THE XYLOSE ABSORPTION TEST IN SHEEP BY ACTIVATION OF THE RETICULAR GROOVE REFLEX

1984 ◽  
Vol 64 (5) ◽  
pp. 187-188 ◽  
Author(s):  
T. NICHOLSON

Activation of the reticular groove reflex in adult sheep by copper sulphate allowed orally administered xylose to pass directly to the abomasum. Peak plasma concentrations occurred 1.5–2.5 h later. The results are compared with those published for other species. Key words: Xylose absorption, sheep, reticular groove

1978 ◽  
Vol 40 (02) ◽  
pp. 397-406 ◽  
Author(s):  
Joyce Low ◽  
J C Biggs

SummaryComparative plasma heparin levels were measured in normal subjects injected subcutaneously with 5,000 units of the sodium and calcium salts of heparin. Plasma heparin levels were measured up to 7 hr post-injection by an anti-factor Xa assay (Denson and Bonnar 1973). Preliminary studies indicated that heparin levels were reproducible in subjects who received two injections of the same heparin. Peak plasma concentrations (Cmax) and the time at which peak concentration was reached (Tmax) varied greatly from subject to subject. In one group of subjects (15) two commonly used heparins, a sodium heparin (Evans) and a calcium heparin (Choay) were compared. Peak heparin concentrations were not significantly different. However the Tmax for the sodium heparin (1.5 hr) was significantly earlier than the Tmax for the calcium heparin (3 hr) and this was not due to a difference in the volume of the two heparin injections. No significant difference could be detected in the plasma clearance rate and the molecular weight distribution of the two heparins.In two other groups of subjects, sodium and calcium preparations from two manufacturers were compared. In general, the sodium salts gave rise to significantly higher plasma concentrations, which could be interpreted as a greater bioavailability of sodium salts. These results indicate that the salt of the heparin can influence the plasma concentration achieved after subcutaneous injection.


1986 ◽  
Vol 56 (03) ◽  
pp. 299-301 ◽  
Author(s):  
L J Garcia Frade ◽  
S Poole ◽  
S Hanley ◽  
L J Creighton ◽  
A D Curtis ◽  
...  

SummaryThe bioavailability of human recombinant tissue plasminogen activator (rt-PA) in rats was measured after subcutaneous (s.c.) and intramuscular (i.m.) injection. Rt-PA was absorbed after both i.m. and s.c. injection, giving peak plasma concentrations within 30 min and 1 h, respectively, with detectable concentrations up to 6 h. These peak values of bioavailable t-PA were obtained in a functional fibrin plate assay of euglobulin precipitates and expressed as +88% and +243% (for s.c. and i.m. routes respectively) above basal rat fibrinolytic activity. Prior injection of rt-PA, s.c. or i.m., significantly reduced the weights of thrombi induced in the inferior vena cava after injection.


2021 ◽  
Vol 22 (6) ◽  
pp. 3163
Author(s):  
Hirofumi Ohashi ◽  
Feng Wang ◽  
Frank Stappenbeck ◽  
Kana Tsuchimoto ◽  
Chisa Kobayashi ◽  
...  

The development of effective antiviral drugs targeting the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is urgently needed to combat the coronavirus disease 2019 (COVID-19). We have previously studied the use of semi-synthetic derivatives of oxysterols, oxidized derivatives of cholesterol as drug candidates for the inhibition of cancer, fibrosis, and bone regeneration. In this study, we screened a panel of naturally occurring and semi-synthetic oxysterols for anti-SARS-CoV-2 activity using a cell culture infection assay. We show that the natural oxysterols, 7-ketocholesterol, 22(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, and 27-hydroxycholesterol, substantially inhibited SARS-CoV-2 propagation in cultured cells. Among semi-synthetic oxysterols, Oxy210 and Oxy232 displayed more robust anti-SARS-CoV-2 activities, reducing viral replication more than 90% at 10 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), based on the dose-dependent curve for antiviral activity in our cell-based assay. Mechanistic studies suggest that Oxy210 reduced replication of SARS-CoV-2 by disrupting the formation of double-membrane vesicles (DMVs); intracellular membrane compartments associated with viral replication. Our study warrants further evaluation of Oxy210 and Oxy232 as a safe and reliable oral medication, which could help protect vulnerable populations with increased risk of developing COVID-19.


