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Safety and immunogenicity of Onderstepoort Biological Products’ Rift Valley fever Clone 13 vaccine in sheep and goats under field conditions in Senegal Full text
2015
Modou M. Lo | Victor Mbao | Pascale Sierra | Yaya Thiongane | Mariame Diop | Meritxell Donadeu | Baptiste Dungu
This blinded field safety study was conducted in Senegal to assess safety and immunogenicity of administration of the registered dose of Rift Valley fever virus (RVFV) Clone 13 vaccine (Onderstepoort Biological Products) to sheep and goats of West African breeds under natural conditions. A total of 267 small ruminants (220 sheep, 47 goats) were included; half received RVFV Clone 13 vaccine at the recommended dose and half received the diluent (as placebo) only. The study was performed on three commercial farms in the northern and eastern region of Senegal in accordance with veterinary good clinical practices. The animals were observed daily for 3 days after vaccination, and then weekly for 1 year. In both sheep and goats vaccinated against RVFV seroconversion rates above 70% were recorded. No seroconversion related to RVFV was observed in placebo-treated animals. No statistically significant differences were determined between placebo and vaccinated groups for mean rectal temperatures for the first 3 days after administration (p > 0.05). No abnormal clinical signs related to treatment were noted, and only one slight injection site reaction was observed in one vaccinated animal for 2 days after vaccination. Out of 176 births assessed over 1 year (93 from the vaccinated group, 83 from the placebo group), 9 were abnormal in the placebo group and 3 in the vaccinated group (p > 0.05). The frequency of adverse events was similar in the placebo and vaccinated groups. RVFV Clone 13 vaccine administered according to the manufacturer’s instructions was safe and well tolerated in West African breeds of sheep and goats, including animals of approximately 6 months of age and pregnant females, under field conditions in Senegal. Antibody levels persisted up to 1 year after vaccination.
Show more [+] Less [-]The effect of Rift Valley fever virus Clone 13 vaccine on semen quality in rams Full text
2015
Geoff Brown | Estelle H. Venter | Paul Morley | Henry Annandale
The effect of Rift Valley fever virus Clone 13 vaccine on semen quality in rams Full text
2015
Geoff Brown | Estelle H. Venter | Paul Morley | Henry Annandale
Rift Valley fever (RVF) is an arthropod-borne viral disease of importance in livestock and humans. Epidemics occur periodically in domestic ruminants. People in contact with infected livestock may develop disease that varies from mild flu-like symptoms to fatal viraemia. Livestock vaccination may assist in disease control. Rift Valley fever virus (RVFV) Clone 13 is a relatively new vaccine against RVF, derived from an avirulent natural mutant strain of RVFV, and has been shown to confer protective immunity against experimental infection with RVFV. The hypothesis tested in the current trial was that rams vaccinated with RVFV Clone 13 vaccine would not experience a reduction in semen quality (measured by evaluating the percentage progressively motile and percentage morphologically normal spermatozoa in successive ejaculates) relative to unvaccinated control animals. Ram lambs were screened for antibodies to RVFV using a serum neutralisation test. Animals without detectable antibodies (n = 23) were randomly allocated to either a test group (n = 12) or a control group (n = 11). Animals in the test group were vaccinated with RVFV Clone 13 vaccine. Daily rectal temperature measurements and weekly semen and blood samples were taken from all animals. Seven animals were eliminated from the statistical analysis because of potential confounding factors. Logistic regression analysis was performed on data gathered from the remaining animals to determine whether an association existed between animal group, rectal temperature and semen quality parameters. No correlation existed between the treatment group and values obtained for the semen quality parameters measured. There was no statistically significant post-vaccination decline in the percentage of live morphologically normal spermatozoa, or the percentage of progressively motile spermatozoa, either when assessed amongst all animals or when assessed within individual groups. A repeat study with a larger sample size and a more comprehensive pre-screening process may be indicated to avoid the inclusion of unsuitable animals.
