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Mg/kg BW (kg + bw)
Kinds of Mg/kg BW Selected AbstractsNo change in apoptosis in skeletal muscle exposed acutely or chronically to alcoholADDICTION BIOLOGY, Issue 1 2003AG PAICE The pathogenic mechanisms responsible for the deleterious changes in ethanol-exposed skeletal muscle are unknown, although apoptosis may be a causal process. We therefore investigated the responses of skeletal muscle to acute or chronic ethanol exposure in male Wistar rats. In acute studies, rats were dosed with ethanol (75 mmol (3.46 g)/kg BW) and killed after either 2.5 or 6 hours. In chronic studies, rats were fed ethanol as 35% of total dietary energy for 6 weeks. Apoptosis was determined by either DNA fragmentation or TUNEL (terminal deoxynucleotidyl transferase mediated dUTP nick end labelling) assays. The results showed that apoptosis was not increased in the ethanol-exposed muscle in both acute and chronic studies compared to appropriate controls. [source] Measurement of pulmonary surfactant disaturated-phosphatidylcholine synthesis in human infants using deuterium incorporation from body waterJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 7 2005Paola E. Cogo Abstract The aim of the study was to determine surfactant palmitate disaturated-phosphatidylcholine (DSPC-PA) synthesis in vivo in humans by the incorporation of deuterium from total body water into DSPC-PA under steady state condition. We studied three newborns and one infant (body weight (BW) 4.6 ± 2.9 kg, gestational age 37.5 ± 2 weeks, age 9 ± 9 days) and four preterm newborns (BW 1.3 ± 0.6 kg, gestational age 30.3 ± 2.5 weeks, postnatal age 8.8 ± 9.2 h). All infants were mechanically ventilated during the study and the four preterm infants received exogenous surfactant at the start of the study. We administered 0.44 g 2H2O/kg BW as a bolus intravenously, followed by 0.0125 g 2H2O/kg BW every 6 h to maintain deuterium enrichment at plateau over 2 days. Urine samples and tracheal aspirates (TA) were obtained prior to dosing and every 6 h thereafter. Isotopic enrichment curves of DSPC-PA from sequential TA and urine deuterium enrichments were analyzed by Gas Chromatography-Isotope Ratio,Mass Spectrometry (GC-IRMS) and normalized for Vienna Standard Mean Ocean Water. Enrichment data were used to measure DSPC-PA fractional synthesis rate (FSR) from the linear portion of the DSPC-PA enrichment rise over time, relative to plateau enrichment of urine deuterium. Secretion time (ST) was defined as the time lag between the start of the study and the appearance of DSPC-PA deuterium enrichment in TA. Data were given as mean ± SD. All study infants reached deuterium-steady state in urine. DSPC-PA FSR was 6.5 ± 2.8%/day (range 2.6,10.2). FSR for infants who did not receive exogenous surfactant was 5.7 ± 3.5%/day (range 2.6,9.9%/day) and 7.3 ± 2.1%/day (range 5.1,10.2%/day) in the preterms, whereas DSPC-PA ST was 10 ± 10 h and 31 ± 10 h respectively. Surfactant DSPC-PA synthesis can be measured in humans by the incorporation of deuterium from body water. This study is a simpler and less invasive method compared to previously published methods on surfactant kinetics by means of stable isotopes. Copyright © 2005 John Wiley & Sons, Ltd. [source] Dose determination and confirmation of a long-acting formulation of ceftiofur (ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory diseaseJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2002B. HIBBARD Hibbard, B., Robb, E. J., Chester Jr., S. T., Dame, K. J., Boucher, J. F., Alaniz, G. R. Dose determination and confirmation of a long-acting formulation of Ceftiofur (Ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory disease. J. vet. Pharmacol. Therap.25, 175,180. The objective of this work was to determine and confirm an effective dose of ceftiofur crystalline free acid sterile oil suspension (CCFA-SS, 100 mg ceftiofur equivalents (CE)/mL], a long-acting single-administration ceftiofur formulation, for the treatment of the bacterial component of bovine respiratory disease (BRD). Study 1 was a dose determination study that used an intratracheal Mannheimia haemolytica (Pasteurella haemolytica) challenge model to evaluate single-administration doses of CCFA-SS at 0.0, 1.1, 2.2, 3.3, 4.4 or 5.5 mg CE/kg body weight (BW) for the treatment of BRD. Data from this study were used to select doses for field testing in three multi-location clinical studies. In Study 2, the efficacy of a single administration dose of CCFA-SS at 4.4 mg CE/kg BW was compared with a negative control for the treatment of naturally occurring BRD in feedlot cattle. Treatments were administered when uniform clinical signs of BRD were present. Study 3 used a design similar to Study 2, and compared single-administration doses of CCFA-SS at 3.0 or 4.4 mg CE/kg BW with the positive-control tilmicosin (Micotil® 300 Injection, Elanco Animal Health) at 10 mg/kg BW. Study 4 compared the efficacy of single doses of CCFA-SS of 1.1,8.8 mg CE/kg BW with tilmicosin at 10 mg/kg BW. A total of 1176 cattle were included in these clinical studies. In Study 1, a dose of 4.55 mg CE/kg BW was determined to be effective. This was rounded to 4.4 mg CE/kg for field testing. In Study 2, a single dose of CCFA-SS at 4.4 mg CE/kg BW had a higher treatment success rate on day 14 (61%) than negative controls (26%, P < 0.01). However, in Study 3 this dose was judged to be at the beginning of an efficacious dose range for the treatment of BRD when compared with tilmicosin. In Study 4, day 28 treatment success rates were higher for CCFA-SS at 4.4,8.8 CE/kg BW than for tilmicosin (P=0.002) or the noneffective CCFA-SS dose of 1.1 mg CE/kg BW (P < 0.001). Based on decision criteria for Study 4, the effective dose was determined to be 4.4,5.5 mg CE/kg BW. These clinical studies demonstrated that a single dose of CCFA-SS (100 mg CE/mL) administered subcutaneously (s.c.) in the neck at 4.4,5.5 mg CE/kg BW is an effective treatment for BRD in feedlot cattle. However, this route of administration is no longer being considered for this formulation because of the ceftiofur residues that are present at the injection site for extended periods of time. [source] Transplacental mutagenicity of N -ethyl- N -nitrosourea at the hprt locus in T-lymphocytes of exposed B6C3F1 miceENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2001Hillary E. Sussman Abstract Previous studies have compared age-related differences in total mutagenic burden in mice of differing age (preweanling, weanling, or young adult) after single intraperitoneal (i.p.) injections of ethylnitrosourea (ENU). The purpose of the present investigation was to determine the effects of time elapsed since treatment on the frequency of hprt mutant T-cells (Mf) from mice treated transplacentally with single acute vs. multiple split doses of ENU. To this end, pregnant C57BL/6 mice (n = 13,16/group), which had been bred to C3H males, were given i.p. injections of 40 mg ENU/kg bw in a single dose on day 18 of gestation, in a split dose of 6 mg ENU/kg bw on days 12 through 18 of gestation, or DMSO vehicle alone. Groups of pups were necropsied on days 10, 13, 15 (single dose only), 17, 20, 40, and 70 postpartum for T-cell isolations and hprt Mf measurements