bilirubina, kalcijuma, fosfora, ukupne aktivnosti laktat dehidrogenaze (LDH) i izoenzimske distribucije LDH1-5. Na osnovu dobijenih rezultata utvrdili smo, preko izoenzimske distribucije laktat dehidrogenaze, da u toku parazitske infekcije sa S. papillosus dolazi do oštećenja ćelija jetre, srčanog mišića i pluća, dok je nakon terapje albendazolom jetra najoštećeniji organ. Koncentracija glukoze, ukupnih proteina i albumina linearno je opadala sa rastom intenziteta parazitske infekcije (p LT 0,05), a nakon terapije albendazolom pad koncentracije ovih parametara bio je na statistički znatno većem nivou (p LT 0,01). Aktivnost AST, koncentracija uree i ukupnog bilirubina takođe su linearno rasle sa intenzitetom parazitske infekcije (p LT 0,05). Nakon terapije sa ABZ aktivnost AST i koncentracija ukupnog bilirubina bile su na statistički značajno većem nivou (p LT 0,001), dok je koncentracija uree zadržala iste nivoe kao u slučaju parazitske infekcije. Vrednosti koncentracija kalcijuma (p > 0,05) i fosfora (p LT 0,05) takođe linearno opadaju sa rastom intenziteta parazitske infekcije. Trend pada koncentracije ovih makroelemenata, nastavlja se i nakon terapije albendazolom (p LT 0,001). Imajući u vidu naša prethodna istraživanja na polju oksidativnog stresa, fenomena koji se nalazi u osnovi promena utvrđenih u ovom radu, strogo preporučujemo da se u antiparazitske protokole, pored antihelmintika koriste i, The objective of this work was to investigate certain biochemical parameters in the blood of sheep in conditions of different intensity of parasitic infection with Strongyloides papillosus, and also after the therapy with albendazole. The research was carried out on the sheep of Wurtemberg breed (n = 30) in which there was determined low, medium and high intensity of parasitic infection with S. papillosus. The control group (n = 10) consisted of the sheep that were negative to the presence of the parasitic infection. The degree and type of changes were monitored by determining the concentration of glucose, total protein, albumin, Albumin/Globulin ratio, AST, urea, total bilirubin, calcium, phosphorus, lactate dehydrogenase (LDH) total activity and isoenzyme distribution LDH1-5. On the basis of the obtained results it was concluded, through isoenzyme distribution of lactate dehydrogenase, that parasitic infection with S. papillosus can cause damage to the liver, heart muscle and lungs, while after the therapy with albendazole, the most affected organ is the liver. The concentration of glucose, total protein and albumin linearly decreased with the increase of intensity of the parasitic infection (p LT 0,05), and after the therapy with albendazole, a drop in concentration of these parameters was at a statistically significantly higher level (p LT 0,01). AST activity as well as the concentration of urea and total bilirubin grew linearly along with the intensity of the parasitic infection (p LT 0,05). After the therapy with ABZ, AST activity and concentration of total bilirubin were at a statistically significantly higher level (p LT 0,001), while urea concentration kept the same level as in the case of the parasitic infection. The values of calcium concentration (p > 0,05) as well as phosphorus (p LT 0,05) linearly decreased with the parasitic infection intensity growth. Trend towards the decline of the concentration of these macroelements continues even after the thera

Ispitivanja su imala za cilj da se utvrdi uticaj Clostridium perfringens tip A na razvoj patomorfološkog supstrata, njegov intenzitet i distribuciju kod teških roditelja uzrasta petnaest nedelja. Ispitivanje je obavljeno na leševima 8 koka i 7 petlova teških roditelja provenijencije COBB 500. Posle izvršene obdukcije, za histopatološko ispitivanje uzeti su uzorci promenjenih delova jejunuma i jetre, a za bakteriološko i molekularno ispitivanje crevni sadržaj jejunuma. Kod svih leševa u otvorenoj pleuroperitonealnoj šupljini, već in situ, uočava se promenjeni deo jejunuma. On je bio izrazito dilatiran celom dužinom, a njegov zid plavičasto-sive boje sa diseminiranim subseroznim punktiformnim krvnim ekstravazatima. Njegovim otvaranjem iz lumena je izlazio polutečni sadržaj u kojem plivaju krvni koagulumi i krpičasti delovi nekrotične mukoze. Mikroskopskim pregledom isečaka tkiva tankih creva bojenih HE metodom zapažena je difuzna nekroza crevnih resica. One su destruisane i zamenjene eozinofilnom bestrukturnom masom. Pored toga, uočava se edem submukoze, kongestija kapilara i krvni ekstravazati u mukozi, kao i infiltracija neutrofilnih granulocita u lamini propriji. Navedene mikroskopske alteracije oslikavaju hemoragično-nekrotični enteritis. Mikroskopskim pregledom isečka tankih creva bojenih Brown & Brenn metodom ustanovljene su kolonije bakterija u distalnim delovima submukoze. Bakteriološkim ispitivanjem u anaerobnim uslovima, izolovana kultura je identifikovana kao Clostridium perfringens. Primenom multiplex PCR dobijeni izolat je genotipiziran kao Clostridium perfringens tip A. Na osnovu patomorfoloških, bakterioloških i molekularnih ispitivanja može da se zaključi da infekcija teških roditelja Clostridium perfringens tipa A protiče sa slikom difuznog hemoragično-nekrotičnog jejunitisa, da uzročnik duboko penetrira u tkivo jejunuma i da su pšenica i pšenične mekinje činili favorizujući faktor za proliferaciju etiološkog agensa., The aim of the investigation was to determine the influence of Clostridium perfringens type A on the development of pathomorphological substrate, its intensity and distribution in fifteen weeks old heavy breeds broilers. The investigation was carried out on corpses of 8 hens and 7 roosters of heavy breeds of provenance COBB 500. After the completion of the autopsy, samples of altered parts of jejunum and liver were taken for histopathological examination, and jejunum intestinal contents for bacteriological examination. In all the corpses, in open pleuroperitoneal cavity, even in situ, an altered part of jejunum can be noticed. It was extremely dilated the entire length, and its wall was bluish-gray with disseminated subserous punctiform blood extravasates. When opened, semi-liquid content with blood coagulums and patches of necrotic mucosa went out of it. By microscopic examination of small intestine tissue cuttings, colored by HE method, there was observed a diffuse necrosis of intestinal villi. They were desroyed and replaced by eosinophilic structureless mass. Furthermore, there could be noticed submucose oedema, capillary congestion and blood extravasates in mucosa, as well as infiltration of neutrophilic granulocytes in lamina propria. These microscopic alterations reflect hemorrhagic necrotic enteritis. By microscopic examining of small intestine cuttings colored according to Brown & Brenn method, colonies of bacteria in distal parts of the submucosa were found out. Using bacteriological tests in anaerobic conditions, there was isolated a culture identified as Clostridium perfringens. After applying of multiplex PCR, the obtained isolate was genotyped as Clostridium perfringens type A. On the basis of pathomorphological, bacteriological and molecular examinations, it can be concluded that the infection of heavy breeds with Clostridium perfringens type A is manifested by appearance of haemorrhagic-necrotic jejunitis, that the causer penetrates deeply into jejun

