Measurement of protein turnover in skeletal muscle strips

Isolated porcine and bovine muscle strips were incubated in Krebs Ringer bicarbonate buffer to determine in vitro protein synthesis (PS) and protein degradation (PD) rates to validate the in vitro system for use with livestock species. The addition of 5X plasma concentrations of amino acids to the medium stimulated PS 30%. Addition of 3.5 mM leucine to a leucine-deficient buffer supplemented with amino acids decreased PD 37% and stimulated PS 24%. The addition of .1 U/ml insulin reduced PD 28% and increased PS 30%. Protein degradation was elevated in longitudinally split rat soleus and extensor digitorum longus muscles compared to their contralateral intact muscles. Muscle strips must be removed within 15 min of exsanguination because PD rates become greatly elevated thereafter. ATP concentrations declined during incubation, but the addition of ATP or creatine had no effect on either PD or PS. Neither PD nor PS was affected by the addition of transferrin, fetuin, ascorbate, dexamethasone or indomethacin to the incubation medium. However, muscle strips were sensitive to the addition of triiodothyronine (T3), PD was increased up to 75% as T3 concentration was increased, and PS rates doubled compared to controls. Serum from mature barrows or gilts had no effect on protein turnover, but the addition of 10% and 15% serum from boars increased both PD and PS. With fasted pigs a continual decline in PS occurred over 5 d, whereas PD was elevated at 3 d and then declined to rates comparable to the fed state after 5 d. These data suggest that the in vitro system has application for assessing relative changes that occur in vivo following nutritional, physiological and endocrinological manipulation.     

Enhanced Plasma Availability of the Metabolites of Albendazole in Fasted Adult Sheep

Lifschitz, A., Virkel G., Mastromarino, M. and Lanusse C., 1997. Enhanced plasma availability of the metabolites of albendazole in fasted adult sheep. Veterinary Research Communications, 21 (3), 201-211The influence of fasting prior to treatment and of dosing rate on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO2) metabolites was studied in adult sheep grazing on pasture. A micronized suspension of ABZ was administered orally at either 7.5 mg/kg (group A) or 11.3 mg/kg (group C) to sheep fed ad libitum, and at 7.5 mg/kg to sheep subjected to a 24 h fasting period prior to treatment (group B). Blood samples were taken serially over 96 h after treatment, and the plasma was analysed for ABZ and its metabolites by high-performance liquid chromatography. ABZSO and ABZSO2 were recovered from the plasma. Fasting induced marked modifications in the pharmacokinetic behaviour of the ABZ metabolites in sheep. An extended absorption process, with a delayed peak concentration in the plasma, was observed for both metabolites in the fasted sheep. Significantly higher area under the curve (AUC) and peak plasma concentration (Cmax) values were obtained for both metabolites in the fasted animals compared to those fed ad libitum. Delayed elimination with prolonged detection in plasma was also observed in the fasted sheep. Treatment with ABZ at 7.5 mg/kg in the starved animals resulted in bioequivalence to the administration of the compound at a 50% higher dose rate (11.3 mg/kg) in the fed animals. It is suggested that fasting enhances ABZ dissolution and absorption by delaying its passage down the digestive tract.     

Effect of coliform bacteria, feed deprivation, and pH on ruminal D-lactic acid production by steer or continuous-culture microbial populations changed from forage to concentrates

Fecal coliform bacteria were isolated from three herbivores (cattle, horse, and red panda) and shown to produce primarily the D-form of lactate, plus acetate and ethanol when grown anaerobically in 1.0% glucose broth. To evaluate coliform contribution to D-lactate acidosis in cattle, experiments involving a forage-adapted steer (fasted or normally fed) and four 500-ml fermentors were compared during 3 d of grain overload. In both systems, coliforms and D- and L-lactic acid production were greater from fasted than from normally fed steer inoculum. With fasted inoculum, coliform counts peaked (3 x 10(7)/ml at 7 h after initial engorgement) and receded to 10(3)/ml by the time D-lactate concentration peaked, indicating that bacteria other than coliform were responsible for the delayed peaking of D- (48 h) compared with L-lactate (24 h). Increases in lactobacilli more closely mimicked D-lactate increases than did changes in coliforms. The comparisons between the steer and fermentors showed many similar shifts in end-products and groups of bacteria, more so with the experiment initiated with fasted than with normal inoculum. With normal inoculum, VFA content and moles of butyrate/100 mol of VFA were greater in vitro than in vivo; VFA content presumably was larger because of VFA absorption in vivo. In a separate experiment, cultures initiated with identical inoculum and given the same amount of feed accumulated more lactate when pH was permitted to decrease to 5.0 than when pH was maintained at 5.5 for 6.0 or above, indicating the role buffers can have in controlling acidosis during diet change to concentrates.     

