The objective of the current study was to describe and characterize the pharmacokinetics and selected pharmacodynamic effects of morphine and its two major metabolites in horses following several doses of morphine. A total of ten horses were administered a single intravenous dose of morphine: 0.05, 0.1, 0.2, or 0.5 mg/kg, or saline control. Blood samples were collected up to 72 hr, analyzed for morphine, and metabolites by LC/MS/MS, and pharmacokinetic parameters were determined. Step count, heart rate and rhythm, gastrointestinal borborygmi, fecal output, packed cell volume, and total protein were also assessed. Morphine‐3 glucuronide (M3G) was the predominant metabolite detected, with concentrations exceeding those of morphine‐6 glucuronide (M6G) at all time points. Maximal concentrations of M3G and M6G ranged from 55.1 to 504 and 6.2 to 28.4 ng/ml, respectively, across dose groups. The initial assessment of morphine pharmacokinetics was done using noncompartmental analysis (NCA). The volume of distribution at steady‐state and systemic clearance ranged from 9.40 to 16.9 L/kg and 23.3 to 32.4 ml min?1 kg?1, respectively. Adverse effects included signs of decreased gastrointestinal motility and increased central nervous excitation. There was a correlation between increasing doses of morphine, increases in M3G concentrations, and adverse effects. Findings from this study support direct administration of purified M3G and M6G to horses to better characterize the pharmacokinetics of morphine and its metabolites and to assess pharmacodynamic activity of these metabolites. 相似文献
Levosulpiride (LSP) is the l‐enantiomer of sulpiride, and LSP recently replacing sulpiride in several EU countries. Several studies about LSP in humans are present in the literature, but neither pharmacodynamic nor pharmacokinetic data of LSP is present for veterinary species. The aim of this study was to assess the pharmacokinetic profile of LSP after intravenous (IV), intramuscular (IM), and oral (PO) administration in goats. Animals (n = 6) were treated with 50 mg LSP by IV, IM, and PO routes according to a randomized cross‐over design (3 × 3 Latin‐square). Blood samples were collected prior and up to 24 hr after LSP administration and quantified using a validated HPLC method with fluorescence detection. IV and IM administration gave similar concentration versus time curve profiles. The IM mean bioavailability was 66.97%. After PO administration, the drug plasma concentrations were detectable only in the time range 1.5–4 hr, and the bioavailability (4.73%) was low. When the AUC was related to the administered dose in mg/kg, there was a good correlation in the IV and IM groups, but very low correlation for the PO route. In conclusion, the IM and IV administrations result in very similar plasma concentrations. Oral dosing of LSP in goats is probably not viable as its oral bioavailability was very low. 相似文献
1. An experiment was conducted to compare the relative bioefficacy of DL‐methionine hydroxy analogue free acid (DL‐MHA‐FA) with DL‐methionine in broiler chickens. Responses used for comparison were weight gain and food efficiency between 7 and 35 d of age, and breast meat deposition, food cost per kg of breast meat, and abdominal fat at 41 d of age.
2. A total of 2160 seven‐day‐old male broiler chicks were used. The feeding programme consisted of a starter diet from 7 to 21 d, and a finisher diet till the end of the experiment. The starter basal diet contained 6.1 g/kg total sulphur‐containing amino acids (TSAA), and an estimated metabolisable energy (ME) content of 13.2 MJ/kg. The finisher diet contained 5.8 g/kg TSAA and an estimated ME content of 13.6 MJ/kg. Four concentrations of DL‐methionine and DL‐MHA‐FA were added at 0.5g/kg increments on an equimolar basis. Therefore, there were 9 experimental treatments which were each applied to 6 replicates of 40 chicks. Weight gain and food efficiency were determined at 35 d of age. Breast yield and carcase fat were measured at 41 d.
3. Significant responses to graded amounts of both methionine sources were observed in weight gain, food efficiency, breast meat percentage, and food cost per kg of breast meat. The responses fitted exponential regression curves. Based on the regression coefficients, equimolar bioefficacy of DL‐MHA‐FA relative to DL‐methionine was 80% for daily gain, 83% for food efficiency, 51% for breast meat yield, and 66% for food cost per kg of breast meat. Differences between the 2 sources were significant (P< 0.05) for breast meat yield and food cost per kg of meat and (P< 0.10) for food efficiency. 相似文献
1. The dietary inclusion of 15 and 25 g/kg mannose was associated with a reduction in the numbers of Salmonella enteritidis (PT4) in the caecal contents of chicks challenged by the food. The same benefit was not recorded for S. infantis, possibly because this strain, unlike S. enteritidis PT4, lacked mannose‐sensitive fimbriae.
2. The addition of 25 g/kg palm kernel meal (PKM), but not 20 g/kg desiccated coconut, to the food reduced the degree of salmonella colonisation in the intestinal tract of broiler chicks given diets contaminated with S. kedougou or S. enteritidis from the day of their arrival from the hatchery.
3. The beneficial effect of PKM was also demonstrated at an inclusion rate of 5 g/kg and was similar for preparations with a particle size of either < 150 μm or < 300 μm.
4. Day‐old birds challenged orally with S. enteritidis and given food supplemented with 25 g/kg PKM, became clear of infection by 3 weeks of age while birds given unsupplemented food remained infected.
5. These preliminary results suggest that the inclusion of PKM, which contains inter alia, oligosaccharides containing mannose, in the diet of chicks may reduce the extent to which the intestine is contaminated with salmonellas. 相似文献
1. The effect of three metabolisable energy (ME) concentrations 12.2, 11.3 and 10.5 MJ ME/kg and two forms of diet (mash and pellet) on egg production in summer and winter were studied. The different ME values were obtained by diluting the 12.2 MJ ME/kg diet with sugar beet pulp of 2.88 MJ/kg DM. In a 3rd summer experiment the water intake of hens on these diets was examined. Data were analysed by factorial analysis of variance, and the relationship between performance and dietary energy concentration was examined by regression analysis.