Ispitivanja su imala za cilj da se utvrdi uticaj Clostridium perfringens tip A na razvoj patomorfološkog supstrata, njegov intenzitet i distribuciju kod teških roditelja uzrasta petnaest nedelja. Ispitivanje je obavljeno na leševima 8 koka i 7 petlova teških roditelja provenijencije COBB 500. Posle izvršene obdukcije, za histopatološko ispitivanje uzeti su uzorci promenjenih delova jejunuma i jetre, a za bakteriološko i molekularno ispitivanje crevni sadržaj jejunuma. Kod svih leševa u otvorenoj pleuroperitonealnoj šupljini, već in situ, uočava se promenjeni deo jejunuma. On je bio izrazito dilatiran celom dužinom, a njegov zid plavičasto-sive boje sa diseminiranim subseroznim punktiformnim krvnim ekstravazatima. Njegovim otvaranjem iz lumena je izlazio polutečni sadržaj u kojem plivaju krvni koagulumi i krpičasti delovi nekrotične mukoze. Mikroskopskim pregledom isečaka tkiva tankih creva bojenih HE metodom zapažena je difuzna nekroza crevnih resica. One su destruisane i zamenjene eozinofilnom bestrukturnom masom. Pored toga, uočava se edem submukoze, kongestija kapilara i krvni ekstravazati u mukozi, kao i infiltracija neutrofilnih granulocita u lamini propriji. Navedene mikroskopske alteracije oslikavaju hemoragično-nekrotični enteritis. Mikroskopskim pregledom isečka tankih creva bojenih Brown & Brenn metodom ustanovljene su kolonije bakterija u distalnim delovima submukoze. Bakteriološkim ispitivanjem u anaerobnim uslovima, izolovana kultura je identifikovana kao Clostridium perfringens. Primenom multiplex PCR dobijeni izolat je genotipiziran kao Clostridium perfringens tip A. Na osnovu patomorfoloških, bakterioloških i molekularnih ispitivanja može da se zaključi da infekcija teških roditelja Clostridium perfringens tipa A protiče sa slikom difuznog hemoragično-nekrotičnog jejunitisa, da uzročnik duboko penetrira u tkivo jejunuma i da su pšenica i pšenične mekinje činili favorizujući faktor za proliferaciju etiološkog agensa., The aim of the investigation was to determine the influence of Clostridium perfringens type A on the development of pathomorphological substrate, its intensity and distribution in fifteen weeks old heavy breeds broilers. The investigation was carried out on corpses of 8 hens and 7 roosters of heavy breeds of provenance COBB 500. After the completion of the autopsy, samples of altered parts of jejunum and liver were taken for histopathological examination, and jejunum intestinal contents for bacteriological examination. In all the corpses, in open pleuroperitoneal cavity, even in situ, an altered part of jejunum can be noticed. It was extremely dilated the entire length, and its wall was bluish-gray with disseminated subserous punctiform blood extravasates. When opened, semi-liquid content with blood coagulums and patches of necrotic mucosa went out of it. By microscopic examination of small intestine tissue cuttings, colored by HE method, there was observed a diffuse necrosis of intestinal villi. They were destroyed and replaced by eosinophilic structureless mass. Furthermore, there could be noticed submucose oedema, capillary congestion and blood extravasates in mucosa, as well as infiltration of neutrophilic granulocytes in lamina propria. These microscopic alterations reflect hemorrhagic necrotic enteritis. By microscopic examining of small intestine cuttings colored according to Brown & Brenn method, colonies of bacteria in distal parts of the submucosa were found out. Using bacteriological tests in anaerobic conditions, there was isolated a culture identified as Clostridium perfringens. After applying of multiplex PCR, the obtained isolate was genotyped as Clostridium perfringens type A. On the basis of pathomorphological, bacteriological and molecular examinations, it can be concluded that the infection of heavy breeds with Clostridium perfringens type A is manifested by appearance of haemorrhagic-necrotic jejunitis, that the causer penetrates deeply into jeju

GABAergic and cholinergic systems in the neuromuscular system of the parasitic nematodes are the main target of action for anthelmintic drugs. In the nematode cholinergic system pharmacological importance has primarily nicotinic-acetylcholine receptor (nAChR). On the other hand, the GABA-receptor was originally identified as the main site of action for the Avermectins and Milbemicins. However, later was shown that these drugs work on a new, previously never described glutamate-gated chloride ion channel, located in the nematode pharynx. The most important problems that are endangering the success of antiparasitic therapy are the development of resistance in the parasites and often occurrences of the toxic effects of antiparasitic drugs in host. In the order to elucidate the mechanisms of action of GABAergičkih and cholinergic anthelmintic, we examined the pharmacological characteristics of the representatives of these two groups of drugs in the isolated nerve-muscle preparation of large pig nematode Ascaris suum. Also, it was important to examine comparatively differences in the effects of cholinergic and GABAergic anthelmintic on the corresponding receptors in mammals (investigations were performed on isolated rat diaphragm and ileum), and thus to analyze the mechanisms of their adverse effects. In presented investigations we measured the effects of contraction or relaxation on isolated nematode or mammalian preparations and analyzed the results by using appropriate statistical methods (non-linear regression, ANOVA, t-test). Based on the results obtained in our investigations the following conclusions may be presented: (1) Agonists of L, N and B type of nematode nicotinic acetylcholine receptor (nAChR) studied on a model of neuromuscular preparations of A. suum, showed variable efficacy. Highest efficiency in the first group of tested agonists has pyrantel (agonist of L-type nAChR, EC50=0.010 μM, Emax=2.5g), then bephenium (agonist of B-type nAChR, EC50=0.37μM, Ema, Gabaergički i holinergički sistem u neuro-mišićnom sistemu parazitskih nematoda su glavna ciljna mesta delovanja antihelmintika. U okviru holinergičkog sistema nematoda, farmakološki značaj ima pre svega nikotinski-acetilholinski receptor (nAChR). S druge strane, GABA-receptor parazitskih nematoda je prvobitno označen kao glavno mesto dejstva avermektina i milbemicina. Međutim, vremenom se pokazalo da ovi lekovi deluju i na jedan potpuno nov, do tada neopisani glutamat-zavisni hloridni jonski kanal u farinksu nematoda. Pored toga, značajno je da neki aktivni principi etarskih ulja imaju dokazana antiparazitska svojstva, i da postoje indicije da deluju upravo preko ova dva receptorska sistema. Osnovni problemi koji danas ugrožavaju antiparazitsku terapiju su razvoj rezistencije i često ispoljavanje toksičnih efekata antiparazitskih lekova. Da bi se bolje razumeli mehanizmi dejstva gabaergičkih i holinergičkih antihelmintika ispitali smo farmakološke karakteristike predstavnika ove dve grupe lekova na neuro-mišićnom preparatu velike nematode svinja Ascaris suum. Takođe, značajno je bilo komparativno ispitati razlike u dejstvu gabaergičkih i holinergičkih antihelmintika na odgovarajuće receptore sisara (ispitivanja su izvršena na izolovanoj dijafragmi i ileumu pacova) i na taj način analizirati mehanizme njihovih neželjenih efekata. U našim istražvanjima mereni su efekti kontrakcije ili relaksacije izolovanih preparata i odgovarajućim statističkim metodama obrađivani dobijeni rezultati (nelinearna regresija, ANOVA, t-tets). Na osnovu rezultata dobijenih u ispitivanjima doneti su sledeći zaključci: (1) Agonisti L, N i B tipa nikotinskog-acetilholinskog receptora (nAChR) nematoda, ispitivani na modelu neuro-mišićnog preparata A. suum, ispoljili su različitu efikasnost. Najvišu efikasnost u prvoj grupi ispitivanih agonista, ispoljio je pirantel (agonista L-tipa nikotinskog receptora EC50=0.010μM, Emax=2.5g), zatim befinijum (agonista B-tipa nikotinskog receptora EC50=0.37

У патогенези инфламације септичког или асептичког порекла бол је један од основних знакова инфламације. Јачина и трајање бола који прати упална стања, зависи од места на коме се развија запаљенски процес и узрока запаљења. Тако, инфламаторни бол може бити слабог до умереног интензитета или јако изражен, какав је код канцерске болести. Постоперативни бол, који настаје као последица циљане озледе ткива (оперативни рез, остеосинтеза, кастрација...), је обично јаког интензитета, али краћег трајања, па и медикаментозна контрола оваквог бола траје краће (до 3 дана). Терапија инфламаторног и постоперативног бола код животиња спроводи се применом неопиоидних и опиоидних аналгетика, гликокортикоида, антихистаминика и флогистика/рубефацијенса који су индиковани за контролу бола код хроничне инфламације (тендинитис, бурзитис, миозитис, артритис, спондилоза...). Код одабира лека за терапију бола од пресудног значаја је клиничка ефикасност лека, изостајање нежељених ефеката и питање каренце, када се лек примењује код животиња чија су ткива и производи намењени за исхрану људи., In the pathogenesis of inflammation septic or aseptic origin, pain is one of the main signs of inflammation. The strength and duration of pain that accompanies inflammatory conditions, depends on the site of a developing inflammation and causes of inflammation. Thus, inflammatory pain can be low to moderate intensity, or very strong as is the cancer diseases. Postoperative pain, which occurs as a result of target tissue injury (surgical incision, ostheo synthesis, castration...) is usually high intensity, but short duration, and even control this pain medication is shorter (up to 3 days). Treatment of inflammatory and chronic pain in animals is carried out by applying non-opioid and opioid analgesics, glucocorticosteroids, antihistamines, and flogistics / rubefacients, which are indicated for the control of pain in chronic inflammation (tendinitis, bursitis, myositis, arthritis, spondylosis). When choosing a drug for the treatment of pain is crucial clinical efficacy, absence of side effects and the question of withdrawal, when the drug is administered to an animal whose tissues and products intended for human consumption.

