Browsing by Subject "eläinlääketiede"

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  • Orro, Toomas (Helsingin yliopisto, 2008)
    The early protection mechanism of the host against infection, trauma or other tissue damage comprises a set of reactions known as the acute phase response (APR). During APR, circulating concentrations of acute phase proteins (APPs) change. These proteins can serve as indicators of host response during various inflammatory conditions. In this thesis, APR in reindeer was investigated for the first time. Systemic concentrations of APPs during the neonatal period were studied in reindeer and cattle. APPs were also investigated during spontaneous bovine respiratory disease (BRD) in dairy calves. Escherichia coli endotoxin challenge in adult reindeer increased concentrations of serum amyloid A (SAA) in all animals. Haptoglobin (Hp) showed a less pronounced increase. SAA and Hp were concluded to be acute phase reactants in reindeer. In reindeer calves SAA concentrations increased during the first 2 weeks of life and decreased afterwards. Serum Hp concentrations increased throughout the first month after birth. In dairy calves SAA and lipopolysaccharide binding protein (LBP) concentrations changed similarly during first month of age as in reindeer calves. However, Hp concentrations generally remained low after birth. SAA rise in calves were not derived from colostrum as mammary specific SAA isoforms were not found from calves serum samples. Results of these two studies indicated that newborn reindeer and dairy calves have an inflammatory response during the first weeks of life and the age of young animals should by considered when interpreting APP concentrations. Very similar SAA changes in the two ruminant species also suggest that this inflammatory response may have role in the adaptation process of newborns to extrauterine life. The effect of different bovine respiratory pathogens on concentrations of APPs (SAA, LBP, Hp, alpha1-acid glycoprotein and fibrinogen) was studied in calves. Isolation of Pasteurella multocida was associated with increased concentrations of all APPs tested. In another study, concentrations of APPs were investigated in dairy calves during an outbreak of BRD. Initial cause for BRD outbreak was bovine respiratory syncytial virus (BRSV) infection. Concentrations of SAA and LBP increased in parallel with clinical symptoms at week 1 and peaked at week 3 of outbreak. Some calves had high Hp concentrations at week 3. Higher SAA, LBP and Hp concentrations at a later stage of BRD (week 3) were associated with lower BRSV-specific IgG1 production, suggesting that these calves had enhanced inflammatory response to secondary bacterial infection. In conclusion, APPs proved to be useful in exploring host response in bovine respiratory infections.
  • Valkeisenmäki, Iina (Helsingin yliopisto, 2019)
    Akupunktion suosio sekä ihmisten että eläinten hoitomuotona on lisääntynyt merkittävästi. Tutkimusnäyttöä akupunktion tehosta ja vaikutusmekanismeista etenkin kivun hoidossa löytyy, mutta sen hyödyntämistä kotieläinten lisääntymisongelmissa on tutkittu vähemmän. Vaikutusmekanismitutkimuksista on kuitenkin havaittu, että akupunktio voi vaikuttaa useiden lisääntymishormonien pitoisuuksiin sekä lisääntymiselimiin niin sanottujen somatoviskeraalisten refleksien välityksellä. Tämän lisensiaatin tutkielman tavoitteena oli tutkia, voiko akupunktiohoidolla olla vaikutusta narttukoirien valeraskausoireiden voimakuuteen tai kestoon. Valeraskaus on leikkaamattomilla narttukoirilla diestruksen eli jälkikiiman aikana esiintyvä fysiologinen syndrooma, jonka oireita ovat esimerkiksi nisien kasvaminen, maidon erittyminen sekä lelujen tai muiden esineiden hoivaaminen. Valeraskauteen on olemassa lääkehoito, mutta sen hoitoon on käytetty myös akupunktiota esimerkiksi koirilla, joiden omistajat eivät doping-säädösten takia halua lääkehoitoa. Aiempaa julkaistua tutkimusnäyttöä hoidon tehosta ei kuitenkaan ole. Tutkimus toteutettiin satunnaistettuna, sokkoutettuna kliinisenä kokeena, johon osallistui 13 valeraskaudesta kärsivää narttukoiraa. Akupunktioryhmän koirat saivat tutkimuksen aikana kaksi kertaa akupunktiohoitoa, kun taas kontrolliryhmien koiria ei hoidettu lainkaan. Koirien omistajat olivat sokkoutettu koirien ryhmäjaolta, eivätkä he tienneet koiransa ryhmäjakoa. Omistajat arvioivat koiriensa valeraskausoireiden kehitystä kyselylomakkeiden sekä oirepäiväkirjan avulla. Oirepäiväkirjojen perusteella ryhmien välillä ei havaittu tilastollisesti merkittävää eroa oireiden voimakkuudessa tai kestossa. Sekä akupunktioryhmän että kontrolliryhmän valeraskausoireet kestivät keskimäärin 15 päivää ensimmäisen tutkimuskäynnin jälkeen. Oirepäiväkirjojen vastauksissa ei myöskään havaittu merkittäviä eroja kaikkien oireiden keskiarvon voimakkuudessa tai yksittäin tarkastelluissa oireissa tutkimuskäyntien aikana tai sen jälkeen. Myöskään oireiden voimakkuuden muutoksissa ensimmäiseen tutkimuskäyntiin verrattuna ei havaittu ryhmien välillä tilastollisesti merkittävää eroa. Loppukyselyn perusteella 60% akupunktioryhmän koirien omistajista koki koiransa valeraskausoireiden olleen koirien aiempiin verrattuna lyhyemmät ja 40% koki oireiden olleen saman mittaiset kuin aiemmin. 100% kontrolliryhmän koirien omistajista kokivat koiransa valeraskausoireiden olleen yhtä pitkät kuin aiemmin. Ero tutkimus- ja kontrolliryhmän välillä oli tilastollisesti merkittävä (p = 0,030). Omistajien kokemuksissa koirien valeraskausoireiden voimakkuudesta ei kuitenkaan ollut loppukyselyn perusteella tilastollisesti merkittävää eroa. Tutkimuksen tulosten perusteella ei voida päätellä, tehoaako akupunktio valeraskausoireiden voimakkuuteen tai kestoon. Akupunktioryhmän omistajien kokemus valeraskausoireiden lyhyemmästä kestosta saattaa antaa viitteitä positiivisesta vaikutuksesta, mutta loput tulokset eivät tue tätä yksittäistä tulosta. Tutkimus oli kooltaan pieni, ja siinä ei mahdollisesti ollut riittävästi tilastollista voimaa tilastollisesti merkittävän eron saamiseksi. Hoitotuloksien mittaaminen osoittautui erittäin haastavaksi, ja tutkimusasetelmasta löytyi useita mahdollisia virhelähteitä. Lisää laajempia tutkimuksia tarvitaan, jotta akupunktion mahdollista tehoa valeraskauteen voidaan arvioida luotettavasti.
