Additional studies on the therapeutic efficacy of sulphadimidine sodium in experimental Escherichia coli infection of broilers

In contrast with the recommended dose of 2,000 ppm sulphadimidine sodium in the drinking water for treatment of broilers against colibacillosis, it appeared that under experimental conditions, treatment at 500 ppm (60 mg/kg body weight) gave the best therapeutic effects. At higher concentrations, drinking water consumption and body weight gain were reduced significantly. During treatment high blood plasma-concentrations were measured.     

Comparative toxicology of monensin sodium in laboratory animals

The toxicology of monensin has been studied in several laboratory animal species. There was considerable species variation in acute oral LD50 values. The consistent signs of acute toxicity were: anorexia, hypoactivity, skeletal muscle weakness, ataxia, diarrhea, decreased weight gain and delayed deaths. The 3-mo study in rats fed diets containing 0, 50, 150 or 500 ppm monensin resulted in no effects at the lowest dose level, slight reduction of body weight gain in the middle-dose group and severe depression in body weight gain, skeletal and cardiac lesions, and deaths in the highest dose group. The 3-mo study in dogs given daily oral doses of 0, 5, 15 or 50 mg/kg monensin resulted in no effects at the lowest dose level. Dogs in the 15 and 50 mg/kg groups developed, during test wk 1 to 4, anorexia, weakness, ataxia, labored respiration, body weight loss, increased serum muscle enzyme values, severe skeletal muscle degeneration and necrosis with less severe heart lesions and deaths. Mice fed diets containing 0, 37.5, 75, 150 or 300 ppm monensin for 3 mo had reduced body weight gain in all test groups but no other physical signs. Serum creatine phosphokinase (CPK) values were increased in mice in the two highest dose groups and minimal heart lesions were found in the highest dose group. Dogs given daily oral doses of 0, 1.25, 2.5, 5 or 7.5 mg/kg monensin for 1 yr survived with no evidence of toxicity in the two lowest dose groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Additional studies on the therapeutic efficacy of sulphadimidine sodium in experimental Eschericha coli infection of broilers

Summary

In contrast with the recommended dose of 2,000 drinking ppm sulphadimidine sodium in the water for treatment of broilers against colibacillosis,it appeared that under experimental conditions, treatment at 500 ppm (60 mg/kg body weight) gave the best therapeutic effects. At higher concentrations, drinking water consumption and body weight gain were reduced significantly. During treatment high blood plasma‐concentrations were measured.     

Elimination of sulfamethazine from edible tissues, blood, urine, and feces of turkey poults.

Sulfamethazine was administered to 8- to 10-week-old turkey poults intravenously (IV) at the dose level of 71.5 mg/kg of body weight, orally at the dose level of 143 mg/kg of body weight, or in the drinking water at the concentration of 0.1% over a 6-day period. The concentrations of free sulfamethazine in blood, muscle, skin, kidney, and liver were determined and semilogarithmic plots of concentration vs time for the various tissues indicated that the curve had a linear portion within the first 72-hour period of drug withdrawal. The rates of disappearance of sulfamethazine from the various tissues were proportional to the concentration in the tissues. After 72 hours of withdrawal and for as long as 14 days, sulfamethazine concentrations in kidney, liver, and skin of turkeys given the drug in the drinking water fluctuated between 0.1 and 0.4 ppm. Only 8.6% of the oral dose (143 mg/kg) and 16.5 to 17% of the IV dose (71.5 mg/kg) were recovered in urine and feces as the parent compound during the initial 72-hour period.     

A comparison of the sedative effects of three α2-adrenoceptor agonists (romifidine, detomidine and xylazine) in the horse

The sedative effects of a new alpha 2-adrenoceptor agonist, romifidine, were compared with those of xylazine and detomidine. Five horses were treated with two doses of romifidine (40 micrograms/kg body weight and 80 micrograms/kg body weight), two doses of detomidine (10 micrograms/kg body weight and 20 micrograms/kg body weight) and one dose of xylazine (1 mg/kg body weight) given by intravenous injection using a Latin-square design. The dose of 80 micrograms/kg romifidine appeared equipotent to 1 mg/kg xylazine and 20 micrograms/kg detomidine, although at these doses both xylazine and detomidine had a shorter action. Detomidine 20 micrograms/kg and xylazine both produced greater lowering of the head and a greater degree of ataxia than romifidine at either dose. Romifidine produced sedation similar to that of the other drug regimes. The effect upon imposed stimuli was similar.     

