Original research. Meloxicam as adjunctive therapy in treatment and control of porcine respiratory disease complex in growing pigs.

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1 Peer reviewed Originl reserch Meloxicm s djunctive therpy in tretment nd control of porcine respirtory disese complex in growing pigs Ionnis E. Georgoulkis, DVM, PhD; Evnthi Petridou, DVM, Dr Med Vet; Georgios Filiousis, DVM, Dr Med Vet; Constntinos Alexopoulos, DVM, Dr Med Vet, Diplomte ECAR; Spiros C. Kyrikis, DVM, Dr Med Vet, Diplomte ECAR; Ionnis Pptss, DVM, Dr Med Vet. Summry Ojective: To determine the efficcy of injectle meloxicm s djunctive therpy to ntimicroil mediction in tretment nd control of porcine respirtory disese complex (PRDC) in growing pigs. Methods: A totl of 162 ninety-dy-old pigs showing erly clinicl signs of PRDC were weighed (Dy 0) nd llocted into two tretment groups, s (n = 82) nd Meloxicm (n = 80), in rndomized lock design (pproximtely 20 pigs per pen, four pens per tretment per replicte). In-feed chlortetrcycline (800 g per tonne; 20 mg per kg ody weight per dy) ws dministered to oth groups for 8 consecutive dys (Dys 0 to 7). On Dy 0, s received single injection of plceo nd the Meloxicm group received single injection of meloxicm (0.4 mg per kg ody weight). Respirtory signs were ssessed per individul niml nd per tretment group Dys 0 to 7. Frequency of dditionl injectle medictions, mortlity rte, nd growth rte were ssessed until the end of the growing phse (117 dys of ge; Dy 27). The lungs of ll ded nimls were sumitted for cteriologicl culture nd pthologicl exmintion. Results: Clinicl scores, frequency of tretment with dditionl injectle medictions, nd mortlity rte were lower nd growth performnce ws etter in meloxicm-treted nimls thn in s. Implictions: Meloxicm s n djunct to orl ntiiotic therpy my contriute to tretment nd control of PRDC y ccelerting recovery from respirtory inflmmtion, enhncing restortion of norml growth rte, nd reducing mortlity rte. Keywords: swine, meloxicm, porcine respirtory disese complex Received: April 11, 2005 Accepted: Octoer 20, 2005 IEG: School of Agriculture, Animl Production nd Hydtic Environment, University of Thessly, , Volos, Greece. EP: Lortory of Microiology nd Infectious Diseses, Fculty of Veterinry Medicine, Aristotle University of Thessloniki, , Mcedoni, Greece. GF: 3 rd Greek Army Veterinry Hospitl, Thessloniki, Mcedoni, Greece. CA: Clinic of Ostetrics nd Artificil Insemintion, Fculty of Veterinry Medicine, Aristotle University of Thessloniki, , Mcedoni, Greece. SCK: Clinic of Productive Animl Medicine, Fculty of Veterinry Medicine, Aristotle University of Thessloniki, , Mcedoni, Greece. IP: Boehringer Ingelheim Ells AE, , Thessloniki, Mcedoni, Greece. Corresponding uthor: Dr Ionnis Pptss, POB 46, GR-57010, Asvestochori, Thessloniki, Mcedoni, Greece; Tel: ; Fx: ; E-mil: pptss@th. oehringer-ingelheim.com. This rticle is ville online t Georgoulkis IE, Petridou E, Filiousis G, et l. Meloxicm s djunctive therpy in tretment nd control of porcine respirtory disese complex in growing pigs. J Swine Helth Prod. 2006;14(5): Journl of Swine Helth nd Production Volume 14, Numer 5 Resumen El meloxicm como un terpi djunt en el trtmiento y control del complejo respirtorio porcino en cerdos en crecimiento Ojetivos: Determinr l eficci del meloxicm inyectle como terpi djunt l medicción ntimicroin en el trtmiento y control del complejo respirtorio porcino (PRDC por sus sigls en inglés) en cerdos de crecimiento. Métodos: Se pesron un totl de 162 cerdos de novent dís de edd que mostrn los primeros signos clínicos de PRDC (Dí 0) y se colocron en dos grupos de trtmiento, (n = 82) y Meloxicm (n = 80), en un diseno de loques l zr (proximdmente 20 cerdos por