  • Keto-Timonen, Riikka (Helsingin yliopisto, 2008)
    In epidemiological studies, techniques that effectively discriminate between individual bacterial strains are essential. Recent developments in molecular techniques necessitate an ongoing need to tailor new genotyping methods for optimal characterization of different bacterial species and to evaluate their performance and suitability for research purposes. In this thesis amplified fragment length polymorphism (AFLP) analysis was tailored for optimal characterization of Listeria monocytogenes and Clostridium botulinum. The suitability of the developed AFLP protocol to type L. monocytogenes, C. botulinum and Clostridium perfringens at strain level was evaluated. AFLP proved to be a highly reproducible, easy-to-use, relatively fast and highly discriminative approach. When AFLP was applied to L. monocytogenes strains, its discriminatory power was shown to equal that of PFGE, which is considered the current gold standard for molecular fingerprinting of L. monocytogenes. These features make AFLP analysis a useful alternative to other genotyping methods in, for example, outbreak investigations and contamination route studies. Since phenotypic identification of Clostridium isolates is laborious, the suitability of AFLP for genomic species identification was assessed. The AFLP technique was applied to 129 strains representing 24 different Clostridium species. AFLP differentiated all species tested, except for Clostridium ramosum and Clostridium limosum. AFLP also differentiated between six different Listeria species. If AFLP profiles of well-defined strains are collected in identification libraries, the database can be a valuable additional tool for identification of Clostridium and Listeria species. Due to high throughput of samples, AFLP proved to be especially suitable for screening large numbers of isolates. AFLP was also used to trace contamination routes of L. monocytogenes in a chilled food processing plant producing ready-to-eat and ready-to-reheat meals during an 8-year period. Cleaning routines, product type and degree of compartmentalization seemed to have an influence on the contamination status in compartments that produced cooked meals. In addition, raw materials were shown to cause contamination of uncooked meals. Thus, special attention should be paid to quality control of raw ingredients when uncooked ready-to-eat meals are produced. This work also demonstrated that structural adjustments of a production line may facilitate the eradication of L. monocytogenes from the food processing environment. AFLP and PFGE analysis of sporadic L. monocytogenes strains and strains that cause persistent plant contamination revealed that persistent strains differ from sporadic strains. However, no specific evolutionary lineage of persistent strains was observed.
  • Herva, Tuomas (Helsingin yliopisto, 2015)
    Animal welfare (AW) is an issue of growing concern in Finland as well as in other developed countries. A public debate has focused on the potential AW problems resulting from current production systems. Possibilities to find mutual benefit for animals, farmers, industry and society have received less attention. According to the reviewed literature the inconsistency of determination and perception of AW appeared to be a major barrier to enhance AW. Farmers should be confident that their measures to promote AW satisfy public opinion and are ecomically sustainable. The main objective of the study was a thorough understanding of relationships between AW and beef production economics to find barriers and opportunities for enhanced AW. A version of the Animal Needs Index (ANI/TGI 35L), modified for Finnish beef production, called A-index was used for AW assessments. The A-Index was modified and evaluated based on Test Theory. On-field associations between A-index and production parameters were determined on 180 farms and over 12 000 bulls using statistical multilevel models. Economic evaluation of AW was based on comparison between cold and warm housing using the confirmed association between AW and production results. AW was associated with good production results. A-Index and the best subset of items used as welfare score (WFS) were covering different aspects of AW. The association between the used measures and production results, reflecting AW in certain degree, can be considered as a proof of the criterion validity of A-Index and WFS. Cold housing with enhanced welfare and bedding based on own straw at a reasonable price was economically favourable. Profitability of cold housing was sensitive to fluctuation in bedding price. Developing a reasonably priced market for bedding material would be a major way to enhance AW. Rubber covered slats were found to be a profitable way to enhance AW in warm housing. A reform of the subsidy system was suggested to be needed to fulfil the aims of the subsidy regime to support AW.
  • Olkkola, Satu (Helsingin yliopisto, 2016)
    Campylobacteriosis is the most common cause of human bacterial gastroenteritis in the developed world. The most often isolated causative agent from diseased humans is C. jejuni, but also C. coli and C. upsaliensis, common colonizers of pigs and dogs, respectively, are known to cause disease. Campylobacteriosis is usually self-limiting but antimicrobial treatment is warranted in severe cases, with macrolides and fluoroquinolones being the first and second options, respectively. Intravenous aminoglycosides are indicated in Campylobacter bacteraemia. However, high rates of fluoroquinolone-resistant Campylobacter spp. have emerged in many parts of the world. Also, in several studies, high proportions of streptomycin-resistant C. coli or C. upsaliensis, have been found. Yet, the mechanisms of STR resistance have been only partially characterized in C. jejuni and C. coli and completely ignored in C. upsaliensis. The primary aim of this thesis was to investigate the molecular mechanisms of STR resistance in porcine C. coli and canine C. upsaliensis isolates. We were able to associate high level of STR resistance in porcine C. coli to mutations in the rpsL gene. In C. upsaliensis, a mutation in rpsL was also noted in all the low- and high-level STR-resistant isolates. All highly STR-resistant C. upsaliensis isolates had, in addition to the rpsL mutation, significant truncation of rsmG, encoding a conserved methyltransferase responsible for methylation of the ribosomal STR binding site. Even though STR resistance conferring mutations in rpsL and rsmG have been well documented in other bacterial species, they were first time described in Campylobacter spp. in the present study. Further, using genomics and insertional mutagenesis, a novel STR resistance-conferring gene was identified in the intermediately STR-resistant C. coli isolates. This gene is homologous, albeit at a low level, to other previously described aminoglycoside 6-adenylyltransferase encoding genes, and does not appear to originate from Gram-positive bacterial species. Based on our findings, we hypothesize that this gene could have evolved from a proto-resistance element in Campylobacter spp. Altogether these results provide a significant advance in understanding the mechanisms of STR resistance in Campylobacter spp. and will aid in predicting the phenotypic resistance from genome data. Fluoroquinolone resistance-associated mutations in the DNA gyrase-encoding gene gyrA were characterized in porcine C. coli treated with danofloxacin as well as among canine C. upsaliensis. The commonly described C257T mutation was found in both species. In C. coli this caused the amino acid change T86I in DNA gyrase and high levels of ciprofloxacin resistance, while in C. upsaliensis the predicted amino acid change was T86M causing only minor increase in CIP MIC but a high level of nalidixic acid resistance. Therefore, danofloxacin does not seem to induce novel mutations in C. coli in vivo but the same mutation appears not to be sufficient to cause a high level of fluoroquinolone resistance in C. upsaliensis.
