bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resuscitation with Lipid versus Epinephrine in a Rat Model of Bupivacaine Overdose
Authors: Weinberg Guy L. , Di Gregorio Guido , Ripper Richard , Kelly Kemba , Massad Malek , Edelman Lucas , Schwartz David , Shah Nirali , Zheng Sophie , Feinstein Douglas L. 
Published: April 2008

Background
Lipid emulsion infusion reverses cardiovascular compromise due to local anesthetic overdose in laboratory and clinical settings. The authors compared resuscitation with lipid, epinephrine, and saline control in a rat model of bupivacaine-induced cardiac toxicity to determine whether lipid provides a benefit over epinephrine.

Methods
Bupivacaine, 20 mg/kg, was infused in rats anesthetized with isoflurane, producing asystole in all subjects. Ventilation with 100% oxygen and chest compressions were begun immediately, along with intravenous treatment with 30% lipid emulsion or saline (5-ml/kg bolus plus continuous infusion at 0.5 ml . kg . min) or epinephrine (30 microg/kg). Chest compressions were continued and boluses were repeated at 2.5 and 5 min until the native rate-pressure product was greater than 20% baseline. Electrocardiogram and arterial pressure were monitored continuously and at 10 min, arterial blood gas, central venous oxygen saturation, and blood lactate were measured. Effect size (Cohen d) was determined for comparisons at 10 min.

Results
Lipid infusion resulted in higher rate-pressure product (P < 0.001, d = 3.84), pH (P < 0.01, d = 3.78), arterial oxygen tension (P < 0.05, d = 2.8), and central venous oxygen saturation (P < 0.001, d = 4.9) at 10 min than did epinephrine. Epinephrine treatment caused higher lactate (P < 0.01, d = 1.48), persistent ventricular ectopy in all subjects, pulmonary edema in four of five rats, hypoxemia, and a mixed metabolic and respiratory acidosis by 10 min.

Conclusions
Hemodynamic and metabolic metrics during resuscitation with lipid surpassed those with epinephrine, which were no better than those seen in the saline control group. Further studies are required to optimize the clinical management of systemic local anesthetic toxicity.
Two GATA Transcription Factors Are Downstream Effectors of Floral Homeotic Gene Action in Arabidopsis
Authors: Mara Chloe D. , Irish Vivian F. 
Published: April 2008

AbstractFloral organogenesis is dependent on the combinatorial action of MADS-box transcription factors, which in turn control the expression of suites of genes required for growth, patterning, and differentiation. In Arabidopsis (Arabidopsis thaliana), the specification of petal and stamen identity depends on the action of two MADS-box gene products, APETALA3 (AP3) and PISTILLATA (PI). In a screen for genes whose expression was altered in response to the induction of AP3 activity, we identified GNC (GATA, nitrate-inducible, carbon-metabolism-involved) as being negatively regulated by AP3 and PI. The GNC gene encodes a member of the Arabidopsis GATA transcription factor family and has been implicated in the regulation of chlorophyll biosynthesis as well as carbon and nitrogen metabolism. In addition, we found that the GNC paralog, GNL (GNC-like), is also negatively regulated by AP3 and PI. Using chromatin immunoprecipitation, we showed that promoter sequences of both GNC and GNL are bound by PI protein, suggesting a direct regulatory interaction. Analyses of single and double gnc and gnl mutants indicated that the two genes share redundant roles in promoting chlorophyll biosynthesis, suggesting that in repressing GNC and GNL, AP3/PI have roles in negatively regulating this biosynthetic pathway in flowers. In addition, coexpression analyses of genes regulated by AP3, PI, GNC, and GNL indicate a complex regulatory interplay between these transcription factors in regulating a variety of light and nutrient responsive genes. Together, these results provide new insights into the transcriptional cascades controlling the specification of floral organ identities.
Clinical relevance of serum levels of matrix metallopeptidase‐2, and tissue inhibitor of metalloproteinase‐1 and ‐2 in patients with malignant melanoma
Authors: YOSHINO Yuichiro , KAGESHITA Toshiro , NAKAJIMA Motowo , FUNAKUBO Minako , IHN Hironobu 
Published: April 2008

