Some pharmacokinetic observations of carbadox medication in pigs

Concentrations of carbadox and a first metabolite, desoxycarbadox, were measured in contents of the porcine gastrointestinal tract after in-feed administration of carbadox in therapeutic dosages (100-150 ppm). The levels of carbadox in the relevant parts of the gastrointestinal tract were found to be lower than the MIC-values reported for enteropathogenic microorganisms at their sites of action. The presented observations do not provide a pharmacological rationale for the therapeutic use of carbadox in the treatment of dysentery and diarrhoea in swine. The carbadox levels encountered in the proximal part of the gut (stomach, duodenum) however, seem to indicate that in-feed administration of 50 ppm carbadox can provide an effective prophylaxis against Treponema hyodysenteriae, a causative agent in swine dysentery. The timecourse of the blood levels of carbadox and desoxycarbadox after in-feed administration of carbadox (50 ppm) and the concentration profiles in the gastrointestinal tract are discussed with regard to the disposition of this drug in pigs.     

Accidental carbadox overdosage in pigs in an Irish weaner-producing herd

A weaner ration containing carbadox at concentrations of 331 to 363 mg/kg was accidentally fed to suckling and weaned pigs in an 84 sow herd. Discarded ration was fed to 36 sows. One hundred and sixty five weaner pigs died in a 10 week period with clinical signs including refusal to eat, ill thrift, the passing of hard pelleted faeces, posterior paresis and death in seven to nine days. The surviving weaners did not thrive and some males showed poor testicular development. Sows and suckling pigs that consumed the ration also failed to thrive as did the progeny of affected sows. The main pathological finding was obliteration of the zona glomerulosa of the adrenal cortex. Increased potassium and decreased sodium concentrations in serum were the most notable and consistent biochemical findings.     

Health and performance of commingled feeder pigs as affected by lincomycin and carbadox

Purchased feeder pigs from 12 farms were commingled and divided into three treatment groups of carbadox, lincomycin and controls. Health and performance evaluations included serology, bacterial isolations, fecal examinations and post-mortem examinations at slaughter, weight gain, and feed efficiency.Serological tests for influenza, Aujeszky's disease and Mycoplasma hyopneumoniae were negative throughout the study. Bordetella bronchiseptica was isolated from 14% of the pigs on arrival and from 42% of the pigs 30 days after commingling. No Salmonella spp. were isolated from fecal swabs on arrival; Salmonella typhimurium was isolated from 2.5% of the pigs on Day 30, but no Salmonella was isolated on Day 90. Fecal examination on arrival revealed that 12.5% were infected with gastrointestinal parasites (5.0% Trichuris suis, 5.0% Ascaris suum and 2.5% Strongyloides ransomi).During the 30-day treatment period immediately following purchase and commingling, carbadox and lincomycin improved growth rate by 7.6% and 10.2%, respectively. The treatments also improved feed efficiency, by 9.9% and 5.7%, respectively, and uniformity of growth. Growth rate and feed efficiency were not affected by treatment from Days 30 to 90 following removal of the feed additives from the diet.Growth rate varied greatly, depending on the farm of origin. Although the reasons for the differences in performance were not well established, results suggested that transmission of B. bronchiseptica between pigs resulted in decreased growth rate following infection. Carbadox was significantly more effective than lincomycin in preventing transmission of B. bronchiseptica between commingled pigs.Post-mortem examination at slaughter revealed turbinate atrophy in 5.8% of the noses and pneumonia in 18% of the lungs. One liver exhibited evidence of ascarid larval migration. Treatments produced no significant effect (P>0.05) on post-mortem examination results.     