Comparative toxicity of coniine, an alkaloid of Conium maculatum (poison hemlock), in chickens, quails, and turkeys

Coniine, an alkaloid of Conium maculatum (poison hemlock), was administered by gavage to immature chickens, quails, and turkeys at 0, 25, 50, and 100 mg/kg body weight. At 25 mg coniine/kg body weight, clinical signs were observed only in quails (2/10) and consisted of excitement, depression, hypermetria, seizures, opisthotonos, and flaccid paralysis. Chickens (9/10) and quails (8/10) dosed at 50 mg/kg body weight were affected, and several birds of each species died (2/10 and 5/10, respectively). Turkeys (7/10) were affected only when dosed at 100 mg/kg body weight, and quails (6/10), turkeys (4/10), and chickens (10/10) died at this dose. There were no gross or microscopic lesions. Coniine was detected in skeletal muscle and liver of birds dying after ingestion and was present in some survivors 7 days post-treatment.     

Plasma salicylate concentrations in immature dogs following aspirin administration: comparison with adult dogs

Aspirin disposition in immature and adult dogs, assessed by plasma salicylate concentrations following single doses of aspirin given orally (p.o.) and intravenously (i.v.), was compared. Using a cross-over design, four immature (12–16-weeks-old) and eight adult (1– 2-years-old) dogs were given a single dose of aspirin at 17.5 mg/kg body weight i.v. and a single dose of buffered aspirin at 35 mg/kg body weight p.o. Blood was collected from the jugular vein for 24 h following each dose. A fluorescence polarization immunoassay was used for determination of salicylate in plasma. Significant differences in aspirin disposition were identified between the two groups. Immature dogs had significantly shorter salicylate half-life, lower mean residence time, and more rapid salicylate clearance than adult dogs. The difference in volume of distribution between the two groups was not significantly different. Immature dogs had lower mean (± SD) peak plasma salicylate concentrations (64.5 ± 2.38 mg/L) than adult dogs (95.9 ± 12.2 mg/L) following a single oral dose of buffered aspirin at 35 mg/kg body weight. Predicted plasma salicylate concentration-time curves were constructed for various aspirin dosage regimens. This analysis showed that the previously recommended buffered aspirin dose for adult dogs of 25 mg/kg body weight p.o. every 8 h would be ineffective in maintaining plasma salicylate concentrations > 50 mg/L in immature dogs.     

Anthelmintic efficacy of extracts of Spigelia anthelmia Linn on experimental Nippostrongylus braziliensis in rats

Spigelia anthelmia Linn is used as a herb and is a common annual weed of cultivation in open re-growths, on unused land in towns as well as on road sides. The plant can grow to approximately 30 cm in height. The aim of this study was to screen extracts of Spigelia anthelmia for their anthelmintic activity against an experimental Nippostrongylus braziliensis infection in rats. Acute oral toxicity occurred at a dose of 1,140mg/kg, while anthelmintic trials against Nippostrongylus braziliensis in rats using the aqueous fraction showed a progressive decrease in worm count with increasing dose (10, 13, 16, 20 and 25 mg per kg body weight) (p < 0.05). At 25 mg per kg body weight, the worm count was significantly lower than that at 10mg per kg body weight (p < 0.05).     

Biologic activity of dirlotapide, a novel microsomal triglyceride transfer protein inhibitor, for weight loss in obese dogs

Dirlotapide is a novel microsomal triglyceride transfer protein inhibitor intended for the treatment and management of obesity in dogs. The biologic effects of dirlotapide, weight loss, decreased food intake, increased fecal fat, decreased serum cholesterol, and body composition, were evaluated in a controlled, blinded study. Sixteen obese beagles were randomized to treatment with placebo ( n  = 4) or dirlotapide ( n  = 12) following a 2-week acclimation period in which baseline data were collected. The dirlotapide dose, adjusted to produce weight loss for 3 months and then stabilize body weight for 1 month (weight management), produced a significant difference (expressed as a percentage of baselines) in weekly weight loss, food intake, fecal fat, serum cholesterol concentration, and body composition (measured by dual energy X-ray absorptiometry) compared with placebo treatment ( P  < 0.05). The initial dirlotapide dosage of 0.5 mg/kg (10 times the initial label dose) resulted in a high rate of weight loss (3.3% weekly) and anorexia, emesis, and loose stools for some dogs. A 25% dose reduction (mean dosage: 0.36 mg/kg) followed by biweekly 25% dose adjustments based on individual weight loss, produced 1–2% weekly weight loss and total weight loss of 18.8% in 12 weeks at a final mean dosage of 0.41 mg/kg (range: 0.15–0.60); a dosage range of 0.10–0.34 mg/kg stabilized body weight. Body weight changes for placebo-treated dogs were −0.8% to +0.9% weekly; total weight gain during the weight loss phase was 10.6%. No apparent change in food intake, percentage of fecal fat, and serum cholesterol was observed in the placebo group. Food intake and body weight increased when dirlotapide was discontinued. Dirlotapide produced weight loss by both reducing appetite (about 90% of the weight loss activity) and by increasing fecal fat excretion (about 10% of the weight loss activity).     