ABSTRACTThe interaction and/or balance between matrix metallopeptidase (MMP)‐2 and tissue inhibitor of metalloproteinase (TIMP)‐2 in vivo may play important roles in the process of tumor growth, invasion and metastasis of malignant melanoma. In this study, we investigated the serum levels and immunohistochemical expression of MMP‐2, TIMP‐1 and TIMP‐2 in patients with melanoma and analyzed the correlation with clinicopathological parameters. The level of serum MMP‐2 in patients was significantly higher than that of the control. Moreover, the level of MMP‐2 was significantly higher than that of the control in patients who were: (i) female; (ii) pT1 and pT4; (iii) with and without lymph node (LN) metastasis; (iv) in stage I and stage IV; (v) with and without recurrence; and (v) alive and dead. The level of serum TIMP‐1 in patients with melanoma was significantly higher than that of the control. Among melanoma patients, the level of TIMP‐1 with pT4 was significantly higher for patients who were: (i) pT1 and pT3; (ii) with LN metastasis (vs those without); (iii) in stage IV (vs those in stages I, II and III); and (iv) dead (vs those alive). The level of serum TIMP‐2 in patients with melanoma was not different from the control. However, the level of TIMP‐2 in patients with pT4 was significantly higher than for patients who were: (i) pT1, pT3 and control; (ii) with LN metastasis (vs those without metastasis and control); (iii) with stage IV (vs those in stages I and II and control); (iv) in recurrence (vs control); and (v) dead (vs those alive and control). These results suggest that increased serum levels of TIMP‐1 and TIMP‐2 reflected the extent of metastatic melanoma lesions, and that serum levels of TIMP‐1 may be a new useful marker for melanoma progression.
Childhood and adolescent predictors of heavy drinking and alcohol use disorders in early adulthood: a longitudinal developmental analysis
Authors: Englund Michelle M. , Egeland Byron , Oliva Elizabeth M. , Collins W. Andrew 
Published: April 2008

ABSTRACTAims  To identify childhood and adolescent factors differentiating heavy alcohol users in early adulthood from more moderate users or abstainers.Design  Low‐income participants followed from birth to age 28 years.Participants  A total of 178 adults (95 males) who were first‐born children of low‐income mothers recruited in Minneapolis, Minnesota, during their third trimester of pregnancy.Measurements  Maternal hostility (24/42 months), externalizing and internalizing behavior problems (9 years), peer acceptance and academic achievement (12 years), maternal alcohol use and participants' drinking behavior (16 years), quantity of alcohol use per occasion (19, 23 and 26 years), alcohol use disorders (28 years).Findings  For men: (i) higher amounts of alcohol consumption at age 16 increased the odds of being a heavy drinker compared to an abstainer (age 19) and a moderate drinker (ages 23 and 26); (ii) lower achievement scores at age 12 and having a mother who drank more when the participant was age 16 increased the odds of being a heavy drinker compared to moderate drinker (age 26). Higher levels of externalizing behavior problems at age 9 and drinking more when the participants were age 16 increased the odds that men would have a current alcohol use disorder at age 28. For women: (i) drinking more at age 16 increased the odds of being a heavy drinker compared to being either an abstainer or a moderate drinker (age 26); (ii) having higher levels of achievement at age 12 increased the odds of being a heavy drinker compared to an abstainer at age 23. Adolescent alcohol use mediated the relation between externalizing behavior at age 9 and alcohol use at age 26 for women.Conclusions  Problem drinking may be the result of a long‐term developmental process wherein childhood externalizing behavior problems sets a pathway leading to heavy drinking during and after adolescence.
Cardiovascular effects of intravenous administration of tetracycline in cattle
Authors: GYRD‐HANSEN N. , RASMUSSEN FOLKE , SMITH MOGENS 
Published: April 2008