Show more [+] Less [-]The effect of Rift Valley fever virus Clone 13 vaccine on semen quality in rams Full text
2015
Brown, Geoff(University of Pretoria Department of Production Animal Studies) | Venter, Estelle H.(University of Pretoria Department of Veterinary Tropical Diseases) | Morley, Paul(Colorado State University Diagnostic Medicine Center) | Annandale, Henry(University of Pretoria Onderstepoort Veterinary Academic Hospital)
Rift Valley fever (RVF) is an arthropod-borne viral disease of importance in livestock and humans. Epidemics occur periodically in domestic ruminants. People in contact with infected livestock may develop disease that varies from mild flu-like symptoms to fatal viraemia. Livestock vaccination may assist in disease control. Rift Valley fever virus (RVFV) Clone 13 is a relatively new vaccine against RVF, derived from an avirulent natural mutant strain of RVFV, and has been shown to confer protective immunity against experimental infection with RVFV. The hypothesis tested in the current trial was that rams vaccinated with RVFV Clone 13 vaccine would not experience a reduction in semen quality (measured by evaluating the percentage progressively motile and percentage morphologically normal spermatozoa in successive ejaculates) relative to unvaccinated control animals. Ram lambs were screened for antibodies to RVFV using a serum neutralisation test. Animals without detectable antibodies (n = 23) were randomly allocated to either a test group (n = 12) or a control group (n = 11). Animals in the test group were vaccinated with RVFV Clone 13 vaccine. Daily rectal temperature measurements and weekly semen and blood samples were taken from all animals. Seven animals were eliminated from the statistical analysis because of potential confounding factors. Logistic regression analysis was performed on data gathered from the remaining animals to determine whether an association existed between animal group, rectal temperature and semen quality parameters. No correlation existed between the treatment group and values obtained for the semen quality parameters measured. There was no statistically significant post-vaccination decline in the percentage of live morphologically normal spermatozoa, or the percentage of progressively motile spermatozoa, either when assessed amongst all animals or when assessed within individual groups. A repeat study with a larger sample size and a more comprehensive pre-screening process may be indicated to avoid the inclusion of unsuitable animals.
Show more [+] Less [-]Cystic echinococcosis amongst small ruminants and humans in central Ethiopia Full text
2015
Habtamu Assefa | Belay Mulate | Shahid Nazir | Alula Alemayehu
Cystic echinococcosis amongst small ruminants and humans in central Ethiopia Full text
2015
Habtamu Assefa | Belay Mulate | Shahid Nazir | Alula Alemayehu
This study was conducted to determine the prevalence of cystic echinococcosis (CE) in small ruminants and humans in Addis Ababa, central Ethiopia. A cross-sectional study involving systematic random sampling was conducted to estimate the prevalence of CE in 512 small ruminants (262 sheep and 250 goats) slaughtered at Addis Ababa Abattoir Enterprise between October 2011 and March 2012. Hydatid cysts were identified macroscopically during postmortem examination and their fertility and viability were determined. CE was observed in 21 (8.02%) sheep and 17 (6.80%) goats. In sheep 13 (4.96%) of the lungs, 10 (3.81%) livers and 1 (0.381%) heart were found to be infected with hydatid cysts. Involvement of lung and liver in goats was found to be 10 (4.0%) and 8 (3.2%) respectively, with no cysts recorded in the heart. Of the total of 77 and 47 cysts encountered in sheep and goats, 33 (42.85%) and 15 (31.91%) respectively were fertile. Viability of protoscoleces from fertile cysts in sheep (29 [87.87%]) was higher than in goats (6 [40.0%]). For humans, retrospective analysis covering five years of case reports at two major hospitals in Addis Ababa between January 2008 and December 2012 showed that of the total of 25 840 patients admitted for ultrasound examination, 27 CE cases were registered, a prevalence of 0.1% and mean annual incidence rate of approximately 0.18 cases per 100 000 population. Liver was the major organ affected in humans (81.5% in affected patients) followed by spleen (11.1%) and kidney (7.4%). Logistic regression analysis showed that prevalence of CE varied significantly in relation to host age in the small ruminants (OR = 3.93, P < 0.05) as well as in humans (95% CI, R = 4.8). This epidemiological study confirms the importance of CE in small ruminants and humans in central Ethiopia, emphasising the need for integrated approaches to controlling this neglected preventable disease.
