Dairy cows can suffer from a negative energy balance (NEB) during their transition from the dry period to early lactation, which can increase the risk of postpartum diseases such as clinical ketosis, ...mastitis, and fatty liver. Zeolite clinoptilolite (CPL), due to its ion-exchange property, has often been used to treat NEB in animals. However, limited information is available on the dynamics of global metabolomics and proteomic profiles in serum that could provide a better understanding of the associated altered biological pathways in response to CPL. Thus, in the present study, a total 64 serum samples were collected from 8 control and 8 CPL-treated cows at different time points in the prepartum and postpartum stages. Labelled proteomics and untargeted metabolomics resulted in identification of 64 and 21 differentially expressed proteins and metabolites, respectively, which appear to play key roles in restoring energy balance (EB) after CPL supplementation. Joint pathway and interaction analysis revealed cross-talks among valproic acid, leucic acid, glycerol, fibronectin, and kinninogen-1, which could be responsible for restoring NEB. By using a global proteomics and metabolomics strategy, the present study concluded that CPL supplementation could lower NEB in just a few weeks, and explained the possible underlying pathways employed by CPL.
The aim of this study was to investigate serum paraoxonase-1 (PON1) activity and lipid status in cows with subclinical and clinical mastitis in order to evaluate systemic inflammatory and oxidative ...stress responses. The study was conducted on a total of 90 Holstein-Friesian dairy cows kept in farms in eastern Croatia. Cows were assigned into three groups: the cows suffering from clinical mastitis (CLM), the cows with subclinical mastitis (SCM) and control (CTL) group. In collected sera, PON1, lipid status and calcium concentration were measured. Total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C) and calcium concentrations were significantly lower in the CLM group of cows compared to the SCM and CTL groups (P < 0.05). There were no significant differences in the lipid status and calcium level between the CTL and SCM groups. PON1 activity was significantly lower in both the SCM and CLM groups compared with CTL indicating that PON1 could be considered as a potential biomarker for the diagnosis of subclinical form of the disease.
In the past two decades many substances of natural or synthetic origin were studied as potential alternatives to antibiotic growth promoters (AGP) and some of them, particularly immunomodulators ...(IMs) and nutraceuticals (NCs), have shown to be capable of stimulating functions of the immune system and improving general health. At the same time, they were shown to be harmless for animals and the environment. Promising results have been obtained with natural clay minerals, zeolites among which clinoptilolite (CPL) is the best known as zootechnical and biomedical feed ingredient widely reported in scientific literature and used in farm animal nutrition. CPL has a potential to replace AGP due to its unique anti-bacterial properties, safety and efficacy as dietary supplement in food animals unifying potentials of an IM and NC. Currently, there are many reasons for CPL utilization in animal biotechnology and veterinary medicine because of it’s detoxificating, antioxidant, hemostatic, anti-diarrheic, growth-promoting and immunostimulating properties. Also, in human medicine it is an adjuvant in immunodeficiency states, oncology (after chemotherapy and radiotherapy) or reducer of radioactive elements. The aims of this review were to compile and discuss scientific data on safety and efficiency of nutritive modulation by dietary CPL (and other zeolites) as an alternative to AGP in animals of veterinary importance In particular the aim is to analyse its potentials and limitations in cattle regarding metabolic and endocrine status, oxidative stress and systemic/local inflammatory responses involved in reproductive and metabolic disorders of dairy cows. Altogether, these analyses will contribute to objective validation of practical significance of CPL as a novel feed additive able to maintain and improve health, fertility and performance in cattle production.
The objective of this study was to evaluate the effects of in-feed clinoptilolite (CPL) on serum metabolic and antioxidative biomarkers, acute phase proteins and reproductive performance in cows ...during pregnancy and lactation. A total of 78 Holstein-Friesian cows were randomly assigned into two groups: the treatment group, cows fed CPL (n = 38) which received 50 g of powdered CPL twice a day from day 180 before parturition to day 60 postpartum; and the control group (n = 40). Blood samples were taken on days 180, 90, 60, 30 and 10 before parturition, on day of calving and on days 5, 12, 19, 26, 33, 40 and 60 postpartum, and were analysed for metabolic biomarkers: glucose, triglycerides, total cholesterol, high density lipoprotein cholesterol, non-esterified fatty acids, beta-hydroxybutyrate (BHB), antioxidative biomarkers and acute phase proteins: paraoxonase-1 (PON1), apolipoprotein A-I, haptoglobin (Hp) and serum amyloid A (SAA). CPL supplementation increased concentration of glucose and significantly decreased (P < .05) level of BHB during puerperium. The SAA concentration in CPL-fed cows was significantly decreased (P < .05) on days 33, 40 and 60 postpartum as well as Hp concentration on days 0 and 12 postpartum. The results of this study suggest that the CPL-fed cows may have improved metabolic status due to the tendency of greater glucose levels and decreased BHB values during early lactation. In addition, acute phase response was lower (P < .05) in CPL-fed cows. Such an outcome might be attributed to the effect of dietary CPL on intensity and severity of the negative energy balance and inflammatory response in dairy cows.