Tetracycline chloride dissolved in saline was injected intravenously to seven cows. Two doses of tetracycline were used: 5 and 10 mg/kg b.wt, and the injections were given over a period of either 10, 60 or 300 sec.A number of the cows collapsed shortly after the injection was completed, usually when the 10 mg dosage was given in 60 sec. When the same dose was given over a period of 5 min none of the cows collapsed. A more or less pronounced drop in blood pressure could be detected during or shortly after the injection; in those cows which collapsed the blood pressure fell almost to zero. The predominant change in pulse rate in connection with the tetracycline administration was a decrease which could be quite marked, pulse rates falling as low as 10–20 per min. Simultaneously with these changes in blood pressure and pulse rate severe abnormalities in ECG could be observed. Pre‐treatment with a normal therapeutic dose of calcium borogluconate intravenously prevented collapse in the cows and diminished the drop in blood pressure associated with an ensuing tetracycline injection.It is concluded that intravenous injection of tetracycline is hazardous, but that collapse can be avoided by giving the injection very slowly over a period of no less than 5 min.
A pharmacokinetic study of digoxin in the horse
Authors: BRUMBAUGH GORDON W. , THOMAS WILLIAM P. , ENOS L. REED , KANEKO JIRO J. 
Published: April 2008

Digoxin was administered orally and intravenously to seven healthy adult mares and geldings in two separate trials. At a dose of 44 μg digoxin/kg body weight, the oral study was characterized by an absorption phase with a mean (± 1 standard deviation) peak serum digoxin concentration of 2.21 ng/ml (± 0.45) at a mean of 2.29 h (± 1.52) after administration. A second rise in serum digoxin concentration started about 6–8 h after administration and extended to about 20 h after administration. The mean bioavailability (F) was 23.38% (± 5.96).At a dose of 22 μg digoxin/kg body weight, the intravenous study was characterized by a two‐compartment model with the following mean pharmacokinetic measurements: distribution rate constant (α), 1.391 h‐1 (± 0.1909); zero‐time serum digoxin concentration determined from the distribution phase (A), 21.247 ng/ml (± 5.6614); elimination rate constant (β), 0.0409 h‐1 (± 0.0069); zero‐time serum digoxin concentration determined from the elimination phase (B), 3.82 ng/ml (± 0.433); apparent specific volume of distribution uncorrected for protein binding (Vdβ), 5.003 1/kg (± 0.5177). The mean β corresponded to a biological half‐life (t1/2 ±) of 16.9 h.Based upon results of this study, theoretically achievable steady‐state serum digoxin concentrations were calculated for maintenance doses given by oral and intravenous routes of administration with appropriate two‐compartment, multiple‐dose formulae. Loading doses were also calculated for each route. It is the opinion of the authors that the oral route of administration of digoxin is effective in the horse and may preclude the potential risks posed by the high serum digoxin concentrations immediately following intravenous administration.
Population distributions of phenylbutazone and oxyphenbutazone after oral and i.v. dosing in horses
Authors: CHAY S. , WOODS W. E. , NUGENT T. E. , WECKMAN T. , HOUSTON T. , SPRINKLE F. , BLAKE J. W. , TOBIN T. , SOMA L. R. , YOCUM J. , SMITH J. D. 
Published: April 2008

