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Pharmacokinetics and metabolism of ketoprofen after intravenous and intramuscular administration in camels.

The pharmacokinetics of ketoprofen were determined after an intravenous (i.v.) and intramuscular (i.m.) dose of 2.0 mg/kg body weight in five camels (Camelus dromedarius) using gas chromatography/mass spectrometry (GC/MS). The data obtained (median and range) following i.v. administration was as follows: the elimination half-life (t(1/2beta)) was 4.16 (2.65-4.29) h, the steady state volume of distribution (Vss) was 130.2 (103.4-165.3) mL/kg, volume of distribution (area method) (Vd(area)) was 321.5 (211.4-371.0) mL/kg, total body clearance (Cl) was 1.00 (0.88-1.08) mL/min x kg and renal clearance was 0.01 (0.003-0.033) mL/min x kg. Following i.m. administration, the drug was rapidly absorbed with peak serum concentration of 12.2 (4.80-14.4) microg/mL at 1.50 (1.00-2.00) h. The systemic availability of ketoprofen was complete. The apparent half-life was 3.28 (2.56-4.14) h. A hydroxylated metabolite of ketoprofen was identified by (GC/MS) under electron impact (EI) and chemical ionization (CI) scan modes. The detection times for ketoprofen and hydroxy ketoprofen in urine after an intravenous (i.v.) dose of 3.0 mg/kg body weight was 24.00 and 70.00 h, respectively. Serum protein binding of ketoprofen at 20 microg/mL was extensive; (99.1+/-0.15%).

Animals↗

The parotid, mandibular and lateral retropharyngeal lymph nodes of the camel (Camelus dromedarius).

The parotid, mandibular and lateral retropharyngeal lymph nodes of the dromedary camel were examined using both light and electron microscopy. All three lymph nodes were lobulated. They did not show the characteristic medulla, cortex and paracortex of typical lymph nodes. Instead, they contained lymphatic nodules, dense anodular lymphoid tissue and diffuse lymphoid tissue dispersed throughout the lymph node. Networks of sinuses were present in the diffuse lymphoid tissue. The diffuse lymphoid tissue in the periphery of all lymph nodes examined was characterized by numerous erythrocytes within and around its network of sinuses. The nodal sinuses were contiguous with the septal vessels, which are considered the possible source of erythrocytes seen in this study. The lymph nodes that were seen in this study resembled the haemolymph nodes of other mammals with regard to their content of erythrocytes but were unique in being located in sites that were typical of ordinary lymph nodes. Morphometric analysis has shown that the percentage volume densities of the stroma and the various parenchymal components were similar in the three lymph nodes.

Animals↗

Morphological, morphometric and histochemical characterization of the gastric mucosa of the camel (Camelus dromedarius).

Mucosal morphology, morphometry and mucin histochemistry of the stomach were studied in the one-humped camel. The lining of the stomach was divided into eight grossly identifiable regions. The first region was non-glandular, occupied the body of the first compartment of the stomach and constituted 53.2% of the gastric mucosa. The other seven regions were lined by a glandular mucosa. Histological, histochemical and morphometric investigations have shown that glandular mucosa comprises pseudo-cardiac, cardiac, fundic and pyloric regions. The pseudo-cardiac region was characterized by widely separated short tubular serous glands. It constituted 36.2% of the gastric mucosa; it extended over the entire lining of the second compartment and parts of the first and third compartments. The cardiac region was confined to the initial zone of the third compartment amidst the psuedo-cardiac region but contiguous with the distal end of the gastric groove. It constituted 3.4% of the gastric mucosa and was characterized by neutral and acid mucin positive glands. The fundic and pyloric regions occupied the distal distended part of the third compartment. The fundic region constituted 4.3% of the gastric mucosa. It was packed with typical fundic glands characterized by chief cells, parietal cells and acid mucin positive neck cells. The pyloric region constituted 2.9% of the gastric mucosa. Its glands were positive to acid mucins except for their bases that were positive to neutral mucins. Differences in volume densities of the mucosal components and reactivity of the surface epithelium and gastric pits to mucin stains were noted in the different regions of the stomach.

Animals↗

Entropion, corneal ulcer and corneal haemorrhages in a one-humped camel (Camelus dromedarius).