Differences in plasma and abomasal kinetics of albendazole and its metabolites in calves grazed on pasture or fed a grain-based diet

We evaluated the comparative plasma and abomasal fluid disposition kinetics of albendazole (ABZ) and its metabolites in calves either grazing on pasture or fed a grain-based concentrate diet. Six male Holstein calves (weight 180 to 200 kg) were allowed to graze on lush pasture for three weeks before intraruminal administration of ABZ at 10 mg kg-1(pasture group). After a three-week wash-out period, the same animals were housed and fed on a grain-based concentrate diet for three weeks prior to receiving the same ABZ treatment (concentrate group). Jugular blood and abomasal fluid samples were collected over 120 hours post-treatment. Plasma and abomasal fluid samples were analysed by high performance liquid chromatography (HPLC). The digesta transit time was measured using cobalt (Co) as a fluid marker; abomasal fluid and faecal samples were collected and Co concentrations measured by atomic absorption spectrophotometry. Complementary studies of the in vitro dissolution of ABZ particles at different pH values were also conducted. The pH of abomasal fluid collected from animals kept under both feeding conditions was registered. Increased concentrations of ABZ sulphoxide (ABZSO) and sulphone (ABZSO2) in plasma, resulting in significantly higher Cmax and area under the curve (AUC) values for both metabolites, were obtained in calves fed on the concentrate diet compared to those grazing on pasture. Enhanced abomasal fluid levels of ABZ and ABZSO were observed in concentrate-fed calves. The mean retention time of the digestive fluid marker in the gastrointestinal (GI) tract was significantly longer in the animals fed the grain-based diet. The in vitro dissolution of ABZ at a pH value equivalent to that obtained in the abomasum of the concentrate-fed calves (1.75) was significantly greater than that obtained at the pH registered in pasture-fed animals (2.00). The characterisation of the kinetic/metabolic behaviours and the resultant efficacy of antiparasitic drugs in animals reared under different management conditions may be relevant in increasing parasite control in livestock.     

The effect of fasting on the plasma disposition of triclabendazole following oral administration in goats

This study was designed to investigate the effect of feeding on the plasma disposition of triclabendazole (TCBZ) in goats following oral administration. A total of eight goats, aged 14–16 months and weighing 20–30 kg were used in this study. The animals were allocated into two groups (fasted and fed groups) of four animals each. The goats in fed group were fed ad libitum but the animals in fasted group were not fed 24 h before and 6 h after drug administration. Commercial oral drench formulation of TCBZ (Endex-K, 5%) was administered orally to animals in two groups at dose of 10 mg/kg bodyweight. Heparinized blood samples were collected between 1 and 192 h after treatment and the plasma samples were analysed by high performance liquid chromatography (HPLC) for TCBZ, TCBZ sulphoxide (TCBZ–SO), and TCBZ sulphone (TCBZ–SO₂). Relatively very low concentration of TCBZ parent drug was detected between 2 and 48 h, but TCBZ–SO and TCBZ–SO₂ metabolites were present between 2 and 192 h in the plasma samples of fed and fasted animals. Fasting significantly enhanced the plasma concentration of TCBZ and its metabolites. The availability of TCBZ, TCBZ–SO and TCBZ–SO₂ in the plasma samples of fasted goats were markedly greater compared to those of fed goats. It was concluded that fasting decreases the digesta flow rate and prolongs the retention of the drug into the gastrointestinal tract, resulting in enhanced quantitative gastrointestinal absorption or systemic availability of TCBZ and its metabolites in fasted goats.     