Experiments to determine the residual plasma concentrations of phenylbutazone and its metabolites found in horses racing on a ‘no‐race day medication’ or 24‐h rule were carried out. One dosing schedule (oral‐i.v.) consisted of 8.8 mg/kg (4g/1000 lbs) orally for 3 days, followed by 4.4 mg/kg (2g/1000 lbs) intravenously on day 4. A second schedule consisted of 4.4 mg/kg i.v. for 4 days. The experiments were carried out in Thoroughbred and Standardbred horses at pasture, half‐bred horses at pasture, and in Thoroughbred horses in training.After administering the i.v. schedule for 4 days to Thoroughbred and Standard‐bred horses at pasture, the mean plasma concentrations of phenylbutazone increased from 0.77 μg/ml on day 2 to 2.5 μg/ml on day 5. The shape of the frequency distribution of these populations was log‐normal. These data are consistent with one horse in 1,000 yielding a plasma level of 8.07 μg/ml on day 5.After administration of the oral‐i.v. schedule to Thoroughbred and Standard‐bred horses at pasture, the mean plasma concentrations of phenylbutazone were 3.4 μg/ml on day 2 and 3.5μg/ml on day 5. The range on day 5 was from 1.4 to 8.98 μg/ml and the frequency distribution was log‐normal. These data are consistent with one horse in 1000 having a plasma level of 15.8 μg/ml on day 5.In a final experiment, the oral dosing schedule was administered to 62 Thoroughbred horses in training. Plasma concentrations on day 5 in these horses averaged 5.3 μg/ml. The range was from 1.3 to 13.6 μg/ml and the frequency distribution was log‐normal. Statistical projection of these values suggests that following this oral dosing schedule in racing horses about one horse in 1000 will yield a plasma level of 23.5 μg/ml of phenylbutazone 24h after the last dose.
Effect of probenecid on the pharmacokinetics of cefotaxime in sheep
Authors: GUERRINI V. H. , FILIPPIGH L. J. , ENGLISH P. B. , CAO G. R. , BOURNE D. W. A. 
Published: April 2008

Guerrini, V.H., Filippich, L.J., English, P.B., Cao, G.R. &: Bourne, D.W.A. Effect of probenecid on the pharmacokinetics of cefotaxime in sheep. J. vet. Pharmacol. Therap. 8, 38–46.The effect of probenecid given by intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) injection on the pharmacokinetics of cefotaxime was studied in six Merino ewes. When given intravenously, probenecid increased significantly (P < 0.05) the plasma half‐life of cefotaxime three‐fold (to 0.94 ± 0.32 h) and the area under the curve (AUG) approximately two‐fold (to 41.1 ± 16.8 μg.h/ml), and decreased plasma cefotaxime clearance (ClB) 45% (to 0.648 ± 0.191 1/h/kg). When given with probenecid intravenously, renal clearance (ClR), volume of the central compartment (VC), volume of distribution steady slate (Vd(ss)). and the amount excreted in urine unchanged did not alter significantly.When given by i.m. injection, probenecid and cefotaxime were well tolerated and cefotaxime was well absorbed (101 ± 45%). When given by s.c. injection, only 40 ± 25% cefotaxime was absorbed. When given intramuscularly or subcutaneously, probenecid appeared to reduce the ClB and ClR of cefotaxime, probably because plasma probenecid concentrations are prolonged. Probenecid did not appear to affect the distribution of cefotaxime. Dr D.W.A. Bourne, Department of Pharmacy, University of Queensland, St Lucia, QLD 4067, Australia.
Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison
Authors: SCHWARTZ‐PORSCHE DOROTHEA , LÖSCHER W. , FREY H.‐H. 
Published: April 2008

Schwartz‐Porsche, D., Löscher, W. & Frey, H.‐H. Therapeutic efficacy of phenobarbital and primidone in canine epilepsy: a comparison. J. vet. Pliannacol. Therap. 8, 113–119.The efficacy of phenobarbital and primidone against canine epilepsy was compared in a controlled study. Thirty‐five dogs showing generalized tonic‐clonic seizures (grand mal), treated for a minimum of 6 months, were included in the study; fifteen of these were treated with phenobarbital, the other twenty with primidone. Both drugs were dosed according to the clinical requirement; the daily doses ranged from 5‐17mg/kg phenobarbital and from 17‐70mg/kg primidone. The plasma concentrations of phenobarbital, or of primidone and its metabolites phenobarbital and phenylethylmalondiamide (PEMA), were routinely monitored. Complete control of tonic‐clonic seizures for 6 months, at least, was attained in six out of fifteen dogs of the phenobarbital group, and in five out of twenty dogs in the primidone group. A further six dogs on phenobarbital, and seven dogs on primidone, were classified as ‘improved’, i.e. the rate of seizures was reduced by at least 50%. The rest of the dogs were not improved by the treatment. The difference between the efficacy of phenobarbital and primidone was not significant, but primidone gave rise to signs of liver toxicity in fourteen out of twenty dogs, as indicated by considerable elevations of liver enzyme values (alanine transferase, glutamate dehydrogenase, alkaline phosphatase). Phenobarbital is, therefore, regarded as the drug of first choice for the treatment of canine epilepsy. Dr H.‐H. Frey, Laboratory of Pharmacology and Toxicology, School of Veterinary Medicine, Free University of Berlin, Koserstrafie 20, D‐1000 Berlin‐West 33, Germany.
Cefadroxil in the horse: pharmacokinetics and in vitro antibacterial activity
Authors: WILSON W. DAVID , BAGGOT J. DESMOND , ADAMSON PETER J. W. , HIRSH DWIGHT C. , HIETALA SHARON K. 
Published: April 2008