  • Hielm-Björkman, Anna (Helsingin yliopisto, 2007)
    The series of investigations presented in this thesis examined different methods of assessing chronic pain in dogs suffering from osteoarthritis (OA) and compared the effects of three different treatments. Data were obtained from two cohorts; 41 dogs with OA due to canine hip dysplasia (CHD) (I,III) and 61 dogs with OA due to CHD or elbow dysplasia (II,IV,V). Questionnaires, veterinary evaluations, visual analog scales (VAS), plasma hormones, radiographs, and force plate evaluations were assessed as OA treatment outcome measures and/or measurements of chronic pain. The results indicated that the multidimensional pain scale including 11 questions with 5-point scale responses was a valid and reliable tool for evaluating chronic pain. This Helsinki chronic pain index (HCPI) can be applied as an outcome measure in clinical trials where chronic pain is evaluated by owners. Of the evaluated complementary therapies for chronic pain due to OA, all three indicated a positive treatment outcome. In the first trial, gold bead implants resulted in a significant positive treatment outcome for the treatment group. However, the placebo group in this study also improved significantly. A positive effect was seen in 65% of the placebo dogs and this exceptionally high incidence of amelioration suggests that the placebo group may have got an effect of unintentional needle acupuncture. The results of this study are therefore controversial and treatment guidelines based on these findings cannot be given. The second trial tested two ingestible OA remedies, green lipped mussel and a homeopathic low-dose combination preparation. Both treatments resulted in statistically significant positive treatment outcomes compared with placebo, but with the positive control (carprofen) being more effective than either of them. The results suggest that both tested treatments may be beneficial for chronic OA. To establish the true role of all these three treatments in outcome-based animal analgesia, more clinical trials, using larger cohorts, should be conducted. Possible mechanisms of action should also be studied.
  • Pohjola, Leena (Helsingin yliopisto, 2017)
    There is an increasing interest in keeping backyard poultry in many countries, including Finland. However, several studies in Western Europe and North America have identified the involvement of backyard poultry flocks in avian influenza virus outbreaks occurring in commercial poultry. In addition, commonly without any signs of illness, poultry can be carriers of enteric bacterial agents that are human pathogens. Farm management and biosecurity practices among 178 backyard poultry flocks were investigated using a questionnaire. Furthermore, the main causes of mortality of backyard chickens were studied through a retrospective study of necropsy data from the Finnish Food Safety Authority Evira from 2000 to 2011. In addition, voluntary backyard poultry farms were visited during October 2012 and January 2013, and blood samples, individual cloacal samples as well as environmental boot sock samples were collected from 51 farms and 457 chickens. The results of the questionnaire study revealed that the backyard poultry farms in Finland were mainly small (91 % ≤ 50 birds) and most flocks (98 %) had access to outdoors. Biosecurity practices, such as hand washing and changing shoes after bird contact were rare, 35 % and 13 % respectively. The farms were mainly located distantly (94 % > 3 km) from commercial poultry farms. The subjectively reported flock health was good (96 %). The most common postmortem diagnosis were Marek s disease (27 %) and colibacillosis (17 %). Of the zoonotic bacterial pathogens, Campylobacter jejuni and Listeria monocytogenes were frequently detected on the farms, 45 % and 33 %, respectively. Yersinia enterocolitica was also often isolated on the farms (31 %); however, all isolates were yadA negative, i.e. non-pathogenic. C. coli, Y. pseudotuberculosis and Salmonella enterica were rarely detected (2 %). All enteric bacteria were highly susceptible to most of the antimicrobials studied and only few AmpC- and no ESBL-producing E. coli were found. Avian encephalomyelitis virus, chicken infectious anemia virus and infectious bronchitis virus (IBV) antibodies were commonly found from the studied flocks, 86 %, 86 % and 47 %, respectively. The IBV detected from backyard poultry flocks were QX-type IBV strains differing from the strains found from commercial farms, suggesting different routes of infection for commercial and backyard poultry. The results indicated that among backyard poultry flocks pathogens circulate posing a risk to transmit infection to commercial poultry in Finland, but because of the distant locations and small flock sizes, the risk is relatively small. Notifiable avian diseases that also are of zoonotic potential (AIV and NDV) are very rare. Backyard chickens are a reservoir of C. jejuni strains and thus a potential source of C. jejuni infection for humans. Because of the lack of good hygiene after bird contact, the risk of transmission of the pathogen from birds to humans exists
  • Ikonen, Juhani (Helsingin yliopisto, 2020)
    Antibiootit ovat olleet suuressa roolissa mahdollistamassa nykyisten ruoantuotantoketjujen muodostumisen. Lemmikkieläinten määrä on samaan aikaan kasvanut ja lemmikkejä hoidetaan tänä päivänä yhä enemmän antibiooteilla. Antibioottien käyttö on kuitenkin johtanut antibiooteille vastustuskykyisten bakteereiden kehittymiseen, mikä vaikeuttaa jo nyt eläinten sekä ihmisten bakteeri-infektioiden hoitoa. Useat tahot tekevät työtä antibioottien vastuullisen käytön edistämiseksi ja resistenssiongelman torjumiseksi. Samalla on myös etsitty antibiooteille vaihtoehtoisia hoitomuotoja, joista bakteriofagit ovat yksi esimerkki. Bakteriofagit eli faagit ovat luonnossa esiintyviä, bakteereita infektoivia ja tuhoavia viruksia. Bakteriofagien monimuotoisuuden vuoksi jokaiselle bakteerille arvioidaan löytyvän sitä infektoimaan pystyvä faagi. Bakteriofagihoidolla tarkoitetaan bakteriofagien hyödyntämistä bakteeri-infektioiden hoidossa tai torjunnassa. Eläinten hoitoon bakteriofageja on käytetty ensimmäisen kerran jo 1920-luvulla eli ennen antibioottien löytämistä. Penisilliini ja muut tehokkaat antibiootit veivät kuitenkin huomion pois bakteriofageista, kunnes kiinnostus bakteriofageihin jälleen heräsi antibioottiresistenssin myötä. Bakteriofagihoidon onnistumisen kannalta on olennaista ymmärtää bakteerin, bakteriofagin ja elimistön välisiä vuorovaikutuksia. Hoitoon käytettävät bakteriofagit tulee valita huolella hoidon turvallisuuden sekä tehokkuuden takaamiseksi. Yksilöllisessä bakteriofagihoidossa taudinaiheuttajabakteeri eristetään ja juuri tälle patogeenille tehokkaista bakteriofageista valmistetaan hoitotuote. Toinen mahdollisuus on käyttää ennakolta valmistettuja hoitotuotteita, joita voidaan käyttää jo ennen patogeenin eristämistä. Bakteriofagihoidon erityispiirteisiin kuuluvat spesifisyys isäntäbakteerin suhteen, synergiaedut yhdistettyinä antibiootteihin tai toisiin faageihin sekä kustannustehokkuus. Eläimillä bakteriofagitutkimus on painottunut tuotantoeläimiin ja lemmikkieläimiä koskevia julkaisuja on vain muutamia. Tuotantoeläimillä tutkimusta on etenkin tehty yleisistä, taloudellisesti merkittävistä tai elintarvikehygieniaa vaarantavista sairauksista ja taudinaiheuttajista. Bakteriofagihoidon tehokkuus on ollut tutkimuksissa vaihtelevaa. Naudan utaretulehdus on yksi eniten tutkijoita kiinnostanut sairaus ja tältä osin bakteriofageilla ei pääsääntöisesti ole saavutettu haluttua hoitovastetta. Bakteriofageilla ei myöskään ole onnistuttu vähentämään metisilliinille resistentin Staphylococcus aureus -bakteerin (MRSA) määrää siassa. Sen sijaan bakteriofagien tehokkuudesta on saatu näyttöä vasikkaripulin, porsaiden vieroitusripulin ja koiran ulkokorvantulehduksen hoidossa sekä siipikarjassa zoonoottisesti merkittävien salmonella- ja kampylobakteerien torjunnassa. Myös useamman kalataudin torjunnassa bakteriofagien hyödyntämisessä on edistytty. Tutkimus eläinten bakteeri-infektioiden hoidosta bakteriofageilla on niukkaa. Saadut tulokset ovat vaihtelevia ja osittain myös keskenään ristiriitaisia. Antibiootteja täydentäville hoitomuodoille on aitoa tarvetta, ja bakteriofagit ovat ominaisuuksiensa takia mielenkiintoinen vaihtoehto. Kirjallisuuskatsauksen perusteella bakteriofagien mahdollinen soveltuvuus eläinten bakteeri-infektioiden hoitoon jää odottamaan lisätutkimuksia.
