![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
College of
*
Pharmacy and Nutrition and
Western College of Veterinary Medicine, University of Saskatchewan, SK, S7N 5C9, Canada
2To whom correspondence should be addressed. E-mail: zello{at}sask.usask.ca
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
KEY WORDS: • D-lactic acid • acidosis • high performance liquid chromatography • calves • diarrhea
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
and in many other species, including calves
(2)
. Metabolic acidosis is an important complication of
diarrhea regardless of the causal agents (3
,4)
. Metabolic
acidosis may contribute to cardiac arrhythmia or death from heart
failure by decreasing myocardial potassium, elevating extracellular
potassium and changing membrane potential (5
,6)
.
Therapeutic studies show that correction of acidosis is essential to
the well being of calves (7)
and humans (4)
with diarrhea. Furthermore, preventing the development of acidosis has
long-term benefits on the demeanor and survival of diarrheic calves
(8)
. Because acidosis has such an important bearing on the
severity of illness and outcome in diarrhea, a proper understanding of
its origins and nature is important.
The most commonly accepted causes of metabolic acidosis in diarrheic
humans and calves are fecal bicarbonate loss and L-lactic
acidosis (9
,10)
. L-lactic acidosis is thought
to arise from poor tissue perfusion because of dehydration or
endotoxemia with subsequent anerobic glycolysis and decreased hepatic
clearance of L-lactate (11
12
13
14
15
16)
. We postulate
that L-lactate is unlikely to be the only organic acid
responsible for acidosis in diarrheic calves because in a study of
neonatal diarrheic calves anion gap was increased in 24 of 53 calves
but only 3 calves with high anion gaps had increased plasma
L-lactate (3)
. Although D-lactic
acidosis is not presently regarded as a complication of enteritis, it
has been recorded as a complication of jejunoileal by-pass, short
bowel syndrome
(SBS)3
in humans (17
,18)
or metabolic acidosis without
dehydration in calves with no or minimal diarrhea (19)
. We
propose that D-lactic acidosis might contribute to
metabolic acidosis in diarrheic calves through mechanisms similar to
those that operate in jejunoileal by-pass.
Because diarrhea causes malnutrition (20)
, several bodies,
including the World Health Organization (1)
, recommend the
continuation of appropriate food administration during diarrhea against
the traditional practice of withholding food. This preserves the
patient’s nutritional status (21)
. However,
gastrointestinal dysfunction resulting in diarrhea may be accompanied
by small intestinal malabsorption (22)
. Unabsorbed
nutrients may subsequently be fermented by colonic bacteria, as occurs
in patients with SBS (18)
. Gut fermentation may lead to
the production of lactate, in which case both the D and
L isomers should be produced (23)
. Because the
L-form but not the D-form is rapidly
metabolized (24
,25)
in the body, the D-form
may accumulate in the blood and be a contributor to acidosis in
diarrheic patients.
We hypothesized that intestinal bacterial substrate fermentation
contributes to acidosis in diarrhea caused by enteritis. We used a
neonatal calf model because calves are fed milk, like human infants,
often develop a severe acidosis when diarrheic and most causes of calf
diarrhea, including enterotoxigenic Escherichia coli,
rotavirus and coronavirus (26
,27)
are accompanied by
villous atrophy. We used stereospecific and nonstereospecific HPLC
methods previously developed and validated in our laboratory
(28)
to detect unusual organic acids.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Two groups of single-suckle beef calves were used, healthy and
diarrheic; all were between 1 and 45 d old. Diarrheic calves
(n = 21) were selected in the study based on the
finding of diarrhea on physical examination of sick calves presented to
the large animal clinic of the Western College of Veterinary Medicine,
University of Saskatchewan. All diarrheic calves had access to their
dam’s milk before presentation to the clinic by their owners. Some had
been treated with oral electrolyte solutions containing glucose,
glycine and electrolytes. Twenty-one calves from a local beef farm
that were normal on physical examination were used as healthy controls.
Healthy calves also had access to their dam’s milk. The physical
condition of each scouring calf was assessed at time of entry into the
study (29)
. The study was approved by the Animal Care
Committee, University of Saskatchewan and carried out in accordance
with the principles and guidelines specified by the Canadian Council on
Animal Care.