Gabaergički i holinergički sistem u neuro-mišićnom sistemu parazitskih nematoda su glavna ciljna mesta delovanja antihelmintika. U okviru holinergičkog sistema nematoda, farmakološki značaj ima pre svega nikotinski-acetilholinski receptor (nAChR). S druge strane, GABA-receptor parazitskih nematoda je prvobitno označen kao glavno mesto dejstva avermektina i milbemicina. Međutim, vremenom se pokazalo da ovi lekovi deluju i na jedan potpuno nov, do tada neopisani glutamat-zavisni hloridni jonski kanal u farinksu nematoda. Pored toga, značajno je da neki aktivni principi etarskih ulja imaju dokazana antiparazitska svojstva, i da postoje indicije da deluju upravo preko ova dva receptorska sistema. Osnovni problemi koji danas ugrožavaju antiparazitsku terapiju su razvoj rezistencije i često ispoljavanje toksičnih efekata antiparazitskih lekova. Da bi se bolje razumeli mehanizmi dejstva gabaergičkih i holinergičkih antihelmintika ispitali smo farmakološke karakteristike predstavnika ove dve grupe lekova na neuro-mišićnom preparatu velike nematode svinja Ascaris suum. Takođe, značajno je bilo komparativno ispitati razlike u dejstvu gabaergičkih i holinergičkih antihelmintika na odgovarajuće receptore sisara (ispitivanja su izvršena na izolovanoj dijafragmi i ileumu pacova) i na taj način analizirati mehanizme njihovih neželjenih efekata. U našim istražvanjima mereni su efekti kontrakcije ili relaksacije izolovanih preparata i odgovarajućim statističkim metodama obrađivani dobijeni rezultati (nelinearna regresija, ANOVA, t-tets). Na osnovu rezultata dobijenih u ispitivanjima doneti su sledeći zaključci: (1) Agonisti L, N i B tipa nikotinskog-acetilholinskog receptora (nAChR) nematoda, ispitivani na modelu neuro-mišićnog preparata A. suum, ispoljili su različitu efikasnost. Najvišu efikasnost u prvoj grupi ispitivanih agonista, ispoljio je pirantel (agonista L-tipa nikotinskog receptora EC50=0.010μM, Emax=2.5g), zatim befinijum (agonista B-tipa nikotinskog receptora EC50=0.37, GABAergic and cholinergic systems in the neuromuscular system of the parasitic nematodes are the main target of action for anthelmintic drugs. In the nematode cholinergic system pharmacological importance has primarily nicotinic-acetylcholine receptor (nAChR). On the other hand, the GABA-receptor was originally identified as the main site of action for the Avermectins and Milbemicins. However, later was shown that these drugs work on a new, previously never described glutamate-gated chloride ion channel, located in the nematode pharynx. The most important problems that are endangering the success of antiparasitic therapy are the development of resistance in the parasites and often occurrences of the toxic effects of antiparasitic drugs in host. In the order to elucidate the mechanisms of action of GABAergičkih and cholinergic anthelmintic, we examined the pharmacological characteristics of the representatives of these two groups of drugs in the isolated nerve-muscle preparation of large pig nematode Ascaris suum. Also, it was important to examine comparatively differences in the effects of cholinergic and GABAergic anthelmintic on the corresponding receptors in mammals (investigations were performed on isolated rat diaphragm and ileum), and thus to analyze the mechanisms of their adverse effects. In presented investigations we measured the effects of contraction or relaxation on isolated nematode or mammalian preparations and analyzed the results by using appropriate statistical methods (non-linear regression, ANOVA, t-test). Based on the results obtained in our investigations the following conclusions may be presented: (1) Agonists of L, N and B type of nematode nicotinic acetylcholine receptor (nAChR) studied on a model of neuromuscular preparations of A. suum, showed variable efficacy. Highest efficiency in the first group of tested agonists has pyrantel (agonist of L-type nAChR, EC50=0.010 μM, Emax=2.5g), then bephenium (agonist of B-type nAChR, EC50=0.37μM, Ema

Ispitivano je moguće hematotoksično, hepatotoksično i nefrotoksičano dejstvo eugenola kod pacova posle dvonedeljne i četvoronedeljne kontinuirane p.o. primene. Ogled je izveden na 72 mužjaka pacova soja Wistar podeljenih u šest grupa. Četiri grupe tretirane su različitim dozama eugenola (10 mg/kg tm/dan, 50 mg/kg tm/dan, 200 mg/kg tm/dan i 400 mg/kg tm/dan). Peta, kontrolna grupa dobijala je vehikulum (0,5% metil-celuloza, 20% propilen-glikol i voda), a šesta je bila apsolutna, netretirana kontrola. Eugenol i vehikulum aplikovani su gastričnom sondom, svakodnevno tokom četiri nedelje u količini od 1 ml/100 g telesne mase pacova. Krv je uzorkovana kardijalnom punkcijom anestetisanih pacova 14. i 28. dana ogleda u cilju određivanja hematoloških i biohemijskih parametara krvi: hematokrit, broj eritrocita, leukocita i trombocita, leukocitna formula, koncentracija hemoglobina, MCV, MCH, koncentracija proteina, albumina, uree, kreatinina, kao i aktivnost alanin-aminotransferaze (ALT), alkalne fosfataze (ALP) i kreatin-kinaze (CK). Rezultati su pokazali da eugenol primenjivan tokom dve i četiri nedelje u dozama od 10, 50, 200 i 400 mg/kg tm/dan ne ispoljava hematotoksično, hepatotoksično niti nefrotoksično dejstvo. Eugenol davan tokom četiri nedelje ne utiče značajno na broj eritrocita, koncentraciju hemoglobina, hematokrit, zapreminu eritrocita, broj leukocita i leukocitnu formulu. Primenjivan tokom dve nedelje, prouzrokuje značajno povećanje mase hemoglobina po eritrocitu. Ovaj efekat je nespecifičan i ne zavisi niti doze, niti od dužine tretmana. Doze eugenola od 10 i 200 mg/kg/dan primenjivane tokom četiri nedelje prouzrokuju značajno smanjenje broja trombocita, dok najviša ispitivana doza (400 mg/kg/dan) prouzrokuje značajno povećanje, u poređenju sa brojem trombocita kod pacova tretiranih dozom od 10 i 200 mg/kg/dan. Promene broja trombocita izazvane eugenolom kvalitativno su različite i ne zavise od doze, niti od dužine tretmana. Eugenol primenjivan tokom dve i četi, The possible haematotoxic, hepatotoxic and nephrotoxic effects of eugenol in rats after two-week and the four-week continuous use were tested. The experiment was conducted on 72 male Wistar rats divided into six equal groups. Four were treated with different doses of eugenol (10 mg/kg bw/day, 50 mg/kg/d, 200 mg/kg bw/d and 400 mg/kg bw/d), the control group received the vehikulum (0.5% methyl cellulose, 20% propylene glycol and water), and the sixth group was the absolute, untreated control. Eugenol and the vehikulum were administered with a gastric probe, on a daily basis, for four weeks at a rate of 1 ml/100 g body weight of rats. Blood was collected by cardiac puncture of the anesthetised rats on days 14 and 28 in order to assess the haematological and biochemical blood parameters: haematocrit, red blood cell count, white blood cell and platelet counts, leukocyte formula, hemoglobin, MCV, MCH, total protein concentration, albumin, urea, creatinine, and the activity of the alanine aminotransferase (ALT), alkaline phosphatase (ALP) and creatine kinase (CK). The results showed that, having been applied for two and four weeks at doses of 10, 50, 200 and 400 mg/kg bw/day, eugenol did not show any haematotoxic, hepatotoxic or nephrotoxic effects. Eugenol administered for four weeks does not significantly affect the number of erythrocytes, haemoglobin concentration, haematocrit, red blood cell volume, leukocyte count and leukocyte formula. Applied for two weeks it caused a significant increase in the mass of haemoglobin in erythrocytes. This effect is not specific and does not depend on the dose or the treatment duration. Eugenol in doses of 10 and 200 mg/kg/day applied for four weeks caused a significant reduction in the number of platelets, whilst the highest dose tested (400 mg/kg/day) caused a significant increase in comparison to the number of platelets in rats treated with 10 and 200 mg/kg/day. Changes in the number of platelets induced by eugenol qualitatively di