corrl, cutro corrles por trtmiento por réplic). Se dministró clorotetrciclin (800 g por toneld; 20 mg por kg de peso corporl por dí) mos grupos por 8 dís consecutivos (Dís 0 7). En el Dí 0, los es reciieron un inyección únic de plceo y el grupo de Meloxicm reciió un inyección únic de meloxicm (0.4 mg por kg de peso corporl). Se vlorron los signos respirtorios por niml individul y por grupo de trtmiento los Dís 0 7. Se vloró l frecuenci de medicmentos inyectles dicionles, índice de mortlidd, e índice de crecimiento hst el finl de l etp de crecimiento (117 dís de edd; Dí 27). Los pulmones de todos los nimles muertos se environ pr cultivo cteriológico y exmen ptológico. Resultdos: Los puntjes clínicos, l frecuenci del trtmiento con medicmentos inyectles dicionles, y el índice de mortlidd fueron más jos y el desempeno del crecimiento fue mejor en nimles trtdos con meloxicm que en los es. Implicciones: El meloxicm como un djunto l terpi ntiiótic orl puede contriuir l trtmiento y control del PRDC celerndo l recuperción de l inflmción respirtori, l resturr el índice de crecimiento norml, y reducir el índice de mortlidd. Résumé Utilistion du meloxicm comme thérpie supplémentire pour le tritement et le controle du complexe respirtoire porcin chez les porcs en engrissement 253

2 Ojectifs: Déterminer l efficcité du meloxicm injectle comme thérpie supplémentire à l dministrtion d ntimicroiens pour le tritement et le contrôle du complexe respirtoire porcin (PRDC) chez les porcs en engrissement. Méthodes: Un totl de 162 porcs âgés de 90 jours et montrnt des signes cliniques hâtifs de PRDC ont été pesés (Jour 0) et réprtis en deux groupes de tritement, Témoin (n = 82) et Meloxicm (n = 80), selon un dispositif en locs létoires (environ 20 porcs pr prc, qutre prcs pr tritement pr répliction). De l chlortétrcycline joutée à l nourriture (800 g pr tonne; 20 mg pr kg de poids corporel pr jour) été dministrée u deux groupes pour 8 jours consécutifs (Jour 0 à 7). Au Jour 0, les nimux du groupe Témoin ont reçu une injection unique d un plceo et le groupe trité reçu une dose unique de meloxicm (0.4 mg pr kg de poids corporel). Les signes respirtoires ont été évlués pour chque niml et pour chque groupe de tritement du Jour 0 u Jour 7. L fréquence d injections dditionnelles de médicments, le tux de mortlité, et le tux de croissnce ont été évlués jusqu à l fin de l période de croissnce (117 jours d âge; Jour 27). Les poumons de tous les nimux morts ont été soumis pour culture ctérienne et exmen pthologique. Résultts: Le pointge clinique, l fréquence de tritement vec des médicments injectles dditionnels, et les tux de mortlité étient inférieure et les performnces de croissnce étient meilleures chez les nimux trités vec le meloxicm que pour les nimux témoins. Implictions: Le meloxicm utilisé comme thérpie supplémentire à une thérpie ntiiotique orle peut contriuer u tritement et u controle de PRDC en ccélérnt l guérison d une inflmmtion respirtoire, en méliornt le rétlissement d un tux de croissnce norml, et en réduisnt le tux de mortlité. Porcine respirtory disese complex (PRDC) of growing-finishing pigs is mjor economic thret to the modern pig industry worldwide. Numerous virl nd cteril gents my contriute to pthogenesis of PRDC either s primry or secondry etiologic gents, nd etiology vries from frm to frm. 1-4 Pthogens implicted include porcine reproductive nd respirtory syndrome virus (PRRSV), pseudories virus (PRV), swine influenz virus (SIV), Mycoplsm hyopneumonie, Psteurell multocid, nd Actinocillus pleuropneumonie (APP). 1-4 Use of vccintion nd mediction strtegies trgeted ginst specific gents is widely ccepted method to minimize losses. 