[Show abstract][Hide abstract] ABSTRACT: Obesity and insulin resistance have been shown to be risk factors for laminitis in horses.
The objective of the study was to determine the effect of changes in body condition during
the grazing season on insulin resistance and the expression of genes associated with obesity
and insulin resistance in subcutaneous adipose tissue (SAT). Sixteen Finnhorse mares
were grazing either on cultivated high-yielding pasture (CG) or semi-natural grassland (NG)
from the end of May to the beginning of September. Body measurements, intravenous glucose
tolerance test (IVGTT), and neck and tailhead SAT gene expressions were measured
in May and September. At the end of grazing, CG had higher median body condition score
(7 vs. 5.4, interquartile range 0.25 vs. 0.43; P=0.05) and body weight (618 kg vs. 572 kg ±
10.21 (mean ± SEM); P=0.02), and larger waist circumference (P=0.03) than NG. Neck fat
thickness was not different between treatments. However, tailhead fat thickness was
smaller in CG compared to NG in May (P=0.04), but this difference disappeared in September.
Greater basal and peak insulin concentrations, and faster glucose clearance rate
(P=0.03) during IVGTT were observed in CG compared to NG in September. A greater decrease
in plasma non-esterified fatty acids during IVGTT (P<0.05) was noticed in CG compared
to NG after grazing. There was down-regulation of insulin receptor, retinol binding
protein 4, leptin, and monocyte chemoattractant protein-1, and up-regulation of adiponectin
(ADIPOQ), adiponectin receptor 1 and stearoyl-CoA desaturase (SCD) gene expressions in
SAT of both groups during the grazing season (P<0.05). Positive correlations were observed
between ADIPOQ and its receptors and between SCD and ADIPOQ in SAT
(P<0.01). In conclusion, grazing on CG had a moderate effect on responses during IVGTT,
but did not trigger insulin resistance. Significant temporal differences in gene expression
profiles were observed during the grazing season.
[Show abstract][Hide abstract] ABSTRACT: Objective
The objectives of this investigation were to: (1) Determine if acute hemorrhage is associated with increased plasma cardiac troponin I (cTnI) concentration or cardiac arrhythmias, (2) to describe the types of arrhythmias and their clinical course in horses following acute hemorrhage, (3) to determine the ability of clinical or clinicopathological variables to predict an increase in cTnI concentration and the presence of arrhythmias, and (4) to determine the associations of cTnI and cardiac arrhythmias with outcome.DesignProspective observational study.SettingLarge animal veterinary teaching hospital.AnimalsEleven client-owned adult horses admitted for treatment of acute hemorrhage (HG) and 4 adult horses undergoing controlled blood collection (BDG).Methods
Serial cTnI concentrations were measured and continuous ECGs were obtained from the HG and BDG groups. Statistical tests were used to determine associations among acute hemorrhage and plasma cTnI concentrations, the presence of cardiac arrhythmias, clinicopathologic data (heart rate [HR], packed cell volume [PCV], total plasma protein [TPP], plasma lactate, and plasma creatinine concentrations), and outcome.ResultsPlasma cTnI concentration and ECG were within reference intervals at all time points in the BDG. All horses in the HG had increased cTnI (ranging from 0.1–29.9 ng/mL). Arrhythmias were detected in 8 of these horses. There was an association between acute hemorrhage and increased cTnI (P = 0.004, ρ = 0.77), and the presence of arrhythmias (P = 0.026, ρ = 0.64). There were associations among plasma cTnI concentration and the presence of arrhythmias (P = 0.005), arrhythmias requiring treatment (P = 0.036), and poor outcome (P = 0.024).Conclusions
Acute hemorrhage results in myocardial injury that can be detected by measuring cTnI concentration. Arrhythmias were frequent in hospitalized horses following acute hemorrhage.