The use of sarmazenil in the treatment of a moxidectin intoxication in a foal

A13-day-old Arabian Thoroughbred filly weighing 40 kg (88 1b) was presented to the University of Zurich Equine Clinic with a history of depression after deworming with moxidectin at a dose of 2 mg/kg (recommended dose 0.4 mg/kg body weight)^a the day before admission. The foal was found recumbent 12 hours after drug administration and was in an unconscious state 6 hours later     

Effect of ibuprofen on coccidiosis in broiler chickens

Ibuprofen (IBU)-a nonsteroidal anti-inflammatory drug-inhibits the biosynthesis of prostaglandins with pro-inflammatory and immunosuppressive properties and is therefore proposed as a candidate molecule for the treatment of coccidiosis in broiler chickens. In all experiments, IBU was administered via drinking water. In a first experiment, chickens were infected at 10 or 21 days of age with oocysts of Eimeria acervulina (5 X 10(4)), Eimeria maxima (3 X 10(4)), and Eimeria tenella (7.5 X 10(3)) and medicated with IBU at a dose of 15 mg/kg body weight (BW). In a second experiment, chickens were infected at 6 days of age with 10(4) oocysts of E. acervulina and medicated with IBU at a dose of 100 mg/kg BW. In the third experiment, an inoculum consisting of 5 x 10(4) or 10(5) E. acervulina oocysts was administered at 6 days of age to chickens medicated with IBU at a dose of 100 mg/kg BW. In a fourth experiment, the effect of IBU on sporulation and infectivity of E. acervulina oocysts was studied. Coccidial lesion scores (CLSs), oocyst shedding, and weight gain were used as evaluation parameters in all experiments except the fourth, where weight gain was not taken into account. In addition, the sporulation percentage was determined in the last experiment. No influence of IBU on the indicated parameters was observed after providing the drug at a dose of 15 mg/kg BW, whereas CLSs and oocyst shedding were reduced when IBU was provided at a dose of 100 mg/kg BW. However, IBU did not significantly show any effect on the degree of sporulation and infectivity of E. acervulina oocysts at a dose of 100 mg/kg BW.     

Lasalocid toxicity in cattle: acute clinicopathological changes

Thirty-six steers (148 to 500 kg) divided into six equal groups were used in a toxic syndrome study of lasalocid and monensin given as a single oral dose. One group was given a placebo, a second group received monensin (25 mg/kg body weight) and the other four groups received lasalocid at 1, 10, 50 or 100 mg/kg body weight (bw). No toxic signs developed in cattle given placebo or lasalocid at 1 or 10 mg/kg bw dose. The earliest toxic signs were muscle tremors, tachycardia and rumen atony. After 24 h, the cattle were dehydrated, anorectic and had diarrhea. Deaths occurred between d 1 and 22.5 in the groups receiving lasalocid at 50 and 100 mg/kg bw and monensin. Altered values in blood leucocytes, erythrocytes, hemoglobin, hematocrit, total protein, albumin, creatinine, urea nitrogen, total bilirubin, creatine kinase, lactic dehydrogenase, calcium, chloride and inorganic phosphate occurred 1 d after dosing: urine pH and specific gravity also changed 1 d after dosing. Maximum changes occurred at d 3. Most of the changes were indicative of dehydration rather than specific organ damage.     