Experimental protocol.
At admission, blood (2.5 mL) was collected anerobically from the jugular vein of the calves in a preheparinized plastic syringe (Smooth; Radiometer America, Westlake, OH) for blood gas measurements. A second blood sample (2.5 mL) for the determination of organic acid concentration was also collected at admission and placed in a tube containing no anticoagulant (Vacutainer; Becton Dickinson, Rutherford, NJ). This blood was allowed to stand for between 20 and 40 min. On clotting, serum was separated by centrifugation and frozen at -20°C until analyzed. All calves were resting when the blood samples were drawn. Fecal samples were collected simultaneously after perineal massage and frozen until HPLC assay.
Blood gas measurements.
All acid-base parameters (pH, bicarbonate concentration, anion gap, partial pressure of carbon dioxide and base excess) were determined within 15 min of blood collection using an automated blood gas analyzer (Ciba Corning 288 blood gas system; Ciba Corning Canada, Markham, Ontario). Bicarbonate, pH and PCO2 values were corrected to the calf’s rectal temperature. Plasma sodium, potassium and chloride concentrations were also determined simultaneously using a spectrophotometric autoanalyzer (Abbott Spectrum System, North Chicago, IL). Anion gap was measured as the difference between the sum of the serum concentrations of the readily measured cations, Na+ + K+, and the readily measured anions, Cl- + HCO3-.
Organic acid measurements.
Serum and fecal samples collected were analyzed for organic acid concentrations by HPLC 1 wk after the last sampling. Before HPLC analysis, serum samples were deproteinized by ultrafiltration. To an Ultrafree-MC centrifugal filter unit (Millipore, Milford, MA), 100 µL of standard adult bovine serum was added along with 50 µL internal standard solution and made up to 200 µL with aqueous solution of standard DL-lactate for calibration purposes. The internal standards used were citric acid and malonic acid for the nonstereospecific and stereospecific assays, respectively. For quantification purposes, aliquots (100 µL each) of each sample were used instead of standard bovine serum and 50 µL of double distilled water (DDW) replaced standard DL-lactate. The resulting solution was spun at 10,600 x g for 30 min. Aliquots of 20 µL from the filtrate were then injected into the HPLC system. For the stereospecific analysis of lactate, fecal samples (0.5 g each) were mixed with 5 mL DDW and centrifuged at 10,600 x g for 20 min. The supernatant was drawn off with a syringe and was further purified by filtration through an Acrodisc PF (0.8/0.2)-µm syringe filter (Pall Corporation, Ann Arbor, MI). These filtrates (100 µL) were subsequently deproteinized in the same manner as the serum samples, using DDW instead of standard bovine serum. Aliquots of 20 µL from the filtrates were then injected into the HPLC system.
Both the stereospecific and nonstereospecific assays made use of the
same HPLC system, under different conditions as previously described
(28)
. The HPLC system consisted of a Waters Model 600
pump, a Waters 486 tunable wavelength ultraviolet absorbance detector
and a Waters 710 Ultra WISP autoinjector (Waters, Mississauga, ON).
Data collection, integration and calibration were performed using a
Waters Millennium chromatography manager, Version 2.1 (Waters,
Mississauga, ON). The nonstereospecific analysis used a
reverse-phase, 300- x 8.0-mm analytical column (Shodex RSPAK
KC-811; Showa Denko K.K., Tokyo, Japan) for the chromatographic
analyses of lactic acid, pyruvate, acetate and citric acid (internal
standard). Lactic acid, pyruvic acid and acetic acid were identified
based on their retention times with known standards of each acid and
recovery was determine from the internal standard. Concentrations of
pyruvate, acetate and lactate were determined from standard curves made
with solutions of the appropriate acid (28)
. The mobile
phase, consisting of 0.1% phosphoric acid and DDW, was pumped at 0.7
mL/min in the isocratic mode, with the column temperature maintained at
50°C. Ultraviolet light detection was at 205 nm, representing the
ultraviolet maxima of a solution of lactate in the nonstereospecific
mobile phase (28)
.