•Dietary clinoptilolite improves metabolic status in dairy cows.•Acute phase response was lower in clinoptilolite-in feed supplemented cows.•Clinoptilolite supplementation could affect severity of the NEB in dairy cows.•Dietary clinoptilolite improved reproductive performance in dairy cows.•Clinoptilolite supplement had a positive influence on milk yield in dairy cows.
The objectives of this study were to investigate whether or not the synthetic compounds, levamisole (LEVA) and polyoxyethylene-polyoxypropylene (POE-POP) copolymers, well-known to act as ...immunomodulators (IMs) in swine, may positively influence the cellular and humoral immune parameters of weaned pigs, without negatively affecting their hematological (HE), serum biochemistry (SB) and gut histocytological (HC) homeostasis. The pigs from a commercial swine farm were weaned at 26 days of age, randomly divided into 3 groups comprising 20 animals each, and kept in separate pens within the same rearing facility. At the age of 28 days (Day 0 of the experiment), the pigs were treated as follows: (1) control pigs perorally (p.o.) received 10 mL of saline, and the principals were p.o. treated with a single dose of 10 mL of either: (2) LEVA with 2.5 mg/kg body weight of the anthelmintic drug or (3) POE-POP with 2.5 mg/mL of the copolymer preparation. The experiment was conducted over 35 days, and 7 pigs per group were sampled for peripheral blood at 7 day intervals, starting at Day 0 before the treatments for immunohematology and SB analyses. At either Day 0 or Day 35 of the experiment 5 pigs per group were euthanatized and sampled for gut HC. The POE-POP-treated pigs had increased proportions of lymphocytes (P < 0.05) at Day 35. These pigs had higher levels of total serum immunoglobulins (P < 0.05) at Day 14. The LEVA-treated pigs had decreased proportions of lymphocytes (P < 0.05) at Day 14, although their total leukocyte count was similar to that recorded in the controls. None of the tested IMs affected the values of HE parameters, indicating that they did not cause any harmful side effects during the observation period of 5 weeks following the treatments. Minor oscillations in SB parameters were observed, but their values were within the normal range for swine and in accordance with the ages of the pigs. The HC features of gut mucosa in the pigs from the principal groups showed very mild damage and were quite normal for farm pigs exposed to natural infections, indicating that the tested IMs did not induce any additional HC changes. The obtained results imply that immunomodulating treatment with tested IMs was not associated with any adverse effects on the monitored HE, SB and gut HC parameters, and thus, does not suggest any putative impairment in the general health status of weaned pigs throughout the experimental period. Key words: immunemodulation, levamisole, copolymers polyoxyethylene-polyoxypropylene, hematology, serum biochemistry, gut histocytology, homeostasis, pigs Ciljevi ovoga rada bili su istraziti mogu li, ili ne, sinteticki spojevi levamisol (LEVA) i polioksietilenskipolioksipropilenski (POE-POP) kopolimeri, dobro znani da djeluju kao imunomodulatori (IM) u svinje, pozitivno utjecati na stanicne i humoralne imunosne pokazatelje odbijene prasadi a da negativno ne djeluju na njihovu hematolosku (HE), serumsku biokemijsku (SB) i crijevnu histocitolosku (HC) homeostazu. Na komercijalnoj svinjogojskoj farmi prasad je bila odbijena u dobi od 26 dana, nasumicno podijeljena u tri skupine od po 20 zivotinja u svakoj, te drzana u odvojenim odjeljcima u istoj uzgojnoj nastambi. U dobi od 28 dana (= 0. dan pokusa), prasad je tretirana kako slijedi: (1) kontrolna prasad je per os (p.o.) primila 10 mL fizioloske otopine, a pokusna je prasad bila p.o. tretirana jednokratnom dozom od 10 mL ili (2) LEVA s 2,5 mg/kg tjelesne tezine antihelmintickog lijeka, ili POE-POP sa 2,5 mg/mL kopolimerskog pripravka. Pokus