4,5 Use of nonsteroidl nti-inflmmtory drugs (NSAIDs) s djunctive therpy in tretment of ovine respirtory disese hs een reported in severl studies in which dministrtion of NSAIDs concurrently with pproprite ntimicroil therpy ccelerted clinicl improvement nd moderted lung inflmmtion. 6-8 Meloxicm, n NSAID of the oxicm clss, exerts potent nti-inflmmtory, nlgesic, ntitoxic, ntipyretic, nd nti-exudtive ctivity y inhiiting modultors nd meditors of the inflmmtory process. 9 Efficcy of meloxicm s djunctive therpy in tretment of respirtory infections in cttle hs een widely demonstrted Meloxicm hs recently een pproved in mny countries for tretment of the mstitis-metritis-glcti (MMA) syndrome 9 nd locomotor disorders 13 in pigs. The ojective of this study ws to investigte the effect of meloxicm (Metcm 2%; Boehringer Ingelheim, Ingelheim, Germny) s djunctive therpy to ntimicroils in tretment nd control of PRDC in growing-finishing pigs. Mterils nd methods Study herd The study ws crried out in 560-sow commercil frrow-to-finish swine frm locted in the region of Centrl Mcedoni (Topigs, commercil hyrid; Vught, The Netherlnds). The qulity of mngement ws poor, especilly in the grower nd finisher, eg, niml density ws high (2.5 pigs per m 2 in the grower nd 2.0 pigs per m 2 in the finisher), ventiltion ws poor (pproximtely 1.1 m 3 per kg per hour), nd iosecurity mesures were inconsistent (eg, use of disinfectnts nd snitizers fter rns were wshed etween groups of pigs). Recurring PRDC episodes in this herd were ssocited with high mortlity oth in the growing phse (71 to 117 dys of ge; verge mortlity 6.2%) nd finishing phse (118 to 170 dys of ge; verge mortlity 4.6%). Nursery pigs (28 to 70 dys of ge) were vccinted t 30 dys of ge with single-dose M hyopneumonie vccine (Ingelvc M hyo; Boehringer Ingelheim). Sows, ors, nd gilts were routinely vccinted with n inctivted PRRSV vccine (Progressis; Meril, Lyon, Frnce) nd lso with vccines ginst PRV (Porcilis-Begoni; Intervet, Boxmeer, The Netherlnds), porcine prvovirus (Noi- Porvc-Prvo; Intervet), swine erysipels (Noi-Porvc-Ery; Intervet), nd trophic rhinitis (Noi-vc AR-T; Intervet). According to the recorded medicl history, the herd ws endemiclly infected with PRRSV, while P multocid, Streptococcus suis, nd APP hd een frequently isolted from cses of PRDC during the previous 2 yers. Serologicl testing ws performed 2 months efore the tril egn. A totl of 40 lood smples were collected (10 smples per ge group) from unvccinted gilts, growing pigs 60 nd 110 dys of ge, nd finishing pigs 170 dys of ge. Unvccinted gilts were housed seprtely from the finishing pigs, nd 60-dy-old nd 110-dy-old pigs nd finishers were housed in seprte rooms in the sme uilding. For ech of the tested ge groups, rndom smples were collected y selecting pigs from different pens in vrious prts of the room. All smples were tested for ntiodies ginst PRV (ge locking ELISA; Svnov, Uppsl, Sweden; OD < 45 considered positive); SIV (H 1 N 1 ELISA; Idexx, Schipol- Rijk, The Netherlnds; smple:positive rtio [S:P] > 0.4 considered positive); PRRSV (PRRS ELISA; Idexx; S:P > 0.4 considered positive); nd porcine circovirus type-2 (PCV-2) (immunofluorescence ssy; Bioscreen GmH, Muenster, Germny; titrtion in smple dilutions from 1:20 to 1:1280, reciprocl titers positive). All smples were seronegtive for PRV nd SIV. Some nimls in ll tested groups were seropositive for PRRSV, including 100% of unvccinted gilts, 30% of 60-dy-old pigs, 90% of 110-dy-old pigs, nd 100% of 170-dy-old pigs. Although no clinicl signs indictive of PCV-2 infection hd een oserved, 90% of tested smples were seropositive. Experimentl design In doule-linded, rndomized study, 162 growing pigs were selected (Dy 0), with equl numers of mles nd femles, t the ge of 90 ± 2 dys, ie, the ge of onset of clinicl signs of PRDC in this herd. Selected nimls were housed in eight pens (8.2 m 2 ) in room of the grower rn 254 Journl of Swine Helth nd Production Septemer nd Octoer 2006

