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The role of active transport in the transcellular movement of the peripheral α2-adrenoceptor antagonist, MK-467: An in vitro pilot study
2017
Bennett, Rachel | Palviainen, Mari | Peltoniemi, Marikki | Vuorilehto, Lauri | Scheinin, Mika | Raekallio, Marja | Vainio, Outi
MK-467 is a peripherally acting α2-adrenoceptor antagonist due to its low lipid solubility and poor penetration of the blood-brain barrier (BBB). The aim of this study was to assess whether MK-467 could be a substrate of an active efflux transport mechanism. Using Madin-Darby Canine Kidney cells (MDCKII) and MDCKII cells transfected with the human multidrug resistance gene 1, drug transport was assessed in apical-basolateral and basolateral-apical directions. MK-467 was studied at 2 concentrations: 200 and 1000 ng/mL. Samples for analysis were taken at 15, 30, 45, 60, and 90 min after drug application. Drug concentrations were measured using liquid chromatography and mass spectrometry. MK-467 showed no apparent permeability in the apical-basolateral direction, transport in the basolateral-apical direction occurred in both cell lines. Efflux ratios were not calculated. However, MK-467 appeared to undergo active cellular transport. The identity of the transporter requires further investigation.
Mostrar más [+] Menos [-]Desflurane and sevoflurane elimination kinetics and recovery quality in horses
2015
OBJECTIVE To evaluate pharmacokinetics, recovery times, and recovery quality in horses anesthetized with 1.2 times the minimum alveolar concentration of sevoflurane or desflurane. ANIMALS 6 healthy adult horses. PROCEDURES Anesthesia was maintained with sevoflurane or desflurane for 2 hours at 1.2 times the minimum alveolar concentration. Horses recovered without assistance. During recovery, end-tidal gas samples were collected until horses spontaneously moved. Anesthetic concentrations were measured by use of gas chromatography. After a 1-week washout period, horses were anesthetized with the other inhalation agent. Video recordings of anesthetic recovery were evaluated for recovery quality on the basis of a visual analogue scale by investigators who were unaware of the anesthetic administered. Anesthetic washout curves were fit to a 2-compartment kinetic model with multivariate nonlinear regression. Normally distributed interval data were analyzed by means of paired Student t tests; ordinal or nonnormally distributed data were analyzed by means of Wilcoxon signed rank tests. RESULTS Horses recovered from both anesthetics without major injuries. Results for subjective recovery evaluations did not differ between anesthetics. Area under the elimination curve was significantly smaller and time to standing recovery was significantly less for desflurane than for sevoflurane, although distribution and elimination constants did not differ significantly between anesthetics. CONCLUSIONS AND CLINICAL RELEVANCE Differences in area under elimination the curve between anesthetics indicated more rapid clearance for desflurane than for sevoflurane in horses, as predicted by anesthetic blood solubility differences in this species. More rapid elimination kinetics was associated with faster recovery times, but no association with improved subjective recovery quality was detected.
Mostrar más [+] Menos [-]Isoelectric focusing of soluble proteins from Fasciola hepatica L, 1758 and Fascioloides magna B, 1875
1992
Lee, C.G. | Zimmerman, G.L. | Mulrooney, D.M.
Isoelectric focusing was performed on the soluble proteins of whole-body and excretory-secretory products (ESP) of Fasciola hepatica and Fascioloides magna. Adult F hepatica flukes were recovered from experimentally infected sheep and ESP obtained from the flukes; portions of liver were cut and frozen at -70 C. Fascioloides magna adults were collected from naturally infected white-tailed deer and ESP obtained; portions of liver were collected from noninfected white-tailed deer. Adult flukes and their host tissues were homogenized and centrifuged; protein concentrations with their ESP were determined and adjusted to < 2.50 mg/ml. Seven ESP samples from F hepatica and 1 from Fascioloides magna were subjected to isoelectric focusing with the 2 species of fluke and their respective host liver homogenates. After separation, gels were stained with silver and scanned on a laser densitometer. Protein banding patterns of the 2 species of flukes were dissimilar. In the pH range of 3.5 to 9.6, the body protein had approximately 30 peaks and ESP about 23 peaks in both species. Overall banding patterns of the body protein and ESP of both species were distinct from those of respective host tissues. Of the peaks reported as dominant, 3 of the body protein and 2 of ESP were shared between the 2 species. Fascioloides magna had more dominant peaks than F hepatica. This technique of soluble protein isoelectric focusing is simple and reproducible, and the 2 fluke species can easily be differentiated by this technique, as well as by morphologic characteristics.