Effect of food on the pharmacokinetics of oral cefuroxime axetil in dogs

Cefuroxime axetil pharmacokinetic profile was investigated in 12 Beagle dogs after single intravenous and oral administration of tablets or suspension at a dose of 20 mg/kg, under both fasting and fed conditions. A three-period, three-treatment crossover study (IV, PO under fasting and fed condition) was applied. Blood samples were withdrawn at predetermined times over a 12-hr period. Cefuroxime plasma concentrations were determined by HPLC. Data were analyzed by compartmental analysis. No statistically significant differences were observed between formulations and feeding conditions on PK parameters. Independently of the feeding condition, absorption of cefuroxime axetil after tablet administration was low and erratic. The drug has been quantified in plasma in 3 out of 6 and 5 out of 6 dogs in the fasted and fed groups. For this formulation, the bioavailability (F), peak plasma concentration (C_max), and area under the concentration–time curve (AUC) of cefuroxime axetil were significantly enhanced (p < .05) by the concomitant ingestion of food (32.97 ± 13.47–14.08 ± 7.79%, 6.30 ± 2.62–2.74 ± 0.66 µg/ml, and 15.75 ± 3.98–7.82 ± 2.76 µg.hr/ml for F, C_max, and AUC in fed and fasted dogs, respectively), while for cefuroxime axetil suspension, feeding conditions affected only the rate of absorption, as reflected by the significantly shorter absorption half-life (T_½(a)) and time to peak concentration (T_max) (0.55 ± 0.27–1.15 ± 0.19 hr and 1.21 ± 0.22–1.70 ± 0.30 for T_½(a) and T_max in fed and fasted dogs, respectively). For cefuroxime axetil tablets, T > MIC (≤1 µg/ml) was <2 hr in fasted and ≈4 hr in fed animals, and for cefuroxime axetil suspension, T > MIC (≤1 µg/ml) was ≈5 hr and for T >MIC (≤4 µg/ml) was ≈2.5 hr for fasted and fed dogs, respectively. Cefuroxime axetil as a suspension formulation seems to be a better option than tablets. However, its short permanence in plasma could reduce its clinical usefulness in dogs.     

FASTING-INDUCED CHANGES TO THE PHARMACOKINETIC BEHAVIOUR OF ALBENDAZOLE AND ITS METABOLITES IN CALVES

The influence of fasting on the bioavailability and disposition kinetics of albendazole (ABZ) and its metabolites in cattle was investigated. ABZ (10 mg/kg) was given by intraruminal (i.r.) (Experiment 1) and intravenous (i.v.) (Experiment 2) administration to Holstein calves either fed ad libitum (control) or subjected to a 48 h fasting period (fasted group) prior to treatment. The rate of passage of digesta through the gastrointestinal (GI) tract was evaluated by measurement of cobalt faecal excretion following the oral administration of the sodium-cobalt-ethylendiamine-tetracetic acid complex to calves subjected to the feeding conditions above described. Jugular blood and abomasal fluid (via cannula) samples were collected over 120 h post-treatment; samples were analysed by high performance liquid chromatography (HPLC) for ABZ, ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO₂). Fasting the animals prior to the i.r. treatment resulted in pronounced modifications to the plasma and abomasal fluid disposition kinetics of ABZ and its metabolites. A greater extent of GI absorption with significantly higher C_max (150%) and AUC (310%) values for ABZSO in plasma, was observed in fasted compared to fed animals following the i.r. administration of ABZ. Extended detection of ABZ metabolites resulting in significantly longer plasma t_½el and MRT was also obtained in fasted compared to fed calves. These results correlated with the substantially enhanced availability of ABZ and its metabolites (AUCs over 200% greater) in the abomasal fluid of the fasted animals. Fasting did not induce changes to the plasma disposition of either ABZ or its metabolites after the i.v. treatment. The digesta passage rate, measured by the amount of cobalt excreted in faeces, was significantly lower in fasted compared to animals fed ad libitum. A delayed GI transit time that decreases the rate of passage of the drug down the digestive tract, may have accounted for enhanced ABZ dissolution and absorption in fasted compared to fed calves. The findings reported in this article show that fasting prior to treatment notably affects the bioavailability and disposition kinetics of ABZ and its metabolites in cattle.     