An unusual case of entropion, corneal ulcer and corneal haemorrhages in a one-humped camel (Camelus dromedaries) is described. The most prominent clinical findings were entropion of both eyelids, severe blephrospasm, epiphora, conjunctivitis, conjunctival oedema, mucopurulent conjunctival discharges, hyperaemia, lacrimation and photophobia. Corneal ulcers and corneal haemorrhages were also observed.

Animals↗

The arterial supply to the digits of the forelimb in the Bactrian camel (Camelus bactrianus).

The arterial supply of the digits of the forelimb of the Bactrian camel is described. The arteries supplying the digits were the palmar metacarpal and common palmar digital arteries III. The palmar metacarpal artery III was the continuation of the deep medial proximal metacarpal branch which was derived from the medial branch of the radial artery. It gave rise to a nutrient branch, medial branch, lateral branch and distal perforating palmar branch at the proximal end of the distal sixth of the cannon bone (fused third and fourth metacarpal bones). The common palmar digital artery III was the continuation of the median artery, which divided into medial and lateral branches. The medial branch of common palmar digital artery III which occasionally arose from the axial palmar proper digital artery III, after giving rise to the axial proximal proximal phalangeal branch, divided into the axial and abaxial palmar proper digital arteries III. The axial palmar proper digital artery III gave off the dorsoaxial distal proximal phalangeal, dorsoaxial proximal middle phalangeal, dorsoaxial distal middle phalangeal, palmoaxial middle phalangeal, palmoaxial distal phalangeal, dorsoaxial distal phalangeal branches, coronal artery and some digital tori branches. The abaxial palmar proper digital artery III gave rise to the abaxial proximal proximal phalangeal, dorsoabaxial distal proximal phalangeal, dorsoabaxial middle phalangeal, palmoabaxial middle phalangeal, palmoabaxial distal phalangeal, dorsoabaxial distal phalangeal branches, coronal artery and some digital tori branches. The lateral branch of the common palmar digital artery III in its origin, course, branching pattern and supply in the fourth digit was similar to the medial branch of common palmar digital artery III in the third digit.

Adaptation, Physiological↗

Incidence and intensity of Onchocerca fasciata Railliet and Henry, 1910 in local camels in Saudi Arabia.

Onchocerca fasciata Railliet & Henry, 1910, which occurs in subcutaneous nodules, shows a site preference to the anterior parts of its host, Camelus dromedarius L., i.e. the nuchal ligaments, neck, and shoulders. Although the incidence of infection was generally high (59%), the infected camels did not exhibit any apparent disease. The intensity of infection ranged between 2 and 29, with a mean of 10.8 nodules per infected host.

Animals↗

Genetic differences between Tunisian camel and sheep strains of the cestode Echinococcus granulosus revealed by SSCP.

Ovine and dromedary Echinococcus granulosus isolates from Tunisia were identified as G1 and G6 strains based on polymorphism of the mitochondrial cytochrome C oxydase CO1. Single strand conformation polymorphism (SSCP) was used in order to examine the genetic variation within and between Tunisian G1 and G6 strains and to estimate the extent of selfing. The dromedary isolates are genetically distinct from sheep isolates (high value of genetic variation between populations: Fst= 0.46). No significant deficiency in heterozygotes was found in sheep isolates, whereas heterozygote deficiency (suggesting selfing) was found in a limited number of camel isolates.

Animals↗

Assessment of blood glutathione peroxidase activity in the dromedary camel.

Blood glutathione peroxidase (GSH-Px) levels in 709 normal dromedary camels (442 females and 267 males) were assessed in the Canary Islands. All animals were intensively reared, and three different nutritional systems were evaluated, depending on selenium content of the diet. Mean GSH-Px level in the total population was 288.5+/-157.2 IU x g(-1) Hb. Reference ranges were estimated and enzymatic activities below 51 IU x g(-1) Hb were considered inadequate. GSH-Px activities obtained in females (298.1+/-155.7 IU x g(-1) Hb) were significantly (P = 0.037) higher than in males (272.6+/-157.2 IU x g(-1) Hb). When age groups were compared, only males between 6 and 12 months old exhibited significantly lower mean GSH-Px (P = 0.006) than females. A high correlation (r = 0.88) between serum selenium concentration and blood GSH-Px activity was estimated, and the regression equation was y = 2.5101x + 42.423. Selenium content of the diet above 0.1 mg x kg(-1) DM seems to supply adequate selenium requirements for dromedaries under intensive husbandry.

Age Factors↗

The pharmacokinetics of promethazine after intravenous administration in camels.