Show more [+] Less [-]Cystic echinococcosis amongst small ruminants and humans in central Ethiopia Full text
2015
Assefa, Habtamu(Wollo University School of Veterinary Medicine) | Mulate, Belay(Wollo University School of Veterinary Medicine) | Nazir, Shahid(Wollo University School of Veterinary Medicine) | Alemayehu, Alula(Wollo University School of Veterinary Medicine)
This study was conducted to determine the prevalence of cystic echinococcosis (CE) in small ruminants and humans in Addis Ababa, central Ethiopia. A cross-sectional study involving systematic random sampling was conducted to estimate the prevalence of CE in 512 small ruminants (262 sheep and 250 goats) slaughtered at Addis Ababa Abattoir Enterprise between October 2011 and March 2012. Hydatid cysts were identified macroscopically during postmortem examination and their fertility and viability were determined. CE was observed in 21 (8.02%) sheep and 17 (6.80%) goats. In sheep 13 (4.96%) of the lungs, 10 (3.81%) livers and 1 (0.381%) heart were found to be infected with hydatid cysts. Involvement of lung and liver in goats was found to be 10 (4.0%) and 8 (3.2%) respectively, with no cysts recorded in the heart.Of the total of 77 and 47 cysts encountered in sheep and goats, 33 (42.85%) and 15 (31.91%) respectively were fertile. Viability of protoscoleces from fertile cysts in sheep (29 [87.87%]) was higher than in goats (6 [40.0%]). For humans, retrospective analysis covering five years of case reports at two major hospitals in Addis Ababa between January 2008 and December 2012 showed that of the total of 25 840 patients admitted for ultrasound examination, 27 CE cases were registered, a prevalence of 0.1% and mean annual incidence rate of approximately 0.18 cases per 100 000 population. Liver was the major organ affected in humans (81.5% in affected patients) followed by spleen (11.1%) and kidney (7.4%). Logistic regression analysis showed that prevalence of CE varied significantly in relation to host age in the small ruminants (OR = 3.93, P < 0.05) as well as in humans (95% CI, R = 4.8). This epidemiological study confirms the importance of CE in small ruminants and humans in central Ethiopia, emphasising the need for integrated approaches to controlling this neglected preventable disease.
Show more [+] Less [-]Pattern of antimicrobial usage in livestock animals in south-western Nigeria: The need for alternative plans Full text
2015
Hezekiah K. Adesokan | IfeOluwapo O. Akanbi | Ibikunle M. Akanbi | Ruth A. Obaweda
Pattern of antimicrobial usage in livestock animals in south-western Nigeria: The need for alternative plans Full text
2015
Hezekiah K. Adesokan | IfeOluwapo O. Akanbi | Ibikunle M. Akanbi | Ruth A. Obaweda
Resistance to antibiotics has continued to increase, placing future animal and human disease management in real danger. The developing countries characterised by widespread indiscriminate antibiotic use and in which ‘third-generation’ antibiotics are not readily available or affordable are the worst affected. A 3-year (2010–2012) retrospective survey of antibiotic usage in livestock production in three selected states of south-western Nigeria was conducted. Data obtained from eight purposively selected licensed veterinary pharmaceutical sales establishments in the area, based on keeping detailed sales records for the study period, were analysed using Stata Version 12. Results showed that tetracyclines (33.6%), fluoroquinolones (26.5%) and beta-lactams/aminoglycosides (20.4%) constituted the majority of the antibiotics used over the 3 years. The differences in the quantities of antibiotic types used within each antimicrobial class were statistically significant for tetracyclines (F = 59.87; p < 0.0001) and fluoroquinolones (F = 43.97; p < 0.0001) but not for beta-lactams/aminoglycosides (F = 3.21; p = 0.148). Furthermore, antibiotic consumption increased by 40.4% between 2010 and 2012. Although statistically insignificant (F = 0.277; p = 0.762), the increasing trend across the years was at rates of 23.5% between 2010 and 2011 and 13.8% between 2011 and 2012. In addition, the findings show a significantly higher consumption rate (t = 15.21; df = 5; p < 0.0001) during the rainy (52.5%) than the dry (47.5%) seasons. The current increasing trend in antibiotic usage holds a serious danger for the future and therefore calls for alternative plans to safeguard future livestock production, food security and human health. This becomes more imperative considering emerging resistance against tetracyclines and fluoroquinolones, the foremost remedies for livestock diseases in most developing countries.
