Penetration of amoxycillin to the respiratory tract tissues and secretions in Actinobacillus pleuropneumoniae infected pigs

The pharmokinetic properties of amoxycillin, and its penetration into respiratory tract tissue, were determined in 18 Actinobacillus pleuropneumoniae infected pigs, after a single i.v. dose of 8·6 mg amoxycillin kg⁻¹ bodyweight. Pleuropneumoniae was produced experimentally in pigs by an aerosol infection model. The infection created a homogenous response, characterised by depression of breathing and increased body temperature. The clinical symptoms were accompanied by increased haptoglobin levels and circulating white blood cell counts. At necropsy the findings were characterised by a bilateral fibrinous pleuropneumonia. Twenty hours after infection, the pigs were administered amoxycillin i.v. The plasma concentration-time curve was described by a three compartment open model. The mean residence time and the elimination half-life were l·5 and 3·4 hours, respectively. The steady-state volume of distribution was 0·67 litres kgl, and the clearance was 0·46 litres kg⁻¹ hour⁻¹. There were no significant differences between these values and those reported previously for healthy pigs. The concentration of amoxycillin in bronchial secretions, lung tissue and diseased lung tissue peaked two hours after intravenous drug administration, while amoxycillin concentration in pleural fluid, lymph nodes and tonsil tissue peaked at the first sampling point one hour after drug administration. The concentration of amoxycillin in secretions and tissue decreased by a slower rate than amoxycillin concentration in plasma, resulting in an increasing tissue-to-plasma concentration ratio. The distribution ratios (AUC_tissue/JAUC_plasma) was 0·53 for bronchial secretions, 0·44 for pneumonic lung tissue, 0·42 for lung tissue, 1·04 for pleural fluid, 0·58 for lymph nodes and 0·37 for tonsil tissue. The distribution of amoxycillin to secretions was increased compared with that previously reported for healthy pigs, while only minor changes were observed in lung tissue.     

Simultaneous infusions of propofol and ketamine in ponies premedicated with detomidine: a pharmacokinetic study

The pharmacokinetics of propofol and ketamine administered together by infusion were investigated in four ponies. Blood propofol and plasma ketamine and norketamine concentrations were measured by high performance liquid chromatography. After premedication with detomidine (20 μg kg⁻¹) anaesthesia was induced with ketamine (2·2 mg kg ⁻¹ intravenously). The trachea was intubated and the ponies were allowed to breathe 100 per cent oxygen. A bolus dose of propofol (0·5 mg kg⁻¹) was then administered intravenously and propofol and ketamine were infused for 60 and 45 minutes, respectively. The average mean infusion rate of propofol was 0·136 mg kg⁻¹ min⁻¹, and the ketamine infusion rate was maintained at 50 μg kg⁻¹ min⁻¹. The mean (SD) elimination half-lives of propofol and ketamine were 69·0 (8·0) and 89·8 (26·7) minutes, the mean volumes of distribution at steady state were 0·894 (0·161) litre kg⁻¹ and 1·432 (0·324) litre kg⁻¹ the mean body clearances were 33·1 (4·5) and 23·9 (3·8) ml kg⁻¹ min⁻¹ and the mean residence times for the infusion were 87·1 (4·1) and 110·7 (8·2) minutes, respectively. Norketamine, the main metabolite of ketamine, was detected throughout the sampling period. The mean residence time for norketamine was 144 (16) minutes. All the ponies recovered quickly from the anaesthesia; the mean times to sternal recumbency and standing were 11·1 (5·3) and 30·0 (20·8) minutes, respectively, from the end of the infusion.     

Pharmacokinetics of propofol infusions, either alone or with ketamine, in sheep premedicated with acepromazine and papaveretum