1989 ◽  
Vol 67 (10) ◽  
pp. 1288-1293 ◽  
Author(s):  
Pamela E. Houghton ◽  
Thomas J. McDonald ◽  
John R. G. Challis

The purpose of the present experiments was to examine in sheep whether the fetal insulin response to glucose was present by day 110 (d110) of pregnancy and whether the magnitude of the fetal insulin response changed between d110 and d145 (term). We also compared the responses observed in fetuses to those of adult nonpregnant sheep. Basal concentrations of glucose measured in plasma collected from the fetal femoral artery rose progressively between d110 and d145 of gestation, but did not attain the plasma glucose concentrations measured in adult sheep. Peak glucose concentrations in fetuses were achieved 10 min following the bolus injection of glucose (0.8 g/kg estimated fetal body weight) into the fetal femoral vein, and peak values increased with gestational age. Significantly higher peak glucose concentrations were achieved in adult sheep. The concentration of insulin rose rapidly in fetuses at d110, and a similar time course of insulin release in plasma was seen at all gestational ages. The peak plasma insulin concentrations were achieved at 20 min and were significantly greater in older (d140–145) than younger (d125–130) fetuses (p < 0.05). Peak insulin values in fetuses were much less than in adult sheep. In adult sheep glucose and insulin concentrations remained elevated at 120 min following the injection of glucose, whereas in the fetus the concentration of insulin had returned to preinjection values by 60 min. The insulin/glucose ratio did not change in fetal lambs over the last one third of gestation and was not different from the adult sheep. We conclude that (1) the fetal insulin response to an acute glucose load is present by d110 of gestation, and (2) the ratio of insulin released per unit glucose elevation did not change in fetal sheep over the last one third of gestation, nor between fetal and adult sheep.Key words: glucose, insulin, fetal sheep.


2006 ◽  
Vol 13 (1) ◽  
pp. 156-159 ◽  
Author(s):  
Michael Heesen ◽  
Rosemarijn Renckens ◽  
Alex F. de Vos ◽  
Dagmar Kunz ◽  
Tom van der Poll

ABSTRACT Upon injection of Escherichia coli lipopolysaccharide into human volunteers, the monocyte density of CC chemokine receptor 2 (CCR2) decreased. Minimal CCR2 density was observed 4 h after injection. Peak plasma concentrations of the CCR2 ligand monocyte chemotactic protein 1 and of tumor necrosis factor alpha were reached after 4 h and 2 h, respectively.


Author(s):  
Michael S. McEntire ◽  
Jennifer M. Reinhart ◽  
Sherry K. Cox ◽  
Krista A. Keller

Abstract OBJECTIVE To identify the antifungal susceptibility of Nanniziopsis guarroi isolates and to evaluate the single-dose pharmacokinetics of orally administered terbinafine in bearded dragons. ANIMALS 8 healthy adult bearded dragons. PROCEDURES 4 isolates of N guarroi were tested for antifungal susceptibility. A compounded oral solution of terbinafine (25 mg/mL [20 mg/kg]) was given before blood (0.2 mL) was drawn from the ventral tail vein at 0, 4, 8, 12, 24, 48, 72, and 96 hours after administration. Plasma terbinafine concentrations were measured with high-performance liquid chromatography. RESULTS The antifungal minimum inhibitory concentrations against N guarroi isolates ranged from 4,000 to > 64,000 ng/mL for fluconazole, 125 to 2,000 ng/mL for itraconazole, 125 to 2,000 ng/mL for ketoconazole, 125 to 1,000 ng/mL for posaconazole, 60 to 250 ng/mL for voriconazole, and 15 to 30 ng/mL for terbinafine. The mean ± SD peak plasma terbinafine concentration in bearded dragons was 435 ± 338 ng/mL at 13 ± 4.66 hours after administration. Plasma concentrations remained > 30 ng/mL for > 24 hours in all bearded dragons and for > 48 hours in 6 of 8 bearded dragons. Mean ± SD terminal half-life following oral administration was 21.2 ± 12.40 hours. CLINICAL RELEVANCE Antifungal susceptibility data are available for use in clinical decision making. Results indicated that administration of terbinafine (20 mg/kg, PO, q 24 to 48 h) in bearded dragons may be appropriate for the treatment of dermatomycoses caused by N guarroi. Clinical studies are needed to determine the efficacy of such treatment.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Sabrina Passini ◽  
Laura Montoya ◽  
Martín Lupi ◽  
Paula Lorenzini ◽  
María Fabiana Landoni ◽  
...  

Clindamycin plasma and tissue disposition in cats under surgical conditions after a single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration at a dose rate of 10 mg/kg were studied. After intravenous, intramuscular and subcutaneous administration, peak plasma concentrations were 10.93±3.78 μg/mL (Cp(0)), 5.93±1.18 μg/mL (Cmax)) and 6.30±0.88 μg/mL (Cmax)), respectively. Eight hours after clindamycin IV, IM and SC administration plasma concentrations declined to 2.01±0.61 μg/mL, 2.96±0.43 μg/mL and 3.36±0.97 μg/mL, respectively. Sixty to 90 minutes after clindamycin administration, tissue concentrations ranged from a minimum in subcutaneous tissue of 4.90 μg/g (IV), 3.06 μg/g (IM) and, 3.13 μg/g (SC) to a maximum in uterus of 13.41 μg/g (IV), 14.07 μg/g (IM) and, 14.44 μg/g (SC). The lowest tissue/plasma concentration ratio for the three administration routes was observed in subcutaneous tissue, while the highest was observed at genital level (ovary for IV and IM and uterus for SC). Estimated efficacy predictor (AUC/MIC), considering MIC breakpoint for bacteria isolated from animals, indicates that clindamycin administered IV, IM or SC at the studied dose is appropriated for perioperative prophylactic protocols and that given with a dose interval of 12 hours would be effective for susceptible infection treatment in cats.


