Objective—To define the relationship between clinical
expression of a type-1 von Willebrand disease
phenotype and genotype at 2 von Willebrand factor
marker loci in Doberman Pinschers.
Animals—102 client-owned Doberman Pinschers.
Procedures—Dogs were recruited on the basis of
plasma von Willebrand factor concentration, clinical
history, and pedigree. Blood samples and response to
a history questionnaire were obtained for each dog.
Plasma von Willebrand factor concentration was measured
by use of an ELISA, and genotyping was performed
via polymerase chain reaction for 1 intragenic
and 1 extragenic von Willebrand factor marker.
Amplification product size was determined by use of
polyacrylamide gel electrophoresis (intragenic marker)
or automated sequence analysis (extragenic marker).
Western blots were prepared from a subset of
dogs with low plasma von Willebrand factor concentration
to evaluate multimer distribution.
Results—Strong associations were detected
between plasma von Willebrand factor concentration
and von Willebrand factor marker genotype. Twentyfive
dogs had substantial reduction in plasma von
Willebrand factor concentration and multiple hemorrhagic
events. All were homozygous for a 157-basepair
intragenic marker allele and homozygous or compound
heterozygous for 1 of 4 extragenic marker alleles.
These marker genotypes were exclusively
detected in dogs with low plasma von Willebrand factor
concentration, although some dogs with these
genotypes did not have abnormal bleeding.
Conclusions and Clinical Relevance—Type-1 von
Willebrand disease in Doberman Pinschers is associated
with the von Willebrand factor gene locus; however,
the expression pattern in this breed appears
more complex than that of a simple recessive trait.
(Am J Vet Res 2001;62:364–369)
Objective—To evaluate the influence of a 1,4-
butanedisulfonate stable salt of S-adenosylmethionine
(SAMe) administered orally on clinicopathologic
and hepatic effects induced by long-term administration
of prednisolone in dogs.
Animals—12 healthy dogs.
Procedure—Following a pilot study (4 dogs), 2 groups
of 4 dogs received prednisolone (2.2 mg/kg) orally
once daily (84-day trial). One group received SAMe
(20 mg/kg/d divided in 2 doses) for 42 days and then
a placebo for 42 days; the other group received treatments
in the reverse order. Before and during the
trial, numerous variables were monitored, including
serum total alkaline phosphatase (ALP) and glucocorticoid-
induced ALP (G-ALP) activities, serum haptoglobin
concentration, and total and oxidized glutathione
(TGSH and GSSG) and thiobarbiturate-reacting
substances (TBARS) concentrations in erythrocytes
and liver tissue (days 0, 42, and 84). Hepatic
specimens also were examined microscopically.
Results—The stable salt of SAMe was biologically
available; plasma concentrations of SAMe or prednisolone
were not affected by coadministration.
Compared with baseline values, serum ALP and GALP
activities and haptoglobin concentrations
increased and erythrocyte GSSG and TBARS concentrations
decreased with both treatments. Erythrocyte
TGSH concentration decreased with the prednisolone-
placebo treatment. Administration of SAMe
appeared to conserve erythrocyte TGSH values and
did not inhibit hepatocyte glycogen vacuolation but
increased hepatic TGSH concentration and improved
the hepatic tissue GSSG:TGSH ratio.
Conclusions and Clinical Relevance—In dogs,
administration of 20 mg of SAMe/kg/d may mitigate
the apparent pro-oxidant influences of prednisolone
but did not block development of classic clinicopathologic
or histologic features of vacuolar hepatopathy.
(Am J Vet Res 2005;66:330–341)