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1.
Res Vet Sci ; 168: 105154, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38290405

ABSTRACT

An existing model was used to identify key drivers of profitability and estimate the impact on environmental sustainability when immunizing finishing pigs against GnRF with Improvac®. The model estimated performance and economic differences between immunized (IM) and non-IM pigs from the perspective of producers and packers, based on two recent meta-analyses in male and female pigs. It was populated with data from 9 countries in four continents (Europe, Asia, North and Latin-America). One-way sensitivity analyses (OWSA) were used to define key drivers of profitability. When changing the country specific input data over a range of ±20%, most OWSA did not reverse the mathematical sign of incremental net return between IM and non-IM pigs as calculated in base case analyses. Only the difference in feed conversion rate between IM and untreated female pigs was a key driver of profitability. The parameters with the highest impact on outcomes were similar across countries and expectable (feed costs), or explainable (parameters with statistical differences between IM and non-IM pigs in meta-analyses). In both single-gender herds, Improvac® reduced the environmental impact of pig production by improving feed efficiency (FE), the key driver of environmental burden. In a 50/50 mixed gender herd, IM pigs consumed less feed and gained more weight in 7 out of 9 countries; in the other two countries the FE calculated for the additional weight gain in IM pigs was >1.00, i.e., each additional kilogram of weight gain was associated with less than one additional kilogram of feed consumed.


Subject(s)
Immunization , Vaccination , Swine , Female , Male , Animals , Immunization/veterinary , Vaccination/veterinary , Gonadotropin-Releasing Hormone , Weight Gain , Gonadotropins
2.
Res Vet Sci ; 150: 170-178, 2022 Dec 05.
Article in English | MEDLINE | ID: mdl-35842948

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) is currently one of the most economically important health challenges in the global swine industry. The primary aim of this study was to evaluate the overall efficacy of a modified live virus vaccine Fostera® PRRS (F-PRRS) compared to no vaccination as reported in published studies, using meta-analytic techniques. Additionally, we aimed to evaluate the potential impact of age at vaccination and F-PRRS cross-protection against different genetically distanced PRRS strains. In total, 20 papers fulfilled the predefined inclusion criteria. Vaccinated pigs had on average 38.52 g/d higher daily weight gain and a 65% lower mortality (relative risk = 0.35) compared to non-vaccinates. F-PRRS reduced the maximum macroscopic lung lesion score on average by 16.82% points and the maximum viral load in serum by 1.36 log10 PRRSV RNA copies. Vaccination at 1 day and 21 days of age was similarly effective, and the pathogenic PRRS strain(s) used for challenge or being endemic in field studies (PRRSV-1, PRRSV-2, or PRRSV-1 & -2) did not significantly influence the outcomes. Our findings confirm the effectiveness of F-PRRS against heterologous PRRSV infection.


Subject(s)
Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Swine Diseases , Viral Vaccines , Animals , Antibodies, Viral , Porcine Reproductive and Respiratory Syndrome/prevention & control , Swine , Vaccines, Attenuated
3.
Res Vet Sci ; 131: 159-172, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32387811

ABSTRACT

The vaccine against gonadotropin releasing factor (GnRF), Improvac®, has recently emerged as an option for rearing market gilts up to heavier harvest weights. Improvac's® temporary suppression of the ovarian function and gonadal hormones results in greater feed intake and better welfare from avoidance of sexual behavioral problems. Based on 22 published articles, our meta-analysis has quantified the effect of immunizing gilts against GnRF on parameters relevant for pig producers, pork packers and retailers/consumers. The meta-analyses included growth performance and final harvest parameters, general carcass traits and yield of valuable meat, meat and fat quality parameters. Primary analyses considered studies without ractopamine, subgroup and additional analyses assessed the impact of co-variates. From the perspective of pig producers, primary analyses showed that immunized (IM) gilts have significantly (P < 0.001) increased average daily gain (+45.1 g/day) and daily feed intake (+0.19 kg/day), higher final live weight (+4.0 kg) and more backfat (+2.8 mm). From the perspective of the pork packers, IM gilts have heavier carcasses (+3.2 kg; P < 0.001), whereas dressing percentage is similar. IM gilts are less lean (-1.5% units; P < 0.001) and have 0.21% units more intramuscular fat (P = 0.001). The yield of ham, shoulder, and loin is similar, whereas the yield of belly is significantly higher (+0.28 kg; P < 0.001). There are no differences in meat quality parameters (color, pH24, and drip loss) between IM gilts and untreated gilts, whereas a lower iodine value in IM gilts indicates an improved fat quality. Further subgroup and additional analyses confirmed the validity of our meta-analysis.