Investigations covered the possible hematotoxic effect of eugenol in rats following two-week and four-week continuous p.o. application. An experiment was conducted on 72 maleWistar rats divided into six groups. Four groups were treated with different doses of eugenol (10 mg/kg bm/day, 50 mg/kg/day, 200 mg/kg/day and 400 mg/kg bm/day), the control group was administered a vehiculum (0,5 % methylcellulose, 20 % propylene glycol and water), and the sixth group was the absolute untreated control. Eugenol and the vehiculum were administered using a gastric probe in a volume of 1 ml/100 g body mass of rat. Blood was sampled using cardiac puncture on days 14 and 28 of the experiment in order to determine hematological parameters (hematocrit, number of erythrocytes, MCV, haemoglobin concentration, MCH, number of leukocytes, leukocyte formula, and number of thrombocytes). The results have shown that eugenol administered over 14 and 28 days in doses of 10, 50, 200 and 400 mg/kg bm/day has no hemolytic activity. Furthermore, administered over four weeks, it does not significantly affect the number of erythrocytes, haemoglobin concentration, hematocrit, erythrocyte volume, number of leukocytes, and the leukocyte formula. Applied over two weeks, eugenol causes a significant increase in the mass of haemoglobin per erythrocyte, in comparison with controls. This effect is non-specific and does not depend on the dose or on the duration of treatment. The eugenol doses of 10 and 200 mg/kg/day administered over a period of four weeks result in a statistically significant reduction in the number of thrombocytes in comparison with the absolute control, while the highest investigated dose (400 mg/kg) causes a significant increase in comparison with the numbers for rats treated with a dose of 10 and 200 mg/kg/day. The changes in thrombocyte number caused by eugenol are qualitatively different and depend neither on the dose nor on the duration of treatment. Eugenol applied over two or four, Ispitivan je mogući hematotoksični efekat eugenola kod pacova posle dvonedeljne i četvoronedeljne kontinuirane p.o. primene. Ogled je izveden na 72 mužjaka pacova soja vistar podeljenih u šest grupa. Četiri grupe tretirane su različitim dozama eugenola (10 mg/kg tm/dan, 50 mg/kg/dan, 200 mg/kg/dan i 400 mg/kg tm/dan), peta kontrolna grupa dobijala je vehikulum (0,5 % metil-celuloza, 20 % propilen-glikol i voda), a šesta je bila netretirana, apsolutno kontrolna. Eugenol i vehikulum aplikovani su gastričnom sondom u volumenu od 1 ml/100 g telesne mase pacova. Krv je uzorkovana kardijalnom punkcijom 14. i 28. dana ogleda u cilju određivanja hematoloških parametara (hematokrit, broj eritrocita, prosečna vrednost zapremine eritrocita (MCV), koncentracija hemoglobina, prosečna vrednost koncentracije hemoglobina (MCH), broj leukocita, leukocitna formula i broj trombocita). Rezultati su pokazali da eugenol primenjivan 14 i 28 dana u dozama od 10, 50, 200 i 400 mg/kg tm/dan nema hemolitičku aktivnost. Takođe, primenjivan tokom četiri nedelje ne utiče značajno na broj eritrocita, koncentraciju hemoglobina, hematokrit, zapreminu eritrocita, broj leukocita i leukocitnu formulu. Eugenol primenjivan tokom dve nedelje prouzrokuje značajno povećanje mase hemoglobina po eritrocitu u odnosu na kontrolu. Ovaj efekat je nespecifičan i ne zavisi od doze, ni od dužine tretmana. Doze eugenola od 10 i 200 mg/kg/dan primenjivane tokom četiri nedelje prouzrokuju statistički značajno smanjenje broja trombocita u odnosu na apsolutno kontrolnu grupu, dok najviša ispitivana doza (400 mg/kg) izaziva značajno povećanje broja trombocita u poređenju sa dozama od 10 i 200 mg/kg/dan. Promene broja trombocita izazvane eugenolom kvalitativno su različite i ne zavise niti od doze niti od dužine tretmana. Eugenol primenjivan tokom dve i četiri nedelje ne ispoljava značajan uticaj na broj limfocita, monocita i granulocita.

Ispitivan je mogući hematotoksični efekat eugenola kod pacova posle dvonedeljne i četvoronedeljne kontinuirane p.o. primene. Ogled je izveden na 72 mužjaka pacova soja vistar podeljenih u šest grupa. Četiri grupe tretirane su različitim dozama eugenola (10 mg/kg tm/dan, 50 mg/kg/dan, 200 mg/kg/dan i 400 mg/kg tm/dan), peta kontrolna grupa dobijala je vehikulum (0,5 % metil-celuloza, 20 % propilen-glikol i voda), a šesta je bila netretirana, apsolutno kontrolna. Eugenol i vehikulum aplikovani su gastričnom sondom u volumenu od 1 ml/100 g telesne mase pacova. Krv je uzorkovana kardijalnom punkcijom 14. i 28. dana ogleda u cilju određivanja hematoloških parametara (hematokrit, broj eritrocita, prosečna vrednost zapremine eritrocita (MCV), koncentracija hemoglobina, prosečna vrednost koncentracije hemoglobina (MCH), broj leukocita, leukocitna formula i broj trombocita). Rezultati su pokazali da eugenol primenjivan 14 i 28 dana u dozama od 10, 50, 200 i 400 mg/kg tm/dan nema hemolitičku aktivnost. Takođe, primenjivan tokom četiri nedelje ne utiče značajno na broj eritrocita, koncentraciju hemoglobina, hematokrit, zapreminu eritrocita, broj leukocita i leukocitnu formulu. Eugenol primenjivan tokom dve nedelje prouzrokuje značajno povećanje mase hemoglobina po eritrocitu u odnosu na kontrolu. Ovaj efekat je nespecifičan i ne zavisi od doze, ni od dužine tretmana. Doze eugenola od 10 i 200 mg/kg/dan primenjivane tokom četiri nedelje prouzrokuju statistički značajno smanjenje broja trombocita u odnosu na apsolutno kontrolnu grupu, dok najviša ispitivana doza (400 mg/kg) izaziva značajno povećanje broja trombocita u poređenju sa dozama od 10 i 200 mg/kg/dan. Promene broja trombocita izazvane eugenolom kvalitativno su različite i ne zavise niti od doze niti od dužine tretmana. Eugenol primenjivan tokom dve i četiri nedelje ne ispoljava značajan uticaj na broj limfocita, monocita i granulocita., Investigations covered the possible hematotoxic effect of eugenol in rats following two-week and four-week continuous p.o. application. An experiment was conducted on 72 maleWistar rats divided into six groups. Four groups were treated with different doses of eugenol (10 mg/kg bm/day, 50 mg/kg/day, 200 mg/kg/day and 400 mg/kg bm/day), the control group was administered a vehiculum (0,5 % methylcellulose, 20 % propylene glycol and water), and the sixth group was the absolute untreated control. Eugenol and the vehiculum were administered using a gastric probe in a volume of 1 ml/100 g body mass of rat. Blood was sampled using cardiac puncture on days 14 and 28 of the experiment in order to determine hematological parameters (hematocrit, number of erythrocytes, MCV, haemoglobin concentration, MCH, number of leukocytes, leukocyte formula, and number of thrombocytes). The results have shown that eugenol administered over 14 and 28 days in doses of 10, 50, 200 and 400 mg/kg bm/day has no hemolytic activity. Furthermore, administered over four weeks, it does not significantly affect the number of erythrocytes, haemoglobin concentration, hematocrit, erythrocyte volume, number of leukocytes, and the leukocyte formula. Applied over two weeks, eugenol causes a significant increase in the mass of haemoglobin per erythrocyte, in comparison with controls. This effect is non-specific and does not depend on the dose or on the duration of treatment. The eugenol doses of 10 and 200 mg/kg/day administered over a period of four weeks result in a statistically significant reduction in the number of thrombocytes in comparison with the absolute control, while the highest investigated dose (400 mg/kg) causes a significant increase in comparison with the numbers for rats treated with a dose of 10 and 200 mg/kg/day. The changes in thrombocyte number caused by eugenol are qualitatively different and depend neither on the dose nor on the duration of treatment. Eugenol applied over two or four

