In vivo kinetic study on uptake and distribution of intramuscular tritium-labeled polysulfated glycosaminoglycan in equine body fluid compartments and articular cartilage in an osteochondrial defect model

The uptake and distribution of intramuscularly (IM) administered tritium-labeled polysulfated glycosaminoglycan (³H-PSGAG) in serum, synovial fluid, and articular cartilage of eight horses was quantitated, and hyaluronic acid (HA) concentration of the middle carpal joint was evaluated in a pharmacokinetic study. A full-thickness articular cartilage defect, created on the distal articular surface of the left radial carpal bone of each horse served as an osteochondral defect model. ³H-PSGAG (500 mg) was injected IM, between 14 and 35 days after creation of the defects. Scintillation analysis of serum and synovial fluid, collected from both middle carpal joints at specific predetermined times up to 96 hours post-injection, revealed mean ³H-PSGAG concentrations peaked at 2 hours post-injection. ³H-PSGAG was detected in cartilage and subchondral bone 96 hours post-injection in samples from all eight horses. There were no statistically significant differences in ³H-PSGAG concentration of synovial fluid or cartilage between cartilage defect and control (right middle carpal) joints.

HA assay of synovial fluid revealed concentrations significantly increased at 24, 48, and 96 hours post-injection in both joints. The concentration nearly doubled 48 hours post-injection. However, no statistically significant differences were found between synovial concentrations of HA in cartilage defect and control joints.

³H-PSGAG administered IM to horses, was distributed in the blood, synovial fluid, and articular cartilage. HA concentrations in synovial fluid increased after IM administration of polysulfated glycosaminoglycan.     

Comparative lipid and lipoprotein metabolism

This review summarizes a number of recent reports in several areas of lipid and lipoprotein metabolism. Absorption of dietary lipids, cholesterol synthesis, and biliary cholesterol metabolism are mentioned only briefly to be complete. Comparative aspects of lipoprotein metabolism, however, are detailed in an effort to integrate the myriad metabolic events which characterize these important lipid transport particles. Where comparative information is known, those aspects of lipoprotein metabolism that may be protective against atherogenesis in certain mammalian species are also described. Efforts to understand atherogenic resistance comparatively in animals lends a better understanding of the metabolic events leading to coronary artery disease in humans. They also provide an important basis for understanding lipid metabolism in numerous veterinary species.     

Association mapping reveals loci associated with multiple traits that affect grain yield and adaptation in soft winter wheat

Genome-wide association studies (GWAS) are useful to facilitate crop improvement via enhanced knowledge of marker-trait associations (MTA). A GWAS for grain yield (GY), yield components, and agronomic traits was conducted using a diverse panel of 239 soft red winter wheat (Triticum aestivum) genotypes evaluated across two growing seasons and eight site-years. Analysis of variance showed significant environment, genotype, and genotype-by-environment effects for GY and yield components. Narrow sense heritability of GY (h ²  = 0.48) was moderate compared to other traits including plant height (h ²  = 0.81) and kernel weight (h ²  = 0.77). There were 112 significant MTA (p < 0.0005) detected for eight measured traits using compressed mixed linear models and 5715 single nucleotide polymorphism markers. MTA for GY and agronomic traits coincided with previously reported QTL for winter and spring wheat. Highly significant MTA for GY showed an overall negative allelic effect for the minor allele, indicating selection against these alleles by breeders. Markers associated with multiple traits observed on chromosomes 1A, 2D, 3B, and 4B with positive minor effects serve as potential targets for marker assisted breeding to select for improvement of GY and related traits. Following marker validation, these multi-trait loci have the potential to be utilized for MAS to improve GY and adaptation of soft red winter wheat.     

Regulation of T cell homeostasis during fetal and early postnatal life

Before parturition the fetal lamb develops a large pool of long-lived recirculating T cells which provides a large population of naive T cells with a diverse TcR repertoire. After birth and concomitant with exposure to environment antigens, fetal T cells are rapidly replaced by short-lived cells formed postnatally. The majority of thymic emigrants homing to spleen in postnatal lambs are short-lived, in contrast to emigrants targeting lymph nodes where a population appears to be long-lived. The lifespan of thymic emigrants in the fetus is unknown as in the relative importance of antigen-driven processes versus developmental programming in regulating T cell homeostasis in early postnatal life.     

Comparison of methods to assess dog owners' therapeutic compliance

Objective To compare different methods for assessing the compliance of veterinary clients administering medication to their dogs.
Procedure Thirty-one owners whose dogs were prescribed amoxycillin-clavulanate, twice and thrice daily, for a duration of five to seven days were recruited from three Sydney veterinary hospitals. Compliance was assessed by electronic monitoring devices, return medication counts, client self-reports and veterinarians' estimation of likely compliance.
Results Electronic monitoring showed owners administered on average 84% (range 7 to 104%) of prescribed medication to their dogs. Both return medication counts and client self-reports tended to overestimate therapeutic compliance when compared with electronic monitoring. When questioned, the majority of owners (71%) claimed perfect compliance with the prescribed regimen. No correlation was found between veterinarians' estimates of owner compliance and that assessed electronically.
Conclusion Electronic monitoring provided valuable information on dose timing and variation, but proved costly and difficult to employ in veterinary practice. Simplicity and low cost of return medication counts makes this method attractive for use in veterinary compliance studies. Client self-reports reliably detected some noncompliers and permitted identification of individual problems or errors. For practical purposes a combination of return medication counts and client self-reports may have merit in future veterinary compliance studies.     