The pharmacokinetics of propofol were investigated in two groups of five Scottish blackface sheep undergoing surgery for the implantation of subcutaneous tissue pouches. After premedication with acepromazine and papaveretum, anaesthesia was induced with either propofol at 4 mg kg⁻¹ intravenously (group 1) or with a mixture of propofol at 3 mg kg⁻¹ and ketamine at 1 mg kg ⁻¹ intravenously (group 2). Anaesthesia was maintained with a variable infusion rate of either propofol alone (group 1) or propofol and ketamine (group 2). Both regimens produced satisfactory conditions for superficial surgery of the body surface. The mean (SD) duration of anaesthesia was 64·8 (3·1) minutes for group 1 and 60 (0) minutes for group 2; the mean total dose of propofol given to the sheep in group 1 was 801 (84) mg, and the sheep in group 2 received 470 (46) mg of propofol and 267 (30) mg of ketamine. The mean elimination half-life of propofol was 56·6 (13·1) minutes in group 1 and 50·3 (21·4) minutes in group 2; the mean volume of distribution at steady state was 1037 (0480) litre kg⁻¹ in group 1 and 1·515 (0939) litre kg⁻¹ in group 2; the mean body clearance was 85·4 (28·0) ml kg⁻¹ min⁻¹ in group 1 and 1280 (35·0) ml kg⁻¹ min⁻¹ in group 2; the mean residence time corrected for a bolus injection was 12·1 (4·2) minutes in group 1 and 11·9 (6·6) minutes in group 2; for the infusion, the mean residence time was 72·1 (4·2) minutes in group 1 and 69·9 (7·9) minutes in group 2. There were wide variations in the blood propofol concentrations reached in individual sheep by using this standard dosing regimen. All the sheep recovered quickly from anaesthesia; the mean times to extubation, sternal recumbency and standing for the animals in group 1 were 2·8 (0·4) 6·3 (1·2) and 10·9 (1·6) minutes from the end of the infusion, and the times for group 2 were 5·3 (0·9), 11·2 (1·7) and 15·1 (2·2) minutes.     

Respiratory tract distribution and bioavailability of spiramycin in calves

Pharmacokinetic determinants of spiramycin and its distribution into the respiratory tract were studied in 2 groups of calves, 4 to 10 weeks old. Group-A calves (n = 4) were used to determine pharmacokinetic variables of spiramycin after IV (15 and 30 mg/kg of body weight) and oral administrations of the drug (30 mg/kg) and to measure distribution of spiramycin into nasal and bronchial secretions. Group-B calves (n = 4) were used to determine distribution of spiramycin into lung tissue and bronchial mucosa. Spiramycin disposition was best described by use of an open 3-compartment model. Mean (+/- SD) elimination half-life was 28.7 +/- 12.3 hours, and steady-state volume of distribution was 23.5 +/- 6.0 L/kg. Bio-availability after oral administration was 4 +/- 3%. High and persistent concentrations of spiramycin were achieved in the respiratory tract tissues and fluids. Tissue-to-plasma concentration ratio was 58 for lung tissue and 18 for bronchial mucosa at 3 hours after spiramycin administration and 137 and 49, respectively at 24 hours. Secretion-to-plasma concentration ratio was 4 for nasal secretions and 7 for bronchial secretions, and remained almost constant with time. Thus, spiramycin penetrates well into the respiratory tract, although the value in bronchial secretions is lower than that in lung tissues and bronchial mucosa. Calculations indicate that a loading dose of 45 mg/kg, administered IV, followed by a maintenance dose of 20 mg/kg, IV, once daily is required to maintain active concentrations of spiramycin against bovine pathogens in bronchial secretions.     

Pharmacokinetics of oxytetracycline after intramuscular administration with lidocaine in sheep, comparison with a conventional formulation

The pharmacokinetic behaviour of oxytetracycline (OTC) was studied in 11 sheep after intravenous and intramuscular administration at a single dosage of 20 mg kg⁻¹ bodyweight. A conventional formulation was injected by the intravenous route and two different preparations were administered by the intramuscular route: a conventional formulation (T-100) and an aqueous solution of OTC with lidocaine (1 per cent) (OTC-Q. The objective was to determine whether there are differences between both formulations in the disposition kinetics of OTC after intramuscular administration to sheep. After intravenous administration of the conventional formulation, plasma oxytetracycline concentrations were best fitted to an open two-compartment model. Mean apparent volume of distribution was 0·77±0·02 litre kg⁻¹ and the harmonic mean half-life was three hours. The OTC transfer process between central and peripheral compartments was fast and that did not influence the elimination process. After intramuscular administrations of both formulations, half-lives were longer than after intravenous administration (mean values of 14·1 and 58·2 hours for T-100 and OTC-L respectively). In both cases, a biphasic absorption, a ‘flip-flop’ model and a complete bioavailability were found. OTC-L provided therapeutic plasma concentrations over 0·5 μg ml⁻¹ (the minimum inhibitory concentration for most susceptible pathogens) for a longer period of time than T-100 (72 hours compared with 36 or 48 hours).     