using the T-cell cloning assay. The time required to reach maximum Mfs in T-cells isolated from thymus of transplacentally treated animals was 2 weeks, the same time span as previously observed after ENU treatment of adult, weanling, and preweanling mice. Mfs in T-cells isolated from spleens of control animals averaged 2.1 ± 0.3 (SE) × 10,6. In spleens of mice treated transplacentally with ENU in a single dose, Mfs reached a maximum at 15 days postpartum [84.7 ± 15.8 (SE) × 10,6] and decreased to lower but still elevated levels at 40 days postpartum. In spleens of mice treated transplacentally with ENU in a split dose, Mfs reached a maximum at 13 days postpartum [74.0 ± 16.3 (SE) × 10,6] and decreased to background levels at 40 days postpartum. The areas under the curves describing the change in hprt Mfs over time for ENU-treated vs. control mice estimate the mutagenic potency for transplacental single- and split-dose exposures to be 1.9 and 0.8 × 103, respectively. Comparison of the mutagenic potency estimates for mice exposed to ENU in utero to 4-week-old mice given a similar dose of the same lot number of ENU indicates that the mouse is more susceptible to ENU-induced mutagenesis during fetal life. Environ. Mol. Mutagen. 38:30,37, 2001 © 2001 Wiley-Liss, Inc. [source] Seasonal Variation in Fluoride Intake: the Iowa Fluoride StudyJOURNAL OF PUBLIC HEALTH DENTISTRY, Issue 4 2004Barbara Broffitt MS; ABSTRACT Objectives: Although patterns of fluid intake change seasonally, little is known about how fluoride intake varies by season. Since even short-term increases in fluoride intake could potentially lead to more dental fluorosis, it is valuable to assess the degree of seasonal variation to determine if it increases fluoride intake to levels that could be considered a concern in young children. Methods: Questionnaires were mailed periodically to participants in the Iowa Fluoride Study beginning at 6 weeks of age and continuing for a number of years. Parents recorded the date; child's weight; estimates of the amounts of water and other beverages that their child consumed per week; the type and amount of any fluoride supplements used; and the type, amount, and frequency of dentifrice used, with an estimate of the proportion of dentifrice that was swallowed. Documented water fluoride levels from municipal sources and assay of individual sources were linked to water intake amounts. Total fluoride intake per kg body weight was estimated from water, other beverages, fluoride supplements, and ingested dentifrice. Generalized linear models compared temperature-related and seasonal effects after adjusting for the child's age. Results: Separate analyses for ages 0,12 months and 12,72 months showed different results. Children younger than 12 months of age did not exhibit significant seasonal or temperature-related variation in any of the components of fluoride intake. Children aged 12,72 months had higher fluoride intake (mg F/kg bw) from beverages in summer (P <.05), and fluoride intake from beverages increased with monthly temperature (P <.001). Conclusions: Fluoride intake from beverages for children aged 12,72 months is slightly higher in the summer and increases with mean monthly temperature. Fluoride intake from supplements and dentifrice did not change significantly with either season or temperature. [source] Total fluoride intake in children aged 22,35 months in four Colombian citiesCOMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY, Issue 1 2005Ángela M. Franco Abstract , Objective: To obtain information on the level of total fluoride intake from food, beverages and toothpaste by children at the age of 22,25 months of low and high socioeconomic status (SES) in major Colombian cities. Methods:, Daily fluoride intake was assessed by the duplicate plate method and by recovered toothpaste solution during a 3-day period and afterwards analysed by the microdiffusion method. Results:, Mean daily fluoride intake was 0.11 (±0.10), 0.14 (±0.12), 0.10 (±0.07) and 0.07 (±0.06) mg/kg body weight (bw)/day in Bogotá, Medellín, Manizales and Cartagena, respectively. The total fluoride intake was higher in low-SES subjects in the cities of Medellín and Bogotá. In the high-SES children of the four cities, the average intakes ranged from 0.06 to 0.09 mg F/kg bw, whereas, the low-SES children in three cities had intakes between 0.11 and 0.21 mg F/kg bw (Cartagena, 0.07). Toothpaste (containing 1000,1500 ppm F, with 1500 ppm F being more common) accounted for approximately 70% of total fluoride intake, followed by food (24%) and beverages (<6%). More than half the children had their teeth brushed by an adult, on average twice a day, using 0.22,0.65 g of toothpaste. Conclusion:, Children from three Colombian cities have a mean total daily fluoride intake above the ,optimal range'. Health authorities should promote an appropriate use of fluoridated dentifrices discouraging the use of dentifrices containing 1500 ppm F in children younger than 6 years of age and promoting a campaign of education of parents and oral health professionals on adequate toothbrushing practices. [source] Ifosamide, epirubicin and granulocyte colony-stimulating factor: a regimen for successful mobilization of peripheral blood progenitor cells in patients with multiple myelomaHEMATOLOGICAL ONCOLOGY, Issue 2 2001M. Arland Abstract In general, the mobilization of peripheral blood progenitor cells (PBPC) in multiple myeloma (MM) patients is poor and is achieved in most cases by combined cyclophosphamide and G-CSF. This study was performed to examine the efficacy of combined ifosfamide/epirubicine and G-CSF for PBPC mobilization and purging. Sixteen patients suffering from multiple myeloma in stage II/A and III/A according to Durie and Salmon underwent chemotherapy consisting of a total of three cycles of ifosfamide (3,g/m2 on days 1 and 2 and epirubicine 80,mg/m2 on day 1) and G-CSF (10 or 20,µg/kg body weight (BW) daily until harvesting). PBPC harvesting was performed after the first and third cycle of chemotherapy. The median number of PBPC after the first cycle of chemotherapy was 7.79×106 CD34+ cells/kg BW (ranging from 0.94,26.36×106) and 6.38×106 CD34+ cells/kg BW (ranging from 0.79,29.31×106) after the third cycle of chemotherapy. Clinical re-evaluation after three cycles of chemotherapy showed 13 (81 per cent) patients in partial remission (PR), two (12 per cent) in complete remission (CR) and one (6.25 per cent) in stable disease (SD). No major side-effects were observed, six patients developed hematological toxicity stage IV WHO for a median of 3.9 days but no serious infection episodes occurred. Combined ifosfamide/epirubicin and standard G-CSF is able to mobilize sufficient PBPC without serious side-effects for patients with MM and for purging procedures resulting in a high proportion of complete remissions after tandem high-dose melphalan chemotherapy. Copyright © 2001 John Wiley & Sons, Ltd. [source] Analysis of Heritability of Hormonal Responses to Alcohol in Twins: Beta-Endorphin as a Potential Biomarker of Genetic Risk for AlcoholismALCOHOLISM, Issue 3 2000J. C. Froehlich Background: Hormonal responses to alcohol have been reported to differ in subjects with and without a family history of alcoholism which