The pharmacokinetics of promethazine were determined in seven camels (Camelus dromedarius) after an intravenous dose of 0.5 mg kg body weight.-1 The data obtained (median and range) were as follows: the elimination half-life (t1/2 beta) was 5.62 (2.84-6.51) h; the steady state volume of distribution (Vdss) was 8.90 (7.10-12.00) L kg-1, total body clearance (CT) was 24.5 (17.22-33.65) ml kg-1 min-1 and renal clearance (Clr) was 4.81 (1.97-5.48) ml kg-1 min-1.

Animals↗

N-ethylmaliemide (NEM)-stimulated passive potassium transport in camel erythrocytes: inhibitory effects of age, furosemide, sodium fluoride and okadaic acid.

The effects of age, and the inhibitory effects of furosemide, sodium fluoride, and okadaic acid on N-ethylmaliemide (NEM)-stimulated, ouabain-resistant potassium influx were investigated in camel erythrocytes. The NEM-stimulated influx which declined with the age of erythrocytes, was partially inhibited by 2 mmol/L furosemide, 20 mmol/L sodium fluoride, and completely inhibited by 150 nM okadaic acid. The effect of all chemical inhibitors was significant if added before the NEM pretreatment.

Aging↗

Comparison of two different methods for the vitrification of hatched blastocysts from the dromedary camel (Camelus dromedarius).

The uteri of 32 donor camels were flushed non-surgically on Day 6, 7 or 8 after ovulation and a total of 184 embryos was recovered. Sixty Day 6 embryos and 61 Day 7 embryos were vitrified or frozen ultrarapidly using open pulled straws and a modified version of the Vajta protocol. These embryos were subjected to concentrations of either 10% and 20% or 20% and 40% ethanediol as the cryoprotectant before being loaded into open pulled straws (OPS) and plunged into liquid nitrogen. All embryos were subsequently thawed and rehydrated either directly into holding media or into holding media containing 0.2 M sucrose and were incubated for 5 or 10 min before being transferred to holding media before transfer to recipients. Although the survival rate of the embryos immediately after thawing was high (OPS 20%/40% ethanediol resulted in 97% and 100% survival for Day 6 and Day 7 embryos, respectively; OPS 10%/20% ethanediol resulted in 90% and 70% survival for Day 6 and Day 7 embryos, respectively), after 2 h in culture, survival rates had decreased to 46% and 53% for Day 6 and Day 7 embryos, respectively, using OPS 10%/20% and 53% and 63% for Day 6 and Day 7 embryos, respectively, using OPS 20%/40%; however, none of the embryos transferred resulted in a viable fetus. A further 63 embryos (Day 6: n = 31; Day 7: n = 16; Day 8: n = 16) were subsequently exposed to vitrification solution (20% glycerol + 20% ethylene glycol + 0.3 M sucrose + 0.375 M glucose + 3% polyethylene glycol) in three steps and after loading into 0.25 mL straws were plunged into liquid nitrogen. However, a much greater percentage of the Day 7 and Day 8 embryos (43.8% and 81.2% respectively) were fractured or torn after warming and none of the 12 intact embryos transferred resulted in a pregnancy. Better survival rates immediately after thawing and rehydration were obtained with the smaller Day 6 embryos (94%), which resulted in a total of eight fetuses from the 21 embryos transferred.

Animals↗

Purification to homogeneity of camel pituitary pro-opiocortin, the common precursor of opioid peptides and corticotropin.

Pro-opiocortin was purified from camel pituitaries by procedures including high-performance liquid chromatography. The precursor relationship of the pure protein to the opioid peptides and to corticotropin was confirmed. Partial chemical analysis consisting of amino acid analysis and tryptic peptide mapping was carried out with the aid of sensitive fluorescence detection.

Adrenocorticotropic Hormone↗

Optimal design features of camelized human single-domain antibody libraries.

We have constructed a human V(H) library based on a camelized V(H) sequence. The library was constructed with complete randomization of 19 of the 23 CDR3 residues and was panned against two monoclonal antibody targets to generate V(H) sequences for determination of the antigen contact residue positions. Furthermore, the feasibility and desirability of introducing a disulfide bridge between CDR1 and CDR3 was investigated. Sequences derived from the library showed a bias toward the use of C-terminal CDR3 residues as antigen contact residues. Mass spectrometric analyses indicated that CDR1-CDR3 disulfide formation was universal. However, surface plasmon resonance and NMR data showed that the CDR3 constraint imposed by the disulfide bridge was not always desirable. Very high yields of soluble protein products and lack of protein aggregation, as demonstrated by the quality of the (1)H-(15)N HSQC spectra, indicated that the V(H) sequence for library construction was a good choice. These results should be useful in the design of V(H) libraries with optimal features.