  • Pääkkönen, Tarja (Helsingin yliopisto, 2016)
    Although the immature brain reportedly is more prone to seizure activity than the mature brain, there are no previous reports on well-defined juvenile epilepsy syndromes in dogs. This study describes a novel juvenile epilepsy syndrome in Lagotto Romagnolo (LR) dogs, namely benign familial juvenile epilepsy (BFJE). We studied the clinical characteristics of this novel syndrome in 25 affected dogs, while healthy littermates of the affected dogs served as controls. The mean age at onset of focal seizures is 6 weeks, and spontaneous remission of seizures usually occurs by the age of 4 months. Between the seizure episodes, most of the affected puppies are neurologically normal, but puppies with the most severe seizure episodes exhibit some neurological deficits interictally. These deficits also resolve with remission of seizures. Interictal electroencephalography (EEG) shows focal abnormalities, including sharp waves and spikes, in most (88%) of the affected dogs. Conventional imaging examinations, including magnetic resonance imaging (MRI), show no remarkable focal abnormalities in dogs with BFJE. Positron emission tomography (PET) is a nuclear neuroimaging modality that is able to detect abnormal metabolism in the epileptic focus of the brain. We investigated glucose metabolism of the brain in 6 affected and 5 control dogs using radiolabeled glucose, namely 2-[18F]fluoro-2-deoxy-D-glucose (FDG), as a tracer. In dogs with BFJE, FDG-PET shows areas of hypometabolism with good correspondence to focal EEG findings, thus supporting the area of abnormal metabolism being the epileptic zone. Furthermore, we performed a follow-up study by utilizing two previously validated questionnaires on impulsivity and activity levels in dogs, and additionally, we telephone-interviewed the owners of the affected dogs. We evaluated the results based on the data collected for 25 dogs with a history of BFJE and 91 control dogs. We utilized principal component analysis to explore the factorial structure of the questionnaire. Although the life span of affected dogs seems to be comparable with that of healthy control dogs and recurrence of seizures after remission is rare, the dogs with a history of BFJE exhibit abnormalities in behavior reminiscent of attention deficit hyperactivity disorder (ADHD) in humans. This study also reveals the mode of inheritance and the genetic defect behind BFJE. Based on pedigree analysis, we found that BFJE is inherited in a recessive Mendelian form. We further found that a mutation in the gene encoding for protein LGI2 is responsible for BFJE. LGI2, as well as LGI1, interacts with neuronal membrane proteins, namely ADAM22 and ADAM23, in synaptic transmission. LGI1, ADAM22, and ADAM23 have previously been shown to be important in the development of epilepsy, and this study reveals the importance of LGI2 in epileptogenesis of BFJE.
  • Tuomola, Kati (Helsingin yliopisto, 2022)
    Bit-related oral lesions are a common and painful welfare issue in horses. Even though horses have been ridden and driven with a bit and bridle for 6000 years and bit sores have been described already in the 19th century in the veterinary literature, scientific reports on bit-related lesions and their risk factors in horses remain scarce. The aim of this thesis was to (i) determine the occurrence of oral lesions in the bit area in Finnish trotters and event horses after competitions, (ii) create a scoring system for oral lesions in the bit area and demonstrate different lesion types and locations with photographs, (iii) investigate risk factors for bit-related lesions in trotters and event horses, (iv) further investigate different stakeholders’ attitudes towards bit-related lesions in trotters. The rostral part of the mouth of 469 horses (261 trotters, 208 event horses) was examined systematically after a competition. Trotters were examined in 10 racing events in 2017 and event horses in 8 competition events in 2018–2019. Many horses had multiple lesions, and therefore, a lesion scoring system was created in which points were given to each lesion depending on its size, type (bruise or wound), and depth (superficial or deep). Points for each lesion were summed such that each horse received a total lesion score that reflected the overall lesion status. No acute lesions were found in 42 trotters (16%), and lesion status was mild in 55 trotters (21%), moderate in 113 trotters (43%), and severe in 51 trotters (20%). In event horses, no lesions were found in 99 horses (48%), and lesion status was mild in 45 (22%), moderate in 55 (26%), and severe in 9 horses (4%). The most common lesion location was the inner lip commissure. Lesions were also found in the bars of the mandible in front of the first lower cheek tooth, in the buccal area near the first upper cheek tooth, and in the outer lip commissures. Only a few horses had mild lesions involving the tongue and one horse in the hard palate. Although 109 event horses and 219 trotters had oral lesions in the bit area, none of the event horses and only six trotters showed external mouth bleeding. Additionally, one event horse and 26 trotters had blood inside the mouth or on the bit when it was removed from the mouth. Associations between a horse’s moderate-severe oral lesion status and potential risk factors were analyzed with multivariable logistic regression analysis. The association between bit type and lesion location was examined with Fisher’s exact test. Risk factors for moderate-severe oral lesion status in trotters were the use of a Crescendo bit, a mullen mouth regulator bit, or an unjointed plastic bit (model Happy Mouth) and female sex (mare). In event horses, the risk factors were thin (10–13 mm) and thick (18–22 mm) bits, female sex (mare), and other than pony breed. In both disciplines, unjointed bits were associated with lesions in the bars of the mandible. Single-jointed snaffle bits were the most common bit type in trotters and the least associated with moderate-severe lesions. In event horses, double-jointed 14–17 mm bits were most common. Bit thickness of 14–17 mm was the least associated with moderate-severe lesion status. However, these results may at least partly reflect driveability or rideability issues, and thus, rein tension differences because drivers/riders may change to distinctive bit designs if they have difficulty eliciting an appropriate response with rein cues. In the pilot questionnaire study, imaginary scenarios and photographs of lesions from horses’ mouths were presented to different stakeholders (veterinarians and race veterinary assistants, trainers, and others). They were asked in multiple choice questionnaires whether they allow the horse to start in the race, stipulate a health certificate before the next race, or remove the horse from the race. The association between stakeholder groups and their answers was examined with the Pearson Chi-square test. The results of this study indicated differences in attitudes towards bit-related lesions between stakeholder groups but also within a stakeholder group. This might reflect differences in conflicts of interests, moral values, empathy, or over-exposure to oral lesions. Not removing horses with severe oral lesions from the race may compromise horse welfare and society’s trust in the surveillance system. In this study, oral lesions in the bit area were common after a competition, although only few horses showed external bleeding. Oral examination and an oral lesion scoring system with an assistant recording the findings were suitable for field conditions and horses seemed to tolerate the examination well. Even though changing the bit to the bits least associated with lesions may be beneficial, horses with oral lesions might benefit from training modifications. Given the higher risk observed for mares in this study, mare oral health warrants special attention. Results of this thesis encourage adopting bit area monitoring as a new routine by horse handlers and as a welfare measure by competition organizers in order to minimize pain and negative experiences by early diagnosis and treatment of mouth lesions.