Plasma aldosterone concentrations and plasma renin activity in healthy dogs and dogs with hyperadrenocorticism

The mean (se) basal plasma aldosterone concentrations were significantly lower in 31 dogs with pituitary-dependent hyperadrenocorticism (PDH) (75 [9] pmol/litre) than in 12 healthy dogs (118 [14] pmol/litre), whereas in five dogs with hyperadrenocorticism due to an adrenocortical tumour they were significantly higher (205 [109] pmol/litre). The mean basal renin activity was not significantly different between the dogs with PDH (303 [48] fmol/litre/second), the dogs with an adrenocortical tumour (141 [63] fmol/litre/second), and the control dogs (201 [25] fmol/litre/second). At three and four hours after the intravenous administration of 0.1 mg/kg dexamethasone, the concentrations of aldosterone decreased significantly to about 60 per cent of their initial values in the control dogs but did not change in the dogs with PDH or an adrenocortical tumour. In the dogs with PDH the renin activity increased significantly after the administration of dexamethasone.     

Peripheral plasma levels of estrone and progesterone in pregnant pigs treated with dexamethasone

Five pregnant pigs of the Swedish Landrace Breed were treated with dexamethasone i.m. injections during early and late pregnancy. The daily dose of dexamethasone was never more than 100 mg. There were no significant changes in the maternal plasma levels of estrone and progesterone during dexamethasone injections. The dexamethasone initiated neither abortion nor parturition.     

Comparative study of the effect of the effect of carbadox, olaquindox and cyadox on aldosterone, sodium and potassium plasma levels in weaned pigs

To study the effects of olaquindox and cyadox on aldosterone, sodium and potassium in the blood in comparison with the effects of carbadox, weaned pigs were fed these compounds in different doses. Pigs treated with 100 and 200 ppm carbadox showed a significant decline of aldosterone after five and three weeks, respectively, compared with control values. In the 200 ppm group treatment was interrupted at week 4. With olaquindox a continuous, significant decline was found from 50 ppm and above after five weeks, and from 25 ppm and above (but excluding the 100 ppm group), after six weeks. In the cyadox groups a significant decline was measured after six weeks in the 50, 200 and 400 ppm groups. Only the 200 ppm group had an earlier response at three and five weeks. A decrease of sodium to hyponatraemic levels in the carbadox groups was seen after three weeks in the 200, and after five weeks in the 100 ppm group. In the olaquindox groups only the 200 ppm dosage showed a consistent decrease to hyponatraemic levels from four weeks treatment. In the cyadox groups the 200 ppm dosage reached a hyponatraemic level after six weeks. An increase of potassium to hyperkalaemic levels occurred at 100 and 200 ppm carbadox dosage after four and three weeks, respectively, and at 200 ppm olaquindox dosage after four weeks. No hyperkalaemic levels were seen in the cyadox groups. It is concluded that the toxic effect of olaquindox, despite minor differences, is comparable with that of carbadox but that cyadox is less toxic.     

Blood antioxidant status and plasma pyruvate kinase activity of halothane-reacting pigs

Samples of blood were collected (by jugular venipuncture) from 10 homozygote halothane-reacting pigs and 7 homozygote nonreactors. Antioxidant status was assessed by measurement of blood glutathione peroxidase, glucose-6-phosphate dehydrogenase, and superoxide dismutase activities and plasma concentrations of vitamin E. Significant differences in these values were not apparent between halothane-reacting pigs and nonreactors. Halothane-reacting pigs had tissue damage as indicated by significantly increased plasma activities of the enzymes creatine kinase and pyruvate kinase. The latter showed better discrimination between the 2 populations than did creatine kinase and could prove to be a more effective marker for identification of stress-susceptible pigs.     

鸡肉中喹乙醇、卡巴多及其代谢物的残留检测

建立了测定鸡肉组织样品中喹乙醇、卡巴多以及喹噁啉-2-羧酸残留量的高效液相色谱法。鸡肉样品中的药物用乙腈与乙酸乙酯的混合液(1∶1,V/V)提取,经过浓缩、净化,用甲醇定容进行检测。色谱拄为Atlantis C18柱,流动相由甲醇、水和乙酸钠缓冲液(pH 4.6)组成,采用梯度洗脱程序;检测波长为320和380 nm。喹乙醇、卡巴多及噁喹啉-2-羧酸在0.05~1.0μg/mL浓度范围内,药物峰面积与浓度值呈良好的线性关系,其相关系数分别为0.997 5、0.997 9、0.998 2。空白鸡肉中添加药物浓度为0.05、0.1、0.2和0.5μg/?时,喹乙醇的回收率为(70.6±3.1)%~(87.5±3.6)%;卡巴多为(73.2±3.7)%~(91.5±2.7)%;喹噁啉-2-羧酸为(71.9±4.3)%~(86.6±3.5)%。喹乙醇、卡巴多和喹噁啉-2-羧酸的最低检测限分别为0.05、0.015、0.025μg/mL。     

Actinobacillus pleuropneumoniae osteomyelitis in pigs demonstrated by fluorescent in situ hybridization.