suggests that alcohol-induced hormonal changes might be used to identify individuals who are at elevated genetic risk for developing alcoholism. However, before a biological response can be used as a marker of genetic risk for disease, it must first be demonstrated that the response is, in fact, heritable. The present study was designed to determine whether hormonal responses to alcohol are heritable. Methods: The adrenocorticotropic hormone (ACTH), beta-endorphin (,-E), cortisol (CORT), and prolactin (PRL) responses to alcohol were examined in male and female identical (monozygotic or MZ) and fraternal (dizygotic or DZ) twin pairs. Male subjects consumed 0.35g ethanol/kg body weight (BW) and female consumed 0.325 g ethanol/kg BW in each of two alcohol drinking sessions administered 1 hr apar (total dose of 0.7 g/kg BW in males and 0.65 g/kg BW in females). Plasma hormone content was analyzed in samples collected before (resting conditions) and at 15, 60, 75, 120, 180, and 240 min after onset of drinking. Hormonal responses to alcohol were examined with twin analyses using the TWINAN90 program. A separate analysis was performed for each of the four hormones. A subset of subjects from each zygosity was seen on two separate occasions to establish retest reliability. Heritability of hormonal responses to alcohol was estimated using the intraclass correlation approach before and after removing the contribution of covariates that have the potential of influencing the plasma levels of these hormones. Results: Resting plasma levels of all four hormones were within the expected range, and the ,-E, ACTH, and PRL responses to the alcohol challenge evidenced good test-retest reliability. Of the four hormones examined, the only one that showed significant heritability after alcohol drinking was ,-E. Heritability estimates were not altered for any of the four hormones after removal of the variance contributed by covariates, such as gender and age. Conclusions: Taken together with other recent findings, the results suggest that the ,-E response to alcohol may represent a new biomarker that can be used to identify individuals who are at elevated genetic risk for developing alcoholism. [source] Effects of glucose polymer with and without potassium and different diets on glycogen repletion after a treadmill exercise test in endurance horsesJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 11-12 2005T. M. Hess Glycogen repletion involves absorption of glucose and its uptake into the muscle cells through GLUT-4 transporters. In the muscle and adipose tissue GLUT,4 transporters facilitates the glucose transport in the presence of insulin and K+. Potassium supply has been shown to stimulate insulin secretion. This study tested the effects of a glucose polymer added with electrolytes containing potassium (GP+K) compared to a glucose polymer with electrolytes without potassium (GP-K) on glycogen repletion. Also it compared the effect of different diet adaptations on glycogen repletion. Six horses were fed a diet rich in sugar and starch (SS), and six horses a diet rich in fat and fibre (FF) for 6 months before the test. In a crossover designed study, 12 trained Arabian or Arabian cross horses were submitted to a glycogen depleting exercise test on the treadmill. After exercise stopped six horses were supplied with GP-K and six other horses supplied with GP+K, at a dose of 5 g/kg BW, and a rate of 1 g/kg BW/hour through naso-gastric gavage. Muscle biopsies were taken before, just after they stopped exercise, and 16 h after they had been supplied with glycogen replacing formulas, and analysed for muscle glycogen. Blood was taken before, after 3 h of exercise, after the stepwise exercise test, at 0, 1 and 4 h after exercise stopped and analysed for plasma glucose, insulin and [K+]. Muscle glycogen decreased from 516.41 ± 12.92 glucosyl units/kg dry weight muscle to 408.74 ± 12.92 glucosyl units/kg dry weight muscle (79%). Sixteen hours after the repletion protocol horses recovered their muscle glycogen to 458.53 ± 12.91 glucosyl units/kg dry weight muscle (89%). Plasma glucose had a glucose polymer by sampling effect (p = 0.013) and a feed by sampling effect (p = 0.022). Plasma glucose was higher in SS fed horses at 1 and 4 h after exercise. Plasma glucose was lower in GP+K supplied horses 4 h after exercise. Plasma insulin had a trend (p = 0.070) for a glucose polymer effect. No differences were found in muscle glycogen between the two GP treatments. Although the present results demonstrate that intensive nasogastric supplementation with glucose polymer can result in glycogen repletion approaching that following i.v. administration, the addition of potassium conferred no advantage. [source] Milk Fat Globule EGF Factor 8 Attenuates Sepsis-Induced Apoptosis and Organ Injury in Alcohol-Intoxicated RatsALCOHOLISM, Issue 9 2010Rongqian Wu Background:, Despite advances in our understanding of excessive alcohol-intake-related tissue injury and modernization of the management of septic patients, high morbidity and mortality caused by infectious diseases in alcohol abusers remain a prominent challenge. Our previous studies have shown that milk fat globule epidermal growth factor-factor VIII (MFG-E8), a protein required to opsonize apoptotic cells for phagocytosis, is protective in inflammation. However, it remains unknown whether MFG-E8 ameliorates sepsis-induced apoptosis and organ injury in alcohol-intoxicated rats. The purpose of this study was to determine whether recombinant murine MFG-E8 (rmMFG-E8) attenuates organ injury after acute alcohol exposure and subsequent sepsis. Methods:, Acute alcohol intoxication was induced in male adult rats by a bolus injection of intravenous alcohol at 1.75 g/kg BW, followed by an intravenous infusion of 300 mg/kg BW/h of alcohol for 10 hours. Sepsis was induced at the end of 10-hour alcohol infusion by cecal ligation and puncture (CLP). rmMFG-E8 or vehicle (normal saline) was administered intravenously 3 times (i.e., at the beginning of alcohol injection, the beginning of CLP, and 10 hours post-CLP) at a dose of 20 ,g/kg BW each. Blood and tissue samples were collected 20 hours after CLP in alcoholic animals for various measurements. Results:, Acute alcohol exposure per se did not affect the production of MFG-E8; however, it primed the animal and enhanced sepsis-induced MFG-E8 downregulation in the spleen. Administration of rmMFG-E8 reduces alcohol/sepsis-induced apoptosis in the spleen, lungs, and liver. In addition, administration of rmMFG-E8 after alcohol exposure and subsequent sepsis decreases circulating levels of TNF-, and interleukin-6 and attenuates organ injury. Conclusions:, rmMFG-E8 attenuates sepsis-induced apoptosis and organ injury in alcohol-intoxicated rats. [source] Analysis of Heritability of Hormonal Responses to Alcohol in Twins: Beta-Endorphin as a Potential Biomarker of Genetic Risk for AlcoholismALCOHOLISM, Issue 3 2000J. C. Froehlich Background: Hormonal responses to alcohol have been reported to differ in subjects with and without a family history of alcoholism which suggests that alcohol-induced hormonal changes might be used to identify individuals who are at elevated genetic risk for developing alcoholism. However, before a biological