The stereospecific analysis of lactate enantiomers used a stainless
steel 3 µm octodecylsilane packed analytical column (50
x 4.6 mm internal diameter), coated with
N,N-dioctyl-L-alanine as chiral selector
(Chiral Technologies, Exton, PA). The mobile phase consisted of 2
mmol/L copper sulfate containing 1% acetonitrile and was pumped in the
isocratic mode at 0.4 mL/min at room temperature. Ultraviolet light
detection was at 236 nm. This wavelength represented the ultraviolet
maxima of a solution of lactic acid in the stereospecific mobile
phase (28)
. The mobile phases of both assays were filtered
through 0.45-µm membrane filters (Scheicher & Schuell, Keene, NH) and
degassed under vacuum to remove oxygen and contaminants before use. For
each assay, samples were randomly analyzed within each batch.
Statistical analysis.
Statistical data were analyzed with Analysis ToolPak program on Microsoft Excel, Version 5.0, 1985–1994 (Redmond, WA). The mean concentrations of all organic acids were calculated for the healthy and diarrheic calves. Unpaired two-sample t test assuming unequal variances was used to compare blood gas components and measured concentrations lactic acid, its enantiomers and other organic acids were measured and compared between the two groups of calves. All values were expressed as the mean ± SD, and a P value < 0.05 was considered significant.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Average age of calves was 18.8 ± 16.4 and 16.4 ± 13.7 d in healthy and diarrheic calves, respectively. The age of calves
ranged between 1 and 34 d in the healthy group and 5 and 45 d
in the diarrheic group. Diarrheic calves were depressed at presentation
in 19 instances, with 14 of the depressed calves in sternal or lateral
recumbency. Blood gas analysis showed that healthy calves had
significantly higher mean values of pH,
PCO2,
HCO3- and base excess
and a significantly lower anion gap than their diarrheic counterparts
(Table 1
). There were no significant differences in means for plasma sodium,
potassium and chloride concentrations between healthy and diarrheic
calves.
|
Diarrheic calves had significantly higher (P < 0.05)
concentrations of acetic, pyruvic, DL-,
L- and D-lactic acids than
healthy calves (Table 1)
. To determine whether age-related
differences affected D-lactic acid
concentrations in our diarrheic calves, the mean age of diarrheic
calves with either higher D-lactate or higher
L-lactate concentrations was compared. Diarrheic
calves in which D-lactic acidosis predominated
were 15.9 ± 6.4 d old, whereas those in which
L-lactic acidosis predominated were 16.5 ± 11.0 d old.
Fecal concentrations of organic acids.
Overall, fecal samples were collected from 18 diarrheic calves and 20 healthy calves. Fecal samples were not obtained from two diarrheic calves. Fecal lactate concentrations (D and L, respectively) were significantly higher (P < 0.05) in diarrheic calves (9.4 ± 3.0 and 11.9 ± 2.7 mmol/L) compared with healthy calves (1.1 ± 0.1 and 1.6 ± 0.1 mmol/L).
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
,30)
and
provided evidence that this was derived from tissue metabolism
secondary to dehydration. The use of fast and simple HPLC methods of
analysis in this study, however, afforded the simultaneous
investigation of other organic acids that may contribute to metabolic
acidosis.
When diarrheic calves were compared with their healthy counterparts,
they had a moderately severe metabolic acidosis with respiratory
compensation. This is consistent with previous studies
(15
,29)
. The mean anion gap was increased by > 14
mmol/L in diarrheic calves. This represents the total amount of organic
acids that could have been added to serum along with more minor
contributions associated with changes in concentrations or charge of
calcium, magnesium, phosphates and albumin (31)
. The
concentrations of all acids measured in this study, pyruvic, lactic and
acetic acids, were significantly higher in the diarrheic calves. This
indicates that all acids contribute to the lower mean pH value and
higher anion gap in the diarrheic calves.
Although acetic acid and pyruvic acid concentrations were higher in
diarrheic calves, they were present in very low, and sometimes
unmeasurable concentrations, and could only be a minor contributor to
acidosis. Disposal of these acids through the tricarboxylic acid cycle
could be limited by low tissue perfusion and reduced tissue oxygen
supply in diarrhea. Moreover, increased production of volatile fatty
acids from bacterial fermentation in the gastrointestinal tract may
also result in the production of acetic acid (32)
.