je proveden tijekom 35 dana, a od 7 prasadi po skupini uzimani su uzorci periferne krvi za imunohematoloske i SB pretrage u razmacima od 7 dana pocevsi od 0. dana prije tretmana. Po pet prasadi iz svake skupine bilo je eutanazirano 0. i 35. dana pokusa radi uzimanja uzoraka za crijevnu HC. Prasad koja je primila POE-POP imala je veci udjel limfocita (P < 0,05) 35. dana. Ta je prasad imala visu razinu ukupnih serumskih imunoglobulina (P < 0,05) 14. dana. Prasad tretirana s LEVA imala je smanjen udjel limfocita (P < 0,05) 14. dana, premda je ukupan broj njihovih leukocita bio slican onom zabiljezenom u kontrolne prasadi. Niti jedan od testiranih IM nije utjecao na vrijednosti HE pokazatelje, upucujuci na to da nisu uzrokovali nikakve stetne popratne ucinke tijekom razdoblja pracenja pokusa od pet tjedana nakon tretmana. Utvrdene su manje oscilacije pokazatelja SB, ali su te vrijednosti bile u rasponu normalnih vrijednosti za svinju i primjerene dobi prasadi. HC nalazi u sluznici crijeva prasadi pokusnih skupina pokazivali su vrlo blaga ostecenja i bili su gotovo normalni za farmsku prasad koja je izlozena prirodnim infekcijama te upucuju na to da testirani IM nisu izazivali nikakve dodatne HC promjene. Dobiveni rezultati podrazumijevaju da imunomodulacijski tretman s testiranim IM nije bio povezan s bilo kakvim nepovoljnim ucincima na HE, SB i crijevne HC pokazatelje. Kljucne rijeci: imunomodulacija, levamisol, kopolimeri POE-POP, hematologija, serum, biokemijski pokazatelji, histocitoloski nalaz, homeostaza, prasad
Prvi pisani dokazi korištenja životinja u pokusima potječu još iz Staroga vijeka. Sve do otkrića anestetika životinje su u pokusima proživljavale nezamislive patnje. Prvi akt koji je zabranjivao ...okrutnost prema životinjama u pokusu donesen je u Britanskom parlamentu 1876. godine. Sredinom dvadesetog stoljeća znanstvenici Russell i Burch u svome su djelu “Načela humanih pokusnih tehnika” postavili temelje nove primijenjene znanstvene discipli- ne koja je trebala poboljšati postupke u radu s laboratorijskim životinjama, a ujedno i pri- donijeti kvaliteti znanstvenog rada u kojem se te životinje koriste. Raščlamba metoda kojima bi se mogli isključiti neljudski postupci prema životinjama u pokusu rezultirala je stvaranjem koncepta 3R načela: Replacement (zamjena), Re- duction (smanjenje) i Refinement (poboljšanje) s ultimativnim ciljem sadržanim u tek jednoj rije- či‒čovječnost. Razvojem znanosti, tehnologije, ali i evolucijom svijesti kako znanstvenika, tako i šire društvene zajednice, 3R načela svakod- nevno se razvijaju, tako da možemo govoriti i o 11R načelima jer se uz tri prethodno navede- na danas još navode i Reliability (pouzdanost), Relevance (pogodnost‒prikladnost), Reproduci-
bility (ponovljivost), Rehabilitation (oporavak), Responsibility (odgovornost), Respect (poštova- nje), Redundancy avoidance (izbjegavanje nepo- trebnih ponavljanja) i Regulation (zakonitost postupaka). 3R načelo razvijalo se tijekom pro- teklih pedeset godina osiguravajući okvir za izvođenje humanih pokusnih postupaka pre- ma životinjama, a prvi se puta sam naziv „Na- čela zamjene, smanjenja i poboljšanja“ uvodi u zakonodavstvo Europske unije kroz Direktivu 2010/63/EU. Godine 2010. donesena je Baselska deklaracija kojoj je cilj ujediniti napore znan- stvene zajednice u nastojanjima daljnjeg una- prjeđivanja primjene etičkih principa poput 3R načela u pokusima na životinjama sa svrhom postizanja pozitivnog dijaloga znanstvene za- jednice sa zainteresiranom javnošću. Danas projekt “Odgovorno istraživanje i inovacije” (Responsible Research and Innovation, RRI) Eu- ropskog okvirnog programa Obzor 2020 potiče suradnju i dijalog među istraživačima, građa- nima, političarima, itd. tijekom cijelog procesa istraživanja kako bi se taj proces i njegovi isho- di bolje uskladili s vrijednostima, potrebama i očekivanjima društva.
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