response can be used as a marker of genetic risk for disease, it must first be demonstrated that the response is, in fact, heritable. The present study was designed to determine whether hormonal responses to alcohol are heritable. Methods: The adrenocorticotropic hormone (ACTH), beta-endorphin (,-E), cortisol (CORT), and prolactin (PRL) responses to alcohol were examined in male and female identical (monozygotic or MZ) and fraternal (dizygotic or DZ) twin pairs. Male subjects consumed 0.35g ethanol/kg body weight (BW) and female consumed 0.325 g ethanol/kg BW in each of two alcohol drinking sessions administered 1 hr apar (total dose of 0.7 g/kg BW in males and 0.65 g/kg BW in females). Plasma hormone content was analyzed in samples collected before (resting conditions) and at 15, 60, 75, 120, 180, and 240 min after onset of drinking. Hormonal responses to alcohol were examined with twin analyses using the TWINAN90 program. A separate analysis was performed for each of the four hormones. A subset of subjects from each zygosity was seen on two separate occasions to establish retest reliability. Heritability of hormonal responses to alcohol was estimated using the intraclass correlation approach before and after removing the contribution of covariates that have the potential of influencing the plasma levels of these hormones. Results: Resting plasma levels of all four hormones were within the expected range, and the ,-E, ACTH, and PRL responses to the alcohol challenge evidenced good test-retest reliability. Of the four hormones examined, the only one that showed significant heritability after alcohol drinking was ,-E. Heritability estimates were not altered for any of the four hormones after removal of the variance contributed by covariates, such as gender and age. Conclusions: Taken together with other recent findings, the results suggest that the ,-E response to alcohol may represent a new biomarker that can be used to identify individuals who are at elevated genetic risk for developing alcoholism. [source] Pharmacokinetics and pharmacodynamics of clemastine in healthy horsesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2003K. Törneke Clemastine is an H1 antagonist used in certain allergic disorders in humans and tentatively also in horses, although the pharmacology of the drug in this species has not yet been investigated. In the present study we determined basic pharmacokinetic parameters and compared the effect of the drug measured as inhibition of histamine-induced cutaneous wheal formation in six horses. The most prominent feature of drug disposition after intravenous dose of 50 ,g/kg bw was a very rapid initial decline in plasma concentration, followed by a terminal phase with a half-life of 5.4 h. The volume of distribution was large, Vss = 3.8 L/kg, and the total body clearance 0.79 L/h kg. Notably, oral bioavailability was only 3.4%. There was a strong relationship between plasma concentrations and effect. The effect maximum (measured as reduction in histamine-induced cutaneous wheal formation) was 65% (compared with controls where saline was injected) and the effect duration after i.v. dose was approximately 5 h. The effect after oral dose of 200 ,g/kg was minor. The results indicate that clemastine is not appropriate for oral administration to horses because of low bioavailability. When using repeated i.v. administration, the drug has to be administered at least three to four times daily to maintain therapeutic plasma concentrations because of the short half-life. However, if sufficient plasma concentrations are maintained the drug is efficacious in reducing histamine-induced wheal formations. [source] Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression against acute liver injury induced by carbon tetrachloride in sprague-dawley ratsPHYTOTHERAPY RESEARCH, Issue 9 2010Chung Mu Park Abstract The protective effects of common dandelion leaf water extract (DLWE) were investigated by carbon tetrachloride (CCl4) induced hepatitis in Sprague-Dawley rats. The animals were divided into five groups: normal control, DLWE control, CCl4 control, and two DLWE groups (0.5 and 2,g/kg bw). After 1 week of administering corresponding vehicle or DLWE, a single dose of CCl4 (50% CCl4/olive oil; 0.5,mL/kg bw) was administered 24,h before killing in order to produce acute liver injury. The DLWE treatment significantly decreased CCl4 -induced hepatic enzyme activities (AST, ALT and LDH) in a dose dependent manner. Also, the obstructed release of TG and cholesterol into the serum was repaired by DLWE administration. Hepatic lipid peroxidation was elevated while the GSH content and antioxidative enzyme activities were reduced in the liver as a result of CCl4 administration, which were counteracted by DLWE administration. Furthermore, the hepatocytotoxic effects of CCl4 were confirmed by significantly elevated Fas and TNF-? mRNA expression levels, but DLWE down-regulated these expressions to the levels of the normal control. Highly up-regulated cytochrome P450 2E1 was also lowered significantly in the DLWE groups. These results indicate that DLWE has a protective effect against CCl4 -induced hepatic damage with at least part of its effect being attributable to the attenuation of oxidative stress and inflammatory processes resulting from cytochrome P450 activation by CCl4. Copyright © 2010 John Wiley & Sons, Ltd. [source] Pharmacokinetics of ivermectin after maternal or fetal intravenous administration in sheepJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008R. PÉREZ In pregnant sheep at 120,130 days of gestational age, a study was undertaken in order to characterize the pharmacokinetics and transplacental exchange of Ivermectin after maternal or fetal intravenous administration. Eight pregnant Suffolk Down sheep of 73.2 ± 3.7 kg body weight (bw) were surgically prepared in order to insert polyvinyl catheters in the fetal femoral artery and vein and amniotic sac. Following 48 h of recovery, the ewes were randomly assigned to two experimental groups. In group 1, (maternal injection) five ewes were treated with an intravenous bolus of 0.2 mg ivermectin/kg bw. In group 2, (fetal injection) three ewes were injected with an intravenous bolus of 1 mg of ivermectin to the fetus through a fetal femoral vein catheter. Maternal and fetal blood and amniotic fluid samples were taken before and after ivermectin administration for a period of 144 h post-treatment. Samples were analyzed by liquid chromatography (HPLC). A computerized non-compartmental pharmacokinetic analysis was performed and the results were compared by means of the Student t-test. The main pharmacokinetic changes observed in the maternal compartment were increases in the volume of distribution and in the half-life of elimination (t˝,). A limited maternal-fetal transfer of ivermectin was evidenced by a low fetal Cmax (1.72 ± 0.6 ng/mL) and AUC (89.1 ± 11.4 ng·h/mL). While the fetal administration of ivermectin resulted in higher values of clearance (554.1 ± 177.9 mL/kg) and lower values of t˝, (8.0 ± 1.4 h) and mean residence time (8.0 ± 2.9 h) indicating that fetal-placental unit is highly efficient in eliminating the drug as well as limiting the transfer of ivermectin from the maternal to fetal