  • Ekman, Anna (Helsingin yliopisto, 2012)
    Immunological research is dominated by studies on man and mouse, however, only some aspects of this field are universal among vertebrates. Whilst the production of T cells is universal, B cell production cannot be extrapolated from one species to another. As such, ruminant B cell biology has distinctive features not similar to the conventional man or mouse based models. Cattle are large long-lived ruminants, of major significance globally. The bovine ileal Peyer s patch, an organ of B cell follicles along the gut, is where V(D)J immunoglobulin gene rearranged B cells proliferate, however it is not known where and how the DNA rearrangements take place before the B cells enter these follicles. Furthermore, it is unclear whether post-recombinatorial modifications, such as somatic hypermutation or gene conversion, facilitate the generation of more antibody specificities of the immunoglobulin genes in these follicles. Herein, the bovine immunoglobulin light chain genomic locus was characterized and only a moderate number of functional gene segments that cause low combinatorial antibody diversity were found. The lambda locus is the larger of the two light chain loci, containing 25 functional variable gene segments, compared to the kappa locus, which contains only eight. Functional genes comprise less than half of all the variable genes in both loci, the remainder representing unfunctional pseudogenes. The immunoglobulin genes of the fetal ruminant ileal Peyer s patch can possibly be further modified. Accordingly, the expression of activation-induced cytidine deaminase (AID), a mutator protein, was demonstrated here in fetal cattle ileal Peyer s patch. Sequencing of expressed heavy chain variable genes in these follicles showed ongoing hypermutation. The mutations were concentrated on the complementarity determining regions (CDR) of the variable genes, and on the hotspot target sequences of AID. AID-dependent mutations have usually been ascribed to antigen dependent affinity maturation, but this work demonstrates mutations in fetal immunoglobulin genes before exposure to external antigen. Bovine B lymphopoiesis is studied here, its localization in the fetal cattle in particular. By analyzing the expression of RAG1 and RAG2, which take part in the rearrangement of immunoglobulin genes, active B lymphopoiesis was demonstrated in fetal bone marrow and lymph node. The expression of surrogate light chain genes VPREB1 and IGLL1 was also shown in these same tissues. The expression of these genes implicated that a pre-B cell stage exists in cattle. This was further confirmed by the presence of a phenotypic pre-B cell population in fetal bone marrow and lymph node. VPREB2 and VPREB3 were expressed differently from the other surrogate light chain genes, which indicate that their function in cattle might not be related to pre-B cells. Overall, B lymphopoiesis was shown to take place in fetal, but not in adult, bovine tissues. Pre-B cell related genes RAGs, VPREB1 and IGLL1 were not expressed in adult tissues. Further, adult bone marrow cells were not able to differentiate into B lineage cells in cell culture. These results suggest that no new immunoglobulin rearrangements are generated during bovine adult life. Thus it is likely that the animal manages its whole life with the peripheral B cell pool produced during the fetal and neonatal period.
  • Taponen, Suvi (Helsingin yliopisto, 2008)
    Bovine mastitis caused by coagulase-negative staphylococci Mastitis is the most common disease affecting dairy cows, and staphylococci are the most common cause of mastitis. According to Finnish studies, staphylococci are isolated from 36% of clinical and 60% of subclinical mastitis cases. In mastitis diagnostics, staphylococci are divided into coagulase-positive and coagulase-negative based on their ability to coagulate plasma. Majority of staphylococcal mastitis is caused by coagulase-negative staphylococci (CNS). In mastitis diagnostics they are not identified at species level but are treated as a uniform group. Usually they cause subclinical or mildly clinical mastitis, and are considered as harmless bacteria of the normal skin flora. CNS mastitis is most common on the first lactation. It is assumed to cure spontaneously and antimicrobial treatment is not recommended. Although usually subclinical or mildly clinical, CNS mastitis causes increase of milk leucocytes and may decrease the milk quality. CNS mastitis seems to be especially a problem in well managed dairy herds with good udder health. In contrast to the usual assumption that CNS mastitis cures spontaneously, it may persist in the udder throughout the entire lactation. In addition, the CNS species are not necessarily a uniform group but differences between the species in virulence and clinical characteristics may exist. In this dissertation, different aspects of bovine mastitis caused by CNS were studied. The response of CNS mastitis to antimicrobial treatment was investigated, as well as the persistence of CNS intramammary infection when left without antimicrobial treatment. The prevalence of different CNS species in mastitis and on cows skin, and possible differences in clinical characteristics and persistence between CNS species were studied. Species identification was performed based on bacterial phenotype and genotype. Identification using different methods was compared. Majority of CNS mastitis was caused by S. chromogenes or S. simulans. Many other CNS species were isolated from mastitis sporadically. Molecular genetic identification methods based on bacterial genotype proved more reliable than biochemical methods based on bacterial phenotype. In some cases the identification results of genotypic and phenotypic methods disagreed. About half of CNS mastitis detected during lactation persisted without antimicrobial treatment, commonly until the end of lactation. Mastitis caused by penicillin-susceptible CNS cured well, about 90% cured. Of mastitis caused by penicillin-resistant CNS, 60 to 70% cured, although the causing bacteria were susceptible to the antimicrobial used. Most often CNS mastitis was subclinical or mildly clinical. Statistically significant differences in clinical characteristics or persistence between the two most common CNS species were not detected.