Necrotizing osteomyelitis and fibrinopurulent arthritis with isolation of Actinobacillus pleuropneumoniae serotype 2 is reported in two pigs from a herd with lameness and mild coughing problems among 8 to 12-week-old pigs. Application of fluorescent in situ hybridization targeting 16S ribosomal RNA of A. pleuropneumoniae in formalin-fixed tissue was performed to verify the association of A. pleuropneumoniae with the bone and joint lesions. By in situ hybridization A. pleuropneumoniae was demonstrated as multiple microcolonies or single cells dispersed in focal fibrinonecrotizing pleuropneumonia, in joints with arthritis, and in bone necroses including lysis of growth plate and suppurative inflammation in the adjacent trabecular metaphysis, thus demonstrating that well-known infections manifest new, unusual lesions.     

Effect of carbadox on net absorption of ammonia and glucose into hepatic portal vein of growing pigs

Chronic cannulas were placed into the hepatic portal vein, ileal vein and carotid artery of growing pigs trained to consume their daily allowance of 1.2 kg of feed (16% protein corn-soybean meal basal diet) in a single meal. The average preoperative BW of pigs was 44.7 kg for Trial 1 (three pigs) and 35.3 kg for Trial 2 (seven pigs). In Trial 1, net absorption of ammonia (NH3) and glucose into the portal vein was determined three times at weekly intervals. The net portal absorptions were derived by multiplying the porto-arterial plasma concentration difference of NH3 and glucose by portal vein plasma flow rate estimated with the p-aminohippuric acid indicator-dilution technique. Differences in the net portal absorptions of NH3 and glucose among the three weekly measurements were small (P greater than .05). In Trial 2, the first sequence of net portal absorption measurements was conducted when pigs were fed the basal diet, and the second sequence of measurements was conducted after the pigs had been fed the diet supplemented with 55 ppm of carbadox for 7 d. Carbadox supplementation reduced (P less than .05) plasma NH3 concentration in portal plasma during the 2.5-h to 5-h postprandial period and decreased (P less than .05) net portal absorption of NH3 during the 2.5-h to 4-h postprandial period. Carbadox, however, did not affect (P greater than .05) net portal absorption of glucose. We suggest that carbadox suppresses the production of cell-toxic NH3 by intestinal microorganisms and, thus, reduces the injury and turnover of intestinal cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in peripheral leukocytes enzymes activity and plasma metabolite concentrations in growing Holstein calves

Plasma metabolite and immunoreactive insulin concentrations and activities of enzymes related to energy metabolism in peripheral leukocytes were measured in growing Holstein calves. A ratio of girth of abdomen divided by girth of thorax (A/T ratio) of calves was significantly elevated after weaning, and the A/T ratio maybe a good indicator to evaluate rumen development. Plasma glucose and free fatty acid concentrations were changed in calves accompanying change in feeding. Activities of lactate dehydrogenase with pyruvate as substrate (LDH-P) and hexokinase (HK) in cytosolic fractions of peripheral leukocytes decreased significantly after weaning the calves reflecting the change of energy source from milk replacer with high percentages of fat and glucose and lactose as absorbable carbohydrate to pelleted feed containing starch as less absorbable carbohydrate and roughage. Some peripheral leukocyte enzymes such as LDH and HK may be good indicators to evaluate changes in energy metabolism of growing calves.     