The levels of DL-lactate in our healthy calves are
consistent with typical values for blood lactate concentrations in
normal ruminants, which vary between 0.5 and 2.0 mmol/L
(24)
. In our study, concentrations of
DL-lactic acid measured using the nonstereospecific assay
were approximately the same as the sum of D- and
L-lactic acids measured with the stereospecific HPLC method
for each calf. This further demonstrates the reliability of our
analytical approach.
Mean concentrations of L-lactate were elevated in diarrheic
calves, similar to previous findings (15)
.
L-lactate is normally formed by mammalian cells during
anaerobic respiration (14)
. Its concentration is an index
of tissue oxygen deprivation and is helpful in grading the severity of
shock (33)
. It can also be produced in large amounts in
exercising, healthy, muscle (34)
. It has been reported in
neonatal diarrheic calves as a sequela to diarrhea induced dehydration
(15)
. An anaerobic respiration component of
L-lactic acidosis due to limited supply of oxygen because
hypovolemia probably existed in our study. In addition, the finding of
high concentrations of L-lactate in the feces suggests that
some may have been of enteric origin. L-lactic acid alone,
however, can only explain a small part of the acidosis in our diarrheic
calves since the increase in anion gap in diarrheic versus healthy
calves was in excess of 14 mmol/L, whereas the combined increases in
L-lactate and pyruvate was < 3 mmol/L. Others have
reported similar findings (3)
.
Serum D-lactate concentrations were higher in diarrheic
calves, indicating that D-lactic acidosis is a contributory
factor in calves with high anion gap acidosis. D-lactic
acidosis was more severe than lactic acidosis in nine calves. The ages
of the high L- and D-lactic acidosis groups
were similar, so age-related differences in body metabolism or
intestinal flora were not responsible for the difference in types of
lactic acidosis in this study. Overall, increases in D- and
L-lactate totaled 
9 mmol/L and, thus, together accounted
for 9 mmol/L of the 14-mmol/L increase in anion gap.
Studies have previously linked D-lactic acid production
with bacterial fermentation in the gastrointestinal tract
(18
,35
,36)
. Malabsorption of nutrients in the small
intestine of SBS patients, with subsequent fermentation by colonic
bacteria results in D-lactic acidosis in humans
(18
,35
36
37)
. Malabsorption and passage of undigested
nutrients into the distal small intestine may cause the same process in
diarrheic calves. Previous studies of diarrheic calves at our college
show that many are infected by organisms known to cause villus atrophy
(38)
and, consequently, maldigestion and malabsorption of
nutrients (39)
. As a result, excessive delivery of
nutrients to the distal small intestine and large colon could result in
bacterial overgrowth and probably D-lactic acid production.
Presumably, milk lactose could be readily fermented to D-
and L-lactic acids by colonic bacteria.
Our finding of higher fecal D- and L-lactate
concentrations in diarrheic calves supports our hypothesis that
bacterial fermentation of undigested and malabsorbed nutrients take
place in the gut of diarrheic calves. The mechanisms by which these
acids could be absorbed in diarrheic patients are poorly understood.
There may be direct diffusion across inflamed mucosa. In addition, the
mucosal monocarboxylic acid transporter transports L-lactic
acid and a variety of other organic acids and transport is enhanced by
low pH (40)
. Unlike L-lactate, metabolism of
D-lactate in calves, humans and other vertebrates is slow
(25)
or impaired (41)
. Therefore,
accumulation of D-lactic acid is an important contributory
factor to acidosis in neonatal calves with diarrhea. Our study
establishes that acidosis in diarrheic calves is due in part to
D-lactic acid accumulation and that the gastrointestinal
tract seems to be the site of D-lactate production. This
finding was made possible by the new, fast and simple analytical
approach used in this study, which made it possible to partition lactic
acidosis between D and L isomers of lactic
acid.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
3 Abbreviations used: DDW, double distilled water; SBS, short bowel syndrome.
Manuscript received December 19, 2000. Revision accepted May 8, 2001.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
1. World Health Organization The World Health Report. Bridging the Gaps: Report of the Director General 1995 World Health Organization Geneva, Switzerland.
