Publications by authors named "Ulrich Bleul"

22 Publications

  • Page 1 of 1

Haematological findings in 158 cows with acute toxic mastitis with a focus on the leukogram.

Acta Vet Scand 2021 Mar 12;63(1):11. Epub 2021 Mar 12.

Department of Farm Animals, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

Background: In cows with acute toxic mastitis (ATM), the leukogram aids in the assessment of the severity of disease. The goal of our study was to compare the leukogram of 158 cows with ATM (cases) and 168 clinically healthy cows (controls). We hypothesised that the leukograms of surviving and non-surviving cows differ and that there are variables of the leukogram with sufficient prognostic potential to be used in the decision to treat or not to treat a cow with ATM. The cows were examined clinically and underwent haematological and biochemical examination of blood and bacteriological culture of milk samples.

Results: All cows with ATM had a poor appetite or anorexia, and 34 cows (21.5%) were recumbent. A single quarter was affected in 119 cows (75.3%), two quarters in 37 cows (23.4%) and three quarters in two cows (1.3%). Bacteriological culture showed Gram-negative pathogens in 100 cows (63.3%), Gram-positive in 15 (9.5%) and yeast in 4 (2.5%). The median total leukocyte count of cases was 4300 cells/µL (interquartile range = 2300-8200/µL), which was significantly lower than 8000 cells/µL (6525-9300/µL) in controls. Except for band neutrophils and metamyelocytes, the counts of all components of the leukogram were lower in cases compared with controls. Significantly more cows with ATM had leukopenia (60.1 vs. 4.1%) or leukocytosis (10.1 vs. 3.0%) than controls. Diseased cows had significantly lower segmented neutrophil counts than controls (860 vs. 2598 cells/µL), and 69.5 and 17.3%, respectively, had counts below the reference interval. Cases had increased band (77.3%) and metamyelocyte (25.0%) counts compared with controls (0.6 and 0%, respectively). In diseased cows, eosinopenia occurred in 66.4% (controls, 1.8%), monocytopenia in 40.6% (4.2%) and lymphopenia in 60.2% (1.8%). Twenty-one diseased cows (16.4%) had a regenerative and 57 (44.5%) had a degenerative left shift. The median neutrophil-to-lymphocyte ratio was 0.97 in diseased cows and 0.63 in controls. Toxic changes in neutrophils including cytoplasmic basophilia and vacuolisation were seen in 101 (91.8%) of 110 blood smears of diseased cows. The leukogram of the surviving and non-surviving cows did not differ significantly, and the hypothesis was rejected.

Conclusions: ATM results in severe changes in the leukogram particularly leukopenia, lymphopenia, and degenerative left shift. The hypothesis that the leukograms of surviving and non-surviving cows differ was rejected. The leukogram has not sufficient prognostic potential to be used in the decision to treat or not to treat a cow with ATM.
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http://dx.doi.org/10.1186/s13028-021-00576-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953745PMC
March 2021

[Screening of febrile cows using a small handheld infrared thermography device].

Tierarztl Prax Ausg G Grosstiere Nutztiere 2021 Feb 15;49(1):12-20. Epub 2021 Feb 15.

Clinic of Reproductive Medicine, Department of Farm Animals, Vetsuisse-Faculty University Zurich.

Objective: As dairy herds increase in size, close monitoring of health becomes a necessity, but this is expensive and labour-intensive. Early detection of febrile diseases is essential for economical and welfare reasons and to prevent the spread of disease. The goal of this study was therefore to evaluate a mobile, non-invasive technique for measuring the body temperature of cows that precludes the need for restraint of the animals.

Materials And Methods: An infrared thermographic imaging camera installed on a smart phone was used to measure the surface temperature of cows. In experiment 1, a metal block heated to defined temperatures was used to obtain infrared thermographic measurements (THM). The accuracy of THM made at different distances from the block and at 2 different ambient temperatures was determined. In experiment 2, non-febrile cows underwent infrared thermographic imaging, and the body regions with the highest correlations between thermographic and rectal temperature were identified. In experiment 3, THM were made in febrile and neighbouring non-febrile cows.

Results: In experiment 1, the thermographic and true temperatures of the block had the strongest relationships at 0.5 and 1.0 m (r = 0.98). The ambient temperature had a significant effect on the THM, which had larger variations and greater deviations from the block temperature at 14.8 °C than at 23.8 °C. In experiment 2, the maximum temperature at the eye (r = 0.37), THM at the muzzle (r = 0.28) and the medial canthus (r = 0.27) showed the strongest relationships with the rectal temperature. After correcting the THM with the mean difference between thermographic and rectal temperatures of the non-febrile cows, sensitivities of 88, 90 and 82 %, respectively, were calculated for THM at the muzzle, eye and medial canthus in febrile cows in experiment 3. The corresponding specificities were 6, 23 and 32 %.

Conclusion And Clinical Relevance: Based on the low specificities of the infrared THM, the thermographic imaging camera has limited usefulness for the mass screening of dairy cows for febrile conditions. Cattle falsely identified as febrile need to be separated, caught and re-examined, which causes unnecessary stress to the animal and increases labour input.
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http://dx.doi.org/10.1055/a-1307-9993DOI Listing
February 2021

Hypoxia-inducible factor (HIF1alpha) inhibition modulates cumulus cell function and affects bovine oocyte maturation in vitro†.