  • Simojoki, Heli (Helsingin yliopisto, 2011)
    Coagulase-negative staphylococci (CNS) are the most common bacteria isolated in bovine subclinical mastitis in many countries, and also a frequent cause of clinical mastitis. The most common species isolated are Staphylococcus (S) chromogenes, S. simulans, S. epidermidis, and S. xylosus. One half of the intramammary infections (IMI) caused by CNS persist in the udder. The pathogenesis of IMI caused by CNS is poorly understood. This dissertation focuses on host response in experimental intramammary infection induced by S. chromogenes, S. epidermidis and S. simulans. Model for a mild experimental CNS infection was developed with S. chromogenes (study I). All cows were infected and most developed subclinical mastitis. In study II the innate immune response to S. epidermidis and S. simulans IMI was compared in eight cows using a crossover design. A larger dose of bacteria was used to induce clinical mastitis. All cows became infected and showed mild to moderate clinical signs of mastitis. S. simulans caused a slightly stronger innate immune response than S. epidermidis, with significantly higher concentrations of the interleukins IL-1beta and IL-8 in the milk. The spontaneous elimination rate of the 16 IMIs was 31%, with no difference between species. No significant differences were recorded between infections eliminated spontaneously or remaining persistent, although the response was stronger in IMIs eliminated spontaneously, except the concentration of TNF-α, which remained elevated in persistent infections. Lactoferrin (Lf) is a component of the humoral defence of the host and is present at low concentrations in the milk. The concentration of Lf in milk is high during the dry period, in colostrum, and in mastitic milk. The effect of an inherent, high concentration of Lf in the milk on experimental IMI induced with S. chromogenes was studied in transgenic cows that expressed recombinant human Lf in their milk. Human Lf did not prevent S. chromogenes IMI, but the host response was milder in transgenic cows than in normal cows, and the former eliminated infection faster. Biofilm production has been suggested to promote persistence of IMI. Phenotypic biofilm formation and slime producing ability of CNS isolates from bovine mastitis was investigated in vitro. One-third of mastitis isolates produced biofilm. Slime production was less frequent for isolates of the most common mastitis causing species S. chromogenes and S. simulans compared with S. epidermidis. No association was found between the phenotypic ability to form biofilm and the persistence of IMI or severity of mastitis. Slime production was associated with persistent infections, but only 8% of isolates produced slime.
  • Suojala, Leena (Helsingin yliopisto, 2010)
    Bovine mastitis caused by Escherichia coli remains a problem in many countries despite of improvements in managing and housing of dairy cattle. Cows with compromised immune systems, especially those in early lactation, are particularly susceptible to E. coli intramammary infection. Mastitis caused by E. coli varies from mild, with local signs only, to severe systemic. The severe form of E. coli mastitis is associated with loss of milk production and can result in death of the cow. Intramammary infection caused by E. coli is often eliminated spontaneously as the defense mechanisms of the cow are able to clear the bacteria from the udder. The aims of this thesis were to investigate host response to E. coli mastitis in terms of characteristics of bacteria, effect of antimicrobial and non-antimicrobial treatment, and prophylactic effect of recombinant human lactoferrin expressed in milk. Host response was studied using two consecutive intramammary challenges with E. coli in the same cows at a short interval. All cows became infected, but local signs were significantly milder and disappeared faster after the second challenge. The same pattern was recorded for the indicators of inflammation; the differences being statistically significant for serum and milk haptoglobin, milk serum amyloid A, and white blood cell count. Milk production returned to the pre-challenge level significantly faster after the second challenge. This study revealed a possible carry-over or immunizing effect of the previous intramammary infection by the same pathogen. Broad-spectrum antimicrobials have been widely used for treating E. coli mastitis, although the results of treatment studies have been controversial. In our field study, systemic enrofloxacin treatment did not result in better bacteriological or clinical cure of acute clinical mastitis caused by E. coli than supportive treatment alone. Enrofloxacin treatment did not affect survival of the cows, return of quarter milk production or tissue damage of the affected quarter within three weeks post-treatment; nor did it affect the length of time the cow remained in the herd during the six-month follow-up period. The only positive effect of the enrofloxacin treatment was a higher bacteriological cure 2 days post-treatment. On the contrary, clinical cure on day 2 was lower in the enrofloxacin treated cows. Clinical cure assessed 21 days post-treatment was relatively low in both groups, which probably reflects the severe nature of acute E. coli mastitis. Our study did not support the use of parenteral antimicrobial treatment of clinical E. coli mastitis. In severe cases of coliform mastitis, antimicrobial treatment could, however, still be recommended for safety reasons, as it can increase the elimination of bacteria and prevent possible bacteraemia. Our results indicated also that frequent milking at the acute stage of mastitis might improve the initial clinical cure of E. coli mastitis and decrease inflammation and tissue damage in the infected quarter. Most E. coli isolates belonged to the phylogenetic group A, indicating their commensal nature. Close to 40% of the isolates had at least one virulence gene, but combinations of virulence genes varied greatly, each combination being present mainly in a single isolate. Approximately 30% of the isolates showed resistance to one or more antimicrobials tested, most commonly against ampicillin, streptomycin, tetracycline and sulphonamides. No specific virulence factor, phylogenetic group or resistance to antimicrobials was associated with persistence or severity of disease among mastitis E. coli isolates in our field study. These results indicate that characteristics of bacteria are not likely to affect the clinical course and outcome of E. coli mastitis. In 11% of mastitis cases, the same genotype of E. coli was isolated from the affected quarter three weeks post-treatment as originally, indicating persistence of the same genotype of E. coli in the quarter. Non-antimicrobial treatments, such as lactoferrin, which has antibacterial and lipopolysaccharide neutralizing properties, could be beneficial in the treatment of E. coli mastitis. The efficacy of intramammary lactoferrin was compared with that of systemic enrofloxacin in an experimentally induced E. coli model. No significant differences were found in the clinical signs between cows treated with lactoferrin and those treated with enrofloxacin. The results from this study remained inconclusive. The prophylactic effect of lactoferrin against E. coli mastitis was studied in a new model of using hLf-transgenic cows, which expressed recombinant human lactoferrin in their milk. This was the first study to describe an experimentally induced E. coli mastitis model using transgenic cows. The high concentration of lactoferrin in the milk of the transgenic cows did not protect the cows from E. coli intramammary infection, and all of them became infected. No differences were noted in the bacterial growth, times to bacterial elimination, local signs or in any of the milk or blood inflammatory parameters, except in concentrations of haptoglobin and cortisol in the serum. However, systemic signs were significantly milder in transgenic cows. Prevention of E. coli mastitis relies on decreasing the infection pressure in the environment of the cows and improving the cow comfort and herd management. In E. coli mastitis, the treatment should be as efficient as possible, but novel therapeutic approaches are needed, as the efficacy of the current commonly used antimicrobial treatments is not satisfactory.
