Cellular pathogenesis in prion diseases

Prion diseases are characterised by neuronal loss, vacuolation (spongiosis), reactive astrocytosis, microgliosis and in most cases by the accumulation in the central nervous system of the abnormal prion protein, named PrP(Sc). In this review on the "cellular pathogenesis in prion diseases", we have chosen to highlight the main mechanisms underlying the impact of PrP(C)/PrP(Sc) on neurons: the neuronal dysfunction, the neuronal cell death and its relation with PrP(Sc) accumulation, as well as the role of PrP(Sc) in the microglial and astrocytic reaction.     

The new age of renal biomarkers: does SDMA solve all of our problems?

Within clinical small animal practice, diagnosis of both chronic kidney disease and acute kidney injury is common. To assess renal function, measurement of glomerular filtration rate is considered the gold standard. Currently, routine tests of kidney function include surrogate markers of glomerular filtration rate such as serum creatinine, and urea, each with their own limitations, whilst urine protein to creatinine ratio gives an indication of glomerular and tubular handling of protein, and urine specific gravity information about urine concentrating ability by the kidney. These parameters are used together with historical and physical examination data to give a diagnosis of kidney disease following which creatinine, proteinuria and blood pressure are used to stage chronic kidney disease and, together with urine output, grade acute kidney injury according to the International Renal Interest Society. However, there has been much concern that creatinine is insensitive when used to indicate early decline in renal function and this has highlighted the need for additional methods of diagnosing and monitoring these patients, with the potential to allow earlier therapeutic intervention. Symmetric dimethylarginine is a novel biomarker, which has been shown to perform as a surrogate marker of glomerular filtration rate in small animals. This article will review current research on symmetric dimethylarginine and the ways in which it may be utilised in small animal practice; current research supports the use of symmetric dimethylarginine as a screening test for detection of early chronic kidney disease according to International Renal Interest Society guidelines, but further research is required in to the usefulness of symmetric dimethylarginine as a tool for monitoring disease and the effect of non-renal influences.     

Comparative study of plasma leptin concentration between solid ruminal and liquid abomasal feeding in weaned adult sheep

This experiment was conducted to investigate the difference between ruminal (solid feed, SF) and abomasal (liquid feed, LF) feeding on the plasma leptin concentration in sheep. The experiment consisted of 2 weeks to adapt the animals to SF, 4 weeks of feeding on SF, 2 weeks adaptation to LF, 8 weeks of feeding on LF, 2 weeks of adaptation to SF, and 4 weeks of feeding on SF. The LF directory flowed into the abomasums of sheep by bottle feeding. Plasma leptin concentration before morning feeding was almost constant in the SF periods, whereas it showed between‐day variations when measured during the LF periods. Mean plasma leptin levels were higher for LF (7.77 ± 0.76 ng/mL; mean ± SE) than for SF periods (3.95 ± 0.16 ng/mL; mean ± SE). Although plasma leptin concentration did not show any change after feeding in the SF and LF periods, plasma insulin and glucose levels increased within 15 min after liquid abomasal feeding, but not after solid ruminal feeding. The high plasma leptin concentration during the LF periods in weaned sheep could be due to change of digestible energy intake and changes in plasma insulin and glucose levels accompanying the changes in digestive processes and nutrient supply.     

Initial sequence characterization of the rhabdoviruses of squamate reptiles, including a novel rhabdovirus from a caiman lizard (Dracaena guianensis)

Rhabdoviruses infect a variety of hosts, including non-avian reptiles. Consensus PCR techniques were used to obtain partial RNA-dependent RNA polymerase gene sequence from five rhabdoviruses of South American lizards; Marco, Chaco, Timbo, Sena Madureira, and a rhabdovirus from a caiman lizard (Dracaena guianensis). The caiman lizard rhabdovirus formed inclusions in erythrocytes, which may be a route for infecting hematophagous insects. This is the first information on behavior of a rhabdovirus in squamates. We also obtained sequence from two rhabdoviruses of Australian lizards, confirming previous Charleville virus sequence and finding that, unlike a previous sequence report but in agreement with serologic reports, Almpiwar virus is clearly distinct from Charleville virus. Bayesian and maximum likelihood phylogenetic analysis revealed that most known rhabdoviruses of squamates cluster in the Almpiwar subgroup. The exception is Marco virus, which is found in the Hart Park group.     