Biol Reprod 2021 02;104(2):479-491

Vetsuisse Faculty, Institute of Veterinary Anatomy, University of Zurich (UZH), Zurich, Switzerland.

Various metabolic and hormonal factors expressed in cumulus cells are positively correlated with the in vitro maturation (IVM) of oocytes. However, the role of hypoxia sensing both during maturation of cumulus-oocyte complexes (COCs) as well as during the resumption of meiosis remains uncertain. HIF1alpha plays major roles in cellular responses to hypoxia, and here we investigated its role during bovine COC maturation by assessing the expression of related genes in cumulus cells. COCs were divided into the following groups: immature (control), in vitro matured (IVM/control), or matured in the presence of a blocker of HIF1alpha activity (echinomycin, IVM/E). We found an inhibition of cumulus cell expansion in IVM/E, compared with the IVM/control. Transcript levels of several factors (n = 13) were assessed in cumulus cells. Decreased expression of HAS2, TNFAIP6, TMSB4, TMSB10, GATM, GLUT1, CX43, COX2, PTGES, and STAR was found in IVM/E (P < 0.05). Additionally, decreased protein levels were detected for STAR, HAS2, and PCNA (P < 0.05), while activated-Caspase 3 remained unaffected in IVM/E. Progesterone output decreased in IVM/E. The application of PX-478, another blocker of HIF1alpha expression, yielded identical results. Negative effects of HIF1alpha suppression were further observed in the significantly decreased oocyte maturation and blastocyst rates from COCs matured with echinomycin (P < 0.05) or PX-478 (P < 0.05). These results support the importance of HIF1alpha for COC maturation and subsequent embryo development. HIF1alpha is a multidirectional factor controlling intercellular communication within COCs, steroidogenic activity, and oocyte development rates, and exerting effects on blastocyst rates.
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http://dx.doi.org/10.1093/biolre/ioaa196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876663PMC
February 2021

Sonographic characteristics of the placenta, uterine wall, and placentomes during pregnancy in cows.

Tierarztl Prax Ausg G Grosstiere Nutztiere 2019 Dec 6;47(6):355-365. Epub 2019 Dec 6.

Large Animal Reproduction Unit, Clinic of Reproductive Medicine, Vetsuisse Faculty, University of Zurich.

Objective: In human medicine, contrary to bovine medicine, close monitoring of risk pregnancies is an integral part of obstetrics. A prerequisite for this is the knowledge of the normal findings during pregnancy.

Material And Methods: For this purpose serial transrectal sonographic examination of the placentomes, uterine wall, and fetal membranes were carried out in 24 healthy (mean age 8.1 ± 3.7 years, Brown Swiss [n = 21], Red Holstein [n = 2], Simmental [n = 1]) cows from week 6 to 43 of gestation. An 8-MHz linear transducer was used to assess the thickness and appearance of the endometrium and myometrium, the height and width of placentomes, the thickness of the uterine wall including the adjacent chorion laeve (combined thickness of uterus and placenta, CTUP), and the echogenicity of the fetal fluids. The uterine wall and the placentomes were measured in 4 different zones of both uterine sides including a zone near the cervix, at the corpus near to the bifurcation, at the middle, and near the tip of the uterine horn.

Results: Placentome height and width were closely correlated with gestational age (height: r = 0.78; width: r = 0.83; both p < 0.0001). Placentome size increased progressively in all uterine zones until week 27, after which time their growth slowed until week 31 and then plateaued until parturition. Placentomes in the fetus-bearing horn were larger than in the non-fetus-bearing horn (p < 0.01) and were significantly smaller (height and width) near the tip of the horn than in the other 3 zones (p < 0.001 to < 0.01). The mean thickness of endometrium and myometrium, myometrium at the base of the placentome, and the mean CTUP did not change significantly during gestation. The echogenicity of the allantoic fluid did not change, but the amniotic fluid became more echogenic during gestation (p < 0.0001).

Conclusion And Clinical Relevance: Sonographic examination of placentomes and amniotic fluid are a promising diagnostic tool for the estimation of the duration of bovine pregnancies and for diagnosing possible complications.
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http://dx.doi.org/10.1055/a-1019-7387DOI Listing
December 2019

Analysis of the equine "cumulome" reveals major metabolic aberrations after maturation in vitro.

BMC Genomics 2019 Jul 17;20(1):588. Epub 2019 Jul 17.

Clinic of Reproductive Medicine, Vetsuisse Faculty, University of Zurich, 8057, Zurich, Switzerland.

Background: Maturation of oocytes under in vitro conditions (IVM) results in impaired developmental competence compared to oocytes matured in vivo. As oocytes are closely coupled to their cumulus complex, elucidating aberrations in cumulus metabolism in vitro is important to bridge the gap towards more physiological maturation conditions. The aim of this study was to analyze the equine "cumulome" in a novel combination of proteomic (nano-HPLC MS/MS) and metabolomic (UPLC-nanoESI-MS) profiling of single cumulus complexes of metaphase II oocytes matured either in vivo (n = 8) or in vitro (n = 7).