Airflow mechanics in models of equine obstructive airway disease under conditions simulating exercise

Effects of respiratory tract obstructions on ventilatory mechanics in horses exercising at high speeds were tested with a fibreglass replica of the airways (nares to mainstem bronchi) of an adult horse. Segmental pressures were recorded at six sites along the model at four different unidirectional flows (1300 – 4100 litre min⁻¹), and the respective resistances (R) to airflow were calculated. The external nares and the larynx made the greatest contributions to the total resistance (R_TOT) when no obstruction was present. Modifying the model to simulate severe pharyngeal lymphoid hyperplasia (PLH) had no effect on R at the larynx or at any point in the trachea under these flow conditions. Two 16 litre anaesthetic rebreathing bags were attached to the bronchial end of the model, and tidal ventilation generated by a piston pump. Upper (nares to pharynx) and lower tract R (R_U and R_L) and R_TOT, and dynamic compliance were determined for pump volumes (V_p) of six and 12 litres, at pumping frequencies (f_p) of 20 – 100 min⁻¹ while the airway was clear, and after modifying it to simulate either PLH or partial bronchial obstruction. Model condition had no effect on R_U. However, R_L and R_TOT were higher in the PLH simulated condition when f_p ≥ 90 and V_P = 12 litres (P<0·05). This suggested that severe PLH may significantly interfere with airflow distal to the site of the lesions during high frequency, high volume ventilation of the type seen in galloping horses. With partial bronchial obstruction R_L and R_TOT were increased when f_p>34 with each V_p. The applicability of the model was verified by comparing results from the unobstructed state with those from normal horses exercising on a treadmill.     

Assessment of orocaecal transit time in cats by the breath hydrogen method: the effects of sedation and a comparison of definitions

Oro-caecal transit times (OCTTs) were assessed in 10 healthy adult cats by the lactulose breath hydrogen method with either no sedation (group A), or after the intramuscular administration of three sedative regimens: a combination of acetylpromazine at 0·1 mg kg⁻¹ with buprenorphine at 10 μg kg⁻¹ (group B), ketamine at 5 mg kg⁻¹ with midazolam at 0·1 mg kg⁻¹ (group C), or medetomidine at 50 μg kg⁻¹ (group D). For each test, the OCTT was defined by four methods: a visual assessment, the first maintained 4 ppm increase in hydrogen production, and the first maintained 0·5 ml hr⁻¹ increase in hydrogen production assessed by two cumulative sum methods. Depending on the definition, the median OCTTs of the cats were between 113 and 131·5 minutes in group A, 86·5 and 97·5 minutes in group B, 218 and 235·5 minutes in group C and 86·5 and 97·5 minutes in group D. By two of the definitions, the median OCTTs in group C were significantly longer than in group A (P≤0·037) and approached significance by the other two definitions. The use of sedatives significantly increased the inter-individual variability of the OCTTs, particularly in groups C and D. There were significant differences between the median OCTTs defined by the four different methods, but all the methods were very highly and significantly correlated (r_s≤0·9503, P<0·0001).     

Kinetic disposition, systemic bioavailability and tissue distribution of apramycin in broiler chickens

Apramycin was administered to chickens orally, intramuscularly and intravenously to determine blood concentration, kinetic behaviour, bioavailability and tissue residues. Single doses of apramycin at the rate of 75 mg kg⁻¹ body weight were given to broiler chickens by intracrop, i.m. and i.v. routes. The highest serum concentrations of apramycin were reached 0·20 and 0·76 hours after the oral and i.m. doses with an absorption half-life () of 0·10 and 0·19 hours and an elimination half life () of 1·22 and 2·31 hours respectively. The systemic bioavailability was 2·0 and 58 per cent after intracrop and i.m. administration, respectively, indicating poor absorption of the drug when given orally.Following i.v. injection, the kinetics of apramycin was described by a two-compartment open model with a () of 1·5 hours, () of 2·1 hours, V_d(ss) (volume of distribution) of 4·82 litre kg⁻¹ and C1_(B) (total body clearance) of 1·88 litre kg⁻¹ hour⁻¹. The serum protein-binding of apramycin was 26 per cent.The highest tissue concentrations of apramycin were present in the kidneys and liver. No apramycin residues were detected in tissues after six hours except in the liver and kidneys following intracrop dosing and kidneys following i.m. administration.     