[Show abstract][Hide abstract] ABSTRACT: There is growing awareness of obesity and insulin resistance in ponies; therefore nutritional management strategies need to be developed. The present study was conducted to investigate the effects of L-carnitine supplementation on body weight (BW) losses, insulin sensitivity and selected metabolic parameters in obese and insulin-resistant ponies during a body weight reduction programme (BWRP). Sixteen obese ponies (mean body condition score of 7.8 +/- 1.5 on a scale of 1-9; and a mean cresty neck score (CNS) of 3.6 +/- 1.0 on a scale of 0-5) were assigned to a randomized, double-blind, placebo-controlled study. During a BWRP lasting 14 weeks, the ponies were fed 1.0-1.2 kg hay/100 kg body weight (BW) daily and 100 g grass meal (estimated energy intake: 7.0-83 MJ/DE/100 kg BW) and moderately exercised for 45 min 6 days a week. Eight ponies received L-carnitine supplementation (1.3 g/100 kg BW, twice a day), and 8 ponies received a placebo supplement. A frequently sampled intravenous glucose tolerance test was used to assess insulin sensitivity. Routine blood samples were collected for analysis of glucose, insulin, leptin, urea, beta-hydroxybutyrate, free fatty acids (FFA) and triglycerides (TG). Ponies lost approximately 1% BW per week over the BWRP (time: P < 0.01, L-carnitine supplementation: P=0.79). BW losses were accompanied by a significant improvement in insulin sensitivity (time: P < 0.01, L-carnitine supplementation: P=039). Significant time-related decreases were observed for plasma glucose, serum insulin, and leptin, while significant increases were observed for serum urea, FFA, and TG during the BWRP, without any further improvement by L-carnitine supplementation. Energy intake of 7 MJ/100 kg BW results in BW losses, thereby improving insulin sensitivity and glucose metabolism. L-carnitine supplementation does not further improve glucose or fat metabolism.
No preview · Article · Aug 2013 · Livestock Science
[Show abstract][Hide abstract] ABSTRACT: The "Equine metabolic syndrome" (EMS) is a cluster of metabolic abnormalities - characterized by insulin-resistance, obesity and laminitis-, which is especially recognized in ponies. These ponies are called easy keepers; a genotype that is predisposed to develop obesity. As obesity has a strong relation to insulin-resistance, body weight reduction is in the focus of an adequate management in obese animals. In this context, it is of interest in which way insulin-sensitivity changes after a body weight reduction. Therefore, the aim of the study was to monitor insulin sensitivity during a body weight reduction program in ponies. 15 obese ponies (body condition score 8±2 (scale 1-9); cresty neck score 4±1 (scale 0-5) were included in a 14 weeks lasting body weight reduction program (BWRP). Ponies were fed with hay (1-12.2 kg hay/100 kg BW), grass meal (0.05 kg/100 kg BW) and a commercial mineral mixture. Calculated energy intake varied around 7-8.4 MJ DE/100 kg BW. At the beginning and at the end of the study insulin sensitivity index (SI) was determined by the frequently sampled intravenous glucose tolerance test (FSIGTT). Serum insulin and plasma glucose were additionally analysed in week 0, 1, 3, 5, 6, 7, 9, 11, 12 and 14 during BWRP At the beginning of the study seven ponies were categorized as insulin-resistant (SI: 0.29±0.25 L/min//jUx 10-4) and eight obese ponies were classified as insulin sensitive (SI: 7.0±7.9 L/min/uUx 10-4). Body weight reduction (1.4-2.8% of BW weekly) improved significantly insulin sensitivity in the initially insulin resistant ponies (SI: 8.7±13.8 L/min//jUx 10-4), whereas insulin sensitivity did not further improved in the initially insulin sensitive ponies (SI: 7.4±1 3.1 LI/min//LfUx 10-4). Serum insulin decreased significantly during BWRR Plasma glucose varied between 3.8-4.6 mmol/L during BWRP In conclusion, body weight reduction is an important nutritional measure to improve insulin-resistance. Concerning the diagnosis of insulin-resistance, a single serum insulin value is a conclusive method and helps to monitor the progress in insulin sensitivity in insulin resistant ponies during BWRR.