3 reserved for the study, nd were er-tgged nd rndomly llocted to two tretment groups, with 20 ± 2 pigs per pen nd four pens per tretment per replicte. Averge ody weight in the tretment groups ws similr (33.9 nd 34.0 kg; P >.05) t the strt of the tril. During the tril period, stndrd grower rtion (msh) sed on corn nd soyens ws fed d liitum to ll nimls up to 117 dys of ge. Two nipple drinkers nd one fully utomted circulr feeder were provided in ech pen, with one feeder plce per four nimls. Both tretment groups received in-feed chlortetrcycline (CTC; 800 g per tonne, 20 mg per kg ody weight per dy) for 8 consecutive dys eginning Dy 0. Selection of CTC for tretment ws sed on ntimicroil sensitivity testing of lung smples from recent niml groups. In ddition, on Dy 0, s (n = 82) received single intrmusculr (IM) injection of plceo (isotonic sline) nd the Meloxicm group (n = 80) received single IM injection of meloxicm (Metcm; Boehringer Ingelheim; 0.4 mg per kg ody weight). This protocol dhered to the Greek Ntionl Presidentil Decree 160/91 requirements for niml welfre tretment nd ws supervised y the Fculty of Veterinry Medicine of Aristotle University of Thessloniki. Clinicl prmeters Clinicl prmeters ssocited with signs of cute respirtory infection were ssessed per niml nd per tril group. Averge dily respirtory score (ADRS) for Dys 0 to 7 (90 to 97 dys of ge) ws scored on scle of 0 (sence of clinicl signs) to 3 (dominl rething nd generlly poor condition chrcterized y depression, reluctnce to rise nd move, inppetence, nd pprent weight loss). Men respirtory score (RS) ws clculted for the 8-dy period etween Dys 0 nd 7. Generl helth sttus (GHS) for Dys 0 to 7 ws scored on four-point scle (0 = norml generl condition nd sence of clinicl signs; 1 = pprent clinicl signs, less ctive thn norml pigs, no ovious growth vrition; 2 = pprent clinicl signs, ovious depression, nd moderte growth vrition; nd 3 = pprent clinicl signs, poor generl condition, long hircot, nd oviously retrded growth). The frequency of dditionl injectle medictions required ws expressed s the percentge of nimls per tretment group tht received dditionl injectle ntimicroil mediction etween 91 dys of ge (Dy 1) nd 117 dys of ge (Dy 27), ie, the end of the growing phse. Clinicl index score (CIS) ws the totl of RS nd GHS scores. Mortlity rte per tretment group ws clculted for Dys 0 to 27. Scoring for ADRS nd GHS per individul niml ws performed twice dily t 4- hour intervl, lwys y the sme investigtor, with ech oservtion period lsting mximum of 2 hours. Two dily vlues per prmeter nd per niml were recorded. The highest of the two recorded dily vlues for ADRS nd GHS per niml were used in dt nlysis. Growth performnce dt All nimls were individully weighed on Dys 0 nd 27. For ech niml nd tretment group, verge dily gin (ADG) ws clculted for the overll tril period (Dy 0 to Dy 27). Bcteriology nd pthology Lungs of ll ded nimls were sujected to pthologicl nd cteriologicl exmintions. Gross pthologicl exmintion ws performed t the frm site. Whole lung smples were sumitted 2 to 3 hours lter to the Lortory of Microiology nd Infectious Diseses of the Fculty of Veterinry Medicine (Thessloniki) for histologicl exmintion nd cteriologicl testing. Sws from the cut surfce of ech lung smple were inoculted on 5% sheep lood gr (incuted t 37 C for 48 hours) for detection of Psteurell spp nd Streptococcus spp nd on 5% sheep lood gr with cross-strek of Stphylococcus epidermidis (incuted t 37 C for 24 hours) for detection of APP. Biochemicl tests were used to identify P multocid nd S suis, nd P multocid isoltes