Neonates have an immature immune system which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is examplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B-cell receptor (BCR) with the Fcg receptor IIB (FcgRIIB) by a vaccine-antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B-cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2) signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing this concept.

Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies.

Creatinine is the analyte most frequently measured in human and veterinary clinical chemistry laboratories as an indirect measure of glomerular filtration rate (GFR). Although creatinine metabolism and the difficulties of creatinine measurement have been reviewed in human medicine, similar reviews are lacking in veterinary medicine. The aim of this review is to summarize information and data about creatinine metabolism, measurement, and diagnostic significance in the dog. Plasma creatinine originates from the degradation of creatine and creatine phosphate, which are present mainly in muscle and in food. Creatinine is cleared by glomerular filtration with negligible renal secretion and extrarenal metabolism, and its clearance is a good estimate of GFR. Plasma and urine creatinine measurements are based on the nonspecific Jaffe reaction or specific enzymatic reactions; lack of assay accuracy precludes proper interlaboratory comparison of results. Preanalytical factors such as age and breed can have an impact on plasma creatinine (P-creatinine) concentration, while many intraindividual factors of variation have little effect. Dehydration and drugs mainly affect P-creatinine concentration in dogs by decreasing GFR. P-creatinine is increased in renal failure, whatever its cause, and correlates with a decrease in GFR according to a curvilinear relationship, such that P-creatinine is insensitive for detecting moderate decreases of GFR or for monitoring progression of GFR in dogs with severely reduced kidney function. Low sensitivity can be obviated by determining endogenous or exogenous clearance rates of creatinine. A technique for determining plasma clearance following IV bolus injection of exogenous creatinine and subsequent serial measurement of P-creatinine does not require urine collection and with additional studies may become an established technique for creatinine clearance in dogs.

Creatinine in the dog: a review.

The objective of this experiment was to determine the effects of age and diet on serum chemistry, hematology, and nutrient digestibility in healthy dogs. Twelve senior (11 yr old; six males and six females) and 12 weanling (age = 8 wk old; six males and six females) beagles were randomly assigned to one of two dietary treatments: 1) an animal product-based (APB) diet or 2) a plant product-based (PPB) diet. The APB diet was primarily composed of brewer's rice, chicken by-product meal, and poultry fat, whereas the primary ingredients of the PPB diet included corn, soybean meal, wheat middlings, and meat and bone meal. Dogs remained on experiment for 12 mo. A 4-d total fecal collection was performed to determine apparent macronutrient digestibilities after 3 and 10 mo. Blood samples were collected at baseline and after 3, 6, 9, and 12 mo on study. After 3 mo, dogs fed the APB diet had greater (P < 0.001) DM (6 percentage units) and OM (7 percentage units) digestibilities than dogs fed the PPB diet. Senior dogs had greater DM (2.5 percentage units; P = 0.07) and OM (3 percentage units; P < 0.01) digestibilities than young dogs. Dogs fed the PPB diet had a lower (P < 0.001) fecal DM percentage (7.5 percentage units) and greater (P < 0.001) fecal output (253 vs. 97 g/d, as-is basis). After 10 mo, age did not affect nutrient digestibility or fecal characteristics. However, the effect of diet after 10 mo was similar to that observed after 3 mo, as dogs fed the PPB diet had a lower (P < 0.001) fecal DM percentage (7 percentage units), lower OM (4 percentage units; P = 0.09) and fat (6 percentage units; P < 0.001) digestibilities, and greater (P < 0.005) fecal output (235 vs. 108 g/d, as-is basis). At baseline, most serum metabolites were different between age groups, with weanlings having several metabolite concentrations outside the reference ranges for adult dogs. Blood cholesterol, red blood cells, hemoglobin, hematocrit, creatinine, total protein, albumin, bilirubin, sodium, chloride, and alanine transaminase were present in greater (P < 0.05) concentrations in senior dogs, but weanling dogs had greater (P < 0.05) concentrations of glucose, platelets, Ca, P, K, and alkaline phosphatase. Over time, blood cholesterol concentrations were affected by age (P < 0.05) and diet (P < 0.01). Senior dogs had greater (P < 0.05) cholesterol concentrations than weanling dogs. Moreover, dogs fed the APB diet had greater (P < 0.05) cholesterol concentrations than dogs fed the PPB diet. Overall, although serum metabolite concentrations of weanlings were different from senior dogs at baseline, as weanlings matured into young adults, metabolite concentrations were similar to those of senior dogs. Diet had the largest effects on nutrient digestibilities and fecal characteristics. Canine age and diet must be considered when interpreting experimental and clinical data.

https://www.igb.illinois.edu/labs/schook/genomics/pdfs/Swanson%20et%20al,%202004%20J%20Anim%20Sci.pdf

Diet affects nutrient digestibility, hematology, and serum chemistry of senior and weanling dogs.