Water medication of a swine herd with amoxycillin

A swine herd, consisting of 201 swine, was treated with amoxycillin. Amoxycillin was administered in the water system for 5 days, at a mean dose of 23 mg/kg body weight per day. Twice a day the water consumption was monitored, and blood samples collected from 10 randomly selected pigs. The plasma concentration of amoxycillin was measured by use of high performance liquid chromatography (HPLC). Three days after initiating amoxycillin treatment, the plasma concentration reached a constant level, at which it varied between a maximum of 1.3 μg/mL and a minimum of 0.5 μg/mL. The plasma concentration was compared with a predicted curve based on pharmacokinetic variables obtained previously. The plasma concentrations were at the same level as the simulated ones. The minimum inhibitory concentration (MIC) values of the common respiratory pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida are about 0.1 μg/mL. In pigs the distribution between bronchial mucosa and plasma ( AUC _mucosa/ AUC _plasma) is 0.3, which indicates a therapeutic plasma concentration of 0.3 μg/mL. Data from the present study indicates that water medication with amoxycillin is effective as follow-up treatment.     

Arterial blood gases and acid-base balance in geriatric dogs

To compare arterial blood gas pressures and acid-base balance in geriatric and young adult dogs, 23 clinically healthy aged dogs (>10 years old) and 16 young adult dogs (two to four years old) were studied. Blood gases (PaO₂ and PaCO₂), pH, Na, K, Ca and Cl were measured in arterial blood samples using selective electrodes. Haemoglobin was quantified with a co-oximeter. Total proteins and phosphorus were measured by spectrophotometry in plasma. The alveolar to arterial PO₂ gradient (P(A-a)O₂), bicarbonate, anion gap and the base excess of blood were calculated. Quantitative analysis of acid-base balance was carried out by calculating unidentified anions. Old dogs had significantly higher P(A-a)O₂ than young dogs (2·5±0·3 versus 1·4±0·3 KPa). Although the differences were not significant, aged dogs also had a lower PaO₂. No differences were detected in PaCO₂, pH, Na, K, Ca, Cl, haemoglobin, phosphorus, bicarbonate and base excess of blood. Plasma proteins were higher in old dogs than in young dogs (7·1±0·2 versus 6·5±0·2 g dl⁻¹). Anion gap was increased in aged dogs; however, no changes were found in unidentified anions. In conclusion, an increase in P(A-a)O₂ has been identified in a group of geriatric dogs. No major changes have been found in the acid-base balance of aged dogs.     

Mineral metabolism in healthy geriatric dogs

To study mineral metabolism in geriatric dogs, parathyroid hormone, calcitriol, ionised calcium, phosphorus, blood urea nitrogen and creatinine were evaluated in 35 geriatric dogs (> 10 years) and in 20 young adult dogs (2–5 years). Parathyroid hormone levels were within the normal range in both groups, but values (mean ± SEM) were greater in the old dogs (34·8 ± 3·6 vs 21·2 ± 2·3 pg ml⁻¹, P=0·005). Calcitriol and ionised calcium were similar in the two groups, and the values for both parameters were within the normal reference range. Plasma phosphorus levels were in the normal range in both groups but tended to be greater in the older dogs (P=0·09). While blood urea nitrogen was similar in the two groups, creatinine levels (mean ± SEM) were higher in the young dogs (82·2 ± 3·5 vs 101 ·7 ± 4·4 μmol litre⁻¹). Even when the dogs were matched for weight, plasma creatinine concentration was still greater in the younger dogs. In conclusion, an increase in parathyroid hormone without changes in calcium, phosphorus and calcitriol has been identified in geriatric dogs.     