Suitability of the peroral administration of the marker creatinine for the quantitative determination of the glomerular filtration rate (GFR) in dogs

Established renal function tests for the quantitative determination of the glomerular filtration rate (GFR) in small animals by means of an exogenous clearance marker like creatinine are based on the intravenous or subcutaneous administration of the marker. In order to simplify performing the test, the suitability of the peroral administration of the marker substance was tested. Exogenous creatinine was administered to 17 Beagle dogs successively by the peroral (dose: 4 g/m2 BSA) and the subcutaneous route (dose: 2 g/m2 BSA). Both routes were tested sequentially in fasted and fed animals. In addition to the peroral administration of creatinine, the absorption marker D-Xylose (dose: 0.5 g/kg body weight) was given per os. Pharmacokinetic parameters were calculated based on serum concentration--time data of both markers. Maximum serum concentrations of the exogenous creatinine (C(max) = 1284 +/- 173 micromol/l) were observed 92 +/- 19 min post-dose (t(max)) in fasted dogs after peroral administration of creatinine. C(max) (956 +/- 209 micromol/l) and t(max) (67 +/- 13 min) were statistically significantly reduced in fed animals. The exogenous plasma clearance of creatinine was about 1/3 lower in fasted animals (94 +/- 15 ml/min/m2) than in fed ones (134 +/- 28 ml/min/m2). The apparent terminal disposition half-life of the exogenous creatinine showed mean values of about 170 min (fasted) and 200 min (fed). After peroral administration of D-Xylose, fasted animals showed higher C(max) (3.9 +/- 0.99 mmol/l) and t(max) values (60 +/- 18 min) than fed dogs (C(max) = 2.2 +/- 0.55 mmol/l, t(max) = 40 +/- 15 min). C(max) and t(max) did not differ between fed and fasted dogs after subcutaneous administration of creatinine. Creatinine clearance was again higher in fed (124 +/- 12.8 ml/min/m2) than in fasted dogs (104 +/- 9.0 ml/min/m2) after subcutaneous administration of the marker. The terminal disposition half-live was, however, similar with about 130-140 min. The route of administration (peroral vs. subcutaneous) did not influence the calculated clearance (no statistical significance when p < 0.01 is required). Creatinine in a dose of 4 g/m2 BSA can be administered by the peroral route of administration for assessing the GFR. For the quantitative determination of GFR standardized condition are required, i.e. animals have to be fasted for > or = 6 hours.     

Comparison of bovine in vivo bioavailability of two sulfamethazine oral boluses exhibiting different in vitro dissolution profiles

The bolus (or oblet) is a dosage form that can be used for the oral administration of pharmaceutical compounds to ruminating species. Unlike traditional tablets, oral boluses may contain quantities of drug on the order of grams rather than milligrams. Due to its size, it is only recently that USP-like in vitro dissolution methods have been developed for this dosage form. However, whether or not these dissolution tests can predict product in vivo performance has yet to be determined. The importance of this issue is apparent when the U.S. Food and Drug Administration Center for Veterinary Medicine is faced with the decision of whether to require additional in vivo bioequivalence study data to support the approval of changes in product chemistry or manufacturing method. The current study was undertaken to determine whether an in vivo/in vitro correlation can be established for bovine sulfamethazine oral boluses and to acquire insight into the magnitude of changes in in vitro product performance that can occur before corresponding changes are seen in in vivo blood level profiles. Based upon the results of this investigation, it is concluded that marked changes in in vitro sulfamethazine bolus performance can be tolerated before resulting in altered in vivo blood level profiles. However, the data also suggest that rumenal absorption may occur for some compounds. Therefore the degree to which variation in product in vitro dissolution profiles can be tolerated may be compound specific.     

Effects of fasting on circulating IGF-binding proteins, glucose, and cortisol in channel catfish (Ictalurus punctatus)

The effects of fasting on IGF-binding proteins (IGFBPs), glucose, and cortisol in channel catfish were examined. Fed fish (controls) were compared to 14-, 30-, and 45-day fasted fish and 45-day fasted fish refed for 15 additional days. Body length and weight changes, condition factor (CF), hepatosomatic index (HSI), and plasma glucose and cortisol were assessed to determine growth and metabolic status. Body length and growth rates were inhibited (P<0.05) after 14, 30, and 45 days of fasting. The 14-, 30-, and 45-day fasted fish exhibited hypoglycemia and reduced CF and HSI. Cortisol levels were increased (22.8 +/- 15.2 ng/ml versus 4.7 +/- 3.9 ng/ml) in 30-day fasted fish compared to fed controls (P<0.05). Associated with the increase in cortisol in fasted fish was a concomitant increase in plasma levels of a 20-kDa IGFBP through day 45. A 35- and a 45-kDa IGFBP were also identified but were similar between fed and unfed fish throughout the experiment. At the end of 15 days of refeeding, 20-kDa IGFBP, glucose, and cortisol levels were similar to fed controls. Refeeding also caused an increase in growth rates. These results suggest the existence of a catfish counter part to mammalian IGFBP-1, similar to lower molecular mass IGFBPs reported in other species of fish. These results also suggest that a 20-kDa IGFBP is upregulated during fasting-induced growth inhibition of channel catfish and provide additional evidence of the conserved nature of the IGF-IGFBP-growth axis in fish.     