compartment. [source] Role of meal carbohydrate content for the imbalance of plasma amino acids in patients with liver cirrhosisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2007Ewert Schulte-Frohlinde Abstract Background and Aim:, Imbalance of circulating branched chain amino acids (BCAA) versus aromatic amino acids (AAA) and hyperinsulinemia are common metabolic alterations in patients with liver cirrhosis. The aim of this study was to characterize the effect of the carbohydrate component of a protein-rich mixed meal on postprandial plasma concentrations of 21 amino acids, insulin and C-peptide in patients with compensated liver cirrhosis. Furthermore, the effect of a dietary intervention on the metabolic alterations in cirrhotic patients was examined. Methods:, Eighteen patients with cirrhosis and 12 healthy volunteers received a protein-rich meal (pork filet 200 g) with or without carbohydrates (bread 50 g, glucose 20 g). A subgroup of four cirrhotic patients received an isoenergetic (117 kJ/kg bw) carbohydrate-enriched (60%) and -restricted (20%) diet for 7 days each. Results:, In the cirrhotic patients, basal plasma insulin and C-peptide concentrations were significantly elevated. The ingestion of a protein-rich meal without additional carbohydrates led to a significantly greater increase of insulin and C-peptide in the cirrhotic patients compared to controls. Postprandial increases of leucine and isoleucine were reduced, whereas those of phenylalanine were higher in cirrhotic patients. The addition of carbohydrates led to higher insulin and C-peptide plasma concentrations in cirrhotic patients. Postprandial BCAA increases were more impaired in the cirrhotic group after additional carbohydrate ingestion (46%vs 82%). After the carbohydrate-restricted diet for 7 days BCAA plasma levels increased but the BCAA/AAA ratio remained unaltered. Conclusions:, The carbohydrate content of a meal enhances reduction of BCAA plasma concentrations in clinically stable cirrhotic patients. An imbalanced BCAA/AAA ratio cannot be avoided by a carbohydrate-reduced diet alone, supporting mandatory BCAA supplementation. [source] Effects of extrusion and supplementation of exogenous enzymes to diets containing Chinese storage brown rice on the carbohydrase activity in the digestive tract of pigletsJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 2 2010J. He Summary Two experiments were conducted to study the effects of extrusion of Chinese storage brown rice and of exogenous enzymes supplementation to diets containing Chinese storage brown rice on the carbohydrase activity in digestive tract of piglets. In Experiment 1, 96 weaned piglets [initially 6.95 ± 0.05 kg body weight (BW)] were used in a 2 × 2 factorial design, the animals were fed the diets containing extruded Chinese storage brown rice or non-treated Chinese storage brown rice and supplemented with or without exogenous enzymes. Each treatment had six replicate pens and four piglets in each pen. The results demonstrated that extrusion significantly increased (p < 0.05) the activity of duodenal maltase after 14 days of treatment and glucoamylase after 28 days of treatment, jejunal lactase, maltase, isomaltase, sucrase and ,-amylase after 28 days of treatment, and jejunal ,-amylase after 14 days of treatment; enzyme supplementation positively influenced (p < 0.05) the activity of pancreatic ,-amylase after 14 and 28 days of treatment, pancreatic glucoamylase after 28 days of treatment and ileal trehalase after 14 days of treatment. Similarly, interaction between extrusion and enzyme addition existed after 14 days of treatment on the activity of pancreatic ,-amylase and duodenal maltase and on the activity of duodenal glucoamylase and isomaltase, jejunal ,-amylase, lactase, maltase, isomaltase and jejunal ,-amylase after 28 days of treatment. In Experiment 2, six piglets (initially 21 ± 1.85 kg BW) fitted with ileal ,T'-cannulas in a 6 × 6 Latin Square Design were used to study the effects of extrusion and addition of exogenous enzymes on ileal carbohydrase activity and nutrients digestibility. The results showed that exogenous enzymes significantly (p < 0.05) increased ileal ,-amylase, glucoamylase and trehalase activity. The interaction between extrusion and enzyme supplementation had positive effect (p < 0.05) on the ileal lactase, cellobiase and sucrase activity. [source] Metabolic responses to oral tryptophan supplementation before exercise in horsesJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-6 2005I. Vervuert Summary This study was conducted to evaluate the effects of oral tryptophan (Trp) supplementation on exercise capacity and metabolic responses in horses. Three horses had to perform an exercise test: a 15-min warm-up followed by a 60-min walk (1.7 m/s, W1), a 10-min trot (3.1 m/s, T1), a second 60-min walk (1.7 m/s, W2), a second 10-min trot (3.1 m/s, T2) and a final 30-min walk (1.7 m/s, W3) until the horses were unwilling to continue. The horses exercised on a treadmill at a 6% incline and with a constant draught load of 40 kg (0.44 kN). Two hours before exercise horses were given 50 g Trp (9.8,10.7 g Trp/100 kg BW) by nasogastric tube. A control exercise test was conducted without Trp. During the control test, one horse was able to finish the final 30-min walk (W3), whereas two horses finished W3 after Trp administration. Higher plasma Trp levels after Trp administration did not change significantly during exercise (Trp: start exercise, 524 ± 41 ,mol/l; end exercise 547 ± 20 ,mol/l; control: start exercise, 70 ± 10 ,mol/l; end exercise, 58 ± 21 ,mol/l). After Trp supplementation, blood lactate concentrations were significantly lower after the first and second trotting periods. Free fatty acids in plasma increased during exercise without any treatment-related differences. Although experimental plasma Trp levels were seven times higher than the control levels, Trp supplementation had no effect on exercise performance and metabolic responses to draught load exercise. [source] Effects of hay intake and feeding sequence on variables in faeces and faecal water (dry matter, pH value, organic acids, ammonia, buffering capacity) of horsesJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 1-2 2004A. Zeyner Summary To investigate effects of hay intake and feeding sequence on indicators of the microbial activity within the hindgut, six horses were fed 1.00 kg oats plus 0.50, 0.67, 0.83 or 1.00 kg hay/100 kg body weight (BW) × day, each for 14 days. Oats was offered either 30 min prior to hay (OA) or in the reversed sequence (HA) in a 2 × 8-week crossover design. Because typically exercised horses should be subjected to the study, faeces was used as substrate. Faecal dry matter (DM), the faecal waters' short-chain fatty acids (SCFA, in mmol/l) and molar percentages (mol%) of propionate and iso-butyrate were highest with OA (p < 0.01). Acetate mol%, acetate,propionate quotient (A/P) and buffering capacities 1 and 2 (BC1: current pH to pH 6; BC2: pH 6 to 5) of the faecal water were highest with HA (p < 0.01). While the hay intake rose, faecal pH, acetate mol%, A/P, BC1 and BC2 (the latter with HA only) increased (p < 0.05), but DM, SCFA and propionate mol% declined (p < 0.05). The hay-induced rise in A/P and BC1 was much