2. The use of low energy diets (10.5 to 11.3 MJ ME/kg) decreased egg production in both seasons, but pelleting diets improved egg production and egg weight in summer. Egg weight was not affected by energy density in winter, but decreased in the summer when energy density increased.
3. In winter, food consumption was not affected by the dietary ME, while in summer food consumption increased when the dietary ME increased. Therefore, energy intake was not the same at all energy densities, but tended to increase as the energy density increased.
4. In summer, pelleting improved food efficiency and egg production and increased water consumption and the ratio of water to food intake. Water intake and water: food ratio decreased with increasing dietary energy concentration. 相似文献
Enterotoxemia caused by Clostridium perfringens type D in sheep is believed to result from the action of epsilon toxin (ETX). However, the sole role of ETX in the intestinal changes of the acute and chronic forms of enterotoxemia in goats remains controversial, and the synergistic action of other C. perfringens toxins has been suggested previously. The current study examined 2 goats that were found dead without premonitory clinical signs. Gross lesions at necropsy consisted of multifocal fibrinonecrotic enterocolitis, edematous lungs, and excess pleural fluid. Histologically, there were multifocal fibrinonecrotic and ulcerative ileitis and colitis, edema of the colonic serosa, and proteinaceous interstitial edema of the lungs. Clostridium perfringens type D carrying the genes for enterotoxin (CPE) and beta2 toxin (CPB2) was cultured from intestinal content and feces of 1 of 2 goats, while C. perfringens type D CPB2-positive was isolated from the other animal. When multiple colonies of the primary isolations from both animals were tested by Western blot, most of the isolates expressed CPB2, and only a few isolates from the first case expressed CPE. Alpha toxin and ETX were detected in ileal and colonic contents and feces of both animals by antigen capture enzyme-linked immunosorbent assay. CPB2, but not CPE, was identified in the small and large intestines of both goats by immunohistochemistry. These findings indicate that CPB2 may have contributed to the necrotic changes observed in the intestine, possibly assisting ETX transit across the intestinal mucosa. 相似文献
Red spherule coelomocytes are immune cells in the sea urchin Lytechinus variegatus that have been characterized as motile O2 transport cells. Video microscopy of living red spherule coelomocytes reveals a constitutive, dynamic array of cellular morphologies and movements. Cells continuously send out and retract membrane blebs all over the cell surface as part of their normal cellular physiology. Disruption of microtubules by perfusion with either nocodazole or taxol had no effect on bleb formation or motility. Perfusion with cytochalasin B abated bleb formation and revealed cells that exhibited multiple small spheres attached by short membrane extensions. Attenuation of blebbing and intracellular organelle motility were restored by washing out with cytochalasin B. Treatment with phalloidin also abated bleb formation and revealed a smooth, spherical cellular morphology. The effects of phalloidin were completely reversible after washout. Red spherule coelomocytes treated with blebbistatin rounded up with an irreversible retraction of blebs into surface blebs that were greatly reduced in size, number and motility. Normal cell surface bleb formation and intracellular organelle motility were not restored after washout of the drug. These results indicate that the acto‐myosin contractile mechanism contributes to the dynamics of constitutive cell surface membrane blebbing in invertebrate immune cells. 相似文献
We investigated whether high‐quality in vitro matured (IVM) oocytes can be distinguished from poor ones based on the morphological changes after treatment with hyperosmotic medium containing 0.2 mol/L sucrose in pigs. We hypothesize that IVM oocytes maintaining round shape have higher quality than mis‐shapened oocytes following dehydration. Oocyte quality was verified by determining embryonic developmental competence using in vitro fertilization, nuclear transfer and parthenogenetic activation. In all cases, the round oocytes had greater (p < .05) developmental competence than that of mis‐shapened oocytes in terms of blastocyst rate and total cell number in blastocysts obtained after 6 days of in vitro culture. We also confirm that round aged oocytes are higher in quality than mis‐shapened aged oocytes. In an attempt to find out why high‐quality oocytes maintain a round shape whereas poorer oocytes become mis‐shapened following sucrose treatment, we examined the arrangement of actin microfilaments and microtubules. Abnormal organization of these cytoskeletal components was higher (p <.05) in mis‐shapened oocytes compared to round oocytes after 52 hr of IVM. In conclusion, sucrose treatment helps selection of high‐quality oocytes, including aged oocytes, in pigs. Abnormal cytoskeleton arrangements partly explain for low developmental competence of mis‐shapened oocytes. 相似文献
Lactic acid bacteria play an essential role in the food industry in the manufacture of many fermented products (cheese, yogurt, fermented vegetables, etc.). Application of these organisms is now being extended to the area of health improvement, as their probiotic activities become known. Probiotics are defined as viable microorganisms that exert a beneficial effect on the health of the host when they are ingested in sufficient quantity. Lactic acid bacteria and bifidobacteria isolated from the human intestine are the most common probiotics used for human consumption. The development of new probiotics with new beneficial effects is eagerly awaited in the food industry. This review introduces Lactococcus, which are one of the genera of lactic acid bacteria and are mainly isolated from dairy products and fermented vegetables, as new probiotics, focusing especially on Lactococcus lactis H61, which improves skin status in Japanese women with oral intake of heat‐killed or live cells. The deduced mechanisms associated with the beneficial effects of strain H61 are also discussed. 相似文献