Serum hormone and metabolite concentrations in fasted young bulls and steers.

The effect of dietary energy restriction on serum insulin, insulin-like growth factor I (IGF-I), growth hormone, (GH), cortisol, plasma urea nitrogen (PUN) and nonesterified fatty acid (NEFA) concentrations was examined. Angus bulls and steers (10 mo) were allotted to two groups of 12 animals and assigned a treatment order. In a switchback design, animals in order 1 were fed a high grain diet, then fasted, while order 2 animals were fasted, and then fed. Animals were allowed 60 hr to acclimate between treatments. Serum and plasma were obtained at 20 min intervals and 60 min, respectively, for 6 hr after feeding and for the last 6 hr of a 30 hr fast. Serum was assayed for insulin, IGF-I, GH, and cortisol (total and free). Plasma was assayed for PUN and NEFA. Mean insulin (ng/ml) differed between fed (.95 +/- .08) and fasted (.26 +/- .08) animals (P less than 01). Both mean total and free cortisol (ng/ml) were lower in fed (11.48 +/- .99) (1.06 +/- .12) than in fasted (17.10 +/- .93) (1.62 +/- .12) animals, respectively (P less than .01). Animals in order 1 differed in mean IGF-I (ng/ml) between fed (199.0 +/- 8.0) and fasted (116.5 +/- 7.2) treatments (P less than .01). Mean IGF-I for animals in order 2 was 146.7 +/- 7.2 in fed and 213.9 +/- 7.2 in fasted animals (P less than .01). Mean GH did not differ between treatments. Mean PUN and NEFA were higher in fasted than in fed animals (P less than .01). Except for % free cortisol (P less than .05), the hormones did not differ between bulls and steers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bioavailability of oxytetracycline, tetracycline and chlortetracycline after oral administration to fed and fasted pigs

The disposition of oxytetracycline (OTC), tetracycline (TC) and chlortetracycline (CTC) was measured after intravenous and oral administration to pigs. Eighteen healthy pigs (six for each compound) weighing 22-43 kg received a dose of 10 mg/kg intravenously, and 45 mg/kg (OTC and TC) or 40 mg/kg (CTC) orally in both a fasted and a fed condition in a three-way crossover design. The three tetracyclines were present in plasma up to 30 hours after intravenous and after oral administration to fasted as well as fed pigs. The volume of distribution was 1.4, 1.2 and 0.7 L/kg body weight for OTC, TC and CTC respectively. The bioavailability was in general low for all the three tetracyclines. The presence of food did not affect the bioavailability of OTC, which was only 3% in both fasted and fed pigs. For TC there was a significantly higher bioavailability in fasted (18%) than in fed (5%) pigs, whereas for CTC the difference was not significant, being 11% in fasted vs. 6% in fed pigs. Even though the presence of food affected the bioavailability only for TC, it prolonged the absorption phase for all three tetracyclines. Based on the bioavailability and the resulting plasma concentrations, it is concluded that it is not possible to obtain a therapeutically active concentration in plasma or tissues after oral administration of any of the three tetracyclines to fed or fasted pigs.     

Effects of fasting on tissue amino acid concentrations and urea-cycle enzymatic activities in young pigs