Subject(s)
Body Composition , Gonadotropin-Releasing Hormone/immunology , Pork Meat/standards , Animals , Female , Immunization , Pork Meat/economics , Swine , Vaccination
4.
Res Vet Sci ; 119: 182-195, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29958153

ABSTRACT

Meta-analysis was used to compare pigs immunocastrated (IC) with Improvac® versus physically castrated (PC) or entire male (EM) pigs. Performance and carcass data as most relevant for producers and packers were analyzed and the risk of boar taint was assessed by comparing the number of pigs exceeding the consumer thresholds of detection (ToD) for skatole and androstenone. A total of 78 articles fulfilled pre-defined inclusion criteria. Compared to PC pigs, IC pigs have a higher average daily gain (ADG; +32.54 g/day, P < 0.0001) and more favorable feed conversion ratio (FCR; -0.234 kg/kg, P < 0.0001), higher live weight and percentage lean, and lower hot carcass weight (HCW) and dressing percentage. Compared to EM pigs, IC pigs have a higher ADG (+65.04 g/day, P < 0.0001), FCR (+0.075 kg/kg, P < 0.0001), live weight and HCW, and a similar dressing percentage. Conventionally raised IC pigs yield more valuable meat compared to PC (+0.628 kg) and EM (+1.385 kg) pigs. Heavy IC pigs (HCW > 97.7 kg) destined for the production of high-quality cured products gain approximately 0.3 kg more ham than their PC counterparts, with backfat and intramuscular fat still fulfilling the requirements for high-quality cured products. The risk of exceeding the ToD for skatole and androstenone is similar in IC and PC pigs, but significantly higher in EM pigs. Results from our meta-analyses confirm growth performance advantages of IC pigs compared with PC or EM pigs, and reveal a higher gain of valuable meat and a similar risk of boar taint as estimated for PC pigs.


Subject(s)
Gonadotropins/blood , Immunization/veterinary , Swine/growth & development , Animals , Male , Meat , Orchiectomy , Red Meat , Skatole
5.
J Anim Sci ; 91(12): 5868-77, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24126273