This chapter elaborates the biochemistry of kidney functions and diseases. Clinical biochemistry in nephrology is mainly used to diagnose and monitor renal dysfunction or damage. This is of special importance in human medicine, because of the frequent observation of renal failure in elderly people, and in canine and feline medicine, especially for the early detection of chronic renal failure. Kidney diseases are uncommon in equids and cattle. The latter show better resistance to a loss of kidney function than monogastric animals because of the filtration function of the rumen epithelium. The mammalian kidney consists of tens of thousands to millions of nephrons that function as parallel units. The larger the species, the greater the number of nephrons per kidney. This chapter begins with discussing the general structure of the kidneys. The chapter then describes the glomerulus and filtration process in kidney. Direct and indirect tests of glomerular function are explained. The chapter also discusses some tests of kidney damage. The chapter concludes with a discussion on biochemical changes that occur during some kidney diseases.

Kidney Function and Damage

The main objective of this study was to examine age-associated changes in laboratory values in dogs in order to establish standard values for dogs of a certain age. These standard values could serve to judge the health status of individual dogs and possibly estimate their remaining life expectancy. Thus, haematological and immunological parameters, plasma constituents, kidney characteristics and the capacity of homeostasis were determined in German shephard dogs (0.5-13.5 years) and beagles (4-9 years). Significant changes were noted. We detected that the number of white blood cells declines with age. The change in a number of organ specific enzymes indicates organ involution and increased cell death. Increased plasma glucose levels and a decreased glucose tolerance point to a diminished sensitivity of tissue to concentrations change due to a decrease in organ production and changes in the immune system, which are also reflected in an impaired lymphocyte proliferation capacity. These factors lead to an increased blood sedimentation rate. Cortisol increases might reflect a reduced stress resistance. Age-related decreases in aldosterone concentration and PAH-clearance were also found.

The Effect of Aging on Laboratory Values in Dogs

Age dependency of hematological values and concentrations of serum biochemical constituents in normal beagles from 1 to 14 years of age.

Antibody titers against canine parvovirus (CPV), canine distemper virus (CDV) and infectious canine hepatitis virus (ICHV) in serum were measured in 6 beagle dams and their 38 puppies bred in our colony, in order to clarify the effects of maternally derived antibodies to antibody responses against the viruses after vaccinations in puppies. Correlation coefficient on antibody titers between puppies and dams were CPV: r = 0. 7935, CDV: r = 0.8194 and ICHV: r = 0.8105. Mean maternal antibody positive rates in 7-day-old puppies from their dams were CPV: 67%, CDV: 46% and ICHV: 45%. Mean half-lives of the maternal antibodies in puppies were estimated to be CPV: 13.5 days, CDV: 15.1 days and ICHV: 15.4 days. The antibody response against CPV vaccination in puppies was mainly observed in dogs being titers of less 1:5 and positivity was 39% (15/38 puppies) after 1st vaccination at 42 days after birth, and 82% (31/38 puppies) after 2nd vaccination at 70 days. That against CDV vaccination (at 56 days after birth) was seen highly in dogs being titers of less 1:10 and positivity was 53% (20/38). Also that against ICHV vaccination (at 56 days after birth) was seen frequently in dogs being titers of less 20 holds and the rate was 87% (33/38). From these results, it was estimated that the age when high antibody response against each vaccination could be expected in puppies might be CPV: between 40 and 69 days, CDV: between 32 and 92 days and ICHV: between 31 and 52 days, respectively.

[Effect of maternally derived antibody levels on antibody responses to canine parvovirus, canine distemper virus and infectious canine hepatitis virus after vaccinations in beagle puppies].

Kazumi Tokita

Papers

Age dependency of hematological values and concentrations of serum biochemical constituents in normal beagles from 1 to 14 years of age.

[Effect of maternally derived antibody levels on antibody responses to canine parvovirus, canine distemper virus and infectious canine hepatitis virus after vaccinations in beagle puppies].