Pharmacokinetic disposition and plasma protein binding (in vitro) of chloramphenicol in Bubalus bubalis I*

Eleven buffalo calves (Bubalus bubalis) of 1-1 1/2 years of age and weighing between 64 and 174 kg were given chloramphenicol at the dose rates of 10 and 20 mg/kg body weight. Pharmacokinetic parameters were determined from the plasma levels. The median elimination half-life was estimated to be 2.95 h and the median volumes of distribution were 1.1667 litres/kg with the 10 mg/kg dose and 0.9699 litres/kg with the 20 mg/kg dose. The median metabolic clearance rates were 288.30 and 234.13 ml/h/kg, respectively. From the average plasma concentrations obtained with the 20 mg/kg i.v. dose, it was considered necessary to repeat the drug by the i.m. route with the same dose (four calves) which resulted in prolonging the therapeutic concentration (> 5 μg/ml) until 18 h. At therapeutic concentrations, about 60% of the drug was bound to plasma proteins. Using the overall elimination rate constant (0.2354 h^-1) and the apparent specific volume of distribution (0.97 litres/kg), different dosage regimens were calculated so as to obtain plasma concentrations (C_p min) of 2, 5 and 10 μg/ml.     

Immunohistochemical and histopathological findings of ovine pulmonary adenocarcinoma (Jaagsiekte) in Egyptian sheep

Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring retrovirus-induced transmissible lung cancer in sheep. Lungs and associated (bronchial and mediastinal) lymph nodes of seven sheep with OPA were examined. Lungs had few multifocal consolidated slightly elevated gray to white masses ranging from 0.5 to 3 cm in diameter. Histopathologically, these masses appeared as well-differentiated acinar adenocarcinoma with little evidence of anaplasia. The acini composed of well-differentiated cuboidal to low columnar epithelium with clear or vacuolated cytoplasm and low mitotic index. No metastases were observed in the bronchial and mediastinal lymph nodes of any animal. The presence of Jaagsiekte sheep retrovirus (JSRV) was demonstrated in the lungs by immunohistochemistry. JSRV protein was detected in all tumor epithelial cells, histologically normal alveolar type II cells, and few bronchiolar epithelial cells, alveolar macrophages, lymphocytes, and plasma cells. This study is the first to confirm the presence of natural OPA in Egypt.     

Ultrasonic observations on the turnover of ovarian follicular cysts and associated changes of plasma LH, FSH, progesterone and oestradiol-17β in cows

Changes in the diameters of individual follicular structures on ovaries were measured by transrectal ultrasonography for 29 to 40 days and the plasma concentrations of luteinising hormone (LH), follicle-stimulating hormone (FSH), progesterone and oestradiol 17β were determined in four cows with ovarian cysts. When these structures decreased in size, new follicular structures appeared and developed into cysts. Progesterone concentrations in plasma were below 1·0 ng ml⁻¹ during the experimental periods. Plasma concentrations of oestradiol-17β fluctuated. The mean concentration of oestradiol-17β in plasma differed (P<0·01) depending on the stage of the cyst. No preovulatory surges of LH were detected during the developmental stage of the cysts.     

Oxygen affinity and Bohr effect responses to 2,3-diphosphoglycerate in equine and human blood

The dependence of blood oxygen affinity and the Bohr effect on the concentration of 2,3-diphosphoglycerate (DPG) in erythrocytes was investigated in 24 trotter horses and 24 healthy men. The oxygen tension at half saturation and standard conditions (P₅₀st at pH 7·4 PCO₂40 mniHg and 37°C) and the carbon dioxide or fixed-acid-induced Bohr effect (dlogP₅₀/dpH) were determined. Samples of fresh blood and blood depleted of or enriched with DPG were studied. In the absence of measurable DPG, the equine and human blood had similar mean (SD) values of P₅₀st (16·6 [0·6] and 16·2 [0·7] mmHg, respectively). In both species these values increased with increasing DPG, but the response of equine blood was significantly lower, at least up to physiological values (P₅₀st =24·6 [0·6] and 26·2 [0·7]) mmHg; DPG=14([1·8] and 12·8 [1·2] μmol gHb⁻¹, respectively, in fresh blood). concentrations above 20 to 25 μmol gHb⁻¹ of DPG the difference between the values of P₅₀st in the two species tended to de crease because the response in human blood reached a plateau. The interactions between the Bohr effect and the concentration of DPG showed that in the horses, as in the men, the level of DPG played an important role in governing the relative magnitude of carbon dioxide and fixed acid factors. The difference between them, which is associated with the oxylabile carbamino binding, was greatest in DPG-depleted blood, but whereas in the men the difference was suppressed by an above normal DPG concentration, in the horses it was still measurable.     