Efficacy of ceftiofur hydrochloride for treatment of experimentally induced colibacillosis in neonatal swine

Ceftiofur hydrochloride was tested for effectiveness against induced colibacillosis in neonatal swine. In this model, pigs less than 12 hours old were inoculated via stomach tube with a virulent, K99+, nalidixic acid-resistant strain of Escherichia coli. Six hours after challenge exposure, 1 dose of ceftiofur was administered either IM or orally in experiment 1 and orally only in experiment 2. Mortality, shedding of bacteria, fecal consistency scores, and body weight changes were monitored for 10 days. In experiment 1 (n = 383 pigs), all treatments at dosage that ranged between 0.5 and 64.0 mg of ceftiofur/kg of body weight significantly (P less than 0.001) reduced mortality, bacterial shedding, and diarrhea and increased weight gain, compared with findings in untreated controls. There were no detectable differences between oral and IM routes, except that there was greater reduction in bacteria shedding associated with the oral route of administration. In experiment 2 (n = 505 pigs), ceftiofur was administered orally either once at 6 hours after challenge exposure or twice at 6 and at 48 hours after the first dose. Dosage of ceftiofur was 0, 5, 10, 20, 30, or 60 mg/kg administered once, or half the same dose was administered at each of 2 times. At the optimal dosage (10 mg/kg), a single dose was as effective as 2 doses. The single administration at all dosages reduced mortality, bacterial shedding, and diarrhea scores and increased body weight gain, compared with findings in untreated pigs (P less than 0.01). In this induced infection model, the optimal treatment dosage was determined to be 10 mg/kg administered once.     

Oral absorption and bioavailability of fenbendazole in the dog and the effect of concurrent ingestion of food

Fenbendazole was administered orally without food to six beagle dogs at 2.5, 5.0, 10, 20, 40 and 80 mg/kg of body weight. Increasing the dose rate did not significantly increase the amount of fenbendazole absorbed. In a separate study fenbendazole was administered to the same six beagle dogs at a dose rate of 20 mg/kg of bodyweight in food with high, medium and low fat content. The food provided 1.52, 0.70 or 0.34 g of fat per kg of body weight. Administration of fenbendazole in food with different fat contents did not affect its relative bioavailability. Administration of fenbendazole at a dose rate of 20 mg/kg in food, irrespective of fat content, did however significantly increase its bioavailability when compared to administration of the same dose as a bolus on an empty stomach.     

复合多糖对小鼠免疫功能及抗应激能力的影响

本试验选用昆明种小鼠160只,分为4组,每组40只,对照组灌胃1 mL生理盐水,各试验组将酵母多糖、虫草菌丝体多糖、灵芝菌丝体多糖、黄芪多糖等量复配溶液,分别按高、中、低三个剂量进行灌胃(140、70 mg/kg体重和35 mg/kg体重)。试验期为30 d。研究不同剂量复合多糖对小鼠增重率、免疫器官指数、吞噬百分率、吞噬指数、IgG和抗应激能力的影响。结果表明,高、中、低剂量复合多糖均能明显提高小鼠的免疫能力和抗应激能力,并且随着添加量的增加和添加时间的延长作用效果越明显。     

The disposition of theophylline in camels after intravenous administration

The pharmacokinetics of theophylline were determined after an intravenous (i.v.) dose of 2.36 mg/kg in six camels and 4.72 mg/kg body weight in three camels. The data obtained (median and range) for the low and high dose, respectively, were as follows: the distribution half-lives (t1/2 alpha) were 1.37 (0.64-3.25) and 2.66 (0.83-3.5) h, the elimination half-lives (t1/2 beta) were 11.8 (8.25-14.9) and 10.4 (10.0-13.5) h, the steady state volumes of distribution (Vss) were 0.88 (0.62-1.54) and 0.76 (0.63-0.76) L/kg, volumes of the central compartment (Vc) were 0.41 (0.35-0.63) and 0.51 (0.36-0.52) L/kg, total body clearances (Clt) were 62.3 (39.4-97.0) and 50.2 (47.7-67.4) mL/h.kg body weight and renal clearance (Vr) for the low dose was 0.6 (0.42-0.96) mL/h.kg body weight. There was no significant difference in the pharmacokinetic parameters between the two doses. Theophylline protein binding at a concentration of 5 micrograms/mL was 32.2 +/- 3.3%. Caffeine was identified as a theophylline metabolite but its concentration in serum and urine was small. Based on the pharmacokinetic values obtained in this study, a dosage of 7.5 mg/kg body weight administered by i.v. injection at 12 h intervals can be recommended. This dosing regimen should achieve an average steady state serum concentration of 10 micrograms/mL with peak serum concentration not exceeding 15 micrograms/mL.     

Metronidazole neurotoxicosis in two cats

Two cats were presented for neurological dysfunction from suspected metronidazole toxicity. One cat was receiving 111 mg/kg body weight per day of metronidazole for 9 weeks. After 9 weeks, the dose was increased to 222 mg/kg body weight per day, and 2 days later the cat began to experience progressive neurological signs that culminated in generalized seizures. The second cat was receiving metronidazole at a total dose of 58 mg/kg body weight per day for 6 months. This cat experienced acute onset of ataxia and alteration in mentation. Laboratory evaluations in both cases were without significant findings. The neurological signs in both cats resolved within days of initiating supportive therapy and withdrawal of the drug. This report describes the two cases and discusses the etiology of metronidazole neurotoxicosis.     