were typed using polymerse chin rection. Lung tissue sections (pproximtely 4 cm 4 cm smples contining oth helthy nd ffected tissue) were plced in formlin for histologicl exmintion. Sttisticl nlysis Tretment-group mens for verge odyweight t the strt of the tril, ADRS, RS, GHS, CIS, nd ADG were compred using Student t test. Mens for prmeters expressed s frequencies, ie, dditionl injectle medictions nd mortlity rte, were compred using Person s chi-squre test. Significnce levels were investigted for α = 0.05 nd α = Results Clinicl prmeters Averge dily respirtory score in the Meloxicm group ws significntly lower thn in the group when pigs were 93, 94, 95, 96, nd 97 dys of ge (Figure 1). Men RS nd CIS were significntly lower in the Meloxicm group thn in the group (Tle 1). Men GHS ws similr for oth groups (Tle 1). A higher proportion of nimls in the group received dditionl injectle medictions (Tle 2). Mortlity rte ws lower in the Meloxicm group (Tle 2). Growth performnce Averge dily gin ws higher in the Meloxicm group (0.667 kg) thn in the group (0.635 kg) (P <.05). Bcteriologicl results The intervl etween deth nd necropsy ws pproximtely 10 to 12 hours for most nimls. Psteurell multocid type A ws isolted from four of the seven group lung smples nd S suis ws isolted from two of the seven group smples. Although pthologicl findings suggested APP infection in some nimls, this orgnism ws not isolted. Pthologicl results Most ded nimls were discovered in the erly morning hours, nd time etween deth nd culture of smples ws t lest 12 hours. In ll nimls tht died, oth mcroscopic lesions (multifocl interstitil pneumoni, trcheoronchil lymphdenopthy, pleurisy with firinous dhesions, ronchopneumoni) nd microscopic lesions (type-2 pneumonocyte nd lveolr hyperplsi, exudtive ronchopneumoni) were typicl of complicted virl respirtory infection. Discussion The results of this study in growing pigs showing clinicl signs of PRDC show tht tretment with injectle meloxicm, in comintion with pproprite ntimicroil mediction, ws ssocited with lower prevlence of respirtory signs nd consequent mortlity, s well s etter growth rte. The requirement for less dditionl injectle mediction lso suggests tht Journl of Swine Helth nd Production Volume 14, Numer 5 255

4 meloxicm contriutes to more rpid recovery from the respirtory inflmmtion triggered y virl nd cteril pthogens in PRDC infection. 256 ADRS The only known mechnism of meloxicm ctivity is inhiition of inflmmtory enzymes produced y tissue inflmmtion. 9 Recent reserch 14 showed tht tretment Figure 1: Averge dily respirtory score (ADRS) for two groups of grower pigs from 90 to 97 dys of ge (Dys 0 to 7) ws grded on scle of 0 (sence of clinicl signs) to 3 (dominl rething nd generlly poor condition chrcterized y depression, reluctnce to rise nd move, inppetence, nd pprent weight loss). At 90 dys of ge, the Meloxicm group received single injection of meloxicm (Metcm; Boehringer Ingelheim, Ingelheim, Germny; 0.4 mg/kg ody weight) nd s received plceo injection. Both groups were treted in-feed with chlortetrcycline (800 g/tonne of feed; 20 mg/kg ody weight/dy) on Dys 0 through 7. Within dy, mens with different superscripts differ significntly (Student t test; P <.01). Meloxicm Age (dys) Tle 1: Mens (± SD) for generl helth sttus (GHS), respirtory score (RS), nd clinicl index score (CIS) for groups of growing pigs showing signs of porcine respirtory disese complex nd treted with Meloxicm (n = 80) or untreted (n = 82)* Prmeter Tretment group P Meloxicm GHS ± ± RS ± ± CIS ± ± * Pigs 90 dys of ge (Dy 0) were treted either with meloxicm (Metcm; Boehringer Ingelheim, Ingelheim, Germny; 0.4 mg/kg ody weight) or with plceo injection (). Both groups received in-feed chlortetrcycline (800 