[Show abstract][Hide abstract] ABSTRACT: Fifteen obese ponies were used in a body weight (BW) reduction programme (BWRP, daily energy intake: 7.0-8.4 MJ/100 kg BW). A frequently sampled intravenous glucose tolerance test was used to assess insulin sensitivity. Subcutaneous adipose tissue biopsies of the tail head were obtained for mRNA gene expression profiles of adiponectin, retinol-binding protein 4 (RBP4), interleukin 6 (IL-6) and macrophage activation marker (CD68) before and after BWRP. Blood samples were analysed for serum leptin, serum RBP4 and plasma adiponectin. Significant BW losses occurred with 7 MJ DE/100 kg BW. Serum leptin and RBP4 were initially similar between insulin-resistant (IR) and insulin-sensitive (IS) ponies, and both significantly decreased during BWRP. Compared with IS ponies, IR ponies initially had significantly lower plasma adiponectin levels. At the beginning of BWRP, mRNA expression of RBP4, adiponectin, IL-6 and CD68 was similar between IR and IS ponies. Plasma adiponectin was strongly related to IR, whereas serum leptin and RBP4 were closely linked to adiposity, independent of insulin sensitivity. Adipose tissue mRNA expression profiles did not clearly reflect these differences. However, the role of subcutaneous adipose tissue in IR remains open.
[Show abstract][Hide abstract] ABSTRACT: Streptococcus equi is the etiologic agent of a highly infectious upper respiratory disease of horses known as strangles. Bacterial culture methods and polymerase chain reaction (PCR) of nasopharyngeal washes and guttural pouch lavages are used routinely to test clinical and carrier animals for the presence of S. equi but no definitive or gold standard test method has been shown to be optimal. We hypothesized that (i) a flocked swab submerged in ten-fold serial dilution suspensions of S. equi prepared in 0.9% NaCl would detect more colony forming units (CFU) than a rayon swab when used to inoculate a blood agar plate, (ii) centrifugation of a 1 ml aliquot of each suspension would improve the limit of detection (LOD) by bacterial culture and PCR compared to the culture or PCR of submerged swab samples, (iii) PCR of the centrifuged samples from each suspension would be more sensitive than aerobic culture alone, and (iv) PCR of a 1 ml aliquot directly from a sample would be more sensitive than PCR of a sample following submersion of a flocked swab in 1 ml saline. Using 7 ten-fold serial dilutions of S. equi in 0.9% NaCl, the LOD for 4 bacterial culture methods and 3 PCR methods were compared. The LOD of direct PCR and flocked swab culture was determined at 1 cfu/ml. All PCR methods were equivalent to each other and were more sensitive than any of the culture methods at the lower dilutions. At higher cell densities (>100 cfu/ml) flocked swab culture was not statistically better than rayon swab culture, but it was superior to all other methods tested.