Rainfall interception and fog precipitation in a tropical montane cloud forest of Guatemala

Tropical montane cloud forest hydrology is complex because of the presence of epiphytic life-forms that increase canopy surfaces and fog persistency. Fog precipitation is a hydrological input common to cloud forests, and forms when fog droplets are intercepted by the canopy and fall to the forest floor. Interception and fog precipitation was determined for a 2100 m site and a 2550 m site in a first-order tributary of the Sierra de las Minas Biosphere Reserve, Guatemala by calculating the difference between throughfall and gross precipitation for a 44-week period. Both sites were situated within closed-canopy cloud forests. The 2100 m site was on the windward slope of Montaña de Miranda near the lower boundary of the cloud forest and the 2550 m site was at the summit. Fog precipitation was found during periods in which throughfall exceeds gross precipitation. Fog precipitation was greater at 2550 m than at 2100 m. Data collected by precipitation and throughfall gauges demonstrate the existence of seasonal fog precipitation with the greatest fog precipitation occurring in the dry season (November–April). Fog precipitation contributes approximately 1 mm per day to the hydrological budget of the cloud forest at 2550 m during the dry season, and 0.5 mm per day during the rainy season (May–October).     

A Polymorphism in the Melanocortin 4 Receptor Gene (MC4R:c.92C>T) Is Associated with Diabetes Mellitus in Overweight Domestic Shorthaired Cats

Background

Feline diabetes mellitus (DM) shares many pathophysiologic features with human type 2 DM. Human genome‐wide association studies have identified genes associated with obesity and DM, including melanocortin 4 receptor (MC4R), which plays an important role in energy balance and appetite regulation.

Hypothesis/Objectives

To identify single nucleotide polymorphisms (SNPs) in the feline MC4R gene and to determine whether any SNPs are associated with DM or overweight body condition in cats.

Animals

Two‐hundred forty domestic shorthaired (DSH) cats were recruited for the study. Of these, 120 diabetics were selected (60 overweight, 60 lean), along with 120 nondiabetic controls (60 overweight and 60 lean). Males and females were equally represented.

Methods

A prospective case‐control study was performed. Genomic DNA was extracted from blood samples and used as template for PCR amplification of the feline MC4R gene. The coding region of the gene was sequenced in 10 cats to identify polymorphisms. Subsequently, genotyping by restriction fragment length polymorphism (RFLP) analysis assessed MC4R:c.92C > T allele and genotype frequencies in each group of cats.

Results

No significant differences in MC4R:c.92C>T allele or genotype frequencies were identified between nondiabetic overweight and lean cats. In the overweight diabetic group, 55% were homozygous for the MC4R:c.92C allele, compared to 33% of the lean diabetics and 30% of the nondiabetics. The differences between the overweight diabetic and the nondiabetics were significant (P < .01).

Conclusions and Clinical Importance

We identified a polymorphism in the coding sequence of feline MC4R that is associated with DM in overweight DSH cats, similar to the situation in humans.     

Kisspeptin,c‐Fos and CRFR Type 2 Co‐expression in the Hypothalamus after Insulin‐Induced Hypoglycaemia

Normal reproductive function is dependent upon availability of glucose and insulin‐induced hypoglycaemia is a metabolic stressor known to disrupt the ovine oestrous cycle. We have recently shown that IIH has the ability to delay the LH surge of intact ewes. In the present study, we examined brain tissue to determine: (i) which hypothalamic regions are activated with respect to IIH and (ii) the effect of IIH on kisspeptin cell activation and CRFR type 2 immunoreactivity, all of which may be involved in disruptive mechanisms. Follicular phases were synchronized with progesterone vaginal pessaries and at 28 h after progesterone withdrawal (PW), animals received saline (n = 6) or insulin (4 IU/kg; n = 5) and were subsequently killed at 31 h after PW (i.e., 3 h after insulin administration). Peripheral hormone concentrations were evaluated, and hypothalamic sections were immunostained for either kisspeptin and c‐Fos (a marker of neuronal activation) or CRFR type 2. Within 3 h of treatment, cortisol concentrations had increased whereas plasma oestradiol concentrations decreased in peripheral plasma (p < 0.05 for both). In the arcuate nucleus (ARC), insulin‐treated ewes had an increased expression of c‐Fos. Furthermore, the percentage of kisspeptin cells co‐expressing c‐Fos increased in the ARC (from 11 to 51%; p < 0.05), but there was no change in the medial pre‐optic area (mPOA; 14 vs 19%). CRFR type 2 expression in the lower part of the ARC and the median eminence was not altered by insulin treatment. Thus, disruption of the LH surge after IIH in the follicular phase is not associated with decreased kisspeptin cell activation or an increase in CRFR type 2 in the ARC but may involve other cell types located in the ARC nucleus which are activated in response to IIH.