Results: A total of 1811 quantifiable proteins and 906 metabolic compounds were identified. The proteome contained 216 differentially expressed proteins (p ≤ 0.05; FC ≥ 2; 95 decreased and 121 increased in vitro), and the metabolome contained 108 metabolites with significantly different abundance (p ≤ 0.05; FC ≥ 2; 24 decreased and 84 increased in vitro). The in vitro "cumulome" was summarized in the following 10 metabolic groups (containing 78 proteins and 21 metabolites): (1) oxygen supply, (2) glucose metabolism, (3) fatty acid metabolism, (4) oxidative phosphorylation, (5) amino acid metabolism, (6) purine and pyrimidine metabolism, (7) steroid metabolism, (8) extracellular matrix, (9) complement cascade and (10) coagulation cascade. The KEGG pathway "complement and coagulation cascades" (ID4610; n = 21) was significantly overrepresented after in vitro maturation. The findings indicate that the in vitro condition especially affects central metabolism and extracellular matrix composition. Important candidates for the metabolic group oxygen supply were underrepresented after maturation in vitro. Additionally, a shift towards glycolysis was detected in glucose metabolism. Therefore, under in vitro conditions, cumulus cells seem to preferentially consume excess available glucose to meet their energy requirements. Proteins involved in biosynthetic processes for fatty acids, cholesterol, amino acids, and purines exhibited higher abundances after maturation in vitro.

Conclusion: This study revealed the marked impact of maturation conditions on the "cumulome" of individual cumulus oocyte complexes. Under the studied in vitro milieu, cumulus cells seem to compensate for a lack of important substrates by shifting to aerobic glycolysis. These findings will help to adapt culture media towards more physiological conditions for oocyte maturation.
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http://dx.doi.org/10.1186/s12864-019-5836-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637639PMC
July 2019

Gestational Age-Dependent Fetal Fluid Dynamics in the Ovine Developmental Model: Establishment of Surrogate Markers for the Differentiation of Stem Cell Origin.

Cells Tissues Organs 2018 10;206(4-5):208-217. Epub 2019 May 10.

Institute for Regenerative Medicine (IREM), University of Zurich, Zurich, Switzerland,

The ovine developmental model represents the standard in vivo model for studies involving maternofetal physiology, amniotic fluid (AF) research, and fetal cell therapy prior to human clinical use. Although being close to the human fetal anatomy, 2 separate extraembryonic fluid compartments remain during gestation, known as the amnion and the allantois. A clear distinction between AF versus allantoic fluid (AL) is therefore indispensable for correct scientific conclusions with regard to human translation. In the presented study, the biochemical composition of AF and AL was evaluated in ovine gravid uteri postmortem (n = 31) over the entire gestation. Four parameters, consisting of Na+, Cl-, Mg2+, and total protein, have been found to allow for specific discrimination of the 2 fetal fluids at all gestational phases and therefore as potential surrogate parameters for gestational age. In addition, volumetric changes of the developing fetus and the 2 fetal fluid cavities were analyzed by contrast-enhanced computed tomography (n = 12). AF showed a significant, linear volumetric increase over gestation, whereas AL volume maintained relatively static independent of gestational age. These results serve as a basis for future studies by providing surrogate markers enabling a reliable distinction of isolated fetal fluids and contained cells in the ovine developmental model over the entire gestation.
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http://dx.doi.org/10.1159/000499504DOI Listing
May 2019

Amniotic Fluid Cells Show Higher Pluripotency-Related Gene Expression Than Allantoic Fluid Cells.

Stem Cells Dev 2017 10 14;26(19):1424-1437. Epub 2017 Aug 14.

1 Institute for Regenerative Medicine (IREM), Center for Therapy Development and Good Manufacturing Practice, University of Zurich , Zurich, Switzerland .

Amniotic fluid represents an abundant source of multipotent stem cells, referred as broadly multipotent given their differentiation potential and expression of pluripotency-related genes. However, the origin of this broadly multipotent cellular fraction is not fully understood. Several sources have been proposed so far, including embryonic and extraembryonic tissues. In this regard, the ovine developmental model uniquely allows for direct comparison of fetal fluid-derived cells from two separate fetal fluid cavities, the allantois and the amnion, over the entire duration of gestation. As allantoic fluid mainly collects fetal urine, cells originating from the efferent urinary tract can directly be compared with cells deriving from the extraembryonic amniotic tissues and the fetus. This study shows isolation of cells from the amniotic [ovine amniotic fluid cells (oAFCs)] and allantoic fluid [ovine allantoic fluid cells (oALCs)] in a strictly paired fashion with oAFCs and oALCs derived from the same fetus. Both cell types showed cellular phenotypes comparable to standard mesenchymal stem cells (MSCs), with trilineage differentiation potential, and expression of common ovine MSC markers. However, the expression of MSC markers per single cell was higher in oAFCs as measured by flow cytometry. oAFCs exhibited higher proliferative capacities and showed significantly higher expression of pluripotency-related genes OCT4, STAT3, NANOG, and REX1 by quantitative real-time polymerase chain reaction compared with paired oALCs. No significant decrease of pluripotency-related gene expression was noted over gestation, implying that cells with high differentiation potential may be isolated at the end of pregnancy. In conclusion, this study suggests that cells with highest stem cell characteristics may originate from the fetus itself or the amniotic fetal adnexa rather than from the efferent urinary tract or the allantoic fetal adnexa.
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http://dx.doi.org/10.1089/scd.2016.0352DOI Listing
October 2017

Prevention of equine herpesvirus myeloencephalopathy - Is heparin a novel option? A case report.