Weanling pigs were fed a 30% crude protein (CP) diet for 18 d and then assigned to one of three regimens for either 4 or 8 d: 1) fasting, 2) 3% CP, i.e., maintenance or 3) 30% CP after which they were bled, then sacrificed for tissue assessment. Relative to pigs fasted or fed 30% CP, feeding 3% CP resulted in decreased urea-N and NH3-N excretion in the urine. Arginase and ornithine transcarbamoylase (OTC) activities in liver, and arginase activity in kidney cortex were markedly lower in pigs fed 3% CP compared with those either fasted or fed 30% CP. Hepatic arginase and OTC, however, were higher in fasted pigs than in those fed 30% CP. Pigs fed 3% CP had much lower levels of free threonine, tyrosine, cystathionine, taurine and branched-chain amino acids in plasma, liver, kidney, muscle and brain than fasted pigs or those fed 30% CP. Threonine concentration in brain, liver, muscle and plasma increased as length of the fast increased. Fasted pigs had decreased free alanine levels in plasma, and decreased free serine levels in plasma and liver when compared with fed pigs. Inter-organ comparisons provided evidence that both alanine and serine were important gluconeogenic amino acids during fasting. In general, free amino acid levels in brain were similar between fasted pigs and those fed 30% CP. Fasting for 8 d caused a 10-fold elevation in urinary taurine excretion relative to that observed for 4-d fasted pigs.     

Influence of fermentable fiber on small intestinal dimensions and transport of glucose and proline in dogs

OBJECTIVE: To determine whether intestinal dimensions and nutrient absorption are influenced by different types of dietary fiber. ANIMALS: 10 adult Beagles of both sexes. PROCEDURE: Dogs were randomly assigned to 2 groups and fed a diet with fermentable fibers (beet pulp and oligofructose) or a nonfermentable fiber (cellulose) for 6 weeks. Effects of the diets on small intestinal dimensions were measured, and transport rates for glucose and proline were determined. Kinetics of glucose and proline uptake were defined in the proximal and middle regions of the small intestine, respectively. RESULTS: Small intestines of dogs fed fermentable fiber had 28% more nominal surface area and 37% more mucosal mass, were 35% heavier, and had 95% higher capacity for carrier-mediated glucose uptake than those of dogs fed a diet with cellulose. Differences were more pronounced in the proximal portion of the intestine. CONCLUSIONS AND CLINICAL RELEVANCE: Diets containing fermentable fibers increase small intestinal dimensions and the capacity for nutrient absorption in dogs. These changes may reduce the risk of enteric infections or aid in treatment of intestinal diseases, particularly those involving reduced nutrient absorption.     

Relationship of plasma lipid concentrations to fat deposition in pigs

The time course for changes in plasma free fatty acid and triglyceride concentration after removal of feed was established. Genetically obese and lean lines of pigs, two types of crossbred female pigs and a group of male pigs were used to establish the relationship between circulating free fatty acid or triglyceride concentrations and adiposity. Pigs were weighed, ultrasonically probed for backfat thickness, bled in a fed state and again in the fasted state. Plasma was analyzed for free fatty acid and triglyceride concentration. Fasting increased plasma free fatty acid, but only slightly increased triglyceride concentrations. There were several significant correlations between backfat thickness and plasma lipid concentrations; however, the low magnitude and inconsistency of these correlations precludes use of plasma lipid concentrations as indicators of adiposity in swine. Fasted obese pigs had lower plasma fatty acid concentrations than lean pigs at 2, 4 and 6 mo of age. If these plasma levels represent in vivo mobilization of fat, the results probably contrast with previously reported in vitro results wherein adipose tissue from obese pigs had lipolytic rates expressed on a cellular basis that were equal to or greater than those form lean pigs.     

Enhanced plasma availability of moxidectin in fasted horses

The influence of fasting prior to treatment on plasma availability and kinetic disposition of moxidectin was studied in horses. Eight adult crossbred saddle horses were allocated to two experimental groups of four horses. One group was fasted for 24 hours before treatment and the other group received their usual feed. Both groups were treated with an oral gel formulation of moxidectin at the manufacturers recommended therapeutic dose of 0.4 mg/kg. Blood samples were collected by jugular puncture at different times between 0.5 and 50 days. After plasma extraction and derivatization, samples were analyzed by HPLC with fluorescence detection. Computerized pharmacokinetic analyses were done. Fasting induced marked modifications in the pharmacokinetic behavior of moxidectin in the horse. An extended absorption process, and significantly higher area under the curve (AUC) values were obtained in the fasted animals compared to those fed their usual rations. It is suggested that fasting decreases intestinal transit time, and may have prolonged time for absorption of moxidectin. Since, biliary excretion and intestinal secretion are major routes of moxidectin elimination, fasting may have reduced bile flow and intestinal secretion. Fasting before treatment may be a useful tool for improved anthelmintic treatment in horses.     