ABSTRACT

The goal of this study was to determine the clinical and economic impact of using tulathromycin as first line treatment for bovine respiratory disease (BRD) compared with other commonly used antimicrobials. Two decision trees were developed simulating the consequences of treating cattle at high risk of developing BRD [control model (CM)] or cattle with first clinical BRD episode [treatment model (TM)]. As comparators florfenicol and tilmicosin were considered in both models whereas enrofloxacin was included in the TM because it was only labeled for treatment of BRD at the time of development of the calculators. A total of 5 (CM) and 10 (TM) comparative clinical studies that reported efficacy data for the selected drugs and indications were identified as suitable for model population. The following outcomes were considered: first treatment success, number of subsequent BRD treatments, chronics, and mortalities. Cost parameters were considered from the perspective of the producer and included treatment costs (first treatment and retreatments) and costs of chronics and deaths derived from published sources for 2010 (default). The models allowed the estimation of clinical and economic consequences according to each individual trial outcomes. Treatment with tulathromycin resulted in more first treatment successes and fewer removals (chronics and deaths) in all comparisons. The average total number of antimicrobial treatments required for the management of BRD was also least with tulathromycin as first treatment option. Because of better efficacy, total costs over the entire study periods were always lowest with tulathromycin. Depending on the study selected as the basis for the efficacy evaluation, cost savings with tulathromycin were calculated in the CM between US$21.00 and $47.86 (vs. florfenicol) and $11.37 and $72.64 (vs. tilmicosin); cost savings in the TM ranged between $28.47 and $143.87 (vs. florfenicol) and $7.75 and $84.91 (vs. tilmicosin) as well as between $23.22 and $47.82 (vs. enrofloxacin), with the ranges reflecting a variety of settings in different trials. Thus, the higher drug costs of tulathromycin were more than offset by reduced BRD treatments, chronics, and mortalities in the herd. Fewer BRD episodes in cattle treated with tulathromycin not only contributes to overall savings in BRD management but also reduces the necessity of repeated antibiotic treatment, supporting prudent use of antimicrobials in livestock.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bovine Respiratory Disease Complex/drug therapy , Disaccharides/therapeutic use , Disease Outbreaks/veterinary , Heterocyclic Compounds/therapeutic use , Animals , Anti-Bacterial Agents/economics , Bovine Respiratory Disease Complex/epidemiology , Cattle , Cost-Benefit Analysis , Decision Support Techniques , Disaccharides/economics , Disease Outbreaks/economics , Female , Heterocyclic Compounds/economics , Housing, Animal , Male , Models, Economic , United States/epidemiology
6.
B-ENT ; 8(3): 153-65, 2012.
Article in English | MEDLINE | ID: mdl-23113377

ABSTRACT

OBJECTIVES: Acute otitis media (AOM) commonly affects young children and occasionally results in serious complications/sequelae. This pilot cost-of-illness study aimed to assess the economic burden of long-term AOM complications/sequelae in Belgium, and to establish a thorough methodology for a larger study. METHODOLOGY: We retrospectively reviewed charts of patients aged 10-20 years with long-term complications/sequelae considered to be AOM-related, and > or = 8 years of follow-up. From a list of 215 eligible patients, we selected 25 patients representing each of seven categories of complications/sequelae. RESULTS: Included patients had a mean age of 12.9 years; nine had chronic suppurative otitis media with cholesteatoma; six sensorineural hearing loss; six chronic perforation of the tympanic membrane; and one each with conductive hearing loss, facial paralysis, neurological impairment after intracranial complications, and complications of surgery. During 8-15 years of follow-up, the most common complications were hearing loss, chronic otitis media (OM), and cholesteatoma. These generally occurred > 5 years after the first AOM event, although chronic OM occurred after a mean time of 3.3 years. Yearly public health care payer (PHCP) costs ranged from Euro 119 to Euro 7957 per patient, and were highest for patients with sensorineural hearing loss. Yearly costs to the patients ranged from Euro 7 to Euro 289 per patient, and were also highest for patients with sensorineural hearing loss. CONCLUSIONS: Although complications/sequelae of AOM are rare, they can result in substantial costs. The applied methodology should be feasible for a larger study, with some minor adjustments.


Subject(s)
Cost of Illness , Hearing Loss, Sensorineural/economics , Otitis Media/economics , Acute Disease , Adolescent , Belgium , Child , Costs and Cost Analysis , Female , Follow-Up Studies , Hearing Loss, Sensorineural/etiology , Hearing Loss, Sensorineural/therapy , Humans , Male , Otitis Media/complications , Otitis Media/therapy , Pilot Projects , Prognosis , Retrospective Studies , Young Adult
7.
Acta Clin Belg ; 64(2): 100-12, 2009.
Article in English | MEDLINE | ID: mdl-19432022