Tierarztl Prax Ausg G Grosstiere Nutztiere 2016 Oct 21;44(5):313-317. Epub 2016 Sep 21.

Dr. Jasmin Walter, Klinik für Reproduktionsmedizin, Vetsuisse-Fakultät der Universität Zürich, Winterthurerstrasse 260, 8057 Zürich, Schweiz, E-Mail:

Equine herpesvirus myeloencephalopathy (EHM) is a severe manifestation of equine herpesvirus 1 (EHV-1) infection. Prevention and treatment of EHM during EHV-1 outbreaks is critical, but no reliable and tested specific medication is available. Due to the thromboischemic nature of EHM and due to the fact that EHV-1 entry in cells is blocked by heparin, it was hypothesized that this compound may be useful in reduction of EHM incidence and severity. Therefore, during an acute EHV-1 outbreak with the neuropathogenic G/D Pol variant, metaphylactic treatment with heparin to prevent EHM was initiated. Clinical signs were present in 61 horses (fever n = 55; EHM n = 8; abortion n = 6). Heparin (25000 IU subcutaneously twice daily for 3 days) was given to 31 febrile horses from day 10 of the outbreak, while the first 30 horses exhibiting fever remained untreated. Treatment outcome was analyzed retrospectively. Heparin-treated horses showed a lower EHM incidence (1/31; 3.2%) than untreated horses (7/30; 23.3%; p = 0.03). Results indicate that heparin may be useful for prevention of EHM during an EHV-1 outbreak. These promising data highlight the need for randomized and possibly blinded studies for the use of heparin in EHV-1 outbreaks.
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http://dx.doi.org/10.15653/TPG-150451DOI Listing
October 2016

A missense mutation in TUBD1 is associated with high juvenile mortality in Braunvieh and Fleckvieh cattle.

BMC Genomics 2016 05 25;17:400. Epub 2016 May 25.

Lehrstuhl fuer Tierzucht, Technische Universitaet Muenchen, Freising, 85354, Germany.

Background: Haplotypes with reduced or missing homozygosity may harbor deleterious alleles that compromise juvenile survival. A scan for homozygous haplotype deficiency revealed a short segment on bovine chromosome 19 (Braunvieh haplotype 2, BH2) that was associated with high juvenile mortality in Braunvieh cattle. However, the molecular genetic underpinnings and the pathophysiology of BH2 remain to be elucidated.

Results: The frequency of BH2 was 6.5 % in 8,446 Braunvieh animals from the national bovine genome databases. Both perinatal and juvenile mortality of BH2 homozygous calves were higher than the average in Braunvieh cattle resulting in a depletion of BH2 homozygous adult animals (P = 9.3x10(-12)). The analysis of whole-genome sequence data from 54 Braunvieh animals uncovered a missense mutation in TUBD1 (rs383232842, p.H210R) that was compatible with recessive inheritance of BH2. The availability of sequence data of 236 animals from diverse bovine populations revealed that the missense mutation also segregated at a low frequency (1.7 %) in the Fleckvieh breed. A validation study in 37,314 Fleckvieh animals confirmed high juvenile mortality of homozygous calves (P = 2.2x10(-15)). Our findings show that the putative disease allele is located on an ancestral haplotype that segregates in Braunvieh and Fleckvieh cattle. To unravel the pathophysiology of BH2, six homozygous animals were examined at the animal clinic. Clinical and pathological findings revealed that homozygous calves suffered from chronic airway disease possibly resulting from defective cilia in the respiratory tract.

Conclusions: A missense mutation in TUBD1 is associated with high perinatal and juvenile mortality in Braunvieh and Fleckvieh cattle. The mutation is located on a common haplotype likely originating from an ancient ancestor of Braunvieh and Fleckvieh cattle. Our findings demonstrate for the first time that deleterious alleles may segregate across closed cattle breeds without recent admixture. Homozygous calves suffer from chronic airway disease resulting in poor growth performance and high juvenile mortality. The respiratory manifestations resemble key features of diseases resulting from impaired function of airway cilia.
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http://dx.doi.org/10.1186/s12864-016-2742-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880872PMC
May 2016

Skin malformations in a neonatal foal tested homozygous positive for Warmblood Fragile Foal Syndrome.

BMC Vet Res 2015 Jan 31;11:12. Epub 2015 Jan 31.

Clinic of Reproductive Medicine, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057, Zurich, Switzerland.