Show more [+] Less [-]Pattern of antimicrobial usage in livestock animals in south-western Nigeria: The need for alternative plans Full text
2015
Adesokan, Hezekiah K.(University of Ibadan Department of Veterinary Public Health and Preventive Medicine) | Akanbi, IfeOluwapo O.(Federal College of Animal Health and Production Technology) | Akanbi, Ibikunle M.(University of Ibadan Department of Veterinary Medicine) | Obaweda, Ruth A.(Federal College of Animal Health and Production Technology)
Resistance to antibiotics has continued to increase, placing future animal and human disease management in real danger. The developing countries characterised by widespread indiscriminate antibiotic use and in which 'third-generation' antibiotics are not readily available or affordable are the worst affected. A 3-year (2010-2012) retrospective survey of antibiotic usage in livestock production in three selected states of south-western Nigeria was conducted. Data obtained from eight purposively selected licensed veterinary pharmaceutical sales establishments in the area, based on keeping detailed sales records for the study period, were analysed using Stata Version 12. Results showed that tetracyclines (33.6%), fluoroquinolones (26.5%) and beta-lactams/aminoglycosides (20.4%) constituted the majority of the antibiotics used over the 3 years. The differences in the quantities of antibiotic types used within each antimicrobial class were statistically significant for tetracyclines (F = 59.87; p < 0.0001) and fluoroquinolones (F = 43.97; p < 0.0001) but not for beta-lactams/aminoglycosides (F = 3.21; p = 0.148). Furthermore, antibiotic consumption increased by 40.4% between 2010 and 2012. Although statistically insignificant (F = 0.277; p = 0.762), the increasing trend across the years was at rates of 23.5% between 2010 and 2011 and 13.8% between 2011 and 2012. In addition, the findings show a significantly higher consumption rate (t = 15.21; df = 5; p < 0.0001) during the rainy (52.5%) than the dry (47.5%) seasons. The current increasing trend in antibiotic usage holds a serious danger for the future and therefore calls for alternative plans to safeguard future livestock production, food security and human health. This becomes more imperative considering emerging resistance against tetracyclines and fluoroquinolones, the foremost remedies for livestock diseases in most developing countries.
Show more [+] Less [-]Identification of immunodominant proteins from Mannheimia haemolytica and Histophilus somni by an immunoproteomic approach Full text
2015
Alvarez, Angel H. | Gutierrez-Ortega, Abel | Hernandez-Gutierrez, Rodolfo
Mannheimia haemolytica and Histophilus somni are frequently isolated from diseased cattle with bovine respiratory disease (BRD). They compromise animal lung function and the immune responses generated are not sufficient to limit infection. Identification of specific immunogenic antigens for vaccine development represents a great challenge. Immunogenic proteins were identified by immunoproteomic approach with sera from cattle immunized with a commercial cellular vaccine of M. haemolytica and H. somni. Proteins of M. haemolytica were identified as solute ABC transporter, iron-binding protein, and hypothetical protein of capsular biosynthesis. Histophilus somni proteins correspond to porin, amino acid ABC transporter, hypothetical outer membrane protein, cysteine synthase, and outer membrane protein P6. Although these antigens share strong similarities with other proteins from animal pathogens, the ABC system proteins have been associated with virulence and these proteins could be considered as potential vaccine candidates for BRD.
Show more [+] Less [-]Effects of fentanyl on isoflurane minimum alveolar concentration in New Zealand White rabbits (Oryctolagus cuniculus) Full text
2015
Barter, Linda S. | Hawkins, Michelle G. | Pypendop, Bruno H.