盐碱胁迫下碱地肤体内的有机酸积累及其草酸代谢特点

本研究对碱地肤幼苗进行盐胁迫或碱胁迫动态处理,通过分析碱地肤的有机酸含量及草酸代谢相关酶活性等指标,以探讨碱地肤的有机酸积累及草酸代谢调控机制的特点。结果表明,随着碱胁迫时间的延长,碱地肤体内草酸等7种有机酸均有所积累,草酸为主的有机酸的大量积累可能与碱胁迫(高pH)密切相关,它们可能起到离子平衡和pH调节的双重作用。碱地肤积累的草酸并非主要来源于抗坏血酸分解途径。此外,磷酸烯醇式丙酮酸羧化酶(PEPcase)参与催化的草酰乙酸裂解途径也不是草酸合成的主要途径。实验确定草酸合成的关键酶是乙醇酸氧化酶(GO)。草酸分解的草酸氧化酶(OxO)活性高低不是内源草酸积累量的关键因子。综上推断,碱地肤体内草酸的大量积累与其OxO分解无关,而是主要取决于其合成的GO关键酶。     

Effects of collection time and food consumption on the urine protein/creatinine ratio in the dog

Effects of collection time and food consumption on the variability of the urine protein/creatinine ratio were determined in 10 healthy dogs. In trial 1, dogs were fasted for 12 hours, and urine specimens were obtained by bladder catheterization every 2 hours over an 8-hour collection period during the day. After a 1-week rest, the dogs were entered into trial 2. Dogs were fed at least 60 kcal of a high protein meal/kg of body weight, and urine specimens were obtained every 2 hours over an 8-hour period during the day. Urine total protein and urine creatinine concentrations and the urine protein/creatinine ratio were determined for each urine specimen obtained. Friedman's 2-way analysis by ranks was used to determine the constancy of this ratio over the 4 periods in the 2 trials (fasted and fed). There was no significant variability (P greater than 0.05) in ratios over the 8-hour collection periods in the fasted or fed trial. Feeding did not significantly alter this ratio, because there was no significant difference (P greater than 0.05) in the urine protein/creatinine ratios of the dogs when they were fasted, compared with those of the dogs when they were fed. Seemingly, urine specimens obtained anytime during the day from dogs in both trials (fasted and fed) reflected the urine protein/creatinine ratio.     

Enzymatic and acidic sensitivity profiles of selected virulent and attenuated transmissible gastroenteritis viruses of swine

This study identifies the in vitro differences (markers) between virulent and attenuated transmissible gastroenteritis (TGE) viruses. Exposure of virulent Miller strain and attenuated Purdue strain TGE viruses to a spectrum of acidities indicated that the Miller strain was more stable at pH 2. Acidities at or above pH 3 did not reduce viral infectivity of either strain. When virulent and attenuated viruses were exposed to gastric fluids of either fed or fasted swine, there was a similar degree of sensitivity. Carboxypeptidase B, alpha-amylase, and alkaline phosphatase present in porcine small intestinal fluids did not cause a significant difference in sensitivity between virulent and attenuated virus isolates. The digestive enzymes: trypsin, alpha-chymotrypsin, pancreatin, peptidase, and carboxypeptidase A did not (or only slightly) inactivate virulent Miller strain TGE virus, but greatly reduced infectivity of attenuated viruses (Purdue strain and TGE vaccine virus isolates). The attenuated strains were significantly more sensitive to small intestinal fluids from both fasted and fed adult swine. Differential sensitivities between virulent and attenuated TGE viruses to digestive fluids from stomach and small intestine further substantiate the notion of differential susceptibility to small intestinal proteases as a correlate of viral virulence.     

玉屏风散与微粉中毛蕊异黄酮葡萄糖苷体外溶出率的研究

建立了玉屏风超微粉中毛蕊异黄酮葡萄糖苷的高效液相色谱检测方法，采用浆法测定了玉屏风超微粉和玉屏风散剂在人工胃液中的溶出率，绘制累积溶出率曲线。结果表明，玉屏风超微粉和散剂散剂的累积溶出率在5 min时迅速达到73%以上。超微粉和散剂的最快溶出时间段分别为0~2 h和0~6 h，最后都在16 h达到溶出平衡，最高累积溶出率分别为80.36%和77.51%。玉屏风超微粉中毛蕊异黄酮葡萄糖苷溶出速度快，达峰时间短，峰浓度高于散剂。