No preview · Article · Apr 2012 · Veterinary Microbiology
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to investigate the changes in selected blood adipokines and subcutaneous adipose tissue adipokine and macrophage activation marker (CD68) mRNA expression profiles in overweight or obese insulin-resistant (IR) ponies during a body weight reduction programme. It was hypothesized that insulin effectiveness (insulin sensitivity or resistance) was accompanied by differences in circulating blood adipokines and different subcutaneous adipose adipokine mRNA expression profiles before and after weight reduction. Fifteen obese ponies were used in a body weight (BW) reduction programme (BWRP, daily energy intake: 7.0-8.4 MJ/100 kg BW). A frequently sampled intravenous glucose tolerance test was used to assess insulin sensitivity. Subcutaneous adipose tissue biopsies of the tail head were obtained for mRNA expression profiles of adiponectin, retinol binding protein 4 (RBP4), interleukin 6 (IL-6) and macrophage activation marker (CD68) before and after BWRP. Blood samples were analyzed for serum leptin, serum RBP4 and plasma adiponectin. Significant BW losses occurred with 7 MJ DE/100 kg BW. Serum leptin and RBP4 were initially similar between insulin-resistant (IR) and insulin-sensitive (IS) ponies, and both significantly decreased during BWRP. Compared with IS ponies, IR ponies initially had significantly lower plasma adiponectin levels. RNA expression of RBP4, adiponectin, IL-6 and CD 68 was similar between IR and IS ponies. Plasma adiponectin appears strongly related to IR, whereas serum leptin and RBP4 are closely linked to adiposity, independent of insulin sensitivity. Adipose tissue mRNA expression profiles did not clearly reflect these differences. However, the role of subcutaneous adipose tissue in IR remains open.
No preview · Article · Jan 2012 · EAAP Scientific Series
[Show abstract][Hide abstract] ABSTRACT: Metformin may be an effective therapeutic option for insulin-resistant (I-R) horses/ponies because, in humans, it reportedly enhances insulin sensitivity (SI) of peripheral tissues without stimulating insulin secretion. To determine the effect of metformin on insulin and glucose dynamics in I-R ponies, six ponies were studied in a cross-over design by Minimal Model analysis of a frequently-sampled intravenous glucose tolerance test (FSIGT). Metformin was administered at 15 mg/kg bodyweight (BW), orally, twice-daily, for 21 days to the metformin-treated group. The control group received a placebo. A FSIGT was conducted before and after treatment. The Minimal Model of glucose and insulin dynamics rendered indices describing SI, glucose effectiveness (Sg), acute insulin response to glucose (AIRg) and the disposition index (DI). The body condition score (BCS), BW and cresty neck score (CNS) were also assessed. There was no significant change in SI, Sg, AIRg, DI, BW, BCS or CNS in response to metformin, or over time in the control group. There were no measurable benefits of metformin on SI, consistent with recent work showing that the bioavailability of metformin in horses is poor, and chronic dosing may not achieve therapeutic blood concentrations. Alternatively, metformin may only be effective in obese ponies losing weight or with hyperglycaemia.
No preview · Article · Feb 2011 · The Veterinary Journal
[Show abstract][Hide abstract] ABSTRACT: To identify factors associated with an increased likelihood that horses would have a serum Streptococcus equi SeM-specific antibody titer > or = 1:1,600.
188 healthy client-owned horses.
A single serum sample from each horse was tested for SeM-specific antibody titer with an ELISA. Multivariate logistic regression was used to identify factors associated with having a titer > or = 1:1,600.
Age, breed, and vaccination status were significantly associated with the likelihood of having a titer > or = 1:1,600. The odds of having a titer > or = 1:1,600 increased by a factor of 1.07 with each 1-year increase in age. Quarter Horses and horses of other breeds were 4.08 times as likely as were Thoroughbreds and warmbloods to have a titer this high. Horses that had previously received an intranasal S equi vaccine were 4.7 times as likely as were horses without any history of vaccination to have a titer this high.
Results indicated that older horses, horses other than Thoroughbreds and warmbloods, and horses that had been vaccinated with an attenuated-live intranasal S equi vaccine between 1 and 3 years previously had an increased likelihood of having a serum SeM-specific antibody titer > or = 1:1,600.