Amino Acid Sequence↗

Protein intermediate trapped by the simultaneous crystallization process. Crystal structure of an iron-saturated intermediate in the Fe3+ binding pathway of camel lactoferrin at 2.7 a resolution.

This is the first protein intermediate obtained in the crystalline state by the simultaneous process of Fe(3+) binding and crystal nucleation and is also the first structure of an intermediate of lactoferrin in the Fe(3+) binding pathway. Lactoferrin is an iron-binding 80-kDa glycoprotein. It binds Fe(3+) very tightly in a closed interdomain cleft in both lobes. The iron-free structure of lactoferrin, on the other hand, adopts an open conformation with domains moving widely apart. These studies imply that initial Fe(3+) binding must be in the open form. The protein intermediate was crystallized by the microdialysis method. The protein solution, with a concentration of 100 mg/ml in 10 mm Tris-HCl, pH 8.0, was loaded in a capillary and dialyzed against the same buffer containing 26% (v/v) ethanol placed in a reservoir. FeCl(3) and CO(3)(2-) in excess molar ratios to that of protein in its solution were added to the reservoir buffer. The crystals appeared after some hours and grew to the optimum size within 36 h. The structure was determined by molecular replacement method and refined to final R- and R-free factors of 0.187 and 0.255, respectively. The present structure showed that the protein molecule adopts an open conformation similar to that of camel apolactoferrin. The electron density map clearly indicated the presence of two iron atoms, one in each lobe with 4-fold coordinations: two by the protein ligands of Tyr-92(433) OH and Tyr-192(526) OH and two other coordination sites occupied by oxygen atoms of bidentate CO(3)(2-) ions leading to a tetrahedral intermediate. The CO(3)(2-) anion is stabilized through hydrogen bonds with the synergistic anion-binding site Arg-121(463) and with Ser-122 Ogamma in the N-lobe and Thr-464 Ogamma in C-lobe. The third oxygen atom of CO(3)(2-) interacts with a water molecule in both lobes.

Animals↗

Poll glands of the one-humped camel (Camelus dromedarius): a histochemical and scanning electron microscopic study.

Poll glands of the one-humped camel were obtained to examine their secretory mechanism by lectin histochemistry, immunohistochemistry and scanning electron microscopy. The glands were composed of numerous conical lobules which consisted of apocrine tubules. Lectins of peanut agglutinin (PNA), Dolicos biflorus agglutinin (DBA) and wheat germ agglutinin (WGA) showed a variety of staining in the Golgi areas and secretory granules in secretory cells of the apocrine tubules. Most myoepithelial cells stained intensely with a-smooth muscle actin. Varicose nerve fibers immunostained with protein gene product 9.5 were scattered among apocrine tubules. Scanning electron microscopy revealed that the luminal surface of secretory cells was covered with microvilli and that secretory cells pinched off smooth-surfaced apocrine blebs. After pinching off, crater-like pits remained on the luminal surface of secretory cells. These findings are similar to those obtained from the infraorbital glands of the serows.

Actins↗

Experimental infection of the one-humped camel (Camelus dromedarius) with Sarcoptes scabiei var. cameli and S. scabiei var. ovis.

Camels were experimentally infected with Sarcoptes scabiei var. cameli and S. scabiei var. ovis. The lesions produced by both mites were progressive and similar in extent and severity. The lesions produced by the mites spread mechanically through gnawing and scratching, and eventually covered most of the body of the host. Skin scrapings from the experimental lesions contained many mites of all stages, proving that S. scabiei var. cameli and S. scabiei var. ovis became equally well established, reproducing actively in the experimental lesions in their 'natural' and 'wrong' host respectively. The histopathological changes produced by S. scabiei var. cameli and S. scabiei var. ovis were similar. The lesions comprised thick scab and keratin formation, with mites beneath the scab and keratin, marked haemorrhages and severe degenerative and necrotic changes. Excellent clinical recovery occurred following the application of HCH (BHC) after removal of crusts and detritus with salicylic acid. The incomplete host specificity of Sarcoptes necessitates the complete isolation of healthy from infected animals regardless of the host species.

Animals↗