Background: Skin malformations that resembled manifestations of Ehlers-Danlos-Syndrome were described in a variety of domestic animals during the last century as cutis hyperelastica, hyperelastosis cutis, dermatosparaxis, dermal/collagen dysplasia, dermal/cutaneous asthenia or Ehlers-Danlos-like syndrome/s. In 2007, the mutation responsible for Hereditary Equine Regional Dermal Asthenia (HERDA) in Quarter Horses was discovered. Several case reports are available for similar malformations in other breeds than Quarter Horses (Draught Horses, Arabians, and Thoroughbreds) including four case reports for Warmblood horses. Since 2013, a genetic test for the Warmblood Fragile Foal Syndrome Type 1 (WFFS), interrogating the causative point mutation in the equine procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1, or lysyl hydroxylase 1) gene, has become available. Only limited data are available on the occurrence rate and clinical characteristics of this newly detected genetic disease in horses. In humans mutations in this gene are associated with Ehlers-Danlos Syndrome Type VI (kyphoscoliotic form).

Case Presentation: This is the first report describing the clinical and histopathological findings in a foal confirmed to be homozygous positive for WFFS. The Warmblood filly was born with very thin, friable skin, skin lesions on the legs and the head, and an open abdomen. These abnormalities required euthanasia just after delivery. Histologic examination revealed abnormally thin dermis, markedly reduced amounts of dermal collagen bundles, with loosely orientation and abnormally large spaces between deep dermal fibers.

Conclusion: WFFS is a novel genetic disease in horses and should be considered in cases of abortion, stillbirth, skin lesions and malformations of the skin in neonatal foals. Genetic testing of suspicious cases will contribute to evaluate the frequency of occurrence of clinical WFFS cases and its relevance for the horse population.
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http://dx.doi.org/10.1186/s12917-015-0318-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327794PMC
January 2015

Evaluation of the i-STAT portable point-of-care analyzer for determination of blood gases and acid-base status in newborn calves.

J Vet Emerg Crit Care (San Antonio) 2014 Sep-Oct;24(5):519-28. Epub 2014 Sep 9.

Department of Farm Animals, Clinic of Reproductive Medicine, Vetsuisse-Faculty, University of Zurich, Switzerland.

Objective: To validate the i-STAT, a portable hand-held analyzer that allows point-of-care measurement of blood gases, acid-base, lactate, and other blood variables in food animal practice for analysis of blood samples of newborn calves.

Design: Prospective observational study.

Setting: University teaching hospital.

Measurements And Main Results: A total of 271 venous blood samples were analyzed for PvO2 , PvCO2 , pH, base excess (BE), HCO3 , venous saturation of oxygen (SvO2 ), and total carbon dioxide (TCO2 ) using an i-STAT and a Rapidlab 248 bench top analyzer that served as the reference method. l-lactate was measured using the i-STAT as well as photometrically. Results from the i-STAT and the reference methods were compared. The analytes BE, HCO3 , and TCO2 showed a constant systematic error across the entire range with 2.3, 1.9, and 2.0 mmol/L lower values, respectively, than the values measured by the reference method. Based on the combined inherent imprecision of the 2 analyzers and after correcting the influences of systematic errors, the PvO2 , HCO3 , and SvO2 were within the acceptable limits in 76% to 91% of the cases. Ninety-five percent of the measurements of PvCO2 and BE were within acceptable limits.

Conclusions: The overall performance of the i-STAT was good except for BE, HCO3 , and TCO2 , thus limiting its usefulness in clinical studies. However this hand-held device allows rapid, reliable, and accurate point-of-care blood analyses and thus can be useful in bovine practice.
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http://dx.doi.org/10.1111/vec.12228DOI Listing
June 2015

In vitro fabrication of autologous living tissue-engineered vascular grafts based on prenatally harvested ovine amniotic fluid-derived stem cells.

J Tissue Eng Regen Med 2016 Jan 24;10(1):52-70. Epub 2013 Jul 24.

Swiss Centre for Regenerative Medicine, University of Zurich, Zurich, Switzerland.

Amniotic fluid cells (AFCs) have been proposed as a valuable source for tissue engineering and regenerative medicine. However, before clinical implementation, rigorous evaluation of this cell source in clinically relevant animal models accepted by regulatory authorities is indispensable. Today, the ovine model represents one of the most accepted preclinical animal models, in particular for cardiovascular applications. Here, we investigate the isolation and use of autologous ovine AFCs as cell source for cardiovascular tissue engineering applications. Fetal fluids were aspirated in vivo from pregnant ewes (n = 9) and from explanted uteri post mortem at different gestational ages (n = 91). Amniotic non-allantoic fluid nature was evaluated biochemically and in vivo samples were compared with post mortem reference samples. Isolated cells revealed an immunohistochemical phenotype similar to ovine bone marrow-derived mesenchymal stem cells (MSCs) and showed expression of stem cell factors described for embryonic stem cells, such as NANOG and STAT-3. Isolated ovine amniotic fluid-derived MSCs were screened for numeric chromosomal aberrations and successfully differentiated into several mesodermal phenotypes. Myofibroblastic ovine AFC lineages were then successfully used for the in vitro fabrication of small- and large-diameter tissue-engineered vascular grafts (n = 10) and cardiovascular patches (n = 34), laying the foundation for the use of this relevant pre-clinical in vivo assessment model for future amniotic fluid cell-based therapeutic applications.
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http://dx.doi.org/10.1002/term.1781DOI Listing
January 2016

Clinical observations and management of a severe equine herpesvirus type 1 outbreak with abortion and encephalomyelitis.