Aspergiloza je često gljivično oboljenje mladih, ali mogu da obole i odrasle jedinke. Infekcija može da nastane već nakon izleganja, udisanjem spora aspergilusa prisutnih u kontaminiranom inkubatoru, ili kasnije, sporama iz fecesa, prostirke, prašine ili hrane. Inače spore mogu da penetriraju i ljusku jajeta i dođu u njegovu unutrašnjost. Bolest se karakteriše zapaljenjem, pre svega respiratornog sistema, mada ponekad protiče i u generalizovanoj formi. Patološke promene u vidu multipnih žućkastih čvorića lokalizovane su najčešće u plućima, vazdušnim kesama, a mogu biti zahvaćeni slezina, mozak, potkožno tkivo i oči. Aspergiloza se teško leči zbog čega je neophodno da se preduzmu sve preventivne mere kojima se smanjuju ili eliminišu uslovi neophodni za nastanak bolesti. Našim istraživanjem je obuhvaćeno 30 embrioniranih ćurećih jaja, iz kojih se u toku inkubacionog perioda nisu izlegli ćurići, a sa ciljem da se utvrdi uzrok embrionalnog mortaliteta. Jaja su poticala od roditeljskog jata ćuraka inkubiranih u inkubatorskoj stanici iz okoline Beograda. Svih 30 jaja je otvoreno, a kod 16 makroskopskim pregledom je ustanovljeno zadebljanje jajčanih opni u području vazdušne komore koja je sa spoljašnje strane difuzno ili cirkumskriptno prekrivena crno-sivim ili sivo-zelenim kolonijama odnosno rastom plesni. Kod tri slučaja veći deo vazdušne komore ispunjavali su razvojni elementi plesni. Za mikroskopsko ispitivanje uzete su promenjene jajčane opne i obrađene standardnom histološkom tehnikom, a dobijeni tkivni rezovi obojeni su HE, PAS i Grocott metodom. Mikroskopskom slikom dominiralo je zadebljanje jajčanih opni kao posledica infiltracije spletom hifa od kojih mnoge dublje penetriraju prema embrionu. Većina njih na izlazu iz opni zauzima vertikalni položaj. Na spoljašnjoj površini opni jasno su se videli slobodni elementi plesni (konidijalne glave sa fijalidama i sporama na njima). Iz sadržaja vazdušnih komora izolovan je Aspergillus fumigatus. Ovako promenjene opne jajet, Aspergillosis is a frequent fungal disease of young and adult poultry in our commercial flocks. Infection can occur after hatching by inhalation of Aspergillus conidia which can be present in contaminated hatcheries, or later, by spores from moldy litter, dust, faeces or feed. Spores from the surface of egg shell can penetrate inside of an egg. The main characteristic of aspergillosis is granulomatous inflammation of respiratory system, although generalized form is possible as well. Multiple yellow nodules can be seen as major patomorphological changes and they are usually localized in lungs, air sacs, and can also be found in spleen, brain, subcutis and eyes. Egg embryos are quite susceptible to infection by Aspergillus fumigatus during incubation. In this study, the history of a case on one local farm with mortality rate of 7.2% in the turkey flock is presented. At the same time, 28 day old 30 incubated hatching turkey eggs were sampled, that were unable to hatch. The aim of the present work was to determine the cause and to identify the agent of embryonic mortality. Total of the 30 eggs were opened, and 16 of them had thickened egg membranes in the area of air sac. Membrane thickening was visible and circumscript or diffuse presence of black-grey or grey-green fungal growth was observed. Only 3 samples air sacs were filled with developed stages of fungi. To evaluate histopathological lesions, changed egg membranes were processed by standard histological technique. Dominant microscopic finding was thickening of egg membranes as a consequence of fungal growth and many of them penetrated deep towards embryo. Most of the hyphae were growing vertically through membranes. On the outside surface of the membranes, the elements of fungi (conidial heads with phialids and spores on them), could be clearly observed. These changes were responsible for embryonic death, which on the basis of the size of dead embryos occurred between 7th and 10th day of incubation. Aspergillus f

The potential toxicity and general tolerability of eugenol following two-week or four-week continuous p.o. administration to rats has been investigated. An experiment was performed on 72 male rats of the Wistar strain. Four groups of rats were treated with different doses of eugenol (10 mg/kg bm/day, 50 mg/kg, 200 mg/kg and 400 mg/kg bm/day), the fifth group was administered vehicle (0.5 % methylcellulose, propylene glycol and water), and the sixth group comprised absolutely untreated controls. The corresponding doses of eugenol and vehicle were applied using a gastric probe in a volume of 1 ml/100 g body mass. The general tolerability of eugenol was evaluated on the basis of the daily intake of water and food, body mass, general health condition, behaviour, and lethality in the course of the experiment. In the investigated doses, eugenol applied p.o. in the course of two or four weeks does not influence significantly the intake of food, water, or body mass of rats. The dose of 400 mg/kg/day produced undesired reactions (agitation and hyperesthesia) that were first observed on day 21 and lasted until the end of the experiment. Low subacute toxicity of eugenol was established following p.o. administration to rats. Eugenol in doses of 200 and 400 mg/kg tm/day has a low toxic potential and is safe for administration to this animal species., Ispitivana je potencijalna toksičnost, odnosno opšta podnošljivost eugenola posle dvonedeljne i četvoronedeljne kontinuirane p.o. primene. Ogled je izveden na 72 mužjaka pacova soja vistar. Četiri grupe pacova tretirane su različitim dozama eugenola (10 mg/kg tm/dan, 50 mg/kg, 200 mg/kg i 400 mg/kg tm/dan), peta grupa dobijala je vehikulum (0,5 % metil-celuloza, propilen-glikol i voda), a šesta je bila kontrolna grupa. Odgovarajuće doze eugenola i vehikuluma aplikovane su gastričnom sondom u volumenu od 1 ml/100 g telesne mase. Opšta podnošljivost eugenola procenjivana je na osnovu dnevnog unosa vode i hrane, telesne mase, opšteg zdravstvenog stanja, ponaš anja i letaliteta tokom ogleda. U ispitivanim dozama eugenol primenjivan p.o. tokom dve ili četiri nedelje ne utiče značajno na unos hrane, vode i telesnu masu pacova. Doza od 400 mg/kg/dan dovela je do neželjenih reakcija (uznemirenost i hiperestezija) koje su prvi put zapažene 21. dana i trajale su do kraja ogleda. Ustanovljena je niska subakutna toksičnost eugenola posle p.o. primene kod pacova. Doze eugenola od 200 i 400 mg/kg tm/dan imaju nizak toksični potencijal i bezbedne su za primenu kod ove vrste životinja.

Ispitivana je potencijalna toksičnost, odnosno opšta podnošljivost eugenola posle dvonedeljne i četvoronedeljne kontinuirane p.o. primene. Ogled je izveden na 72 mužjaka pacova soja vistar. Četiri grupe pacova tretirane su različitim dozama eugenola (10 mg/kg tm/dan, 50 mg/kg, 200 mg/kg i 400 mg/kg tm/dan), peta grupa dobijala je vehikulum (0,5 % metil-celuloza, propilen-glikol i voda), a šesta je bila kontrolna grupa. Odgovarajuće doze eugenola i vehikuluma aplikovane su gastričnom sondom u volumenu od 1 ml/100 g telesne mase. Opšta podnošljivost eugenola procenjivana je na osnovu dnevnog unosa vode i hrane, telesne mase, opšteg zdravstvenog stanja, ponaš anja i letaliteta tokom ogleda. U ispitivanim dozama eugenol primenjivan p.o. tokom dve ili četiri nedelje ne utiče značajno na unos hrane, vode i telesnu masu pacova. Doza od 400 mg/kg/dan dovela je do neželjenih reakcija (uznemirenost i hiperestezija) koje su prvi put zapažene 21. dana i trajale su do kraja ogleda. Ustanovljena je niska subakutna toksičnost eugenola posle p.o. primene kod pacova. Doze eugenola od 200 i 400 mg/kg tm/dan imaju nizak toksični potencijal i bezbedne su za primenu kod ove vrste životinja., The potential toxicity and general tolerability of eugenol following two-week or four-week continuous p.o. administration to rats has been investigated. An experiment was performed on 72 male rats of the Wistar strain. Four groups of rats were treated with different doses of eugenol (10 mg/kg bm/day, 50 mg/kg, 200 mg/kg and 400 mg/kg bm/day), the fifth group was administered vehicle (0.5 % methylcellulose, propylene glycol and water), and the sixth group comprised absolutely untreated controls. The corresponding doses of eugenol and vehicle were applied using a gastric probe in a volume of 1 ml/100 g body mass. The general tolerability of eugenol was evaluated on the basis of the daily intake of water and food, body mass, general health condition, behaviour, and lethality in the course of the experiment. In the investigated doses, eugenol applied p.o. in the course of two or four weeks does not influence significantly the intake of food, water, or body mass of rats. The dose of 400 mg/kg/day produced undesired reactions (agitation and hyperesthesia) that were first observed on day 21 and lasted until the end of the experiment. Low subacute toxicity of eugenol was established following p.o. administration to rats. Eugenol in doses of 200 and 400 mg/kg tm/day has a low toxic potential and is safe for administration to this animal species.