  • Perko-Mäkelä, Päivikki (Helsingin yliopisto, 2011)
    Campylobacter, mainly Campylobacter jejuni and C. coli, are worldwide recognized as a major cause of bacterial food-borne gastroenteritis. Epidemiological studies have shown handling or eating of poultry to be significant risk factors for human infections. Campylobacter contamination can occur at all stages of a poultry meat production cycle. The aim of this thesis was to study the occurrence and diversity of Campylobacter in broiler and turkey production in Finland. In summer 1999, 2.9 % of slaughtered broiler flocks were Campylobacter-positive. From the isolated strains 94 % were C. jejuni and 6% were C. coli. During years 2005-2006 one turkey parent flock, the hatchery, six different commercial turkey farms and different stages of the slaughterhouse were monitored during one and the half year. No Campylobacter were detected in either of the samples from the turkey parent flock or from the hatchery using the culture method. Instead PCR detected DNA of Campylobacter from the turkey parent flock and samples from the hatchery. Six out of 12 commercial turkey flocks were found negative at the farm level but only two of those were negative at slaughter. Campylobacter-positive samples within the flock at slaughter were detected between 0% and 94% with evisceration and chilling water being the most critical stages for contamination. All of Campylobacter isolates were shown to be C. jejuni. Campylobacter-positive turkey flocks were colonized by a limited number of Campylobacter genotypes both at the farm and slaughter level. In conclusion, in our first study in 1999 a low prevalence of Campylobacter in Finnish broiler flocks was detected and it has remained at a low level during the study period until the present. In the turkey meat production, we found that flocks which were negative at the farm became contaminated with Campylobacter at the slaughter process. These results suggest that proper and efficient cleaning and disinfection of slaughter and processing premises are needed to avoid cross-contamination. Prevention of colonization at the farm by a high level of biosecurity control and hygiene may be one of the most efficient ways to reduce the amount of Campylobacter-positive poultry meat in Finland. With a persistent low level of Campylobacter-positive flocks, it could be speculated that the use of logistic slaughtering, according to Campylobacter status at farm, might have be advantageous in reducing Campylobacter contamination of retail poultry products. However, the significance of the domestic poultry meat for human campylobacteriosis in Finland should be evaluated.
  • Viitanen, Sanna (Helsingin yliopisto, 2017)
    Bacterial pneumonia (BP) is an acquired inflammation of the lower airways and lung parenchyma secondary to bacterial infection. BP is difficult to induce experimentally in healthy dogs; the pathogenesis is therefore considered complex, involving several underlying mechanisms. BP was first described in dogs decades ago, but it is still one of the most common systemic bacterial infections in dogs, with a significant morbidity and mortality. Several aspects of BP, including the applicability of inflammatory biomarkers in its diagnosis and follow-up as well as the role of respiratory viruses in its clinical picture and development, warrant further studies. This thesis aimed to describe clinical findings during the disease and recovery periods in dogs with BP and to evaluate the applicability of acute-phase proteins as diagnostic and follow-up markers in BP. The prevalence and role of viral co-infections in dogs with BP were also investigated. We evaluated the diagnostic applicability of serum C-reactive protein (CRP) and noted that CRP is significantly elevated in BP relative to dogs with other lower respiratory tract diseases, such as chronic bronchitis, bacterial tracheobronchitis, canine idiopathic pulmonary fibrosis, and eosinophilic bronchopneumopathy, as well as in cardiogenic pulmonary edema. Our results indicate that serum CRP concentration may be used as an additional biomarker in the diagnosis of canine BP. Serum CRP, serum amyloid A (SAA), and haptoglobin (Hp) were followed during the disease and recovery periods. The follow-up study showed that serum CRP and SAA reflected well the recovery process and declined rapidly after initiation of successful therapy and could therefore be used as markers of treatment response in dogs with BP. Currently, markedly longer antibiotic courses are recommended in dogs with BP than in humans with pneumonia. Since serum CRP is a sensitive inflammatory biomarker, it was hypothesized that normalization of serum CRP could be used as an indicator for the cessation of antimicrobial therapy. In our study, we treated a group of dogs according to conventional recommendations. In another group, antimicrobial therapy was ended 5-7 days after CRP normalization. When the normalization of CRP was used to guide antimicrobial therapy, treatment length was significantly reduced without increasing the number of relapses. According to these results, normalization of serum CRP may be applied to guide the length of antimicrobial therapy in dogs with BP. Respiratory viruses, primarily canine parainfluenza virus, were found frequently in lower respiratory tract samples in dogs with BP. This indicates that viruses may play an important role in the etiology and pathogenesis of BP. Viral co-infections did not affect disease severity or clinical variables. Our findings add new knowledge about the natural course of BP as well as about the possible applications of acute phase protein measurements in the diagnosis and follow-up of BP. The utilization of acute phase protein measurements may allow a more precise diagnosis of BP, enable the early identification of patients with a poor response to treatment, and diminish the use of antimicrobial drugs.