Wilson, W.D., Baggot, J.D., Adamson, P.J.W., Hirsh, D.C. & Hietala, S.K. Cefadroxil in the horse: pharmacokinetics and in vitro antibacterial activity. J. vet. Pharmacol. Therap. 8, 246–253.Sodium cefadroxil was administered as a single intravenous dose (25 mg/kg) to six healthy adult mares. Plasma samples were collected over a 24‐h period and cefadroxil concentrations were measured by microbiological assay. The pharmacokinetic behavior of the drug was appropriately described in terms of a one‐compartment open model. Values for the major pharmacokinetic terms were: extrapolated initial plasma concentration = 59.2 ± 15.0 μg/ml; half‐life = 46 ± 20 min; apparent volume of distribution = 462 ± 191 ml/kg; and body clearance = 7.0 ± 0.6 ml/min.kg. In a subsequent study, a suspension of cefadroxil monohydrate was administered intragastrically (25 mg/kg) to the same six horses. Plasma concentrations of the drug peaked at 1–2 h but, in general, absorption was both poor and inconsistent. The data were unsuitable for determination of cefadroxil bioavailability from this oral dosage form.Ninety‐nine isolates of eleven bacterial species obtained from clinically ill horses were tested for susceptibility to cefadroxil. All strains of Streptococcus equi, Streptococcus zooepidemicus, coagulase‐positive staphylococci, Corynebciclerium pseudotuberculosis and five out of six strains of Actinobacillus suis were highly susceptible to the drug (MIC<4 μg/ml). Escherichia coli, Klebsiella pneumoniae and Salmonella sp. showed intermediate susceptibility (MIC 4–16 μg/ml), while all isolates of Corynebacteriuin (Rhodococcus) equi, Enterobacter cloacae and Pseudomonas aeruginosa proved to be highly resistant to cefadroxil (MIC > 128 μg/ml). Dr W. Dcvid Wilson, Department of Medicine, School of Veterinary Medicine, Universily of California, Davis, CA 95616, U.S.A.
Some dynamic and toxic effects of theophylline in horses
Authors: ERRECALDE J. O. , BUTTON C. , MÜLDERS M. S. G. 
Published: April 2008

Errecalde, J.O., Button, C. & Mülders, M.S.G, Some dynamic and toxic effects of theophylline in horses. J. vet. Plmrmacol. Therap. 8, 320–327.A single intravenous administration of theophylline as aminophylline at 10 mg/kg to four mares induced a diuresis in which maximal urine production was more than seven times the control volume. The diuretic effect was maximal within the first hour post‐administration, and lasted approximately 6 h. Theophylline resulted in dose‐related tachycardia, polypnoea and nervous symptoms (tactile, visual and auditory hypersensitivity, muscle tremor, sweating) in normal mares, but had only minor effects on arterial and central venous blood pressures, intrapleural pressure, red blood cell variables and plasma proteins. The upper limit of safe plasma theophylline concentration in horses is approximately 15 μg/ml. Whenever feasible, the oral or intragastric route of administration should be used as it is safer than the intravenous route. Dr C. Button, Regional Veterinary Laboratory, PO Box 388, Benalla, Victoria 3672, Australia.
Pharmacokinetics and bioavailability of chloramphenicol in normal and febrile goats*
Authors: KUME BABALE B. , GARG RAMESH C. 
Published: April 2008