The clinical efficacy of tulathromycin (TU) and florfenicol (FL) in the treatment of bronchopneumonia (BP) caused by Pasteurella multocida which was isolated from nose swabs of diseased calves has been examined. The symptoms of bronchopneumonia (BP) were quantified by means of the clinical score (CS) with a maximum of 47 points. In the current investigation the average CS in diseased calves was 23.5± 0.15. The clinical efficacy of TU and FL was assessed every day in the first week after the administration of the drugs and was based on the decrease in CS and on microbiological findings on days 7, 28 and 35 after the completion of therapy. Tulathromycin was administered s.c., in the prescribed therapeutic dose (2.5 mg/kg BW), and florfenicol s.c., twice at a 48 h interval, in its respective therapeutic dose (40 mg/kg BW). In spite of the repeated administration of FL, TU was significantly more rapid to decrease the major clinical symptoms in the first four days following the application, in comparison with FL (P lt 0.05). On the fourth day after the administration, the clinical efficacy of TU in the therapy of BP in calves was 43.4±1.5 %, and of florfenicol 27.2±1.6 %. However, five days after the application of TU and two days after the repeated application of FL the assessed clinical efficacy of the two antibiotics was roughly the same. The average efficacy of TU was 57.1±0.0%, and of florfenicol 58.5±0.0%, both the individual and mean CS in the treated calves was 10 points, due to hyperthermia, which remained the only symptom. Six days after the administration of TU and three days after the repeated application of FL both antibiotics had equal maximum efficacy (100%) in the treatment of BP. The clinical efficacy remained unchanged on day seven. The recovery was confirmed by the absence of P. multocida in nose swabs sampled on the seventh day after the initial treatment. However, in 4 calves (21.05 %) of the 19 treated Streptococcus alpha haemolyticus was isolated., Ispitivana je klinička efikasnost tulatromicina (TU) i florfenikola (FL) u lečenju bronhopneumonije (BP) prouzrokovane vrstom Pasteurella multocida, izolovanom iz briseva nosa junadi. Simptomi BP su kvantifikovani da bi se dobio klinički skor (KS) koji definiše težinu kliničke slike kod životinja. Prema korišćenoj skali maksimalna vrednost KS parametara BP iznosi 47 bodova. U našem ogledu, vrednost prosečnog KS kod obolele junadi iznosila je 23,5±0,15. Klinička efikasnost TU i FL procenjivana je svakodnevno, tokom sedam dana, na osnovu povlačenja kliničkih simptoma (smanjivanje vrednosti KS) i prisustva prouzrokovača BP u brisevima nosa 7, 28. i 35. dana od ukidanja terapije. Tulatromicin je aplikovan s.c., jednokratno u terapijskoj dozi od 2,5 mg/kg, a florfenikol s.c., dvokratno u razmaku od 48 h u terapijskoj dozi od 40 mg/kg tm. U ovom ispitivanju TU je u prva četri dana od aplikacije značajno brže od FL (P lt 0,05) dovodio do povlačenja bitnih kliničkih simptoma, iako je aplikacija FL u tom periodu ponovljena. Klinička efikasnost TU u lečenju BP junadi četvrtog dana od primene iznosila je 43,4±1,5 %, a florfenikola 27,2±1,6 %. Međutim, petog dana od aplikacije TU i FL i drugog dana od druge aplikacije FL ustanovljena je približno ista klinička efikasnost ovih antimikrobnih lekova u lečenju BP. Prosečna efikasnost TU bila je 57,1±0,0%, a FL 58,5± 0,0%. Vrednost individualnog i prosečnog KS kod junadi lečene TU i FL iznosila je 10 bodova. Od kliničkih simptoma jedino se hipertermija nije povukla. Šestog dana od aplikacije TU i FL i trećeg dana od druge aplikacije FL oba antibiotika imala su podjednaku, maksimalnu (100%) kliničku efikasnost u lečenju BP. Ista klinička efikasnost zabeležena je i sedmog dana ogleda. Izlečenje je potvrđeno odsustvom P. multocida u brisevima uzetim sedmog dana od početka lečenja. Međutim, kod 4 juneta (21,05 %) od ukupno 19 izolovan je Streptococcus alpha haemolyticus. Četiri nedelje od obustavljanja primene TU i FL uočen je recidiv B

Resistance to antibiotics is not a modern phenomenon. On the contrary, penicillin resistance in some bacterial strains developed quickly after its introduction into daily practice. At the same time some bacterial strains developed resistance to almost all known antibiotics, vancomycin included. Vancomycin was for a long time the only efficient antibiotic against staphylococcal infections. It is of special concern the fact that antibiotics are in everyday exploitation in agriculture and veterinary clinical practice which use them not only as a mean of therapeutic treatment, but as an additive in animal feedstuffs in order to promote growth and prevent bacterial infections. The same antibiotics are used in human medicine, which is a persistent problem. In such a way it is possible to develop resistance which can be transferred to human pathogenic bacteria via mobile genetic elements. The incidence of resistant bacterial strains increases year after year not only on a local level, but on a global scale, as well. Monitoring of the use of antibiotics and chemotherapeutics in the Republic of Serbia is not established as such, our intention was to study a number of bacteria isolated from cattle, pigs, poultry, dogs and cats. At this time we are presenting the results for pathogenic strains of E. coli in order to determine the use of antibiotics and chemotherapeutics of the old and new generations in domestic animals. E. coli sensitivity was investigated with the disc diffusion test for: ampicillin, amoxicillin with clavulanic acid, tetracycline, chloramphenicol, gentamicin, and ceftriaxon, sulphamethoxasole with trimethoprim, ciprofloxacin and florfenicol. E. coli strains resistant to three or more antibiotics were tested by means of agar dilution method for ciprofloxacin, tetracycline, chloramphenicol, gentamicin and amoxicillin with clavulanic acid by determination of the minimal inhibitory concentration (MIC). The tested E. coli strains resulted resistant to all antibio, Rezistencija na antibiotike nije skorašnji fenomen, naprotiv, rezistencija na penicilin kod nekih sojeva bakterija javila se vrlo brzo posle njegove primene u praksi. Takođe, neki sojevi bakterija postali su rezistentni na praktično sve antibiotike u kliničkoj upotrebi, pa čak i na vankomicin koji je duže vreme bio jedini efikasan antibiotik u lečenju stafilokoknih infekcija. Poseban razlog za zabrinutost predstavlja upotreba antibiotika u poljoprivredi i veterinarskoj kliničkoj praksi jer se osim primene u lečenju životinja, iako su zabranjeni, koriste kao promoteri rasta i u prevenciji bakterijskih infekcija, a isti antibiotici (ili sa istim načinom delovanja na bakterije) primenjuju se i u humanoj medicini. Na taj način je moguće da se neodgovornom upotrebom antibiotika razvije rezistencija koja može znatno brže da se prenese na patogene bakterije ljudi preko mobilnih genetičkih elemenata. Pojava rezistentnih sojeva bakterija se povećava iz godine u godinu, kako na lokalnom, tako i na globalnom nivou. Kako monitoring korišćenja antibiotika i hemioterapeutika u veterinarskoj medicini u Republici Srbiji nije uspostavljen, a problem rezistencije bakterija na antibakterijske lekove je prisutan, ovim ispitivanjem želeli smo da obuhvatimo više vrsta bakterija izolovanih od goveda, svinja, živine, pasa i mačaka. Rezultate dobijene u ovom ispitivanju iznosimo samo za patogene sojeve E. coli, kako bi na indirektan način ustanovili primenu antibiotika i hemioterapeutika starije i novije generacije kod pomenutih životinja. Osetljivost navedenih sojeva E. coli ispitivana je na: ampicilin, amoksicilin sa klavulanskom kiselinom, tetraciklin, hloramfenikol, gentamicin, ceftriakson, sulfometoksazol sa trimetoprimom, ciprofloksacin i florfenikol, primenom disk difuzione metode. Kod sojeva E. coli kod kojih je primenom disk-difuzione metode ustanovljena rezistencija na tri i više antibiotika, odnosno multi rezistencija dalje ispitivanje je vršeno i dilucionom metodom u agaru na: c

Ispitivana je klinička efikasnost tulatromicina (TU) i florfenikola (FL) u lečenju bronhopneumonije (BP) prouzrokovane vrstom Pasteurella multocida, izolovanom iz briseva nosa junadi. Simptomi BP su kvantifikovani da bi se dobio klinički skor (KS) koji definiše težinu kliničke slike kod životinja. Prema korišćenoj skali maksimalna vrednost KS parametara BP iznosi 47 bodova. U našem ogledu, vrednost prosečnog KS kod obolele junadi iznosila je 23,5±0,15. Klinička efikasnost TU i FL procenjivana je svakodnevno, tokom sedam dana, na osnovu povlačenja kliničkih simptoma (smanjivanje vrednosti KS) i prisustva prouzrokovača BP u brisevima nosa 7, 28. i 35. dana od ukidanja terapije. Tulatromicin je aplikovan s.c., jednokratno u terapijskoj dozi od 2,5 mg/kg, a florfenikol s.c., dvokratno u razmaku od 48 h u terapijskoj dozi od 40 mg/kg tm. U ovom ispitivanju TU je u prva četri dana od aplikacije značajno brže od FL (P LT 0,05) dovodio do povlačenja bitnih kliničkih simptoma, iako je aplikacija FL u tom periodu ponovljena. Klinička efikasnost TU u lečenju BP junadi četvrtog dana od primene iznosila je 43,4±1,5 %, a florfenikola 27,2±1,6 %. Međutim, petog dana od aplikacije TU i FL i drugog dana od druge aplikacije FL ustanovljena je približno ista klinička efikasnost ovih antimikrobnih lekova u lečenju BP. Prosečna efikasnost TU bila je 57,1±0,0%, a FL 58,5± 0,0%. Vrednost individualnog i prosečnog KS kod junadi lečene TU i FL iznosila je 10 bodova. Od kliničkih simptoma jedino se hipertermija nije povukla. Šestog dana od aplikacije TU i FL i trećeg dana od druge aplikacije FL oba antibiotika imala su podjednaku, maksimalnu (100%) kliničku efikasnost u lečenju BP. Ista klinička efikasnost zabeležena je i sedmog dana ogleda. Izlečenje je potvrđeno odsustvom P. multocida u brisevima uzetim sedmog dana od početka lečenja. Međutim, kod 4 juneta (21,05 %) od ukupno 19 izolovan je Streptococcus alpha haemolyticus. Četiri nedelje od obustavljanja primene TU i FL uočen je recidiv B, The clinical efficacy of tulathromycin (TU) and florfenicol (FL) in the treatment of bronchopneumonia (BP) caused by Pasteurella multocida which was isolated from nose swabs of diseased calves has been examined. The symptoms of bronchopneumonia (BP) were quantified by means of the clinical score (CS) with a maximum of 47 points. In the current investigation the average CS in diseased calves was 23.5± 0.15. The clinical efficacy of TU and FL was assessed every day in the first week after the administration of the drugs and was based on the decrease in CS and on microbiological findings on days 7, 28 and 35 after the completion of therapy. Tulathromycin was administered s.c., in the prescribed therapeutic dose (2.5 mg/kg BW), and florfenicol s.c., twice at a 48 h interval, in its respective therapeutic dose (40 mg/kg BW). In spite of the repeated administration of FL, TU was significantly more rapid to decrease the major clinical symptoms in the first four days following the application, in comparison with FL (P LT 0.05). On the fourth day after the administration, the clinical efficacy of TU in the therapy of BP in calves was 43.4±1.5 %, and of florfenicol 27.2±1.6 %. However, five days after the application of TU and two days after the repeated application of FL the assessed clinical efficacy of the two antibiotics was roughly the same. The average efficacy of TU was 57.1±0.0%, and of florfenicol 58.5±0.0%, both the individual and mean CS in the treated calves was 10 points, due to hyperthermia, which remained the only symptom. Six days after the administration of TU and three days after the repeated application of FL both antibiotics had equal maximum efficacy (100%) in the treatment of BP. The clinical efficacy remained unchanged on day seven. The recovery was confirmed by the absence of P. multocida in nose swabs sampled on the seventh day after the initial treatment. However, in 4 calves (21.05 %) of the 19 treated Streptococcus alpha haemolyticus was isolated.