Current research and theories on the pathogenesis of acute laminitis in the horse

A large number of studies have been undertaken in recent years aimed at furthering our understanding of the complex mechanisms underlying the common and debilitating condition of acute laminitis in the horse. Many of these studies have either reinforced or cast doubt on previously held theories on the pathogenesis of this disease, while others have suggested new mechanisms which may play a key role in its development. This review seeks to put the current hypotheses into the context of this recent body of evidence. While a unifying theory may not yet seem to be achievable, this review demonstrates that most of the current theories are not mutually exclusive. Studies utilising in vitro and in vivo models of the disease, particularly addressing the areas of inflammation, haemodynamic disturbances and enzyme activation in the hoof, as well as the preceding events occurring in the hindgut, have helped to explain many clinical observations of the disease and may possibly lead to more effective therapies and means of prevention in the future.     

Blood lipid concentrations and lipoprotein patterns in captive and wild American black bears (Ursus americanus)

OBJECTIVE: To compare blood lipid concentrations and lipoprotein patterns for captive and wild American black bears (Ursus americanus). ANIMALS: 7 captive and 9 wild adult (> or = 4 years old) black bears. PROCEDURE: Blood was collected from 2 groups of captive black bears (groups A and B) and 1 group of wild black bears (group C). Blood triglyceride (TG) and cholesterol concentrations were compared among groups. Plasma lipoproteins were isolated by use of a self-generating gradient of iodixanol, and lipoprotein patterns were compared between groups A and B. RESULTS: Captive bears (mean +/- SD, 187.8 +/- 44.4 kg) weighed significantly more than wild bears (mean, 104.8 +/- 41.4 kg), but mean body weight did not differ between groups A and B. Mean blood TG concentrations for groups B (216.8 +/- 16.0 mg/dL) and C (190.7 +/- 34.0 mg/dL) were significantly higher than that of group A (103.9 +/- 25.3 mg/dL). Mean blood cholesterol concentration was also significantly higher for group B (227.8 +/- 8.2 mg/dL) than for groups A (171.7 +/- 35.5 mg/dL) or C (190.8 +/- 26.8 mg/dL). Mean very-low-density lipoprotein TG and low-density lipoprotein cholesterol concentrations were 2- and 3-fold higher, respectively, for group B, compared with concentrations for group A. CONCLUSIONS AND CLINICAL RELEVANCE: Blood lipid concentrations vary significantly among populations of black bears. Plasma lipoprotein patterns of captive bears differed significantly between colonies and may have reflected differences in diet or management practices.     

Assessment of endothelium-dependent vasodilation in equine digital resistance vessels

Haemodynamic disturbances leading to ischaemia and reperfusion injury of the digit are thought to be involved in the pathophysiology of acute equine laminitis. Identification of physiological regulators of blood flow through the equine digit is important in identifying factors, which may predispose animals to laminitis. A method was developed to assess endothelium-dependent responses of the isolated Krebs-perfused equine digit by co-administration of 5-hydroxytryptamine (5-HT) with vasodilator agents, carbachol (CCh), bradykinin (BK) and substance P (SP). Bolus co-administration of CCh (0.02-2 micromol), BK and SP (0.02-0.2 nmol), caused inhibition of the 5-HT pressor response by 50-60%. The vasodilator responses were abolished by the detergent, CHAPS, indicating endothelium dependency; whereas vasoconstrictor responses to 5-HT were potentiated. CCh-induced relaxation was significantly reduced by the nitric oxide synthase inhibitor L-NAME (79.7 +/- 3.4% inhibition), whereas a large proportion of BK and SP-induced relaxation remained (34.1 +/- 6.3% and 33.6 +/- 5.3% inhibition). L-NAME potentiated vasoconstrictor responses to 5-HT. In conclusion, this study demonstrates that endothelium-derived NO modulates the response to vasoconstrictors such as 5-HT and is likely to be an important regulator of blood flow in the digital resistance vascular bed. Other factor(s) released by the endothelium are also important in regulating blood flow, whose identity remains to be established.     