OBJECTIVE To determine effects of increasing plasma fentanyl concentrations on the minimum alveolar concentration (MAC) of isoflurane in rabbits. ANIMALS 6 adult female New Zealand White rabbits (Oryctolagus cuniculus). PROCEDURES Rabbits were anesthetized with isoflurane in oxygen; ventilation was controlled and body temperature maintained between 38.5° and 39.5°C. Fentanyl was administered IV by use of a computer-controlled infusion system to achieve 6 target plasma concentrations. Isoflurane MAC was determined in duplicate by use of the bracketing technique with a supramaximal electrical stimulus. Blood samples were collected for measurement of plasma fentanyl concentration at each MAC determination. The MAC values were analyzed with a repeated-measures ANOVA followed by Holm-Sidak pairwise comparisons. RESULTS Mean ± SD plasma fentanyl concentrations were 0 ± 0 ng/mL (baseline), 1.2 ± 0.1 ng/mL, 2.2 ± 0.3 ng/mL, 4.4 ± 0.4 ng/mL, 9.2 ± 0.4 ng/mL, 17.5 ± 2.6 ng/mL, and 36.8 ± 2.4 ng/mL. Corresponding mean values for isoflurane MAC were 1.92 ± 0.16%, 1.80 ± 0.16%, 1.60 ± 0.23%, 1.46 ± 0.22%, 1.12 ± 0.19%, 0.89 ± 0.14%, and 0.70 ± 0.15%, respectively. Isoflurane MAC for plasma fentanyl concentrations ≥ 2.2 ng/mL differed significantly from the baseline value. In 3 rabbits, excessive spontaneous movement prevented MAC determination at the highest plasma fentanyl concentration. CONCLUSIONS AND CLINICAL RELEVANCE Fentanyl reduced isoflurane MAC by approximately 60% in New Zealand White rabbits. Further studies will be needed to investigate the cardiorespiratory effects of isoflurane and fentanyl combinations in rabbits; however, fentanyl may prove to be a useful adjunct to inhalation anesthesia in this species.
Show more [+] Less [-]Characterization of endothelial colony-forming cells from peripheral blood samples of adult horses Full text
2015
Salter, Margaret M. | Seeto, Wen J. | DeWitt, Blake B. | Hashimi, Sarah A. | Schwartz, Dean D. | Lipke, Elizabeth A. | Wooldridge, Anne A.
OBJECTIVE To isolate and characterize endothelial colony-forming cells (ECFCs; a subtype of endothelial progenitor cells) from peripheral blood samples of horses. SAMPLE Jugular venous blood samples from 24 adult horses. PROCEDURES Blood samples were cultured in endothelial cell growth medium. Isolated ECFCs were characterized by use of functional assays of fluorescence-labeled acetylated low-density lipoprotein (DiI-Ac-LDL) uptake and vascular tubule formation in vitro. Expression of endothelial (CD34, CD105, vascular endothelial growth factor receptor 2, and von Willebrand factor) and hematopoietic (CD14) cell markers was assessed through indirect immunofluorescence assay and flow cytometry. The number of passages before senescence was determined through serial evaluation of DiI-Ac-LDL uptake, vascular tubule formation, and cell doubling rates. RESULTS Samples from 3 horses produced colonies at 12 ± 2.5 days with characteristic endothelial single layer cobblestone morphology and substantial outgrowth on expansion. Equine ECFCs formed vascular tubules in vitro and had uptake of DiI-Ac-LDL (74.9 ± 14.7% positive cells). Tubule formation and DiI-Ac-LDL uptake diminished by passage 5. Equine ECFCs tested positive for von Willebrand factor, vascular endothelial growth factor receptor 2, CD34, and CD105 with an immunofluorescence assay and for CD14 and CD105 via flow cytometry. CONCLUSIONS AND CLINICAL RELEVANCE ECFCs can be isolated from peripheral blood of horses and have characteristics similar to those described for other species. These cells may have potential therapeutic use in equine diseases associated with ischemia or delayed vascularization.
Show more [+] Less [-]Intraocular pressure in clinically normal dromedary camels (Camelus dromedarius) Full text
2015
Marzok, Mohamed A. | El-khodery, Sabry A.
OBJECTIVE To determine the intraocular pressure (IOP) in healthy dromedary camels (Camelus dromedarius). ANIMALS 24 clinically normal dromedary camels. PROCEDURES For each camel, the IOP of both eyes was measured with applanation tonometry. Three measurements with < 5% variance were obtained for each eye on the same day of the week for 3 consecutive weeks. Mean IOP was calculated for each eye on each day for comparison purposes. RESULTS Mean ± SD IOPs for the right (31.1 ± 2.1 mm Hg) and left (30.8 ± 1.9 mm Hg) eyes of immature camels were significantly higher than those for the right (27.1 ± 1.2 mm Hg) and left (28.2 ± 1.2 mm Hg) eyes of mature camels. Intra-assay and interassay coefficients of variation (CVs) for IOP measurements of the right and left eyes did not differ significantly between immature and mature camels. Interassay CVs of IOP measurements for the right and left eyes ranged from 1.5% to 12.1% and 1.2% to 10.3%, respectively, for immature camels and from 1.2% to 17.2% and 1.7% to 18.8%, respectively, for mature camels. Intra-assay CVs of IOP measurements for the right and left eyes ranged from 1.5% to 10.6% and 1.9% to 9.6%, respectively, for immature camels and from 2.8% to 16.9% and 2.7% to 12.4%, respectively, for mature camels. Age was negatively correlated (r = −0.403) with IOP. CONCLUSIONS AND CLINICAL RELEVANCE Results provided a reference and might aid in the diagnosis of glaucoma and uveitis during complete ophthalmic examinations of dromedary camels.