Concentrations of the NSAID metamizol sodium (MmNa) in the synovial fluid and hyaline cartilage of inflamed knee and elbow joints of pigs after i.v. application and iontophoresis (IPh) were investigated. The research was conducted on 14 male pigs divided equally into two experimental groups and exposed to artificial inflammation of knees and elbows prior to the application of MmNa. The first group (A) was administered 2.5 g (twice the maximum therapeutic dose) MmNa intravenously, whilst the second group (B) was exposed to the same dose, but applied by IPh into contralateral knee and elbow joints. Four hours after the application of MmNa biopsies of the affected knee and elbow joints were performed. The average concentration of MmNa in the synovial fluid of inflamed joints in group A was 9.81±1.96μg/g, while in group B was 170.66±2.07 μg/g, being 17 times higher. The average concentration of MmNa in the hyaline cartilage was 2.29±1.16μg/g following i.v. administration and 98.36±21.58μg/g after IPh, i.e. approximatelly 43 times higher. This led to the conclusion that IPh of MmNa, resulting in incomparably higher concentrations in inflamed joints without any adverse systemic effects, has an advantage over i.v. application., U sinovijalnoj tečnosti i hijalinoj hrskavici inflamiranog kolenog i lakatnog zgloba svinja određivane su koncentracije metamizol-natrijuma (MmNa) aplikovanog i.v. i putem elektroforeze. Arteficijelno zapaljenje kolena i lakta prasadi izazvano je terpentinskim uljem. Metamizol-natrijum je primenjen u dozi od 2.5 g u prvoj grupi prasadi intravenski, a u drugoj putem elektroforeze u kontalateralni koleni i lakatni zglob. Četiri sata posle aplikacije MmNa urađena je biopsija tretiranih zglobova. Prosečna koncentracija MmNa u sinovijalnoj tečnosti inflamiranih zglobova prasadi posle i.v. aplikacije iznosila je 9,81±1,96μg/g, a posle elektroforeze bila je 170,66±2,07μg/g tkiva, odnosno oko 17 puta viša. Izmerena prosečna koncentracija MmNa u hijalinoj hrskavici iznosila je 2,29±1,16μg/g posle i.v. aplikacije i 98,36±21,58μg/g posle aplikacije elektroforezom, odnosno oko 43 puta više. Zaključujeno je da MmNa primenjen elektroforezom postiže statistički veoma značajno više prosečne koncentracije u inflamiranim zglobovima u odnosu na i.v. aplikaciju. Primena MmNa elektroforezom ima značajnu prednost nad i.v. aplikacijom ovog leka ne samo zbog postizanja značajno viših koncentracija u inflamiranim zglobovima, već i zbog izostajanja sistemskih neželjenih reakcija.

The acaricide efficacy, tolerance and safety of eugenol (10 and 20 %) in the treatment of sarcoptic mange in sheep have been investigated. The results were compared with those corresponding for benzyl benzoate (25 %), which was applied to sheep in the same way. The treatment was applied on sheep three times in one-week intervals. Skin scrapings were sampled seven days after each treatment, as well as twenty-eight days following the third one. The changes on the skin were quantified and the mean recovery response (MRR) was calculated. The clinical efficacy was assessed according to the MRR and the number of mites in the samples. Following the first treatment 10%eugenol was not significantly less efficacious in comparison with the higher concentration. Having been applied twice 20% eugenol was significantly more efficacious when compared to the lower concentration, which remained the same seven and twenty-eight days after the third application. The efficacy of 10% eugenol in the therapy of mange was significantly higher in comparison with benzyl benzoate following one, two or three administrations. The efficacy of benzyl benzoate four weeks after the third treatment was still significantly lower in comparison with 10% eugenol. The efficacy of 20% eugenol was significantly higher in comparison with its lower concentration as well as that of benzyl benzoate, following the second, and seven and twenty-eight days after the third one. No signs of local or systemic intolerance were observed in sheep treated with either 10 or 20% eugenol, or 25 % benzyl benzoate. ., Ispitivana je akaricidna efikasnost, podnošljivost i bezbednost eugenola (10 i 20%) u lečenju sarkoptes-šuge ovaca. Rezultati ispitivanja upoređivani su sa odgovarajućim podacima dobijenim posle primene benzil-benzoata (25 %) primenjivanog na isti način u lečenju šuge ovaca. Tretiranje ovaca je obavljeno tri puta u vremenskom intervalu od po sedam dana. U cilju provere efikasnosti primenjenih lekova uzorci kože su uzimani 7 dana posle svakog tretmana, kao i 28 dana posle trećeg tretmana. Promene na koži izazvane šugarcima su kvantifikovane, na osnovu čega je određivan klinički skor (mean recovery response, MRR). Klinička efikasnost lekova procenjivana je na osnovu povlačenja kliničkih simptoma šuge kao i na osnovu broja prisutnih šugaraca u uzorcima strugotine kože. Eugenol u koncentraciji od 10 % posle prvog tretmana nije imao značajno manju efikasnost u odnosu na veću koncentraciju. Posle drugog tretmana efikasnost eugenola od 20 % bila je statistički značajno veća u odnosu na nižu koncentraciju, što je dokazano i 7 i 28 dana nakon trećeg tretmana. Eugenol je u koncentraciji od 10 % imao statistički značajno veću efikasnost od benzilbenzoata u terapiji šuge ovaca, kako posle prvog, tako i posle drugog i trećeg tretmana. Proverom efikasnosti benzil-benzoata posle 4 nedelje od trećeg tretmana dokazano je da je ona i dalje značajno manja u odnosu na eugenol u koncentraciji od 10 %. Efikasnost eugenola u koncentraciji od 20 % u lečenju sarkoptes-šuge ovaca bila je statistički značajno veća u odnosu na efikasnost eugenola u koncentraciji od 10 %, kao i benzil-benzoat, i posle drugog tretmana i posle 7 i 28 dana posle trećeg tretmana. Tokom trokratne primene eugenola u koncentraciji od 10 i 20%i benzil-benzoata u koncentraciji od 25% nisu zapaženi bilo kakvi znaci lokalne i sistemske nepodnošljivosti kod tretiranih ovaca.