ABSTRACT

Trastuzumab (Herceptin, Roche) is a recombinant, humanized monoclonal antibody directed against the neu-HER2 protein, since May 2002 reimbursed in Belgium for the treatment of metastatic HER2+ breast cancer and since June 2007 also in adjuvant therapy of HER2+ early stage breast cancer. The purpose of this study was to estimate the cost-effectiveness from the Belgian health care payer perspective of reimbursing trastuzumab in the Latter indication. A Markov state transition model was designed to adequately capture the natural history and course of disease for early stage breast cancer patients, and to simulate cost and disease progression over a life time perspective. The model estimates differences in outcomes for patients treated with adjuvant trastuzumab during 1 year compared to current therapy, and captures cost consequences and health benefits of trastuzumab treatment. Health benefits were expressed in terms of quality-adjusted life years gained, and future benefits were discounted at 1.5%. Costs were calculated from the perspective of the Belgian authorities' health care budget, and future costs were discounted at 3%. Where relevant, the costs per Markov state were obtained from the IMS Hospital Disease database. Additionally, an expert opinion analysis on resource use during the follow-up of treated early breast cancer patients provided the cost estimates for states with minor or without hospital costs. The incremental cost-effectiveness ratio based on a life time simulation was estimated at Euro 10,315 per quality-adjusted life year gained. It can be concluded that trastuzumab treatment of HER2+ early stage breast cancer patients is cost-effective from the perspective of the Belgian health care authorities.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Health Care Costs , Neoplasm Staging/methods , Antibodies, Monoclonal/economics , Antibodies, Monoclonal, Humanized , Belgium/epidemiology , Breast Neoplasms/economics , Breast Neoplasms/epidemiology , Cost-Benefit Analysis , Female , Humans , Morbidity/trends , Trastuzumab , Treatment Outcome
8.
J Toxicol Environ Health A ; 65(18): 1289-305, 2002 Sep 27.
Article in English | MEDLINE | ID: mdl-12227953

ABSTRACT

The methodology used to detect a polychlorinated biphenyl (PCB)/dioxin contamination in a Belgian cattle population that was not exposed to the PCB/dioxin incident in 1999 is presented. This population is directly or indirectly destined for human consumption. The methodology consisted in the systematic sampling of all calf-fattening stations and groups of cattle destined for export, and in the random sampling of slaughter cattle. This approach is compared to the method described in directive 96/23/CE from the European Council. When PCB concentrations exceeded the tolerance level of 0.2 micro g/g body fat (seven congeners with numbers 28, 52, 101, 118, 138, 153, and 180), dioxins (seventeen 2,3,7,8-substituted congeners of PCDD and PCDF) were also determined. The prevalence of Belgian slaughter cattle with PCB concentrations above this cutoff was 0.3% (95% confidence interval: 0.01-1.50%). Results indicate that the incidence of contamination was minimal, with environmental origin and common in all industrial countries. The maximal potential exposure of an adult human consumer to dioxins through diet of bovine origin is estimated in two worst-case scenarios. The first one corresponds to the consumption of contaminated food products by a small number of consumers during a long period (local consumption) and the second simulates the consumption of contaminated products by a large number of consumers during a short period (supermarket purchase). The theoretical maximum daily intake of dioxins in adults was respectively 374 and 123 pg TEQ/d. The estimated maximum increase of dioxin body burden corresponds to 7 pg TEQ/g fat in the local consumption scheme and 0.07 pg TEQ/g fat in the supermarket consumption scheme.