Acta Vet Scand 2013 Mar 5;55:19. Epub 2013 Mar 5.

Klinik für Reproduktionsmedizin, Vetsuisse-Fakultät Universität Zürich, Winterthurerstrasse 260, 8057, Zurich, Switzerland.

Latent equine herpesvirus type 1 (EHV-1) infection is common in horse populations worldwide and estimated to reach a prevalence nearing 90% in some areas. The virus causes acute outbreaks of disease that are characterized by abortion and sporadic cases of myeloencephalopathy (EHM), both severe threats to equine facilities. Different strains vary in their abortigenic and neuropathogenic potential and the simultaneous occurrence of EHM and abortion is rare. In this report, we present clinical observations collected during an EHV-1 outbreak caused by a so-called "neuropathogenic" EHV-1 G(2254)/D(752) polymerase (Pol) variant, which has become more prevalent in recent years and is less frequently associated with abortions. In this outbreak with 61 clinically affected horses, 6/7 pregnant mares aborted and 8 horses developed EHM. Three abortions occurred after development of EHM symptoms. Virus detection was performed by nested PCR targeting gB from nasal swabs (11 positive), blood serum (6 positive) and peripheral blood mononuclear cells (9 positive) of a total of 42 horses sampled. All 6 fetuses tested positive for EHV-1 by PCR and 4 by virus isolation. Paired serum neutralization test (SNT) on day 12 and 28 after the index case showed a significant (≥ 4-fold) increase in twelve horses (n = 42; 28.6%). This outbreak with abortions and EHM cases on a single equine facility provided a unique opportunity for the documentation of clinical disease progression as well as diagnostic procedures.
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http://dx.doi.org/10.1186/1751-0147-55-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630004PMC
March 2013

Effect of a prostaglandin F2α analogue on the cyclic corpus luteum during its refractory period in cows.

BMC Vet Res 2012 Nov 14;8:220. Epub 2012 Nov 14.

Clinic for Reproductive Medicine, Vetsuisse-Faculty University of Zurich, Zurich, Switzerland.

Background: The goal of this study was to examine the response of the cyclic corpus luteum of cows to the administration of a prostaglandin F2α analogue (PGF) during the transition of refractoriness to responsiveness by investigating ultrasonographic changes in the corpus luteum and changes in plasma progesterone concentration in cows following the administration of PGF 3 and 5 days after ovulation.

Results: All cows that responded to PGF given on day 5 ovulated on day 9. In the cows that did not respond on day 5, the luteal cross-sectional area stagnated after treatment, whereas the plasma progesterone concentration continued to increase. In the cows that received PGF on day 3 of the oestrous cycle, the luteal cross-sectional area and the plasma progesterone concentration continued to increase.

Conclusions: The results of this study suggest that the transition of the bovine corpus luteum from refractoriness to responsiveness to PGF occurs during day 5 of the oestrous cycle because in 5 of 8 cows given PGF on day 5, early luteal regression was evident during the examination 24 hours after PGF administration.
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http://dx.doi.org/10.1186/1746-6148-8-220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538667PMC
November 2012

Quantification of friction force reduction induced by obstetric gels.

Med Biol Eng Comput 2009 Jun 24;47(6):617-23. Epub 2009 Feb 24.

Department of Mechanical and Process Engineering, ETH Zurich, Switzerland.

The objective of this study was to quantify the reduction of friction forces by obstetric gels aimed to facilitate human childbirth. Lubricants, two obstetric gels with different viscosities and distilled water, were applied to a porcine model under mechanical conditions comparable to human childbirth. In tests with higher movement speeds of the skin relative to the birth canal, both obstetric gels significantly reduced dynamic friction forces by 30-40% in comparison to distilled water. At the lowest movement speed, only the more viscous gel reduced dynamic friction force significantly. In tests modifying the dwell time before a movement was initiated, static friction forces of trials with highly viscous gel were generally lower than those with distilled water. The performed biomechanical tests support the recommendation of using obstetric gels during human childbirth. Using the presented test apparatus may reduce the amount of clinical testing required to optimize gel formulation.
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http://dx.doi.org/10.1007/s11517-009-0460-1DOI Listing
June 2009

Respiratory distress syndrome in calves.

Authors:
Ulrich Bleul

Vet Clin North Am Food Anim Pract 2009 Mar;25(1):179-93, vii

Clinic of Reproductive Medicine, Department of Farm Animals, Vetsuisse-Faculty, University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland.

Respiratory disease syndrome (RDS) is a condition of neonatal calves in which insufficient oxygen uptake and increased retention of carbon dioxide result in respiratory acidosis. This condition is more common in premature calves and seems to be associated with a deficiency of surfactant. Although there is no uniform definition of RDS, clinical signs appear as tachypnea and expiration accentuated by an abdominal lift and expiratory grunt, and they occur in association with characteristic blood gas changes. This article discusses the pathophysiology of RDS in calves, along with the clinical findings, diagnosis, and treatment options.
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http://dx.doi.org/10.1016/j.cvfa.2008.10.002DOI Listing
March 2009

Effect of intranasal oxygen administration on blood gas variables and outcome in neonatal calves with respiratory distress syndrome: 20 cases (2004-2006).