Effect of feeding glucose, fructose, and inulin on blood glucose and insulin concentrations in normal ponies and those predisposed to laminitis

Identification of ponies (Equus caballus) at increased risk of pasture-associated laminitis would aid in the prevention of the disease. Insulin resistance has been associated with laminitis and could be used to identify susceptible individuals. Insulin resistance may be diagnosed by feeding supplementary water-soluble carbohydrate (WSC) and measuring blood glucose and insulin concentrations. The aim of this study was to assess the glycemic and insulinemic responses of 7 normal (NP) and 5 previously laminitic (PLP), mixed breed, native UK ponies fed glucose, fructose, and inulin [1 g/(kg(.)d) for 3 d] or no supplementary WSC (control) in spring and fall after a 7-d adaptation to a pasture or hay diet. Blood samples were taken for 12 h after feeding on each day, and baseline and peak concentrations and area under the curve (AUC) for glucose and insulin were recorded. Linear mixed models were used for statistical analysis. Differences between PLP and NP groups were most marked after glucose feeding with differences in peak glucose (P = 0.02) and peak insulin (P = 0.016) concentrations. Season and diet adaptation also affected results. Peak concentrations of glucose and insulin occurred 2 to 4 h after WSC feeding. Peak insulin concentration was greater and more variable in fall, particularly in PLP adapted to fall pasture. Baseline glucose and insulin concentrations varied between individuals and with season and diet adaptation but were not greater in PLP than NP. Insulin AUC was greater in PLP than NP after feeding both glucose and fructose (P = 0.017), but there were no differences between PLP and NP in glucose AUC. Glycemic and insulinemic changes were less (P ≤ 0.05) after feeding fructose than glucose, although differences between PLP and NP were still evident. Minimal changes in glucose and insulin concentrations occurred after inulin feeding. Measurement of peak insulin 2 h after feeding of a single dose of glucose (1 g/kg) may be a simple and practical way to aid identification of laminitis-prone ponies before the onset of clinical disease, particularly when ponies are adapted to eating fall pasture.     

The effect of glycerol inclusion on broiler performance and nutrient digestibility

1. Crude glycerol from biodiesel production was offered ad libitum to broiler chickens in a 21-d feeding and digestibility trial. The study was designed as a 3*2?+?1 factorial design with 3 concentrations (33, 67, 100?g/kg) of glycerol from 2 sources, A and B (PRS Environmental Ltd and John Thompson and Sons Ltd) and a control diet. The diets were formulated to contain apparent metabolisable energy (AME) of 12·95?MJ/kg (assuming 14·6?MJ/kg for glycerol).

2. No significant interactions occurred, so only the main effects were discussed. At 7–14?d, feed conversion ratio (FCR) showed a significant linear response with increased glycerol inclusion. However quadratic responses on FCR were observed for the 21–28?d period and 7–28?d.

3. Glycerol digestibility was significantly greater with birds offered the 67?g/kg and 100?g/kg glycerol-based diets in contrast to the digestibility of 33?g/kg glycerol-based diets.

4. Glycerol inclusion level also had an effect on AME, which increased linearly with increasing glycerol inclusion. Birds offered the diets containing glycerol also required less energy per unit gain in contrast to birds offered the control diet.

5. When examining the effect of source of glycerol, source A glycerol resulted in the highest AME (15·20 vs. 14·72?MJ/kg). There was no significant effect of glycerol source on the other performance parameters.

6. Glycerol digestibility was significantly greater with glycerol from source B (John Thompson and Sons, Ltd) with a mean value of 0·848 in contrast to source A (PRS Environmental), which had a somewhat lower mean glycerol digestibility of 0·757.

7. In conclusion, glycerol source did not affect performance and increasing level of glycerol improved FCR, with 67?g/kg inclusion resulting in the most efficient conversion of feed to gain without any negative effects upon nutrient digestibility.