Subject(s)
Environmental Exposure , Environmental Pollutants/pharmacokinetics , Food Contamination , Polychlorinated Biphenyls/pharmacokinetics , Public Health , Adult , Animals , Belgium , Body Burden , Cattle , Diet , Environmental Pollutants/analysis , Humans , Meat , Polychlorinated Biphenyls/analysis
9.
Prev Vet Med ; 41(4): 239-55, 1999 Aug 23.
Article in English | MEDLINE | ID: mdl-10530424

ABSTRACT

In Belgium, pseudorabies in swine has been the subject of a mandatory eradication programme since 1993. From December 1995 to February 1996, a survey was conducted in the five provinces of northern Belgium to estimate the provincial pseudorabies virus (PRV) herd seroprevalence. Seven hundred and twenty randomly selected herds were included in this survey. To detect recently infected animals, only young sows were sampled. The results show that 44% of these herds had an important number of PRV-seropositive young sows. The highest herd seroprevalence was observed in West Flanders (68%), followed by Antwerp (60%), East Flanders (43%), Limburg (18%), and Flemish Brabant (8%). Assuming a diagnostic test sensitivity and specificity of 95% and 99%, respectively, and a true PRV within-herd prevalence of 43%, the overall true PRV herd prevalence was estimated to be 35%. A logistic multiple-regression revealed that the presence of finishing pigs was associated with a two-fold increase in odds of a herd being seropositive (odds ratio (OR)=2.07, 95% confidence interval (CI) = 1.31-3.26); a breeding herd size > or =70 sows was associated with a four-fold increase in odds of a herd being seropositive (OR = 4.09, 95% CI = 2.18-7.67); a pig density in the municipality of >455 pigs/km2 was associated with a 10-fold increase in odds of a herd being seropositive (OR = 9.68, 95% CI = 5.17-18.12). No association was detected between the PRV herd seroprevalence and purchase policy of breeding pigs (purchased gilts, or use of homebred gilts only).


Subject(s)
Antibodies, Viral/blood , Herpesvirus 1, Suid/immunology , Pseudorabies/epidemiology , Swine Diseases/epidemiology , Animal Husbandry , Animals , Belgium/epidemiology , Enzyme-Linked Immunosorbent Assay/veterinary , Female , Interviews as Topic , Logistic Models , Pilot Projects , Pseudorabies/prevention & control , Risk Factors , Sensitivity and Specificity , Seroepidemiologic Studies , Statistics, Nonparametric , Swine , Swine Diseases/prevention & control , Viral Envelope Proteins/chemistry , Viral Envelope Proteins/immunology
10.
Stroke ; 28(9): 1783-8, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9303026

ABSTRACT

BACKGROUND AND PURPOSE: Timely intravenous administration of recombinant tissue-type plasminogen activator (alteplase, rTPA) to patients with evolving ischemic stroke improves neurological outcome. The present study was designed to compare the effects of rTPA and recombinant staphylokinase (Sak), a highly fibrin-specific thrombolytic agent, in an experimental model of rabbit embolic stroke. METHODS: Groups of 5 to 12 rabbits were given intravenous saline or heparin and aspirin with, in addition, either Sak (1 or 2 mg/kg infused over 30 minutes or 2 mg/kg injected over 1 minute) or rTPA (3 or 6 mg/kg infused over 30 minutes or 6 mg/kg injected over 1 minute). Infusions were started 15 minutes after selective injection of standardized 125I-fibrin labeled rabbit plasma clots into the internal carotid artery. RESULTS: Mean clot lysis over 60 minutes increased from 3.8% after saline to between 27% and 44% after Sak regimens (P = .0001 versus control) and to between 15% and 34% after rTPA regimens (P = .0001). Median volume of the ischemic lesion at 5 hours decreased from 190 mm3 after saline to between 11 and 17 mm3 after Sak (P = .02) and to between 0.5 to 54 mm3 after rTPA (P = .04). Mean neurological impairment at 5 hours (on a scale of 0 to 3) decreased from 2.3 after saline to between 1.3 to 1.6 after Sak (P = .003) and to between 1.1 to 1.9 after rTPA (P = .02). At the highest doses used, fibrinogen depletion was marginal with Sak but total with rTPA. Marked prolongation of car puncture and cuticle bleeding times was only observed after bolus administration of rTPA. CONCLUSIONS: In the present rabbit model of embolic stroke, Sak was significantly more fibrin-specific than rTPA and at least as effective in lysing arterial emboli and limiting ischemia and neurological impairment.