Show more [+] Less [-]Effects of nitric oxide on blood-brain barrier permeability in common carp (Cyprinus carpio L.) Full text
2015
Kovacic, Sanja | Rumora, Lada | Gjurcevic, Emil | Segvic, Maja | Ivkic, Goran
OBJECTIVE To determine in vivo effects of nitric oxide (NO) on blood-brain barrier (BBB) permeability in common carp (Cyprinus carpio L.). ANIMALS 148 carp. PROCEDURES Carp received glyceryl trinitrate (1 mg/kg) as an NO donor or received no treatment (control group). Nitrite and nitrate concentrations in carp sera were determined 0.25, 1, 3, 6, 8, 12, and 24 hours after treatment. In control and treatment groups, BBB permeability was analyzed by assessment of leakage of Evans blue dye into various brain areas at 6, 12, and 24 hours after glyceryl trinitrate treatment. Brain edema was determined by means of the wet-dry weight method and assessed with light microscopy on H&E-stained preparations of tissues obtained 6 and 24 hours after glyceryl trinitrate treatment. RESULTS Treatment with glyceryl trinitrate induced endogenous synthesis of NO, which was upregulated 6 and 8 hours after treatment. Increased NO synthesis was associated with increased permeability of the BBB, which developed 6 hours after treatment with the NO donor. Although the BBB became impermeable again by 12 hours after glycerol trinitrate treatment, brain edema still persisted 24 hours after treatment. CONCLUSIONS AND CLINICAL RELEVANCE In this study, treatment with an NO donor caused reversible opening of the BBB and brain edema in common carp. An intact BBB is important to prevent influx of potentially harmful substances into the brain. This investigation highlighted the possibility of BBB disarrangement caused by NO, a substance found in the CNS of all vertebrates evaluated.
Show more [+] Less [-]Estimation of glomerular filtration rate in dogs by a single-blood sample method involving iodixanol Full text
2015
Sasaki, Yui | Iwama, Ryosuke | Shimamura, Shunsuke | Katayama, Masaaki | Uzuka, Yuji | Yabe, Koichi | Takasuna, Kiyoshi | Satoh, Hirohsi | Furuhama, Kazuhisa
OBJECTIVE To establish a simplified single-blood-sample method (SBSM) involving iodixanol to estimate glomerular filtration rate (GFR) in dogs and compare data provided by that procedure with data provided by a conventional multiple-blood-sample method (MBSM) involving inulin. ANIMALS 26 healthy dogs and 36 dogs with naturally occurring renal disease. PROCEDURES Dogs were used in various preliminary experiments to establish protocols for the SBSM and the MBSM of GFR estimation. To evaluate the relationship between GFRs obtained by the SBSM and the MBSM each involving iodixanol, iodixanol (40 mg of I/kg) was administered IV to 26 healthy dogs and 36 dogs with renal disease; blood sample collection was performed before and at 60, 90, and 120 minutes after the injection. To evaluate the relationship between GFRs obtained by the SBSM involving iodixanol and the MBSM involving inulin, iodixanol (40 mg of I/kg) and inulin (50 mg/kg) were coadministered IV to 22 healthy dogs and 3 dogs with renal disease, followed by blood sample collection 30, 60, 90, and 120 minutes later. Serum iodixanol and inulin concentrations were separately determined by reverse-phase high-performance liquid chromatography. RESULTS Findings revealed a correlation (r = 0.99) between GFR estimated by the SBSM and MBSM each involving iodixanol. Likewise, GFR estimated by the SBSM involving iodixanol was correlated (r = 0.89) with that estimated by the MBSM involving inulin. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the SBSM involving iodixanol can be applied to estimate GFR in dogs, instead of use of an MBSM.
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