The effect of induced fever on the plasma concentrations and disposition kinetics of chloramphenicol (CHPC) was studied in adult goats. Fever was induced and maintained for 12 h by injecting Escherichia colt endotoxin (0.1 μ/kg, i.v.) and repeating it at half the dose (0.05 μ/kg) 8 h later. Pharmacokinetics of CHPC was studied in both normal (n= 6) and febrile (n = 6) animals following intravenous administration of CHPC Na‐succinate (25 mg/kg). Intramuscular bioavailability of the drug was also investigated in both normal and febrile animals.Pharmacokinetics of CHPC following intravenous administration could be described by a two‐compartment open model in both normal and febrile animals. In normal animals the half‐life of CHPC was 73.0 ± 4.95 min and the volume of distribution was 2.217 ± 0.24 1/kg. These and other pharmacokinetic parameters did not differ significantly (P < 0.05) between normal and febrile animals, except for Cop and A. Absorption of CHPC following intramuscular administration was good as indicated by its high bioavailability in both normal (83.34%) and febrile (81.98%) animals.Volume of distribution is usually expected to change when the febrile state is induced. Lack of such an effect in the present study could be due to high individual variation, or to the fact that CHPC already has a relatively large volume of distribution, which is less likely to be altered by a febrile state of short duration.
An evaluation of apramycin soluble powder for the treatment of naturally acquired Escherichia coli infections in broilers
Authors: CRACKNELL V. C. , ANDREOTIS J. , FACIBENI G. , OWAIS E. , PRADELLA G. 
Published: April 2008

During 1983, a series of trials was carried out in Greece, Italy and Jordan, to test the efficacy of the aminocyclitol antibiotic apramycin as a treatment for naturally acquired Escherichia coli infections in broilers. The trials involved a total of 40,389 broilers, 27–39 days of age, in twelve houses at eight different production sites. Three levels of apramycin medication were evaluated: 125, 250 and 500 mg activity/litre drinking water, administered for five consecutive days. Treatment was only initiated after disease had been confirmed by laboratory examination of dead birds. Not all treatments were evaluated in every house. However, each house contained a group of unmedicated birds as controls, while the remaining birds were allocated to one or more apramycin treatment groups.There was a reduction in mortality and an improvement in the final weight and the economic feed conversion ratio in all three treatment groups. The data presented provide support for the use of apramycin sulphate administered in the drinking water for the treatment of E. coli infections in broilers.
Pharmacokinetics of florfenicol in veal calves
Authors: VARMA K.J. , ADAMS P. E. , POWERS T. E. , POWERS J. D. , LAMENDOLA J. F. 
Published: April 2008

Varma, K.J., Adams, P.E., Powers, T.E., Powers, J.D. & Lamendola, J.F. Pharmacokinetics of florfenicol in veal calves. J. vet. Pharmacol. Therap. 9, 412–425.The pharmacokinetic disposition of florfenicol was described in veal calves after administration of a single 22‐mg/kg dose intravenously, orally after a 12‐h fast and orally 5 min post feeding. Both serum concentrations and urinary excretion were studied. After intravenous administration the median elimination half‐life was 171.9 min while the half‐life of the distribution phase was 5.9 min. The median body clearance (Cl) and apparent volume of distribution (Vz) were 2.85 ml/kg/min and 0.78 1/kg, respectively. Following oral administration the median bio‐availability (f) was 0.88 for calves dosed after a 12‐h fast and 0.65 for calves dosed 5 min post feeding. Calves given the oral doses had a complex absorption pattern with delayed absorption. Slightly more than 50% of the administered dose both orally and intravenously was recovered as unchanged florfenicol in the urine by 30 h.