  • Rikula, Ulla Kaisa (Helsingin yliopisto, 2008)
    Canine distemper (CD) is one of the longest-known infectious diseases of dogs and many other carnivores. Control of CD among dogs relies heavily on vaccination, while in fur farms and zoos biosecurity measures in some cases offer the only available means for CD control. Modified live CD virus vaccines have been successfully used to control CD among farmed mink, and since no licensed vaccines for other species kept for fur exist, they have also been used for foxes and raccoon dogs in CD emergency situations. CD vaccines for dogs and mink were studied in experimental settings for their ability to induce virus-neutralising (VN) antibodies in target species. Mink vaccines were also assessed in silver foxes, blue foxes and raccoon dogs. Purpose-bred beagle dogs were vaccinated twice with one of three CD vaccines: Candur® SHP, Canlan®-3 or Dohyvac® DA2P, and the levels of VN antibodies were determined at the time of vaccination and one month after the second vaccination. Fur animals were vaccinated once with Distemink®, Distem®-R-TC or vaccine 3 and the levels of VN antibodies were determined at vaccination and 2-4 times 1-4 months afterwards. Significant differences among vaccine groups were found both in the proportion of animals with measurable levels of VN antibodies and in the mean titres of antibodies. The levels of VN antibodies were also determined from a large field sample (n = 4 627) of vaccinated dogs. In addition to the three CD vaccines in the seroconversion study above, additional two vaccines, Duramune®-4 and Nobivac® DHP, had been used in the field. Each dog with a known vaccination history, date of birth, sex and breed was sampled once. Based on the overall geometric mean titre of the dogs vaccinated with a single vaccine brand, vaccines were divided into high-take (Candur®, Nobivac® and Duramune®) and low-take (Dohyvac® and Canlan®) groups. The vaccine groups differed significantly among dogs less than two years of age both in the proportion of dogs with detectable VN antibodies and in the mean titres. Both the number of vaccinations and age were associated with the titre and vaccine usage. To control for possible confounding factors, the comparison of titres among vaccine usage groups was adjusted by classifying them according to the number of vaccinations (one to four) and the age group (less than one, one to two, or over two years old). The same division into low- and high-take vaccines was observed, irrespective of the number of vaccinations the dogs had received. The observations of this seroprevalence study regarding Candur®, Canlan® and Dohyvac® were consistent with the results of the seroconversion study. CD was reintroduced into Finland in 1990 after 16 years of absence. The disease remained at a low endemic level in 1990-1994, reached epidemic proportions in 1994-1995 and disappeared during 1995. The epidemic also involved vaccinated dogs. Among the virologically-confirmed cases the proportion of Dohyvac®-vaccinated dogs was higher than expected from the market shares on the assumption that all the vaccines had an equal take. As a result of this observation, Dohyvac® was withdrawn from and Nobivac® and Duramune® introduced to the market during 1995. A drastic redistribution of the market shares between the low-take and high-take vaccines took place, and this coincided with the decline and dying out of the outbreak. The observed occurrence pattern of CD from 1990-1996 was largely attributed to the changes in the level of HI, although the possible contribution of other factors, such as developments in the dog demographics, was also recognized. It was concluded that an HI above 75% is needed to keep CD in check, i.e., only sporadic cases of CD, at most, can occur. With the currently used vaccines an HI of 80% corresponds to a vaccine coverage of some 94%. It was concluded that the development of vaccine-induced immunity is a multifactorial process depending on the properties of the vaccine, on the individual variation, age, species and other factors influencing the immunocompetence of the host. On the individual level the prevention of clinical signs is sufficient, but on the population level, halting the circulation of the virus is crucial for the definitive control of CD. The ultimate test and criterion for a vaccine is its contribution to herd immunity.
  • Laurila (os. Heikkilä), Henna (Helsingin yliopisto, 2015)
    Canine idiopathic pulmonary fibrosis (CIPF) is a chronic interstitial lung disease of unknown origin mainly affecting West Highland white terriers (WHWT). No curative treatment exists. Differentiating CIPF from other chronic respiratory diseases is difficult. Therefore, a measurable biomarker would be helpful. CIPF shares clinical features with human idiopathic pulmonary fibrosis (IPF), but the histopathological resemblance of the two diseases has been unclear. We described the clinicopathological and diagnostic imaging findings in dogs with CIPF and compared them with those of healthy WHWTs. The most typical clinical signs were cough and exercise intolerance. Inspiratory Velcro crackles were characteristic and an abdominal breathing pattern was often present. Many dogs were hypoxemic. Bronchointerstitial opacity was the most common radiographic finding. In high resolution computed tomography, ground glass opacity was a consistent feature, whereas honeycombing and traction bronchiectasis were less common. Bronchoalveolar lavage fluid (BALF) total cell count was elevated in CIPF and bronchial changes were common. We investigated the serum and BALF concentrations of two potential fibrosis biomarkers, endothelin-1 (ET-1) and procollagen type III amino terminal propeptide (PIIINP) in dogs with CIPF, chronic bronchitis (CB), eosinophilic bronchopneumopathy (EBP) and healthy dogs. Serum ET-1 was higher in dogs with CIPF than in other groups. BALF ET-1 was measurable only in dogs with CIPF. BALF PIIINP was higher in dogs with CIPF than in dogs with CB or healthy dogs, but not different from dogs with EBP. Serum PIIINP was not useful. We defined the histopathological lesions and their distribution in WHWTs with CIPF and compared them with those of human usual interstitial pneumonia (UIP), which is the histopathological pattern of human IPF, and human nonspecific interstitial pneumonia (NSIP), which is an important differential diagnosis of human IPF. A diffuse mature interstitial fibrosis of varying severity, resembling human NSIP, was seen in the lungs of all CIPF dogs. The majority of CIPF dogs also had multifocal areas of accentuated subpleural and peribronchiolar fibrosis with occasional honeycombing and profound alveolar epithelial changes, reminiscent of human UIP. Interstitial fibroblastic foci, characteristic of UIP, were not seen in WHWTs. In this thesis we provide a detailed description of the clinicopathologic and diagnostic imaging features of CIPF and present quantitative values for arterial blood gases and BALF cytology. Serum ET-1 and BALF PIIINP are elevated in dogs with CIPF and could differentiate CIPF from CB. Histopathologically, CIPF is characterised by two types of interstitial fibrosis and shares features of both human UIP and NSIP.
  • Määttä, Merita (Helsingin yliopisto, 2022)
    Reflux aspiration is considered as a potential cause or disease aggravating factor for several respiratory diseases in humans including idiopathic pulmonary fibrosis (IPF). Regarding dogs, this information is very limited. One method to detect reflux aspiration is to measure gastrointestinal components from airway samples. Canine idiopathic pulmonary fibrosis (CIPF) affects mainly West Highland white terriers (WHWTs) and shares many features with human IPF. Both CIPF and IPF are characterized by an accumulation of extracellular matrix (ECM) components, mainly collagen, in the lungs. Matrix metalloproteinases (MMPs) are endoproteinases capable of ECM remodeling and especially MMP-7 is considered as a potential disease biomarker for human IPF. In the first part of this thesis, we evaluated the presence of bile acids in bronchoalveolar lavage fluid (BALF) of dogs with various respiratory diseases. Bile acids were detected in all disease groups and bile acid concentrations were significantly higher in CIPF, healthy WHWTs, laryngeal dysfunction (LD), and chronic bronchitis (CB) groups compared to healthy Beagles. In the second part of this thesis, we compared MMP-2, -7 and -9 activities in blood and BALF samples of CIPF WHWTs with healthy dogs and dogs with other lung diseases. Significantly higher serum pro-MMP-7 activities were observed in CIPF WHWTs compared to groups of CB, eosinophilic bronchopneumopathy (EBP) and healthy dogs of other breeds. Both pro-MMP-9 and pro-MMP-2 activities were significantly higher in BALF of CIPF WHWTs compared to healthy WHWTs. The CIPF WHWTs had significantly higher activities of pro-MMP-9 compared to dogs with CB and additionally higher pro-MMP-2 activities compared to dogs with CB and EBP. In the third part of this thesis, we evaluated the BALF proteomic profile in CIPF and healthy WHWTs. Several inflammatory and fibrotic proteins were elevated in CIPF WHWTs. Additonally, we studied the proteome of canine gastric juice and vomitus in order to find protein biomarkers for reflux aspiration. Two potential biomarker proteins were detected. The finding, that aspiration occured in both CIPF and healthy WHWTs may indicate the role of reflux aspiration in the etiopathogenesis of CIPF. Measurement of certain proteins such as MMPs may provide practical tool to improve diagnostic work up of CIPF.