g/tonne of feed; 20 mg/kg ody weight/dy) Dys 0 through 7. GHS scle: 0 = norml generl condition nd sence of clinicl signs; 1 = pprent clinicl signs, less ctive thn norml pigs, no ovious growth vrition; 2 = pprent clinicl signs, ovious depression, nd moderte growth vrition; nd 3 = pprent clinicl signs, poor generl condition, long hircot, nd oviously retrded growth. Men RS = men verge dily respirtory score (ADRS) for Dys 0 through 7, with ADRS grded on scle of 0 (sence of clinicl signs) to 3 (dominl rething nd generlly poor condition chrcterized y depression, reluctnce to rise nd move, inppetence, nd pprent weight loss). CIS = GHS + RS. Vlues within row with different superscripts re different (Student t test; P <.05). with meloxicm in pigs chllenged with Escherichi coli endotoxins ws ssocited with less severe clinicl signs nd lower levels of the inflmmtory enzyme thromoxne-b 2, which is gretly incresed y respirtory-trct inflmmtion. Moreover, the role of other inflmmtory enzymes, principlly cyclooxygense-2, tht re expressed through the lung inflmmtion process nd triggered y respirtory pthogens in pigs, hs lso een demonstrted Further investigtion of the possile inhiitory effect of meloxicm on cyclooxygense-2 ctivity would enhnce our knowledge concerning use of this gent s routine djunctive therpy in respirtory infections in growing nd finishing pigs. Poor mngement on the study frm ws n importnt issue. Implementtion of mesures to improve mngement nd hygienic conditions on long-term sis should e the primry gol, efore ntimicroil nd djunctive therpy re prescried for tretment nd control of PRDC. The long intervl etween deth nd disptching of lung smples to the lortory (ie, 12 hours) likely contriuted to filure to recover APP from lung tissue in this study. Although mesurement of verge dily feed intke nd clcultion of feed conversion rtio might hve een vlule prmeters in this study, the utomtic feeding system, type of feeder, nd ville equipment in this fcility did not llow collection of these dt. Vrile results hve een reported in series of studies concerning efficcy of NSAIDs in tretment of respirtory infections. The present study focused on just one production phse. Further reserch evluting dditionl growth prmeters nd use of meloxicm in recurring PRDC episodes, especilly during the finishing phse, is needed. Different nd possily more convenient routes of dministrtion of NSAIDs for tretment nd control of PRDC, either in-feed or vi drinking wter, should e investigted. Implictions Prevlence of clinicl signs of PRDC nd requirement for dditionl injectle medictions my e lower in growing pigs treted with injectle meloxicm nd pproprite ntimicroil Journl of Swine Helth nd Production Septemer nd Octoer 2006

5 Tle 2: Frequency of dditionl injectle medictions (AIM) nd mortlity rte per tretment group for growing pigs showing signs of porcine respirtory disese complex nd either treted with meloxicm or plceo () t 90 dys of ge* Prmeter Tretment group χ 2 Meloxicm AIM 10/82 (12.2) 2/80 (2.5) 4.23 Mortlity 6/82 (7.3) 0/80 (0.0) 4.20 * Pigs 90 dys of ge were treted either with meloxicm (Metcm; Boehringer Ingelheim, Ingelheim, Germny; 0.4 mg/kg ody weight), or with plceo injection (). Both groups received in-feed chlortetrcycline (800 g/tonne of feed; 20 mg/kg ody weight/dy) from 90 to 97 dys of ge. Numer of treted nimls/totl numer of nimls in the group (%). Numer of ded nimls/totl numer of nimls in the group (%). Vlues within row with different superscripts differ significntly (Person s chisqure test; P <.05). mediction thn in pigs treted with the sme ntimicroil lone. Meloxicm used s djunctive therpy in tretment nd control of PRDC my minimize growth retrdtion nd mortlity in ffected nimls. Acknowledgements The uthors