Mostrar más [+] Menos [-]Keratin and associated proteins of the equine hoof wall
1992
Grosenbaugh, D.A. | Hood, D.M.
In this study, we described water-insoluble proteins extracted from the germinative regions (stratum internum and coronary band epithelium) and the cornified outer surface (stratum medium) of the equine hoof wall. Two major types of polypeptides were identified: the intermediate filaments (IF) and the IF-associated proteins. The IF, including keratins, composed a major portion of this fraction, had electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the range of 40 to 80 kDa, and reacted with acidic or basic keratinspecific monoclonal antibodies. Differences in the composition of keratins between germinative layers and the stratum medium were seen. Another less well-characterized group of polypeptides associated with the IF also were extracted with the water-insoluble polypeptide fraction. These associated proteins had an apparent molecular weight between 10 and 30 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and contained a higher percentage of sulfur-containing amino acids than did the IF. Water-insoluble protein fractions compared favorably with those found in other less-specialized keratinizing tissue with respect to size, immunoreactivity with monoclonal antibody, and amino acid composition.
Mostrar más [+] Menos [-]Effects of dietary fiber supplementation on glycemic control in dogs with alloxan-induced diabetes mellitus
1991
Nelson, R.W. | Ihle, S.L. | Lewis, L.D. | Salisbury, S.K. | Miller, T. | Bergdall, V. | Bottoms, G.D.
The effect of a high insoluble-fiber (IF) diet containing 15% cellulose in dry matter, high soluble-fiber (SF) diet containing 15% pectin in dry matter, and low-fiber (LF) diet on glycemic control in 6 dogs with alloxan-induced insulin-dependent diabetes mellitus was evaluated. Each diet contained > 50% digestible carbohydrate in dry matter. A crossover study was used with each dog randomly assigned to a predetermined diet sequence. Each dog was fed each diet for 56 days. Caloric intake was adjusted weekly as needed to maintain each dog within 1.5 kg of its body weight measured prior to induction of diabetes mellitus. All dogs were given pork lente insulin and half of their daily caloric intake at 12-hour intervals. Mean (+/- SEM) daily caloric intake was significantly (P < 0.05) less when dogs consumed the IF diet vs the SF and LF diets (66 +/- 3 kcal/kg, 81 +/- 5 kcal/kg, and 79 +/- 4 kcal/kg, respectively). Serum alkaline phosphatase activity was significantly (P < 0.05) higher when dogs consumed the LF diet vs the iF and SF diets (182 +/- 37 IU/L, 131 +/- 24 IU/L, and 143 +/- 24 IU/L, respectively). Mean postprandial plasma glucose concentration measured every 2 hours for 24 hours, beginning at the time of the morning insulin injection, was significantly (P < 0.05) lower at most blood sampling times in dogs fed IF and SF diets, compared with dogs fed the LF diet. As a result, 24-hour mean plasma concentration of glucose (IF, 165 +/- 17 mg/ dl; SF, 169 +/- 19 mg/dl; LF, 218 +/- 29 mg/dl), 24-hour mean plasma-glucose fluctuation (IF, 49 +/- 2 mg/dl; SF, 47 +/- 4 mg/dl; LF, 63 +/- 7 mg/dl), and 24-hour urine-glucose excretion (IF, 31 +/- 10 g/d; SF, 42 +/- 16 g/d; LF, 67 +/- 13 g/d) were significantly (P < 0.05) lower in dogs fed IF and SF diets, compared with dogs fed the LF diet. These variables were not significantly different between dogs fed IF and SF diets. Mean glycosylated hemoglobin concentration also was significantly (P < 0.05) lower when dogs consumed the IF diet, compared with the LF diet (4.3 0.4% vs 5.2 +/- 0.4%, respectively). In dogs with alloxan-induced insulin-dependent diabetes mellitus, consumption of diets containing 15% cellulose or 15% pectin and > 50% digestible carbohydrate on a dry-matter basis resulted in improvement in glycemic control, compared with consumption of a diet containing > 50% digestible complex carbohydrate without added fiber.