J Am Vet Med Assoc 2008 Jul;233(2):289-93

Clinic of Reproductive Medicine, Department of Farm Animals, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.

Objective: To determine the effect of intranasal oxygen administration on blood gas variables and outcome in neonatal calves with respiratory distress syndrome (RDS).

Design: Retrospective case series.

Animals: 20 neonatal calves with RDS.

Procedures: Arterial partial pressure of oxygen (PaO(2)), arterial partial pressure of carbon dioxide, and arterial oxygen saturation (SaO(2)) before and after intranasal administration of oxygen were analyzed.

Results: There were significant increases in PaO(2) and SaO(2) in the first 24 hours after oxygen administration was begun, with mean +/- SD PaO(2) increasing from 38.4+/-8.8 mm Hg to 58.7+/-17.8 mm Hg during the first 3 hours of treatment. Calves with PaO(2)>55 mm Hg within the first 12 hours after oxygen administration was begun had a significantly higher survival rate (9/10) than did calves that did not reach this threshold (4/10).

Conclusions And Clinical Relevance: Results suggested that intranasal oxygen administration was a simple method of improving blood gas variables in neonatal calves with RDS and that PaO(2) could be used to predict outcome.
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http://dx.doi.org/10.2460/javma.233.2.289DOI Listing
July 2008

Obstetric gel shortens second stage of labor and prevents perineal trauma in nulliparous women: a randomized controlled trial on labor facilitation.

J Perinat Med 2008 ;36(2):129-35

Happy Child Birth Holding AG Basel, Switzerland.

Objective: To determine whether the obstetric gel shortens the second stage of labor and exerts a protective effect on the perineum.

Method: A total of 251 nulliparous women with singleton low-risk pregnancies in vertex position at term were recruited. A total of 228 eligible women were randomly assigned to Group A, without obstetric gel use, or to Group B, obstetric gel use, i.e., intermittent application into the birth canal during vaginal examinations, starting at the early first stage of labor (prior to 4 cm dilation) and ending with delivery.

Results: A total of 183 cases were analyzed. For vaginal deliveries without interventions, such as C-section, vaginal operative procedure or Kristeller maneuver, obstetric gel use significantly shortened the second stage of labor by 26 min (30%) (P=0.026), and significantly reduced perineal tears (P=0.024). First stage of labor and total labor duration were also shortened, but not significantly. Results did not show a significant change in secondary outcome parameters, such as intervention rates or maternal and newborn outcomes. No side effects were observed with obstetric gel use.

Conclusion: Systematic vaginal application of obstetric gel showed a significant reduction in the second stage of labor and a significant increase in perineal integrity. Future studies should further investigate the effect on intervention rates and maternal and neonatal outcome parameters.
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http://dx.doi.org/10.1515/JPM.2008.024DOI Listing
July 2008

Effects of hypertonic sodium bicarbonate solution on electrolyte concentrations and enzyme activities in newborn calves with respiratory and metabolic acidosis.

Am J Vet Res 2007 Aug;68(8):850-7

Department of Farm Animals, Clinic of Reproductive Medicine, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland.

Objective: To determine concentrations of electrolytes, total bilirubin, urea, creatinine, and hemoglobin; activities of some enzymes; and Hct and number of leukocytes and erythrocytes of newborn calves in relation to the degree of acidosis and treatment with a hypertonic sodium bicarbonate (NaHCO(3)) solution.

Animals: 20 acidotic newborn calves with a blood pH < 7.2 and 22 newborn control calves with a blood pH > or = 7.2.

Procedures: Approximately 10 minutes after birth, acidotic calves were treated by IV administration of 5% NaHCO(3) solution. The amount of hypertonic solution infused was dependent on the severity of the acidosis.

Results: Treatment resulted in a significant increase in the mean +/- SEM base excess from -8.4 +/- 1.2 mmol/L immediately after birth to 0.3 +/- 1.1 mmol/L 120 minutes later. During the same period, sodium concentration significantly increased from 145.3 +/- 0.8 mmol/L to 147.8 +/- 0.7 mmol/L. Mean chloride concentration before NaHCO(3) administration was significantly lower in the acidotic calves (99.6 +/- 1.1 mmol/L) than in the control calves (104.1 +/- 0.9 mmol/L). Calcium concentration in acidotic calves decreased significantly from before to after treatment. Concentrations of potassium, magnesium, and inorganic phosphorus were not affected by treatment.

Conclusions And Clinical Relevance: Administration of hypertonic NaHCO(3) solution to acidotic neonatal calves did not have any adverse effects on plasma concentrations of several commonly measured electrolytes or enzyme activities. The treatment volume used was smaller, compared with that for an isotonic solution, which makes it more practical for use in field settings.
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http://dx.doi.org/10.2460/ajvr.68.8.850DOI Listing
August 2007

Floppy kid syndrome caused by D-lactic acidosis in goat kids.