wish to thnk the owner nd the technicl stff of the tril frm who contriuted in the process of this study, regrdless of the high worklod required. The ssistnce of Dr Griele Friton in the presenttion of this rticle is lso grtefully cknowledged. Dr Pptss ws employed y Boehringer Ingelheim Vetmedic GmH while the study nd nlysis were eing conducted. References 1. Dee SA. The porcine respirtory disese complex: Are supopultions importnt? Swine Helth Prod. 1996;4: *2. Hlur PG, Pul PS, Andrews JJ. Virl contriutors to the porcine respirtory disese complex. Proc AASP. Knss City, Missouri. 1993; *3. Stevenson GW. Bcteril contriutors to the porcine respirtory disese complex. Proc AASP. Knss City, Missouri. 1993; Christensen G, Sorensen V, Mousing J. Diseses of the respirtory system. In: Strw BE, D Allire S, Mengeling WL, Tylor DJ, eds. Diseses of Swine. 8 th ed. Ames, Iow: Iow Stte University Press; 1999: *5. Desrosiers R. Dignosis nd control of swine respirtory diseses. Proc AASP. Queec, Cnd. 1997; Deleforge J, Thoms E, Dvot JL, Boisrme B. A field evlution of the efficcy of tolfenmic cid nd oxytetrcycline in the tretment of ovine respirtory disese. J Vet Phrmcol Therp. 1994;17: *7. Clrke CR, Burrows GE, Ames TR. Therpy of ovine cteril pneumoni. Vet Clin North Am: Food Anim Prct. 1991;7: US Deprtment of Agriculture. Animl nd Plnt Helth Inspection Service. Tretment of respirtory disese in U.S. feedlots. Info Sheet. Octoer Aville t: usd.gov/vs/ceh/nchs/nhms/feedlot/feedlot99/fd99tretresp.pdf. Accessed Mrch 12, Hirsch AC, Philipp H, Kleemnn R. Investigtion on the efficcy of meloxicm in sows with mstitis-metritis-glcti syndrome. J Vet Phrmcol Therp. 2003;26: Schmidt H, Philipp H, Slmon E, Okking K. The effects of dditionl tretment with Metcm (meloxicm) on the course of cute respirtory disese in ovines. Der prktische Tierrzt. 2000;81: Friton G, Cjl C, Romero Rmirez R, Kleemn R. Clinicl efficcy of meloxicm (Metcm ) nd flunixin (Findyne ) s djuncts to nticteril tretment of respirtory disese in fttening cttle. Berliner und Munchener Tierrtztliche Wochenschrift. 2004;117: *12. Slmon E, Schmidt A, Henderson A, Okking K. Effects of meloxicm on thromoxne in clves with experimentlly induced endotoxemi. Proc World Buytric Congress. 2000;8: Friton G, Hgen P, Schneider T, Kleemn R. Investigtion on the clinicl efficcy nd sfety of meloxicm (Metcm ) in the tretment of non-infectious locomotor disorders in pigs. Berliner und Munchener Tierrtztliche Wochenschrift. 2003;116: *14. Schroedl W, Schmidt H, Duering F, Friton G. Effect of meloxicm (Metcm) in endotoxin chllenged pigs. Proc IPVS Cong. Hmurg, Germny. 2004; Cho WS, Che C. In vitro effects of Actinocillus pleuropneumonie on inducile nitric oxide synthse nd cyclooxygense-2 in porcine lveolr mcrophges. Am J Vet Res. 2003;64: Cho WS, Che C. Expression of cyclooxygense-2 in swine nturlly infected with Actinocillus pleuropneumonie. Vet Pthol. 2003;40: Cho WS, Che C. Immunohistochemicl detection of cyclooxygense-2 in lungs of pigs nturlly infected with Actinocillus pleuropneumonie. J Comp Pthol. 2002;127: Swinkels JM, Pijpers A, Vernooy JC, Vn Nes A, Verheijden JH. Effects of ketoprofen nd flunixin in pigs experimentlly infected with Actinocillus pleuropneumonie. J Vet Phrmcol Therp. 1994;17: Brown NC, Anderson TT, Anderson DL. Dexmethsone nd indomethcin modify endotoxin-induced respirtory filure in pigs. J Appl Physiol. 1985;58: *20. De Jong MF, Smpimon O, Arnud JP, Theunissen G, Groenlnd G, Werf PJ. A clinicl study with non steroid nti inflmmtory drug. Proc IPVS Cong. Bologn, Itly. 1996; Lvl A. Utilistion des nti-inflmmtoires chez le porc. Recueil de Médecine Véterinire. 1992;168: *Non-refereed references. Journl of Swine Helth nd Production Volume 14, Numer 5 257