No preview · Article · Oct 2009 · Journal of the American Veterinary Medical Association
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to develop a mathematical model that accurately describes the rise and decline in plasma progesterone concentrations, and is able to define parameters describing progesterone appearance and disappearance during the bovine oestrous cycle. Daily plasma progesterone data from 27 cows were used to develop a compartmental model consisting of an appearance function and an appearance modulating function. Model outputs included an apparent appearance or secretion duration, appearance rate and an average disappearance rate (expressed as arbitrary units per day; units/d). Shape-based clustering identified three common shape-based groups (or clusters) of progesterone profiles defined as either 'peaked' profile, with the profile reaching a distinguishable peak, 'structured', with the profile exhibiting a wave-like pattern, or 'flat top', with the profile reaching a plateau. Differences in the model parameters for the three different shapes of progesterone profiles were examined: peaked (n=13), flat top (n=7) and structured (n=7). The mean duration of apparent appearance was 11.49 (SD 0.17 d) for all 27 profiles. The model estimates for total appearance of progesterone (area under the curve; ng/ml per cycle), mean appearance rate and maximum appearance rate were 69.04 ng/ml per cycle (SD 15.2 ng/ml per cycle), 3.19 ng/ml per cycle (sd 0.7 ng/ml per d) and 6.70 ng/ml (SD 1.31 ng/ml), respectively. The average disappearance rate was 1.0 units/d (SD 0.04 units/d). The apparent appearance duration was greatest (P<0.01) in the flat top profiles (12.54, SD 0.41 d) followed by the structured (11.77, SD 0.66 d) and the peaked (10.80, SD 0.30 d) profiles. Total and mean progesterone appearance, maximum progesterone appearance rate, and the progesterone disappearance rates were not different between the profiles. The model successfully simulated all components of the progesterone profile and was able to define specific parameters of different shaped progesterone profiles. A simple model able to estimate parameters describing progesterone appearance and disappearance can be used to explore the relationships between profile shapes and reproductive outcomes.
No preview · Article · May 2009 · Journal of Dairy Research
[Show abstract][Hide abstract] ABSTRACT: Quantitative assessment of pancreatic insulin secretion rate in individuals may help advance our understanding and treatment of diabetes. We describe for the first time the application of a long-established numerical deconvolution procedure in which a prescribed input function is used to represent first-phase pancreatic secretion response to an intravenous glucose challenge (intravenous glucose tolerance test [IVGTT]) in individual subjects. We identify that C-peptide secretory response to an IVGTT can be described by a basal secretion rate (S(b)) (picomoles per liter per minute) and a first-phase secretory response characterized by a Gaussian function. The Gaussian function contains 3 parameters: P(1) (picomoles per liter per minute), which represents the peak rate secretion; P(2) (per square minute), which is related to the inverse of peak width at half-peak height; and P(3) (minutes), which is the time of the peak secretion rate. When applied to data from 8 healthy Chinese subjects, the estimated parameter values (mean +/- SD) were 19.2 +/- 12.9 pmol L(-1) min(-1), 1548 +/- 1143 pmol L(-1) min(-1), 1.09 +/- 1.21 min(-2), and 2.94 +/- 1.13 minutes for S(b), P(1), P(2), and P(3), respectively. The Gaussian input functions are shown to have similar shapes and to be highly concordant in magnitude with secretory responses estimated by means of the method of Eaton et al (1980) and by the ISEC computer program. In conclusion, we have presented a simple, integrated, validated, and easily implemented method suitable for quantifying pancreatic C-peptide and insulin secretion in individual human subjects. The superiority of our method in comparison with other methods is that it uses as an input function the Gaussian, which has been experimentally verified as describing in vivo the profile of pulsatile insulin secretion. The particular strength of our method is that the Gaussian parameters and simple indices derived from them provide a standardized and interpretable means for carrying out comparative investigations aimed at quantifying how pancreatic secretory responses to an IVGTT differ in various demographic groups or in response to therapeutic treatments.
No preview · Article · May 2009 · Metabolism: clinical and experimental
[Show abstract][Hide abstract] ABSTRACT: To compare coagulation and platelet function parameters measured using a viscoelastic analyzer in 3 groups: foals presenting to a neonatal intensive care unit with presumed sepsis, normal foals, and adult horses.
Preliminary prospective trial.
Veterinary teaching hospital.