2. Schumann F. J., Townsend H. G., Naylor J. M. Risk factors for mortality from diarrhea in beef calves in Alberta. Can. Vet. J. 1990;54:366-372
3. Grove-White D. H., White D. G. Diagnosis and treatment of metabolic acidosis in calves: a field study. Vet. Rec. 1993;133:499-501[Abstract]
4. Nizet V., Priebe C. J. A new born girl with watery diarrhea, weight loss, and severe metabolic acidosis. Curr. Opin. Pediatr. 1994;6:163-167[Medline]
5. Phillips R. W., Knox K. L. Diarrheic acidosis in calves. J. Comp. Lab. Med. 1969;3:1-3
6. Weldon A. D., Moise N. S., Rebhun W. C. Hyperkalemic atrial standstill in neonatal calf diarrhea. J. Vet. Int. Med. 1992;6:294-297
7. Kasari T. R., Naylor J. M. Clinical evaluation of sodium bicarbonate, sodium L-lactate, and sodium acetate for the treatment of acidosis in diarrheic calves. J. Am. Vet. Med. Assoc. 1985;187:392-397[Medline]
8. Naylor J. M., Petrie L., Rodriguez M. I., Skilnick P. A comparison of three oral electrolyte solutions in the treatment of diarrheic calves. Can. Vet. J. 1990;31:753-760
9. Kasari T. R. Metabolic acidosis in calves. Vet. Clinics N. Am. 1999;15:473-486
10. Moseley R. H. Fluid and electrolyte disorders and gastrointestinal disease. Kokko J. P. Tannen R. L. eds. Fluids and Electrolytes 3rd ed. 1996:675-692 WB Saunders & Company Philadelphia, PA.
11. Astiz M., Rackow E. C., Weil M. H., Schumer W. Early impairment of oxidative metabolism and energy production in severe sepsis. Circ. Shock 1988;26:311-320[Medline]
12. Fectau G., Van Metre D. C., Smith B. P., Pare J. Implications of blood culture results from diarrheic calves. Proc. Annu. Vet. Med. Forum, Am. Coll. Vet. Int. Med. 1992;10:476-478
13. Herdt T. Pathophysiology of diarrhea. Textbook of Veterinary Physiology 2nd ed. 1997:327-330 WB Saunders Company Philadelphia, PA.
14. Mayes P. A. Glycolysis and the oxidation of pyruvate. Murray R. K. Granner D. K. Mayes P. A. Rodwell V. W. eds. Harperís Biochemistry 24th ed. 1996:176-184 Appleton & Lang Stanford, CT.
15. Naylor J. M. Severity and nature of acidosis in diarrheic calves over and under one week of age. Can. Vet. J. 1987;28:168-173[Medline]
16.
Naylor J. M., Kronfeld D. S. In vivo studies of hypoglycemia and lactic acidosis in endotoxic shock. Am. J. Physiol. 1985;248:E309-E316
17. Androgue H. J., Tannen R. L. Ketoacidosis, hyperosmolar states, and lactic acidosis. Kokko J. P. Tannen R. L. eds. Fluids and Electrolytes 3rd ed. 1996:643-674 WB Saunders & Company Philadelphia, PA.
18. Vella A., Farrugia G. D-lactic acidosis: pathologic consequence of saprophytism. Mayo Clin. Proc. 1998;73:451-456[Medline]
19. Schelcher F., Marcillaud S., Braun J. P., Contrepois M., Valarcher V. F., Navetat H. Metabolic acidosis without dehydration and no or minimal diarrhea in sucker calves is caused by hyper D-lactatemia. Proc. XX World Buiatrics Congress 1998;:371-374
20. Guerrant R. L., Schorling J. B., McAnliffe F., De Souza M. A. Diarrhea as a cause and effect of malnutrition: diarrhea prevents catch-up growth and malnutrition increases frequency and duration. Am. J. Trop. Med. Hyg. 1992;47:28-35
21. Sullivan P. B. Nutritional management of acute diarrhea. Nutrition 1998;14:758-762[Medline]
22. Argenzio R. A. Pathophysiology of diarrhea. Anderson N. V. Sherding R. G. Merritt A. M. Whitlock R. H. eds. Veterinary Gastroenterology 2nd ed. 1992:163-172 Lea & Febiger Philadelphia, PA.
23. Garry F. B. Indigestion in ruminants. Smith B. P. eds. Large Animal Internal Medicine 2nd ed. 1996:837-839 Mosby-Year Book St Louis, MO.