Effects on adhesion molecule expression and lymphocytes in the bovine mammary gland following intra-mammary immunisation

Changes to adhesion molecule expression and lymphocyte populations were evaluated in alveolar mammary tissue collected from cows following an immunisation protocol that involved intra-mammary inoculation to induce an IgA response in mammary secretions. The right quarters of the udder were immunised; the left side acted as a control. Antibody titres in secretions showed that at least two animals responded with antigen-specific IgA. Numbers of T-lymphocytes were 4-fold higher in immunised glands compared with controls (P < 0.05). IgA-, IgM- and IgG-positive cell numbers were significantly higher (P < 0.01) in immunised glands compared with controls in three of the four cows. No mucosal addressin molecule-1 (MAdCAM-1), vascular cell-adhesion molecule-1 (VCAM-1) or peripheral node addressin (PNAd) protein expression was detected on smaller venules that stained positively for von Willebrand factor in alveolar mammary tissues, from either immunised or control glands. Both VCAM-1 and PNAd were detected on smaller venules in supramammary lymph nodes, however, there was no significant difference between immunised and control glands. Quantification of MAdCAM-1 mRNA showed very low expression in both immunised and control alveolar tissue compared with Peyer's patch positive-control tissue. These findings suggest that the bovine mammary gland is capable of a mucosal antibody response; however, MAdCAM-1 is not involved with lymphocyte homing to the mammary gland in this species.     

Experimental Infection with Mycobacterium Avium,Serotype 2, in Pigs: 3. Oral Infection with Small Doses of M. Avium*

Pigs were inoculated orally with Mycobacterium avium in doses ranging from 15.6 × 10² to 15.6 × 10⁶ viable units daily for 15 days (Table 1). The animals were necropsied 31–32 days after the last inoculation.Pigs given doses of 15.6 × 10⁶ and 15.6 × 10⁵ viable units showed delayed hypersensitivity to avian tuberculin 24 days after the last inoculation (Table 2). The pig inoculated with 15.6 × 10⁶ viable units showed macro- and/or microscopic lesions of the intestines and the liver, and of the mandibular, mesenteric and hepatic lymph nodes. Cultures showed growth of M. avium from the same tissues and from the spleen and the left tracheobronchial lymph node. The pig inoculated with 15.6 × 10⁵ viable units showed a pronounced granulomatous infiltration in the tonsils and the mesenteric lymph nodes. Growth of M. avium was obtained from the tonsils, the intestinal mucosa (Peyer patch) and the mandibular and mesenteric lymph nodes. Viable unit counts were high in the tonsils and in the mesenteric lymph nodes (Tables 3 and 4).Lower doses gave rise to a minimal tissue reaction and/or very low viable unit counts, and are not considered to be capable of producing a progressive tuberculosis.     

Nitrogen and phosphorus surpluses on Danish dairy and pig farms in relation to farm characteristics

N and P surpluses per hectare at farm level were determined on 63 private pilot farms with data from 2 to 7 years between 1997 and 2003 (a total of 245 observations). Farms were classified in the following four farm types: Conventional mixed dairy, organic mixed dairy, conventional pig farms (indoor) and conventional pig farms with outdoor sows. Import of nutrients with concentrate and fertilizer was the major input to all conventional farm types. On the organic dairy farms major input was N fixation, but also import of nutrients with concentrate and manure were important inputs. Output from the dairy farms was dominated by nutrients in milk. On pig farms nutrients in meat dominated the output, but also export of nutrients with cash crops and manure were important outputs. Farm type, year and farm within farm type significantly affected both N and P surpluses per hectare. Farm type was the major source of variation in both N and P surpluses. In the period investigated N surplus decreased by 6.5 kg N ha^− 1 yr^− 1 and P surplus decreased by 0.7 kg P ha^− 1 yr^− 1. The N and P surpluses observed on the conventional dairy farms significantly exceeded surpluses observed on the organic dairy farms. At equal number of livestock units (LU) per hectare (1.28 LU ha^− 1) the difference was 43 kg N ha^− 1 and 6 kg P ha^− 1. At equal rates of N or P in manure to fields (147 kg N ha^− 1, 29 kg P ha^− 1, respectively) the difference was 45 kg N ha^− 1 and 4 kg P ha^− 1. Conventional dairy farms and pig farms with sows indoors had equal N and P surpluses at equal rates of N or P in manure to fields. Corrected to the average year (1999.5) the estimated average N and P surpluses showed highest levels on pig farms with outdoor sows (251 kg N ha^− 1, 42 kg P ha^− 1) and lowest levels on organic dairy farms (113 kg N ha^− 1, 7 kg P ha^− 1). Surpluses on the conventional dairy farms were 175 kg N ha^− 1 and 16 kg P ha^− 1 and on the indoor pig farms they were 123 kg N ha^− 1 and 13 kg P ha^− 1. The N and P surpluses observed on Danish conventional mixed dairy farms were comparable with intensive dairy farming systems in other European countries.     