Ten clinically healthy foals, 13 clinically healthy adult horses, and 17 foals sequentially admitted for suspected sepsis. Intervention- A single citrated (3.8%) blood sample collected at admission was submitted for coagulation evaluation using a viscoelastic analyzer.
Time to initial clot formation (ACT), clot rate (CR), platelet function, and time to peak parameters were collected from the signature generated with the associated software. Peak clot strength was collected manually from signature tracings. Signalment, presenting complaint, blood culture results, clinical progression, and outcome were collected from the medical record. Kruskal-Wallis testing was used to determine differences in coagulation parameters between groups, as well as to identify any associations between coagulation variables, foal variables, and outcome. Normal foals were more likely to have increased platelet function (P=0.04) compared with normal adult horses. Prolonged ACT (P=0.004) and decreased CR (P=0.03) were associated with foals with positive blood culture. There was a trend toward prolonged ACT and increased likelihood of death (P=0.06).
Healthy foals differ in values measured by the viscoelastic coagulation and platelet function analyzer compared with healthy adult horses. ACT and CR abnormalities were more likely to be observed in foals with positive blood cultures. The viscoelastic coagulation and platelet function analyzer may be useful in identifying early hemostasic and platelet dysfunction in critically ill foals, particularly those that are septic.
[Show abstract][Hide abstract] ABSTRACT: The kinetics of nonesterified fatty acid (NEFA) metabolism in humans requires quantification to facilitate understanding of diseases like type 1 and 2 diabetes, metabolic syndrome, and obesity, and the mechanisms underpinning various interventions. Oral glucose tolerance tests (OGTT) and glucose meal tolerance tests (MTT) are potentially useful procedures for enabling quantification of NEFA kinetics because they both cause transitory, but substantial, declines and then rebounds in plasma NEFA concentrations in response to physiologically relevant increases in plasma glucose. The Boston MINIMAL model of NEFA kinetics was developed to analyze data from the intravenous glucose tolerance test (IVGTT), but in this work, we present for the first time its application to modeling NEFA data from both OGTT and MTT studies. This model enables estimation of SFFA (micromol.l(-1).min(-1)) (a parameter describing the maximum rate of lipolysis), and KFFA (%/min) (a parameter related to NEFA oxidation rate). The model could well describe the trajectories of NEFA concentrations following an OGTT (R2 in excess of 0.97) but was not as successful with the MTT (R2>0.65). Model parameters derived from analysis of OGTT and MTT data were well identified with coefficients of variation generally less than 15%. Type 2 diabetes, body mass index, and dietary treatment (high-fat vs. high-glycemic-index diets) were all shown to have significant effects on model parameters. Modeling plasma NEFA concentrations over 24 h has helped to identify and quantify the extent that periprandial NEFA peaks and nocturnal elevation in plasma NEFA can be accounted for by our model.
Full-text · Article · Jun 2008 · AJP Regulatory Integrative and Comparative Physiology
[Show abstract][Hide abstract] ABSTRACT: Dynamics of nonesterified fatty acid (NEFA) metabolism in humans requires quantification if we are to understand the etiology of such diseases as type 1 and 2 diabetes, as well as metabolic syndrome and obesity, or if we are to elucidate the mechanism of action of various interventions. We present a new compartmental model that employs the pattern of plasma glucose concentrations in healthy young adults to predict dynamic changes that occur in plasma NEFA concentrations during either a glucose-only intravenous glucose tolerance test, or an insulin-modified intravenous tolerance test, or a modified protocol during which variable-rate glucose infusions were administered to prevent plasma glucose from declining below 100 mg/dl. The model described all of the major features of NEFA response to an intravenous glucose tolerance test, including an initial latency phase, a phase during which plasma NEFA concentrations plummet to a nadir, and a rebound phase during which plasma NEFA concentrations may rise to a plateau concentration, which may be substantially higher than the initial basal NEFA concentration. This model is consistent with physiological processes and provides seven adjustable parameters that can be used to quantify NEFA production (lipolysis) and utilization (oxidation). When tested on data from the scientific literature, the range in estimated rate of lipolysis was 24-36 micromol.l(-1).min(-1) and for NEFA oxidation rate was 25-54 micromol.l(-1).min(-1). All model parameters were well identified and had coefficients of variation < 15% of their estimated values. It is concluded that this model is suitable to describe NEFA kinetics in human subjects.