Subject(s)
Cerebrovascular Disorders/drug therapy , Fibrinolytic Agents/therapeutic use , Intracranial Embolism and Thrombosis/drug therapy , Metalloendopeptidases/therapeutic use , Plasminogen Activators/therapeutic use , Tissue Plasminogen Activator/therapeutic use , Animals , Female , Injections, Intravenous , Male , Rabbits , Recombinant Proteins/therapeutic use
11.
Blood ; 90(4): 1527-34, 1997 Aug 15.
Article in English | MEDLINE | ID: mdl-9269770

ABSTRACT

Impaired fibrinolysis, resulting from increased plasminogen activator inhibitor-1 (PAI-1) or reduced tissue-type plasminogen activator (t-PA) plasma levels, may predispose the individual to subacute thrombosis in sepsis and inflammation. The objective of these studies was to show that adenovirus-mediated gene transfer could increase systemic plasma t-PA levels and thrombolytic capacity in animal model systems. Recombinant adenovirus vectors were constructed that express either human wild type or PAI-1-resistant t-PA from the cytomegalovirus (CMV) promoter. Both t-PA-deficient (t-PA(-/-)) and PAI-1-overexpressing transgenic mice were infected by intravenous injection of these viruses. Intravenous injection of recombinant adenovirus resulted in liver gene transfer, t-PA synthesis, and secretion into the plasma. Virus dose, human t-PA antigen, and activity concentrations in plasma and extent of lysis of a 125I-fibrin-labeled pulmonary embolism were all closely correlated. Plasma t-PA antigen and activity were increased approximately 1,000-fold above normal levels. Clot lysis was significantly increased in mice injected with a t-PA-expressing virus, but not in mice injected with saline or an irrelevant adenovirus. Comparable levels of enzyme activity and clot lysis were obtained with wild type and inhibitor-resistant t-PA viruses. Adenovirus-mediated t-PA gene transfer was found to augment clot lysis as early as 4 hours after infection, but expression levels subsided within 7 days. Adenovirus-mediated transfer of a t-PA gene can effectively increase plasma fibrinolytic activity and either restore (in t-PA-deficient mice) or augment (in PAI-1-overexpressing mice) the thrombolytic capacity in simple animal models of defective fibrinolysis.


Subject(s)
Fibrinolysis , Genetic Therapy , Plasminogen Activator Inhibitor 1/metabolism , Thrombosis/therapy , Tissue Plasminogen Activator/metabolism , Adenoviridae , Alleles , Animals , Cells, Cultured , Fibrinolysis/drug effects , Gene Transfer Techniques , Genetic Vectors , Humans , Mice , Mice, Transgenic , Plasminogen Activator Inhibitor 1/genetics , Recombinant Proteins/pharmacology , Tissue Plasminogen Activator/deficiency , Tissue Plasminogen Activator/genetics
12.
Nature ; 383(6595): 73-5, 1996 Sep 05.
Article in English | MEDLINE | ID: mdl-8779717

ABSTRACT

Tissue factor, a member of the cytokine-receptor superfamily and high-affinity receptor and cofactor for plasma factor VII/VIIa (ref. 1), is the primary cellular initiator of blood coagulation. It is involved in thrombosis and inflammation associated with sepsis, atherosclerosis and cancer, and can participate in other cellular processes including intracellular signalling, metastasis, tumor-associated angiogenesis, and embryogenesis. Here we report that inactivation of the tissue factor gene (TF) results in abnormal circulation from yolk sac to embryo beyond embryonic day 8.5, leading to embryo wasting and death. Vitelline vessels from null mice were deficient in smooth-muscle alpha-actin-expressing mesenchymal cells, which participate in organization of the vessel wall. This implies that tissue factor has a role in blood vessel development.