1997 ◽  
Vol 16 (11) ◽  
pp. 645-651 ◽  
Author(s):  
Ian P Dick ◽  
Peter G Blain ◽  
Faith M Williams

1 The absorption and distribution of lindane through skin was examined using human volunteers. Two different preparations were employed, one with acetone as the vehicle and the other, a commercial product, consisting primarily of white spirit as the solvent base. 2 The mean peak plasma concentrations of lindane following exposure to the acetone and white-spirit based applications were 0.91 and 0.47 ng/ml, respec tively. The similarity between these levels did not reflect the 40-fold higher dose of lindane in the acetone vehicle. White spirit enhanced the penetration of lindane with respect to the acetone vehicle, high lighting the influence of vehicle upon percutaneous absorption. Low levels of trichlorophenol glucuronide metabolites, but no lindane, were detected in the urine. 3 The exposure site was washed at 6 h to mimic a decontamination procedure at the end of a working day. The proportion of the applied dose unabsorbed by 6 h was 80% and 10% for the acetone and the white spirit-based formulation, respectively. Small areas of the exposed site were tape stripped at 6 and 24 h to assess any lindane that may be associated with the stratum corneum. High levels were observed in the stratum corneum at 6 h exposure (up to 30% of the applied dose for the white spirit based formulation). However, this level had decreased by 24 h (by at least 90% of the amount found at 6 h). A gauze or gauze/shirt combination covering the application site between 6 and 24 h did account for some of this loss of lindane from the stratum corneum attributed to friction and removal of exfoliated cells. The unaccounted propor tion was presumed to have been absorbed through the skin into the systemic circulation. This demonstrates the absorption of chemicals can occur from a depot in the stratum corneum even following a wash proce dure.


2021 ◽  
Vol 11 ◽  
pp. 204512532110371
Author(s):  
Amir Krivoy ◽  
Eromona Whiskey ◽  
Henrietta Webb-Wilson ◽  
Dan Joyce ◽  
Derek K. Tracy ◽  
...  

Background: Clozapine is the only medication licenced for treating patients with treatment-refractory schizophrenia. However, there are no evidence-based guidelines as to the optimal plasma level of clozapine to aim for, and their association with clinical and functional outcome. Objective: We assessed the relationship between clinical and functional outcome measures and blood concentrations of clozapine among patients with treatment-refractory psychosis. Methods: Data were reviewed in 82 patients with treatment-refractory psychosis admitted to a specialised tertiary-level service and treated with clozapine. Analysis focussed on the relationship between clozapine and norclozapine plasma concentrations and the patient’s clinical symptoms and functional status. Results: Clinical symptom improvement was positively correlated with norclozapine plasma concentrations and inversely correlated with clozapine to norclozapine plasma concentrations ratio. Clozapine concentrations showed a bimodal association with clinical improvement (peaks around 350 and 660 ng/ml). Clinical symptom improvement correlated with functional outcomes, although there was no significant correlation between the latter and clozapine or norclozapine plasma concentrations. Conclusion: Clozapine treatment was associated with optimal clinical improvement at two different peak plasma concentrations around 350 and 650 ng/ml. Clinical improvement was associated with functional outcome; however, functionality was not directly associated with clozapine concentrations. A subset of patients may require higher clozapine plasma concentrations to achieve clinical improvement.


Reproduction ◽  
2002 ◽  
pp. 127-133 ◽  
Author(s):  
S Buchanan ◽  
GW Robertson ◽  
PM Hocking

The aim of this study was to compare the profile of circulating concentrations of LH, progesterone and oestradiol in a multiple ovulating male line with that of a single ovulating line of traditional turkeys. Plasma samples from seven traditional and 12 male-line turkeys were obtained every 3 h for 36 h. Male-line and traditional turkeys had single peaks of LH and progesterone that were of similar duration in both lines. The mean height of the plasma peaks of LH and progesterone were similar in the two lines and there was no detectable peak plasma oestrogen concentration. Mean plasma concentrations of LH and oestrogen were higher in single compared with multiple ovulating turkeys, whereas there were no differences in mean plasma progesterone concentrations. The results indicate that the multiple ovulation state in genetically selected high-growth lines of turkey may be the result of a correlated response in the steroidogenic capacity of ovarian tissue associated with low plasma concentrations of oestrogen rather than of a disturbance in the hormone profile of the ovulatory cycle.


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