24. Dunlop R. H., Hammond P. B. D-Lactic acidosis of ruminants. Ann. N. Y. Acad. Sci. 1965;119:1109-1132[Medline]
25.
Naylor J. M., Kronfeld D. S., Freeman D. E., Richardson D. Hepatic and extrahepatic lactate metabolism in sheep: effects of lactate loading and pH. Am. J. Physiol. 1984;247:E747-E755
26. Acres S. D. Enterotoxigenic Escherichia coli infection in newborn calves. J. Dairy Sci. 1985;68:229-256
27. Mebus C. A., Stair E. L., Rhodes M. B., Twiehaus M. J. Pathology of neonatal calf diarrhea induced by a coronavirus-like agent. Vet. Pathol. 1973;10:45-64[Medline]
28. Omole O. O., Brocks D. R., Nappert G., Naylor J. M., Zello G. A. High-performance liquid chromatographic assay of (±)-lactic acid and its enantiomers in calf serum. J. Chromatogr. B 1999;727:23-29
29. Naylor J. M. A retrospective study of the relationships between age, clinical signs and severity of acidosis in diarrheic calves. Can. Vet. J. 1989;30:577-580[Medline]
30. Kasari T. R., Naylor J. M. Further studies on the clinical features and clinico-pathological findings of a syndrome of metabolic acidosis with minimal dehydration in neonatal calves. Can. J. Vet. Res. 1986;50:502-508[Medline]
31. Groutides C. P., Michell A. R. Changes in plasma composition in calves surviving or dying from diarrhea. Br. Vet. J. 1990;146:205-210[Medline]
32. Westrin K. M., Stierna P., Soderlund K., Carlsoo B. Lactic acid isomers and fatty acids in sinus secretion: a longitudinal study of bacterial and leukocyte metabolism in experimental sinusitis. Scand. J. Infect. Dis. 1992;24:765-772[Medline]
33. Tietz N. W. Tietz N. W. eds. Fundamentals of Clinical Chemistry 1976:936 WB Saunders Company Philadelphia, PA.
34.
Stringer W., Casaburi R., Wasserman K. Acid-base regulation during exercise and recovery in humans. J. Appl. Physiol. 1992;72:954-961
35. Bustos D., Pons S., Pernas J. C., Gonzalez H., Caldrini M. I., Ogawa K., De Paula J. A. Fecal lactate and short bowel syndrome. Dig. Dis. Sci. 1994;39:2315-2319[Medline]
36. Oh S. M., Phelps K. R., Traube M., Barbosa-Saldivar J. L., Boxhill C., Carroll H. J. D-Lactic acidosis in a man with short-bowel syndrome. N. Engl. J. Med. 1979;301:249-252[Medline]
37. Caldarini M. I., Pons S., DíAgostino D., Depaula J. A., Greco G., Negri G., Ascione A., Bustos D. Abnormal fecal flora in a patient with short bowel syndrome. Dig. Dis. Sci. 1996;41:1649-1652[Medline]
38. Naylor J. M. Neonatal ruminant diarrhea. Smith B. P. eds. Large Animal Internal Medicine 2nd ed. 1996:396 Mosby St. Louis, MO.
39. Nappert G., Hamilton D., Petrie L., Naylor J. M. Determination of lactose and xylose malabsorption in preruminant diarrheic calves. Can. J. Vet. Res. 1993;57:152-158[Medline]
40. Tamai I., Sai Y., Ono A., Kido Y., Yabuuchi H., Takanaga H., Satoh E., Ogihara T., Amano O., Izeki S., Tsuji A. Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1. J. Pharm. Pharmacol. 1999;51:1113-1121[Medline]
41. Uribarri J., Oh M. S., Carroll H. J. D-Lactic acidosis: a review of clinical presentation, biochemical features, and pathophysiologic mechanisms. Medicine 1998;77:73-82[Medline]
This article has been cited by other articles:
|
|
 |
|
  S. Abeysekara, J. M. Naylor, A. W. A. Wassef, U. Isak, and G. A. Zello D-Lactic acid-induced neurotoxicity in a calf model Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E558 - E565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Petersen D-Lactic Acidosis Nutr Clin Pract, December 1, 2005; 20(6): 634 - 645. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