Mostrar más [+] Menos [-]Effect of diet on struvite activity product in feline urine
1990
Buffington, C.A. | Rogers, Q.R. | Morris, J.G.
Groups of male specific-pathogen-free cats were fed a basal, purified diet (A), with or without 0.45% added magnesium (MgCl2, diet B; MgO, diet C) or 1 of 2 commercial diets (D,E). Urine samples collected for 48 hours after 2 weeks of feeding were analyzed for calcium, magnesium, sodium, potassium, ammonium, sulfate, phosphate, oxalate, and citrate content. Concentrations were used to calculate the negative logarithm of the struvite activity product (pSAP), using a microcomputer-based program for calculation of supersaturation of the urine with crystal solutes. The pSAP value for all samples also was hand-calculated by use of an equation. Consumption of diet B caused a significant (P < 0.05) increase in urine calcium concentration. Total urine phosphate concentration was lower in urine from cats fed diets A, B, or C than in urine from cats fed diets D or E. For the various diets, urine PO4-3 was: 5.3 microM for diet A; 6.3 microM for diet C; 0.9 microM for diet E; 36 nM for diet D, and 0.5 nM for diet B. Consumption of diets B and C caused significant increases in urine magnesium concentration (53.1 nM and 49.1 mM, respectively). Ammonium ion concentration was highest in urine from cats fed diets B and D, 116.2 mM and 100.3 mM, respectively. When the pSAP, hand-calculated assuming ionic strength u = 0.2, was regressed on that calculated by use of the microcomputer program, the coefficient of determination was 0.96 (P less than or equal to 0.01).
Mostrar más [+] Menos [-]Effect of feeding enzyme mixture with Fibrolytic activity in dry and solubulized Forms on the performance of lambs
2023
M.V.A.N. Suryanarayana | J. V. Ramana
One hundred lambs (11.8 kg ± 0.56) divided at random into 4 groups G1, G2, G3 and G4 were supplemented with exogenous fibrolytic enzyme mixture (EFE) in concentrates after 6 hours outside grazing. G1 and G2 were given 200 and 400 g of EFE per 50 kg feed in dry form, G3 and G4 were given EFE in solubulized form at 20 and 40 g per litre of water, respectively. The initial and final weights (kg) were non-significant among treatments. The total weight gain (kg) was higher (P<0.05) for G4 and G2 as compared to other two. Average daily gain (g) was highest (P<0.05) for G4 followed by G2, G1 and G3. Total weight gain (%) is 15, 7.6 and 16.5 lower (P<0.05) for G1, G2 and G3 (Table) as compared to G4. Lowest (P<0.05) FCR was observed for G4 and is in the order of G4< G2< G1< G3. The cost of the feed per kg gain was lower (P<0.05) by 21%, 26% and 13% for G4 as compared to G1, G2 and G3. It can be concluded that addition of EFE in solubulized form was found better for the reason that it forms a stable complex with the feed and thus facilitates for the rumen bacterial attachment earlier for rapid action due to an increase in rumen bacterial population
Mostrar más [+] Menos [-]Diagnosis and treatment of bovine mastitis- A holistic approach.
2010
Ranjan, Rajeev | Gupta, M.K. | Singh, K.K.
A study was carried out in 2161 quarter milk samples of 550 cows in Durg district Chhattisgarh. Out of 550 animals, 385 (70%) animals were found to be positive for sub clinical mastitis (SCM) by Modified White Side Test (MWST), 432 (78.54%) by Modified California Mastitis Test (MCMT) and 462 (84%) by somatic cell count (SCC). The quarter wise prevalence of sub clinical mastitis was 47.99%, 55.25% and 60.90% by MWST, MCMT and SCC respectively. Prevalence of blind teats was 1.77%. prevalence was highest during second and third lactations and at 5 and 6 years of age. Infection rate was higher during early and late stages of lactation. HF and Jersey cross bred cows were more susceptible than indigenous cows. Microorganisms isolated were predominantly Staphylococci. ABST revealed sensitivity to cefotaxime whereas most of the isolates were resistant to ampicillin.
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