Bovine corpus luteum regression and estrous response following treatment with alfaprostol

Two trials evaluated bovine corpus luteum (CL) regression and estrous response following treatment with alfaprostol (AP), a prostaglandin F2 alpha analogue. Expression of at least one estrous cycle (16 to 26 d) and a palpable mid-cycle CL were required prior to random assignment of females to receive 0, .38, .75, 1.50 or 2.25 mg AP/100 kg body weight. Alfaprostol was evaluated in Brahman cows and heifers that were treated on d 11 to 13 (trial 1) and in Simmental X Brahman-Hereford (crossbred) heifers that were treated on d 8 to 10 or d 11 to 13 of the estrous cycle (trial 2). In trial 1, Brahman heifers appeared to require a higher AP dose (greater than .38 mg/100 kg body weight) to elicit luteolysis and expression of estrus than Brahman cows. Alfaprostol treatment (greater than or equal to .75 mg/100 kg body weight) induced (P less than .0001) luteolysis followed by estrus in Brahman cows and heifers. In trial 2, crossbred heifers that received AP on d 8 to 10 appeared to require a higher dose of AP (greater than .38 mg/100 kg body weight) to elicit luteolysis and estrus than heifers that received AP on d 11 to 13 of the estrous cycle. Alfaprostol treatment greater than or equal to .75 mg/100 kg body weight on d 8 to 10 and d 11 to 13 of the estrous cycle induced (P less than .0001) luteolysis followed by estrus in crossbred heifers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Probenecid infusion in mares: effect on para-aminohippuric acid clearance

Para-aminohippuric acid (PAHA, 0.1 mg/min/kg of body weight) was infused IV into 2 mares, followed by concurrent IV infusion of PAHA and probenecid (0.075, 0.15, 0.25, or 0.35 mg of probenecid/min/kg). Probenecid infusion reduced the clearance of PAHA at serum probenecid concentrations greater than 55 micrograms/ml. At 12-hour intervals, probenecid (in 5 repeated doses - 50, 75, 100, or 200 mg/kg) was administered by gavage to 2 mares. Mean serum probenecid concentration was greater than 55 micrograms/ml for all dosages. At dosages less than 200 mg/kg, accumulation of probenecid in the serum was minimal from the 1st to the 5th dose. At a dosage of 200 mg/kg, probenecid accumulated in the serum from the 1st to the 5th dose. Intragastric administration of 5 doses of probenecid (75 mg/kg) at 12-hour intervals to 6 mares reduced the clearance of PAHA by 50%. Bioavailability of probenecid was 117 and 102% for 2 mares after a single intragastric dose, compared with a single IV dose.     

Clearance of indocyanine green in dogs with partial hepatectomy, hepatic duct ligation, and passive hepatic congestion

Clearance of 5 submaximal doses of indocyanine green (ICG) was measured in 5 dogs to determine the maximal removal rate (0.188 mg/kg of body weight/min) and Michaelis constant (Km, 1.25 mg/kg). From these results, 5 mg of ICG/kg of body weight was chosen on the basis of the recommendation that the dose should be at least 4 X Km to achieve sensitivity as a measure of hepatic function and independence from hepatic blood flow. Clearances of low (0.5 mg/kg) and high (5 mg/kg) doses of ICG were measured in 35 healthy dogs to determine reference values. Fractional disappearance was 15.1 +/- 10%/min for the low dose and 3.9 +/- 1%/min for the high dose; plasma half-life was 6.3 +/- 3.6 minutes and 19 +/- 4.8 minutes, respectively. The sensitivity of 2 doses of ICG was evaluated in dogs with 20% and 40% hepatectomy, nonhyperbilirubinemic obstructive cholestasis, or hepatic congestion; sham-operated dogs served as controls. Fractional disappearance and plasma half-life of ICG in the 40% hepatectomy and hepatic congestion groups were significantly different (P less than 0.05) from those in controls using both ICG doses, indicating that both doses were affected by hepatic perfusion, as well as hepatic mass. The fractional disappearance of the dye in the cholestasis group also differed significantly (P less than 0.05) from that of the controls at the high dose. Plasma clearance of both doses by dogs with 20% hepatectomy was not significantly different from that of controls.