No preview · Article · May 2008 · AJP Regulatory Integrative and Comparative Physiology
[Show abstract][Hide abstract] ABSTRACT: To identify risk factors for development of acute laminitis in horses during hospitalization for illness or injury.
Retrospective case-control study.
73 horses that developed laminitis (case horses) and 146 horses that did not develop laminitis (control horses) during hospitalization.
Case and control horses were matched in a 2:1 ratio by the date on which each horse was evaluated. Potential risk factors investigated included age, breed, and sex; highest and lowest values recorded during hospitalization for fibrinogen concentration, WBC count, PCV, and total solids concentration; and comorbid disease states, including pneumonia, endotoxemia, diarrhea, medically treated colic, surgically treated colic, pituitary adenoma, retained placenta or metritis, forelimb lameness, hind limb lameness, acute renal failure, and vascular abnormalities. A univariate screening of all potential risk factors was performed to determine which variables should be selected for further analysis. All factors found to be associated with development of laminitis were included in a multivariate conditional logistic regression model.
Development of laminitis was marginally associated with lowest and highest fibrinogen concentrations, highest PCV, and lowest total solids concentration and significantly associated with pneumonia, endotoxemia, diarrhea, abdominal surgery for colic, and vascular abnormalities. In the multivariate analysis, only endotoxemia was significantly associated with laminitis.
Endotoxemia is an important risk factor for development of acute laminitis in horses during hospitalization for medical or surgical conditions. Early recognition of endotoxemia, or the potential for it to develop in certain disease states, and initiation of treatment directed at endotoxemia or its consequences may help prevent laminitis in horses during hospitalization.
No preview · Article · Apr 2007 · Journal of the American Veterinary Medical Association
[Show abstract][Hide abstract] ABSTRACT: Resumption of development by infective larvae (L3i) of parasitic nematodes upon entering a host is a critical first step in establishing a parasitic relationship with a definitive host. It is also considered equivalent to exit from the dauer stage by the free-living nematode Caenorhabditis elegans. Initiation of feeding, an early event in this process, is induced in vitro in L3i of Strongyloides stercoralis, a parasite of humans, other primates and dogs, by culturing the larvae in DMEM with 10% canine serum and 5mM glutathione at 37 degrees C with 5% CO(2). Based on the developmental neurobiology of C. elegans, resumption of development by S. stercoralis L3i should be mediated, in part at least, by neurons homologous to the ASJ pair of C. elegans. To test this hypothesis, the ASJ neurons in S. stercoralis first-stage larvae (L1) were ablated with a laser microbeam. This resulted in a statistically significant (33%) reduction in the number of L3i that resumed feeding in culture. In a second expanded investigation, the thermosensitive ALD neurons, along with the ASJ neurons, were ablated, but there was no further decrease in the initiation of feeding by these worms compared to those in which only the ASJ pair was ablated.
Preview · Article · Feb 2007 · Experimental Parasitology
[Show abstract][Hide abstract] ABSTRACT: To compare the accuracy of a 3rd (Dolphin Voyager) versus 1st generation pulse oximeter (Nellcor N-180).
Prospective laboratory investigation.
Eight adult dogs.