Subject(s)
Blood Vessels/embryology , Thromboplastin/physiology , Animals , Chromosome Mapping , Culture Techniques , Fetal Death , Gene Targeting , Mice , Regional Blood Flow , Thromboplastin/genetics , Yolk Sac/blood supply , Yolk Sac/ultrastructure
13.
Circulation ; 92(9): 2585-93, 1995 Nov 01.
Article in English | MEDLINE | ID: mdl-7586361

ABSTRACT

BACKGROUND: Circumstantial evidence suggests that the plasminogen/plasmin system plays a role in many biological processes, including hemostasis, cell migration, and development. METHODS AND RESULTS: The in vivo function of the plasminogen/plasmin system was studied by generation of plasminogen-deficient (Plg-/-) mice. Inactivation of the murine plasminogen-gene (Plg) was achieved by replacing, via homologous recombination in embryonic stem cells, genomic sequences encoding the exons containing the catalytic site amino acids His605 and Asp648 with a neomycin phosphotransferase expression cassette. Germline transmission of the mutated allele, as determined by Southern blot hybridization and polymerase chain reaction, was obtained via blastocyst injection. Mendelian inheritance of the inactivated plasminogen allele was observed, and homozygous-deficient mice (Plg-/-) displayed normal viability but retarded growth up to at least 12 weeks of age. At 8 weeks of age, body weight was 21.8 +/- 1.2 g (n = 10) for wild-type (Plg+/+) mice, 21.0 +/- 1.1 g (n = 16) for heterozygous-deficient (Plg+/-) mice, and 17.4 +/- 1.3 g (n = 12) for Plg-/- mice; P < .05 versus Plg+/+ or Plg+/-. None of 36 Plg+/+ or 65 Plg+/- mice but 7 of 37 Plg-/- mice (19%) developed rectal prolapse at 7.4 +/- 0.6 weeks of age (P = .03 versus Plg+/+ and P = .003 versus Plg+/-); 4 of 37 Plg-/- mice (11%) became runted and apathic at 5.3 +/- 0.3 weeks of age (P = .041 versus Plg+/-); and 6 of 37 Plg-/- mice (16%) died prematurely at 8.8 +/- 1.7 weeks of age (P = .057 versus Plg+/+ and P = .029 versus Plg+/-). Although male and female Plg-/- mice were able to sire offspring, the fertility of Plg-/- female mice was reduced, possibly owing to their impaired health. Levels of plasminogen-related antigen in plasma, measured by ELISA, were 84 +/- 8 micrograms/mL (n = 4) in Plg+/+, 35 +/- 2 micrograms/mL (n = 3) in Plg+/-, and 0.076 +/- 0.032 microgram/mL (n = 6) in Plg-/- mice (P < .001 versus Plg+/- and Plg+/+). Plasmin activity generated by urokinase activation was unmeasurable in Plg-/- mice (< 5% of Plg+/+ mice). Plasminogen-specific immunoreactivity was observed in hepatocytes from Plg+/+ mice but not from Plg-/- mice (< 10% of Plg+/+ mice). Neither native nor variant plasminogen mRNA nor translation products could be identified by Northern or Western blot of liver extracts from Plg-/- mice. Spontaneous lysis within 24 hours of a 125I-fibrin-labeled pulmonary plasma clot was 85 +/- 5% (n = 5) in Plg+/+ mice, 62 +/- 7% (n = 3) in Plg+/- mice, and -2 +/- 1% (n = 3) in Plg-/- mice (P < .001 versus Plg+/- and Plg+/+). Delayed clot lysis within 72 hours was 33 +/- 1% (n = 3) in tPA-/- mice and 26 +/- 2% (n = 3) in Plg-/- mice (P = .054). Histological examination of several organs revealed fibrin deposition in the liver; lung; and in the stomach, associated with gastric ulcers, in 6- to 12-week-old Plg-/- mice but not in Plg+/+ or Plg+/- littermates. CONCLUSIONS: Plasminogen-deficient mice survive embryonic development but develop spontaneous fibrin deposition due to impaired thrombolysis and suffer retarded growth and reduced fertility and survival. The Plg-/- phenotype is reminiscent of the combined tPA-/-:uPA-/- phenotype, which suggests that there is no significant additional pathway for physiological plasminogen activation in mice.