The current clinical research on pharmacokinetics of methylprednisolone was performed on male pigs to whom was administered either intravenously or locally, via iontophoresis. Equal doses of methylprednisolone sodium succinate (MPSS) were applied, i.e. 40 mg it total per animal. In all pigs artificial inflammation of knee and elbow joints was provoked four days prior to the treatment. Four hours after the application of methylprednisolone tissue samples (both synovial fluid and hyaline cartilage) were obtained from the inflamed joints and subjected to analysis. The quantification of the drug was performed by HPLC technique. The results indicated high quantities of methylprednisolone both in the synovial fluid and hyaline cartilage, the concentrations being significantly higher in animals after iontophoretic application (17.15±3.11 and 12.70±2.19 μg/g, respectively) in comparison with the animals treated intravenously (0.33±0.11 and 0.21±0.06 μg/g, respectively). Thus, iontophoresis was proved a highly advisable clinical means of application of methylprednisolone, especially having in mind the possibility of avoiding systemic adverse effects which are present after parenteral drug administration. In addition, it enables higher therapeutic concentrations of MPSS to be obtained both in the synovial fluid and in the hyaline cartilage of the treated inflamed joints., Ispitivana je farmakokinetika metil-prednizolona na svinjama muškog pola kojima je ovaj lek aplikovan intravenski ili lokalno, putem elektroforeze. Metilprednizolon-natrijum-sukcinat primenjen je jednokratno, u dozi od 40 mg po životinji. Četiri dana pre tretmana, kod svih svinja je izazvano arteficijelno zapaljenje kolenog i lakatnog zgloba. Četiri sata posle aplikacije metil-prednizolona uzorci tkiva (sinovijalna tečnost i hijalina hrskavica) uzeti su iz inflamiranih zglobova i zatim analizirani. Kvantifikacija metil-prednizolona obavljena je HPLC metodom. Rezultati su ukazali na prisustvo visokih koncentracija metil-prednizolona u sinovijalnoj tečnosti i hijalinoj hrskavici, koje su bile statistički signifikantno veće posle elektroforetske aplikacije (17,15 ± 3,11 u sinovijalnoj tečnosti i 12,70 ± 2,19 μg/g u hrskavici) u poređenju sa koncentracijama dobijenim posle intravenske primene (0,33 ± 0,11 u sinovijalnoj tečnosti i 0,21 ± 0,06 μg/g u hrskavičnom tkivu). Iz ovog razloga, elektroforeza se preporučuje kao način lokalne aplikacije metilprednizolona kod inflamacije zglobova, naročito kada se ima u vidu mogućnost da se time izbegavaju sistemski neželjeni efekti koji nastaju posle parenteralne primene. Elektroforeza obezbeđuje vrlo visoke terapijske koncentracije metilprednizolon-natrijum-sukcinata kako u sinovijalnoj tečnosti, tako i u hrskavici tretiranih inflamiranih zglobova svinja.

Flunixin meglumine (FM) is a potent non-steroidal anti-inflammatory drug used in veterinary clinical practice. Hyperalgesia was induced by mtraplantar (i.pl.) administration of carrageenan (500 mu g) into the rat hind paw. Electronic von Frey apparatus was used to determine paw withdrawal threshold in grams (g). Both, FM (0.095-0.12 mg/kg: s.c.) and N-G-nitro-L-arginine methyl ester (L-NAME 2.5 and 5 mg/kg; i.p.), given 2.5 h after i.pl. injection of carrageenan produced significant dose-dependent antinociceptive effects. When FM (0.095 mg/kg) and subeffective dose of L-NAME (7.5 mg/kg) were co-administered, the anti-nociceptive effect was significantly increased M comparison with the effect of FM alone. L-arginme (10 mg/kg: i.p.) itself did not produce significant effect on carrageenan-induced hyperalgesia, but significantly inhibited the anti-nociceptive effects of both FM and FM + L-NAME combination. The inhibition of production of nitric oxide might be involved in the mechanism of the anti-hyperalgesic effect of FM in a model of carrageenan-induced hyperalgesia in rats.

The protective effect of bentonite (natural and synthetic) in oxidative stress induced by paraquat was studied on 32 adult male Wistar rats. The animals were divided into four groups (n=8). The first group received only paraquat p.o. (via a gastric tube). An hour after administration of paraquat, the second and the third group were treated with natural and synthetic bentonite, respectively, while the fourth group was untreated (control). All three experimental groups were treated once a day, throughout 8 consecutive days. Blood samples were taken 0, 1, 4, 6 and 8 days after the beginning of the treatment. Oxidative stress induced by paraquat was estimated by means of catalase activity (CAT - mmol/H2O2/min/g Hb) and malondialdehyde quantity (MDA - nmol/g Hb). Oxidative stress proved to be significant an hour and 192 hours after the beginning of chronic intoxication by paraquat. Both natural and synthetic bentonite expressed a protective action from oxidative stress in the period from 24 h to 144 h post application, acting through the external capacity of cationic exchange, which is known to be approximately 10%. The absorption of paraquat depends on the size of the molecule and its polarisation and is performed by the mechanisms of ion exchange (ionic and electrostatic interaction). Nevertheless, both absorbents developed a significant protective effect (approximately 50 %) 1 h and 192 h after the first application of paraquat, indicating that these protectors act as molecular sieves and thus suppress the process of lipid peroxidation and the development of even more intensive oxidative stress., U ovom radu su izneti rezultati proučavanja protektivnog efekta prirodnog i sintetskog bentonita tokom oksidativnog stresa indukovanog aplikacijom parahvata pacovima soja Wistar. Ogledne životinje su bile podeljene u četiri jednake grupe. Prva grupa pacova tretirana je samo parahvatom pomoću želudačne sonde. Jedan sat nakon aplikacije parahvata, pacovi druge i treće grupe su bili tretirani prirodnim ili sintetskim bentonitom, aplikovanim per os. Četvrta grupa pacova nije tretirana i služila je kao negativna kontrola. Eksperimentalne grupe životinja su bile tretirane jednom dnevno tokom osam uzastopnih dana. Uzorci krvi su uzimani 0, 1, 4, 6 i 8 dana nakon prvog tretmana. Stepen oksidativnog stresa je procenjivan na osnovu aktivnosti enzima katalaze i na osnovu količine malondialdehida. Prirodni i sintetski bentonit ispoljili su protektivnu aktivnost smanjivanjem parametara oksidativnog stresa u periodu od 24 do 144 sata nakon aplikacije. Autori predpostavljaju da bentonit deluje kao molekularno sito suprimirajući proces lipidne peroksidacije.

The acaricide efficacy, tolerability and safety of the active ingredient of the etheric oil of cloves eugenol was investigated in the treatment of mange in swine, and the obtained results were compared with the results of acaricide efficacy of the synthetic acaricide permethrin, which has been in use for quite a some time. A single application of permethrin in the form of a 1% solution showed maximum efficacy of 62.5%, and after three applications of 75.0% in the treatment of sarcoptes in swine mange. A single application of eugenol in the form of a 10% solution had maximum efficacy of 75.0%, and applied three times an efficacy of 100% in curbing Sarcoptes scabiei var. suis. A single administration of 20% eugenol solution showed maximum efficacy of 87.5%, and applied three times it was 100% efficient in curbing Sarcoptes scabeiei var. suis. The best efficacy in the treatment of sarcoptes mange in swine was achieved with three applications of eugenol in a concentration of 20%. This maximum effect (100%) was obtained already after the second treatment. Eugenol in a concentration of 10% was safe for local application on skin because it does not cause any undesired reactions, while a 20% concentration caused irritation followed by a passing redness and disquiet in a smaller number of treated animals. The results of comparative investigations of acaricide efficacy of permethrin and eugenol demonstrate that there is resistence in Sarcoptes scabiei var. suis to permethrin. The biocide eugenol can safely be recommended for the treatment of sarcoptes mange in swine., Ispitivana je akaricidna efikasnost, podnošljivost i bezbednost aktivnog sastojka eteričnog ulja karanfilića, eugenola, u lečenju šuge svinja i dobijeni rezultati su upoređeni sa rezultatima akaricidne efikasnosti, već duže vreme korišćenog sintetskog akaricida permetrina. Jednokratno primenjen permetrin u obliku rastvora koncentracije od 1% pokazao je maksimalnu efikasnost od 62,5%, a posle trokratne aplikacije od 75,0% u lečenju sarkoptes šuge svinja. Jednokratno primenjen eugenol u obliku rastvora koncentracije od 10% imao je maksimalnu efikasnost od 75,0%, a trokratno primenjen od 100,0% u suzbijanju Sarcoptes scabiei var. suis. Jednokratno primenjen rastvor eugenola u koncentraciji od 20% pokazao je najveću efikasnost od 87,5%, a trokratno primenjen od 100,0% u suzbijanju sa Sarcoptes scabiei var. suis. Najbolja efikasnost u lečenju sarkoptes šuge svinja je postignuta trokratnom primenom eugenola u koncentraciji od 20%. Ovaj maksimalni efekat (100,0%) dobijen je već posle drugog tretmana. Eugenol u koncentraciji od 10% bio je bezbedan za lokalnu primenu na koži, jer ne prouzrokuje bilo kakve neželjene reakcije, dok u koncentraciji od 20% kod manjeg broja tretiranih životinja izazivao je iritaciju praćenu prolaznim crvenilom i uznemirenošću. Rezultati uporednih ispitivanja akaricidne efikasnosti permetrina i eugenola ukazuju da postoji rezistencija Sarcoptes scabiei var. suis na permetrin. Biocid eugenol sa sigurnošću može da se preporuči u lečenju sarkoptes šuge svinja.