J Vet Intern Med 2006 Jul-Aug;20(4):1003-8

Clinic of Reproductive Medicine, Vetsuisse-Faculty, University of Zurich, Switzerland.

Background: Goat kids with floppy kid syndrome have metabolic acidosis, muscle weakness, and depression but no dehydration.

Hypothesis: D-Lactate is the major component of acidemia in goat kids with floppy kid syndrome.

Animals: Fifty-five goat kids with floppy kid syndrome (group F) and 35 clinically healthy goat kids (group C).

Methods: Clinical, biochemical, microbiologic, virologic, parasitologic, and pathologic examinations.

Results: The animals in group F had a blood pH of 7.13 +/- 0.11 and a base excess of -17.8 +/- 3.8 mM, which were both lower than the values in the control animals (pH, 7.32 +/- 0.31; base excess, -0.1 +/- 2.7 mM; P < .001). Floppy kids had a significantly larger anion gap than healthy kids (31.2 +/- 3.7 versus 21.5 +/- 8.5 mM; P < .001). The concentration of L-lactate was lower in floppy kids than in healthy kids (0.67 +/- 0.49 versus 1.60 +/- 1.02 mM), but the concentration of D-lactate was higher in floppy kids (7.43 +/- 2.71 versus 0.26 +/- 0.24 mM; P < .001). Intravenous and oral administration of sodium bicarbonate in floppy kids resulted in a significant increase in blood pH and base excess and a decrease in the anion gap (P < .001). In addition, the concentration of L-lactate increased (P = .039).

Conclusions And Clinical Importance: Metabolic acidosis in goat kids with floppy kid syndrome is caused by an increase in the plasma concentration of D-lactate.
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http://dx.doi.org/10.1892/0891-6640(2006)20[1003:fkscbd]2.0.co;2DOI Listing
October 2006

Fine-mapping and candidate gene analysis of bovine spinal muscular atrophy.

Mamm Genome 2006 Jan 13;17(1):67-76. Epub 2006 Jan 13.

Faculty of Veterinary Medicine, Institute for Animal Breeding, The Ludwig-Maximilians-University Munich, Veterinaerstrasse 13, 80539 Munich, Germany.

Bovine spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative disease, has been mapped at moderate resolution to the distal part of Chromosome 24. In this article we confirm this location and fine-map the SMA locus to an interval of approximately 0.8 cM at the very distal end of BTA24. Despite remarkable similarity to human SMA, the causative gene SMN can be excluded in bovine SMA. However, the interval where the disease now has been mapped contains BCL2, like SMN an antiapoptotic factor, and shown to bind to SMN. Moreover, knockout mice lacking the BCL2 gene show rapid motor neuron degeneration with early postnatal onset, as observed in bovine SMA. A comparative cattle/human map of the distal end of BTA24, based on the emerging bovine genome sequencing data, shows conserved synteny to HSA18 with hints of a segmental duplication and pericentric inversion just after the last available bovine marker DIK4971. This synteny lets us conclude that SMA is in immediate vicinity of the telomere. Candidate gene analysis of BCL2, however, excludes most of this gene, except its promoter region, and draws attention to the neighboring gene VPS4B, part of the endosomal protein-sorting machinery ESCRT-III which is involved in several neurodegenerative diseases.
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http://dx.doi.org/10.1007/s00335-005-0102-3DOI Listing
January 2006

Milk flow and udder health in cows after treatment of covered teat injuries via theloresectoscopy: 52 cases (2000-2002).

J Am Vet Med Assoc 2005 Apr;226(7):1119-23

Department of Food Animals, Clinic of Reproductive Medicine, Vetsuisse-Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland.

Objective: To determine milk flow, somatic cell counts (SCCs), and the incidence of clinical mastitis in cows that had undergone theloresectoscopy for treatment of teat stenosis caused by mucosal detachment in the region of the streak canal or Fürstenberg's rosette.

Design: Retrospective study.

Animals: 52 cows with teat stenosis that were treated via theloresectoscopy.

Procedure: Medical records of eligible cows were reviewed. Additional data regarding milking ease, SCC, development of clinical mastitis of the affected gland, and whether the cow remained in the herd were collected via owner-completed questionnaires.

Results: 49 of 52 questionnaires were completed. At referral, teat sinusitis was diagnosed in 29 of 52 cows. Milk flow was normal in 38 of 41 treated teats at discharge and in 24 of 40 during the next lactation. Thirteen of 49 cows were culled during the next lactation because of abnormal udder health. High SCC and teat sinusitis at referral and development of clinical mastitis during the 10-day period after surgery resulted in high SCCs in the remainder of the current lactation. The incidence of clinical mastitis during the remainder of the current and during the next lactation was higher in cows that had teat sinusitis at the time of surgery, compared with those that did not.

Conclusions And Clinical Relevance: Teat stenoses resulting from mucosal lesions in the region of the streak canal or Fürstenberg's rosette may be successfully treated via theloresectoscopy. Inflammation of the teat sinus and gland at the time of surgery may adversely affect udder health.
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http://dx.doi.org/10.2460/javma.2005.226.1119DOI Listing
April 2005