Subject(s)
Plasminogen/deficiency , Plasminogen/genetics , Thrombosis/metabolism , Animals , Embryonic and Fetal Development/genetics , Female , Fibrinolysis/genetics , Male , Mice , Mice, Mutant Strains , Thrombosis/genetics
14.
Theriogenology ; 41(4): 855-67, 1994.
Article in English | MEDLINE | ID: mdl-16727439

ABSTRACT

The possible application of the bovine in vitro fertilization technique for economical beef production was evaluated by transferring in vitro produced Belgian Blue embryos to synchronized dairy cows and heifers. In total, 4167 oocytes, collected in the slaughterhouse from double-muscled Belgian Blue cows, were matured in vitro. Frozen-thawed semen from 3 Belgian Blue bulls was used for in vitro fertilization. Zygotes were cultured in B(2) + 10% estrous cow serum together with oviductal cells at 39 degrees C in 5% CO(2) in air. After 7 days, 576 (13.8%) transferable embryos were obtained. One hundred and eighteen of the most advanced embryos were selected for fresh transfer into 90 recipients. Some of the remaining embryos were frozen using conventional methods. After fresh transfer, 50 recipients (55.6%) had elevated progesterone at day 23. Thirty cows (33.3%) calved after a mean gestation length of 282.8+/-6.0 days and produced 25 single births and 5 twins. The sex ratio was 71.4%. The mean birth weight was 45.1+/-8.3 kg. Three calves were of the conventional type instead of double-muscled and 2 calves died of congenital malformations. After transfer of in vitro produced frozen-thawed Belgian Blue embryos into 27 recipients (1 embryo/recipient), 2 bull calves (7.4%) were born. Bovine embryo production by in vitro techniques could form a low-cost supply of beef calves. However, to render it commercially attractive, selection of sires and dams has to be performed with great care.

15.
Theriogenology ; 38(5): 905-19, 1992 Nov.
Article in English | MEDLINE | ID: mdl-16727189

ABSTRACT

A study was conducted on early cleavage divisions and timing of compaction in bovine preimplantation-stage embryos. Zygotes were produced using conventional in vitro maturation and fertilization procedures. Twenty hours post insemination, the zygotes were denuded and cultured with oviduct epithelial cells in B2 medium + 10% estrous cow serum. Starting at 24 hours post insemination, the embryos (n=657) were evaluated every 6 hours and then were put into different co-culture drops according to their cell number. Starting from 78 hours post insemination, the cleavage rate was evaluated every 12 hours. Embryos were stained with Hoechst 33342 at the compacted morula stage or when they were degenerated, at 162 hours post insemination. Developmentally capable embryos were characterized by a rapid cleavage rate in the first 3 cell cycles and by an extended 8- to 16-cell stage. Peak concentrations of 2-, 4-, 8- and 16-cell stages emerged at 36, 42, 60 and 102 hours post insemination, respectively. Compaction did not occur until 126 hours post insemination. The rate of compaction was significantly higher in embryos that were at the 2-cell stage before or at 36 hours post insemination (P < 0.05). The mean cell numbers of compacted morulae that were identified at 126 and 138 hours post insemination were 30.9 +/- 6.8 and 31.6 +/- 7.7, respectively. These results indicate that developmentally capable bovine embryos reach the 2-cell stage at 36 hours post insemination, and that they become compacted at the 32-cell stage, which usually occurs between 126 and 138 hours post insemination.

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