higher with HA than with OA. l -Lactate and ammonia were unaffected by the feeding sequence and hay intake. In conclusion, hay intake and feeding sequence influence the microbial activity within the hindgut, although the concentrate level remains consistent. In horse rations with 1.00 kg oats/100 kg BW × day amounts of at least 0.83 kg hay/100 kg BW × day and offering the hay first seem to have the potency to protect the hindgut content from acidification. Behavioural abnormality was not observed any longer first with 1.00 kg hay/100 kg BW × day. [source] Effects of central administration of glucagon on feed intake and endocrine responses in sheepANIMAL SCIENCE JOURNAL, Issue 6 2009Yohei KUROSE ABSTRACT This study was conducted to investigate effects of glucagon intracerebroventricularly administered on feed intake and endocrine changes in sheep. Four male sheep (48,55 kg BW) were used. The animals were acclimatized to be fed alfalfa hay cubes at 12.00 hour. Human glucagon (40 and 80 µg/0.5 mL) was injected into the lateral ventricle at 12.00 hour. Blood samples were taken every 10 min from 30 min before to 180 min after the glucagon injection. Soon after the injection, the animals were given alfalfa hay cubes, and the amounts of the feed eaten within 2 h were measured. Feed intakes were significantly (P < 0.05) suppressed by 80 µg of glucagon. Plasma glucose levels in control animals were gradually decreased after the feeding, whilst those in glucagon-treated animals were temporarily elevated just after the feeding and then kept higher than control levels. Plasma insulin was abruptly elevated after the feeding and was maintained at higher levels than before the feeding in all treatments. Plasma NEFA concentrations were decreased after the feeding in all treatments. A tendency of increase in plasma cortisol levels occurred in glucagon-injected animals. The present study provides the first evidence that glucagon directly acts on the brain, then inhibiting feeding behavior and inducing endocrine responses in ruminants. [source] Reduction of ammonia emission from growing pig rooms by feeding a lower protein diet supplemented with apple pomaceANIMAL SCIENCE JOURNAL, Issue 6 2002Akemi YAMAMOTO ABSTRACT An experiment was conducted to determine the effect of supplementing a reduced crude protein (CP) diet with apple pomace on the ammonia emissions from growing pig rooms. Four pigs (45 kg BW) each were assigned to one of two diets. Each group was housed in a separate room and fed a standard diet (CP 16.6%) or a low CP, amino acid-supplemented diet (CP 9.1%) containing 23.1% of dried apple pomace for two 7-day experimental periods. After the completion of the first period, the pigs were switched to the other diet. The daily ammonia emissions, measured for 3 days after a 4-day adaptation period, were much lower for pigs fed the apple pomace-supplemented diet than for pigs fed the standard diet (0.47 g/pig vs 7.30 g/pig, respectively). The daily nitrogen intake for the standard diet and the apple pomace-supplemented diet was 58.1 and 35.5 g/pig, respectively. The pigs fed the apple pomace-supplemented diet excreted more fecal nitrogen than pigs fed the standard diet (17.5 g/day vs 11.0 g/day, respectively), but urinary nitrogen excretion with the apple pomace-supplemented diet was estimated to be 2.9 g/day, which was much lower than that for the standard diet (27.0 g/day). The addition of apple pomace to a reduced CP, amino acid-supplemented diet reduces urinary nitrogen excretion and thereby ammonia emission. [source] Performance of a new separator system for routine autologous hematopoietic progenitor cell collection in small childrenJOURNAL OF CLINICAL APHERESIS, Issue 6 2007Volker Witt Abstract The AMICUSÔ system was recently introduced for peripheral blood stem cell (PBSC) aphereses in adults. We conducted a single center field evaluation to obtain data about the performance of this system in children with a body weight (bw) < 25 kg. Results of blood priming procedures were compared to historical data obtained with the Fenwal CS3000+ (CS 3000). From August, 2001 to February, 2007, 47/178 (26%) PBSC aphereses procedures were performed in our institution with the AMICUSÔ system in 35 small patients (median bw 13.9 kg; range 6.7,24; age 2.78 years; range 0.97,7.06). The patients suffered from various malignant primary diseases or recurrences. We primed the system with packed RBC in case of >30% dilution of the RBC volume (n = 31) or with saline (n = 16). Compared to the CS3000, the AMICUSÔ revealed comparable collection efficiencies (CE) for CD34+ cells (median 67%, range 26,120), lymphocytes (75%, 25,138), monocytes (54%, 23,173), and granulocytes (10%, 1.5,36), MNC (57% 24,125), but a significantly higher erythrocyte and granulocyte, and a lower platelet CE. There was a significant negative correlation between total leukocyte count and CE for MNC (r = ,0.566; P < 0.001) and CD34+ cells (r = ,0.517; P < 0.001). There was no significant statistical or clinical difference between the CE in blood-primed procedures and saline-primed procedures. With the AMICUSÔ we saw statistically less citrate reactions compared to the CS 3000. We conclude that the AMICUSÔ system is safe and efficient to harvest PBSC on a routine basis in pediatric patients, even in children ,10 kg bw. J. Clin. Apheresis, 2007. © 2007 Wiley-Liss, Inc. [source] Evidence that plasma concentration rather than dose per kilogram body weight predicts ribavirin-induced anaemiaJOURNAL OF VIRAL HEPATITIS, Issue 1 2004K. Lindahl Summary., Ribavirin in combination with interferon alpha-2 or pegylated interferon is the standard treatment for chronic hepatitis C. The current dosage recommendations for ribavirin are based on body weight (bw). Ribavirin is mainly eliminated by the kidneys and we have recently shown that ribavirin plasma concentrations are determined primarily by renal function. It is therefore reasonable to hypothesize that side-effects of ribavirin, i.e. anaemia, should be more closely related to plasma concentrations of ribavirin than to the dose per kg bw. A total of 108 consecutive patients eligible for treatment of chronic hepatitis C were studied. Ribavirin concentrations in plasma were measured by high-performance liquid chromatography (HPLC)-UV after solid-phase extraction in trough samples taken 4, 8 and 12 weeks after the treatment commenced. A total of 213 samples were obtained and the change in the haemoglobin level and the creatinine concentration was measured in addition to ribavirin. The dose of ribavirin per kg bw did not correlate with the drop in haemoglobin level induced by ribavirin. The concentration of ribavirin was non-linearly related to the drop in the haemoglobin level as revealed by fitting a standard Hill equation type dose,response curve. The half maximal drop in haemoglobin was obtained at 4.4 ,m. The results from this study suggest that the anaemia induced by ribavirin depends primarily on the concentration of ribavirin, and not on the dose per kg bw. This lends further support to the idea that ribavirin should be dosed according to renal function. [source] Right atrial stretch alters fore- and hind-brain expression of c-fos and inhibits the rapid onset of salt appetiteTHE JOURNAL OF