Effect of the injection site on the bioavailability of amoxycillin trihydrate in dairy cows

The pharmacokinetic behaviour of amoxycillin sodium and amoxycillin trihydrate-20% aqueous suspension was studied in a group of five dairy cows. Amoxycillin sodium was administered intravenously and amoxycillin trihydrate-20% by four different routes of administration: subcutaneously in the dewlap, intramuscularly in the lateral neck, M. triceps, and buttock (M. semitendineus). The dose level for both drug formulations was 3.83 ± 0.47 mg/kg. The mean plasma concentration–time curve(C_p)for intravenous amoxycillin sodium administration could be described mathematically by the biexponential equation C_p= 15.6 e^-0.033t+ 1.04 e^-0.0091t. The areas under the plasma concentration–time curve (AUC's) obtained after the intravenous injections of sodium amoxycillin were used as references for the bioavailability studies of the four routes of amoxycillin trihydrate administration. Intramuscular injections into the lateral neck or into the M. triceps resulted in similar systemic bioavailabilities, being at 12 h post injection (p.i.) 76.2 and 79.2% of the administered dose. The biological half-lives (t_1/2) were similar, being 6.2 and 6.9 h, respectively. After subcutaneous injection into the dewlap or intramuscular injection into the buttock lower bioavailabilities at 12 h p.i. were observed (24.1 and 49.2%, respectively). The plasma amoxycillin concentration was persistently low. The half-lives of plasma amoxycillin disposition after the buttock and dewlap injections were 13.2 and 44 h, respectively. The plasma concentrations obtained were compared with minimal inhibitory concentrations (MIC) against pathogenic bacteria with respect to the theoretical design of effective antibacterial therapy. The differences observed serve to emphasize the fact that more attention should be paid to the effect of the route of administration on the biological bioavailability of a drug, with particular reference to studies on clinical efficacy. Pre-slaughter withdrawal times were suggested for the different routes of injection of these two drug formations.     

Pathology and molecular diagnosis of paratuberculosis of camels

Camels are the prime source of meat and milk in many desert regions of the world including Saudi Arabia. Paratuberculosis of camels, locally called Silag, is a serious and invariably fatal disease in the Arabian camel. Six camels were used in this study. Five camels with clinical paratuberculosis were used to study the pathology of the disease and confirm its aetiology. The sixth camel was clinically healthy and used as a control. The camels were examined clinically and bled for haematological and blood chemistry analysis. They were then humanely killed with a high intravenous dose of thiopental sodium (10 mg/kg) for pathological studies as well as obtaining tissues for microbiological and molecular studies. The clinical signs of the disease were emaciation, diarrhoea, alopecia, wry neck and pale mucous membranes. Laboratory diagnosis showed reduced haemoglobin concentration, low haematocrit and high activity of the serum enzyme alanine aminotransferase. Serum creatinine concentration was normal. These results indicated the infected camels were anaemic and the function of their livers was affected. Postmortem examination showed thickened and corrugated intestinal mucosa, enlarged granulomatous mesenteric lymph nodes, miliary and diffuse granulomas in the liver (in four camels), generalized lymph node granulomas (in one camel), splenic granuloma (in one camel) and mediastinal lymph node granuloma (in two camels). Histopathological examination showed diffuse infiltration of macrophages in all organs showing lesions. Ziehl–Neelsen staining of tissue scraping and tissue sections showed masses of acid fast bacilli, except for the spleen. Infection with Mycobacterium avium subsp. paratuberculosis was confirmed by PCR by targeting the IS900 gene.