Plasma renin activity and plasma concentrations of aldosterone, cortisol, adrenocorticotropic hormone, and alpha-melanocyte-stimulating hormone in healthy cats

A pathogenetic role of the renin-angiotensin-aldosterone system has been implicated in cats in both systemic arterial hypertension and hypokalemic myopathy. Yet, measurement of plasma aldosterone concentrations (PACs) and plasma renin activity (PRA) has not unequivocally pointed to hyperaldosteronism as a cause of these conditions. To obtain appropriate reference ranges, this study included a large number (130) of healthy house cats of different breeds without a history of recent illness and plasma concentrations of urea and creatinine below the upper limit of the respective reference ranges. In addition, the pituitary-adrenocortical axis was studied by measuring plasma concentrations of adrenocorticotropic hormone (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), and cortisol. Reference ranges for PACs (110-540 pmol/L; 40-195 pg/mL), PRA (60-630 fmol/L/s; 0.3-3 ng/mL/h), and the aldosterone to renin ratio (ARR) (0.3-3.8) were very similar to those established in the same laboratory for humans in a supine position. No breed differences were found. The ARRs in neutered cats were significantly higher than in intact cats, primarily because of low PRA in neutered cats. The ARRs of cats > or = 5 years of age were significantly higher than those of cats < 5 years of age. The plasma concentrations of ACTH, alpha-MSH, and cortisol did not correlate significantly with PAC. Thus, although blood sampling was performed in cats in nonstandardized positions and was associated with a wide variation of stress responses, the references ranges of PAC, PRA, and ARR were similar to the relatively narrow limits established for humans under standardized conditions. The effects of neutering and aging on PRA and ARR warrant further investigation.     

Influence of carbadox on fasting oxygen consumption by portal vein-drained organs and by the whole animal in growing pigs.

Fasting O2 consumption by the whole animal (W) and by portal vein-drained organs (PVDO) during the 24- to 30-h postprandial period were measured in seven growing pigs (36.1 +/- 2.3 kg) with catheters chronically placed in the hepatic portal vein, ileal vein, and carotid artery trained to consume 1.2 kg of a 16% CP corn soybean meal basal diet (B) once daily. The pigs were placed individually into an open-circuit, indirect calorimeter and connected to an arteriovenous (A-V) O2 difference analyzer for hourly simultaneous measurements of O2 consumption by W and PVDO. The PVDO O2 consumption was calculated by multiplying the A-V O2 difference by the portal vein blood flow rate derived from constant infusion of a p-aminohippuric acid solution into the ileal vein. After the initial series of hourly measurements, four pigs remained on the B diet and three pigs were fed a B + 55 ppm carbadox diet. Seven days later, the second series of measurements was made. In pigs fed the diet with carbadox added, the hourly W O2 consumptions were not different (P greater than .05) between the initial and second series and averaged 7.5 mL.min-1.kg of BW-1. However, the A-V O2 differences (mL/dL) were reduced (P less than .05) from 4.6 to 4.0 at 24 h, 4.8 to 4.0 at 25 h, and 4.6 to 4.0 at 29 h postprandial and the fractions of W O2 consumption used by PVDO (percentage) were reduced (P less than .05) from 28.6 to 21.6 at 26 h and 25.2 to 18.2 at 27 h postprandial.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in plasma progesterone concentrations in mares treated with cloprostenol and human chorionic gonadotropin and inseminated during estrus

Daily changes in the plasma progesterone concentrations were determined in eight mares treated with intramuscular injections of 250 μg cloprostenol, a prostaglandin analogue, followed five days later by 2500 I.U. human chorionic gonadotropin. A second cloprostenol injection was given 14 days after the first; the mares were then inseminated on the third and fifth day of the subsequent estrus and a second injection of human chorionic gonadotropin was administered on the fifth day. The onset of estrus following the second cloprostenol treatment was synchronized beginning three to four days after treatment in all eight mares. All eight ovulated, five mares conceived and only four foaled. Evaluation of the progesterone profiles provided reliable indicators of luteolysis, ovulation and luteal function. Decreasing plasma progesterone concentrations were associated with cloprostenol induced luteolysis or preceded spontaneous onset of estrus. The plasma progesterone concentrations increased consistently after ovulation, and in the pregnant mares, the progesterone concentrations remained high during the first month after insemination.