PHYSIOLOGY, Issue 15 2008Juliana Irani Fratucci De Gobbi The inflation of an intravascular balloon positioned at the superior vena cava and right atrial junction (SVC-RAJ) reduces sodium or water intake induced by various experimental procedures (e.g. sodium depletion; hypovolaemia). In the present study we investigated if the stretch induced by a balloon at this site inhibits a rapid onset salt appetite, and if this procedure modifies the pattern of immunohistochemical labelling for Fos protein (Fos-ir) in the brain. Male Sprague,Dawley rats with SVC-RAJ balloons received a combined treatment of furosemide (Furo; 10 mg (kg bw),1) plus a low dose of the angiotensin-converting enzyme inhibitor captopril (Cap; 5 mg (kg bw),1). Balloon inflation greatly decreased the intake of 0.3 m NaCl for as long as the balloon was inflated. Balloon inflation over a 3 h period following Furo,Cap treatment decreased Fos-ir in the organum vasculosum of the lamina terminalis and the subfornical organ and increased Fos-ir in the lateral parabrachial nucleus and caudal ventrolateral medulla. The effect of balloon inflation was specific for sodium intake because it did not affect the drinking of diluted sweetened condensed milk. Balloon inflation and deflation also did not acutely change mean arterial pressure. These results suggest that activity in forebrain circumventricular organs and in hindbrain putative body fluid/cardiovascular regulatory regions is affected by loading low pressure mechanoreceptors at the SVC-RAJ, a manipulation that also attenuates salt appetite. [source] Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression against acute liver injury induced by carbon tetrachloride in sprague-dawley ratsPHYTOTHERAPY RESEARCH, Issue 9 2010Chung Mu Park Abstract The protective effects of common dandelion leaf water extract (DLWE) were investigated by carbon tetrachloride (CCl4) induced hepatitis in Sprague-Dawley rats. The animals were divided into five groups: normal control, DLWE control, CCl4 control, and two DLWE groups (0.5 and 2,g/kg bw). After 1 week of administering corresponding vehicle or DLWE, a single dose of CCl4 (50% CCl4/olive oil; 0.5,mL/kg bw) was administered 24,h before killing in order to produce acute liver injury. The DLWE treatment significantly decreased CCl4 -induced hepatic enzyme activities (AST, ALT and LDH) in a dose dependent manner. Also, the obstructed release of TG and cholesterol into the serum was repaired by DLWE administration. Hepatic lipid peroxidation was elevated while the GSH content and antioxidative enzyme activities were reduced in the liver as a result of CCl4 administration, which were counteracted by DLWE administration. Furthermore, the hepatocytotoxic effects of CCl4 were confirmed by significantly elevated Fas and TNF-? mRNA expression levels, but DLWE down-regulated these expressions to the levels of the normal control. Highly up-regulated cytochrome P450 2E1 was also lowered significantly in the DLWE groups. These results indicate that DLWE has a protective effect against CCl4 -induced hepatic damage with at least part of its effect being attributable to the attenuation of oxidative stress and inflammatory processes resulting from cytochrome P450 activation by CCl4. Copyright © 2010 John Wiley & Sons, Ltd. [source] Colonic sarcoidosis, infliximab, and tuberculosis: A cautionary taleINFLAMMATORY BOWEL DISEASES, Issue 4 2004Prof. Dario Sorrentino MD Abstract The antitumor necrosis factor, infliximab, has been recently shown to be effective in refractory sarcoidosis including the intestinal form of this disease. We have tried this therapy in a 55-year-old woman under immunosuppressive therapy for longstanding sarcoidosis presenting with abdominal pain apparently caused by a colonic localization of the disease. The latter diagnosis was based, as recommended, on the presence of nonnecrotizing granulomas in mucosal biopsies, the presence of systemic disease, and the careful exclusion of other granulomatous diseases, including tuberculosis. After the first IV infusion (10 mg/kg BW), she quickly improved, but the wellbeing lasted approximately 4 weeks. She then received another dose of infliximab, but she soon developed low-grade fever and weakness and shortly succumbed of miliary tuberculosis. Likely, infliximab precipitated a pre-existing mycobacterial infection of the intestine. Given the likelihood of underdiagnosing intestinal tuberculosis,and the risks associated with infliximab treatment,this case suggests that this drug should be used with extreme caution, if at all, when a diagnosis of colonic sarcoidosis is suspected. [source] Long-lasting effects of elevated neonatal leptin on rat hippocampal function, synaptic proteins and NMDA receptor subunitsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2007Claire-Dominique Walker Abstract The high circulating levels of leptin in neonatal rodents do not seem to be regulating energy balance at this age, but rather may play an important role for brain development. We tested the hypothesis that high neonatal leptin levels modify hippocampal function and production of synaptic proteins with possible long-term consequences on long-term potentiation (LTP) in adulthood. We first showed that in postnatal day (PND) 10 neonates, acute leptin treatment functionally activated leptin receptors (ObR) in the CA1 and DG regions of the hippocampus through the induction of phosphoERK1/2, but not phosphoSTAT3 protein although both phospho-proteins were induced in the arcuate nucleus. We next examined whether chronic leptin administration (3 mg/kg BW, intraperitoneally) during the first 2 weeks of life (postnatal day, PND 2,14) produces a functional signal in the hippocampus that alters the expression of NMDA receptor subunits (NR1, NR2A, NR2B), synaptic proteins and LTP in the short and long-term. In PND 10 as in adults (PND 70) rats, chronic leptin treatment increased NR1 expression in the hippocampus while reducing NR2B protein levels. Elevated hippocampal concentrations of synapsin2A and synaptophysin were detected during leptin treatment on PND 10 suggesting increased neurotransmitter release. In adults, only SNAP-25 expression was increased after neonatal leptin treatment. LTP was reduced dramatically by leptin treatment in preweaning rats although the changes did not persist until adulthood. Elevated exposure to leptin during a critical period of neonatal hippocampal development might serve to enhance NMDA-dependent functions other than LTP and have important effects on synaptogenesis and neurotransmitter release. © 2007 Wiley-Liss, Inc. [source] Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantationJOURNAL OF PINEAL RESEARCH, Issue 4 2009Zhanqing Li Abstract:, Free radicals are involved in pathophysiology of ischemia/reperfusion injury (IRI). Melatonin is a potent scavenger of reactive oxygen and nitrogen species. Thus, this study was designed to elucidate its effects in a model of rat kidney transplantation. Twenty Lewis rats were randomly divided into 2 groups (n = 10 animals each). Melatonin (50 mg/kg BW) dissolved in 5 mL milk was given to one group via gavage 2 hr before left donor nephrectomy. Controls were given the same volume of milk only. Kidney grafts were then transplanted into