In anesthetized dogs, arterial oxygen saturation (SpO(2)) was recorded simultaneously with each pulse oximeter. The oxygen fraction in inspired gas (FiO(2)) was successively reduced from 1.00 to 0.09, with re-saturation (FiO(2) 0.40) after each breathe-down step. After each 3-minute FiO(2) plateau, SpO(2) and pulse rate (PR) were compared with the fractional arterial saturation (SaO(2)) and PR determined by co-oximetry and invasive blood pressure monitoring, respectively. Data analysis included Bland-Altman (B-A) plots, Lin's concordance correlation factor (rho(c)), and linear regression models.
Over a SaO(2) range of 33-99%, the overall bias (mean SpO(2) - SaO(2)), precision (SD of bias), and accuracy (A(rms)) for the Dolphin Voyager and Nellcor N-180 were 4.3%, 4.4%, and 6.1%, and 3.2%, 3.0%, and 4.3%, respectively. Bias increased at SaO(2) < 90%, more so with the Dolphin Voyager (from 1.6% to 8.6%) than Nellcor N-180 (from 3.2% to 4.5%). The SpO(2) readings correlated significantly with SaO(2) for both the Dolphin Voyager (rho(c) = 0.94) and Nellcor N-180 (rho(c) = 0.97) (p < 0.001). Regarding PR, bias, precision, and accuracy (A(rms)) for the Dolphin Voyager and Nellcor N-180 were -0.5, 4.6, and 4.6 and 1.38, 4.3, and 4.5 beats minute(-1), respectively. Significant correlation existed between pulse oximeter and directly measured PR (Dolphin Voyager: rho(c) = 0.98; Nellcor N-180: rho(c) = 0.99) (p < 0.001).
In anesthetized dogs with adequate hemodynamic function, both instruments record SaO(2) relatively accurately over a wide range of normal saturation values. However, there is an increasing overestimation at SaO(2) < 90%, particularly with the Dolphin Voyager, indicating that 3rd generation pulse oximeters may not perform better than older instruments. The 5.4-fold increase in bias with the Dolphin Voyager at SaO(2) < 90% stresses the importance of a 93-94% SpO(2) threshold to ensure an arterial saturation of >or=90%. In contrast, PR monitoring with both devices is very reliable.
No preview · Article · Sep 2006 · Veterinary Anaesthesia and Analgesia
[Show abstract][Hide abstract] ABSTRACT: To determine the pharmacokinetics of methylprednisolone (MP) and develop a pharmacokinetic-pharmacodynamic model of the related changes in plasma concentrations of endogenous hydrocortisone (HYD) and cortisone (COR) following intra-articular administration of methylprednisolone acetate (MPA) in horses.
In each horse, 200 mg of MPA was injected intrasynovially into a carpal joint, and plasma MP, HYD, and COR concentrations were determined via liquid chromatography-mass spectrometry.
A 5-compartment pharmacokinetic-pharmacodynamic model was used to describe the concatenated changes in the plasma concentrations of MP, HYD, and COR and to estimate the instantaneous rate of endogenous HYD production. The median transfer half-life (t(1/2t)) of methylprednisolone from the joint to plasma and elimination half-life (t(1/2e)) from plasma were 1.7 and 19.2 hours, respectively. Maximum plasma concentration of methylprednisolone was 7.26 +/- 3.3 ng/mL at 8 hours, which decreased to 0.11 +/- 0.08 ng/mL at 144 hours after injection. At 3 hours after MPA administration, plasma COR and HYD concentrations were significantly decreased from baseline values (from 2.9 +/- 0.28 ng/mL to 2.10 +/- 1.0 ng/mL and from 61.1 +/- 18.9 ng/mL to 25.7 +/- 12.1 ng/mL, respectively).
The sensitivity of the analytic method used allowed complete description of the related kinetics of MP, HYD, and COR following intra-articular administration of MPA. A single intra-articular administration of MPA profoundly affected the secretion of HYD and COR in horses; secretion of endogenous corticosteroids remained suppressed for as long as 240 hours after injection.
No preview · Article · May 2006 · American Journal of Veterinary Research