bilaterally nephrectomized syngeneic recipients after 24 hr of cold storage in Histidine,Tryptophan,Ketoglutarate solution. Both graft function and injury were assessed after transplantation through serum levels of blood urea nitrogen (BUN), creatinine, transaminases, and lactate dehydrogenase (LDH). Biopsies were taken to evaluate tubular damage, the enzymatic activity of superoxide dismutase (SOD) and lipid hydroperoxide (LPO), and the expression of NF-kBp65, inducible nitric oxide synthase (iNOS), caspase-3 as indices of oxidative stress, necrosis, and apoptosis, respectively. Melatonin improved survival (P < 0.01) while decreasing BUN, creatinine, transaminases, and LDH values up to 39,71% (P < 0.05). Melatonin significantly reduced the histological index for tubular damage, induced tissue enzymatic activity of SOD while reducing LPO. At the same time, melatonin down-regulated the expression of NF-kBp65, iNOS, and caspase-3. In conclusion, donor preconditioning with melatonin protected kidney donor grafts from IRI-induced renal dysfunction and tubular injury most likely through its anti-oxidative, anti-apoptotic and NF-kB inhibitory capacity. [source] Effects of Lidocaine Infusion during Experimental Endotoxemia in HorsesJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2010J.R. Peiró Background: The clinical efficacy of IV infusion of lidocaine for treatment of equine endotoxemia has not been studied. Hypothesis: Lidocaine infusion after exposure to lipopolysaccharide (LPS) will inhibit the inflammatory response and have inhibitory effects on the hemodynamic and cytokine responses to endotoxemia. Animals: Twelve horses. Methods: Two equal groups (n = 6): saline (GI) and lidocaine (GII). In all animals, endotoxin (500 ng/kg body weight [BW]) was injected intraperitoneally over 5 minutes. Twenty minutes later, animals received a bolus of GI or GII (1.3 mg/kg BW) over 5 minutes, followed by a 6-hour continuous rate infusion of GI or GII (0.05 mg/kg BW/min). Treatment efficacy was judged from change in arterial blood pressure, peripheral blood and peritoneal fluid (PF) variables (total and differential cell counts, enzyme activities, and cytokine concentrations), and clinical scores (CS) for behavioral evidence of abdominal pain or discomfort during the study. Results: Compared with the control group, horses treated with lidocaine had significantly lower CS and serum and PF tumor necrosis factor-, (TNF-,) activity. At several time points in both groups, total and differential cell counts, glucose, total protein and fibrinogen concentrations, and alkaline phosphatase, creatine kinase, and TNF-, activities were significantly different from baseline values both in peripheral blood and in PF. Conclusions and Clinical Importance: Lidocaine significantly decreased severity of CS and inhibited TNF-, activity in PF. [source] Dose determination and confirmation of a long-acting formulation of ceftiofur (ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory diseaseJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2002B. HIBBARD Hibbard, B., Robb, E. J., Chester Jr., S. T., Dame, K. J., Boucher, J. F., Alaniz, G. R. Dose determination and confirmation of a long-acting formulation of Ceftiofur (Ceftiofur crystalline free acid) administered subcutaneously for the treatment of bovine respiratory disease. J. vet. Pharmacol. Therap.25, 175,180. The objective of this work was to determine and confirm an effective dose of ceftiofur crystalline free acid sterile oil suspension (CCFA-SS, 100 mg ceftiofur equivalents (CE)/mL], a long-acting single-administration ceftiofur formulation, for the treatment of the bacterial component of bovine respiratory disease (BRD). Study 1 was a dose determination study that used an intratracheal Mannheimia haemolytica (Pasteurella haemolytica) challenge model to evaluate single-administration doses of CCFA-SS at 0.0, 1.1, 2.2, 3.3, 4.4 or 5.5 mg CE/kg body weight (BW) for the treatment of BRD. Data from this study were used to select doses for field testing in three multi-location clinical studies. In Study 2, the efficacy of a single administration dose of CCFA-SS at 4.4 mg CE/kg BW was compared with a negative control for the treatment of naturally occurring BRD in feedlot cattle. Treatments were administered when uniform clinical signs of BRD were present. Study 3 used a design similar to Study 2, and compared single-administration doses of CCFA-SS at 3.0 or 4.4 mg CE/kg BW with the positive-control tilmicosin (Micotil® 300 Injection, Elanco Animal Health) at 10 mg/kg BW. Study 4 compared the efficacy of single doses of CCFA-SS of 1.1,8.8 mg CE/kg BW with tilmicosin at 10 mg/kg BW. A total of 1176 cattle were included in these clinical studies. In Study 1, a dose of 4.55 mg CE/kg BW was determined to be effective. This was rounded to 4.4 mg CE/kg for field testing. In Study 2, a single dose of CCFA-SS at 4.4 mg CE/kg BW had a higher treatment success rate on day 14 (61%) than negative controls (26%, P < 0.01). However, in Study 3 this dose was judged to be at the beginning of an efficacious dose range for the treatment of BRD when compared with tilmicosin. In Study 4, day 28 treatment success rates were higher for CCFA-SS at 4.4,8.8 CE/kg BW than for tilmicosin (P=0.002) or the noneffective CCFA-SS dose of 1.1 mg CE/kg BW (P < 0.001). Based on decision criteria for Study 4, the effective dose was determined to be 4.4,5.5 mg CE/kg BW. These clinical studies demonstrated that a single dose of CCFA-SS (100 mg CE/mL) administered subcutaneously (s.c.) in the neck at 4.4,5.5 mg CE/kg BW is an effective treatment for BRD in feedlot cattle. However, this route of administration is no longer being considered for this formulation because of the ceftiofur residues that are present at the injection site for extended periods of time. [source] Bioavailability and disposition of sodium and procaine penicillin G (benzylpenicillin) administered orally with milk to calvesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2001J. M. B. Musser Eighteen 1-week-old Holstein calves were randomly assigned to one of three groups: (a) sodium penicillin G administered intravenously, (b) sodium penicillin G administered orally, or (c) procaine penicillin G administered orally. All calves were dosed with penicillin G at 4.0 mg/kg BW. At 5 weeks of age, the calves were dosed again. Blood samples were taken serially for 24 h after both dosings. Plasma was assayed for penicillin G by high performance liquid chromatography (HPLC). For i.v. administration, the area under the concentration,time curve (AUC), 7456 and 5508 ng/mL h, and systemic clearance, 0.54 and 0.73 L/kg h, were significantly different (P < 0.05) at 1 and 5 weeks of age, respectively. There were no significant differences between orally administered sodium and procaine penicillin G within the same age groups. Following oral (p.o.) administration, there were significant differences (P < 0.01) at 1 and 5 weeks of age in the AUC, 760 and 409 ng/mL h, terminal half-life, 2.1 and 1.6 h, time of maximum concentration (TMAX), 3.0 and 2.3 h, and maximum plasma concentration (CMAX), 85 and 58 ng/mL, respectively. Bioavailability was 10.2 and 7.4% at 1 and 5 weeks, respectively. [source] | ||||||||||||||||||||||||||||