Plasma dispositions and concentrations of ivermectin in eggs following treatment of laying hens.

AIMS: To determine the plasma disposition and concentrations of ivermectin (IVM) in eggs produced by laying hens following S/C, oral and I/V administration. METHODS: Twenty-four laying hens, aged 37 weeks and weighing 1.73 (SD 0.12) kg were allocated to three groups of eight birds. The injectable formulation of IVM was administered either orally, S/C, or I/V, at a dose of 0.2 mg/kg liveweight, following dilution (1:5, v/v) with propylene glycol. Heparinised blood samples were collected at various times between 0.25 hours and 20 days after drug administration. Eggs produced by hens were also collected daily throughout the study period. Samples of plasma and homogenised egg were analysed using HPLC. RESULTS: Maximum concentrations of IVM in plasma and mean residence time of IVM were lower after oral (10.2 (SD 7.2) ng/mL and 0.38 (SD 0.14) days, respectively) than after S/C (82.9 (SD 12.4) ng/mL and 1.05 (SD 0.24) days, respectively) administration (p<0.01). The time to maximum concentration and elimination half-life were shorter following oral (0.14 (SD 0.04) and 0.23 (SD 0.11) days, respectively) than S/C (0.25 (SD 0.00) and 1.45 (SD 0.45) days, respectively) administration (p<0.01). IVM was first detected in eggs 2 days after treatment in all groups and was detected until 8 days after oral and I/V administration, and until 15 days after S/C administration. Peak concentrations of IVM were 15.7, 23.3 and 1.9 µg/kg, observed 2, 5 and 4 days after I/V, S/C and oral administration, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The low plasma bioavailability of IVM observed after oral administration in laying hens could result in lower efficacy or subtherapeutic plasma concentrations, which may promote the development of parasitic drug resistance. Due to high IVM residues in eggs compared to the maximum residue limits for other food-producing animal species, a withdrawal period should be necessary for eggs after IVM treatment in laying hens.

Comparative evaluation of dietary supplementation with mannan oligosaccharide and oregano essential oil in forced molted and fully fed laying hens between 82 and 106 weeks of age.

The aim of this study was to investigate the efficacy of feed-grade preparations of mannan oligosaccharides ( MOS: ) and oregano essential oil ( OEO: ) in forced molted or fully fed 82-week-old, laying hens. A 2 × 3 factorial experiment investigated the influence of molting vs. full feeding and dietary supplements [i.e., unsupplemented control, MOS (1 g/kg) diet, and OEO (24 mg/kg) diet] on production parameters, egg quality, serum stress indicators, blood constituents, tibial characteristics, liver antioxidant status, and cecal microflora composition. A total of 864 Single Comb White Leghorn hens were randomly assigned to 6 treatments, each with 6 replicates of 24 hens each, and studied for 25 wk. Hens were fed a molt diet containing of 50% alfalfa and 50% wheat bran ( AA+WB: ) for 12 d, then returned to the laying ration. Results indicate that molt vs. full feed impacted more on most variables measured than supplementation or supplement type. Significant (P < 0.01) interactions between molting and diet were observed for the egg production, egg weight, egg mass, and feed conversion ratio ( FCR: ). In fully fed hens, MOS supplementation improved (P < 0.01) the egg production, egg weight, and FCR, and an OEO addition significantly improved the egg production and FCR in forced molted hens. Molting improved egg quality despite the significant regression in ovary and oviduct weight (P < 0.01), though supplements showed no influence. The bone ash (P < 0.01) and mineral content (P < 0.05) of molted hens were significantly lower than those of fully fed counterparts; however, poor mineralization was not reflected in the bones' mechanical properties. No significant differences were observed among treatments for hematological characteristics. Both the MOS and particularly the OEO supplementation improved (P < 0.01) liver antioxidant status and mitigated the significant increase in cecal pathogenic bacteria after molt. Our results indicate that full feeding with an aa+wb diet is an effective non-feed-removal method for molted hens, the benefit of which can be improved with MOS and OEO supplementation.

Comparative plasma and milk dispositions, faecal excretion and efficacy of per os ivermectin and pour-on eprinomectin in horses.

The horse milk gains increasing interest as a food product for sensitive consumers, such as children with food allergies or elderly people. We investigated the plasma and milk disposition, faecal excretion and efficacy of per os ivermectin (IVM) and pour-on eprinomectin (EPM) in horses. Ten mares were divided into two groups. The equine paste formulation of IVM and bovine pour-on formulation of EPM were administered orally and topically at dosage of 0.2 and 0.5 mg/kg bodyweight. Blood, milk and faecal samples were analysed using high-performance liquid chromatography. The plasma concentration and persistence of IVM were significantly greater and longer compared with those of EPM. Surprisingly, EPM displayed a much higher disposition rate into milk (AUCmilk/plasma : 0.48) than IVM (AUCmilk/plasma : 0.19). IVM exhibited significantly higher faecal excretion (AUCfaeces : 7148.54 ng·d/g) but shorter faecal persistence (MRTfaeces : 1.17 days) compared with EPM (AUCfaeces : 42.43 ng·d/g and MRTfaeces : 3.29 days). Faecal strongyle egg counts (EPG) were performed before and at weekly intervals after treatment. IVM reduced the EPG by 96-100% for up to 8 weeks, whereas the reduction in the EPM group varied from 78 to 99%. In conclusion, due to the relatively low excretion in milk, EPM and IVM may be used safely in lactating mares if their milk is used for human consumption. Nevertheless, much lower plasma and faecal availabilities of EPM could result in subtherapeutic concentrations, which may increase the risk of drug resistance in nematodes after pour-on EPM administration compared with per os IVM.

Effect of anticoccidial monensin with oregano essential oil on broilers experimentally challenged with mixed Eimeria spp.

Essential oil of oregano ( OEO: ) has proven to be a potential candidate for controlling chicken coccidiosis. The aim of the current study is to determine whether OEO and an approved anticoccidial, monensin sodium ( MON: ), as in-feed supplements could create a synergism when combined at low dosages. Day-old broiler chickens were separated into six equal groups with six replicate pens of 36 birds. One of the groups was given a basal diet and served as the control ( CNT: ). The remaining groups received the basal diet supplemented with 100 mg/kg MON, 50 mg/kg MON, 24 mg/kg OEO, 12 mg/kg OEO, or 50 mg/kg MON + 12 mg/kg OEO. All of the chickens were challenged with field-type mixed Eimeria species at 12 d of age. Following the infection (i.e., d 13 to 42), the greatest growth gains and lowest feed conversion ratio values were recorded for the group of birds fed 100 mg/kg MON (P < 0.05), whereas results for the CNT treatment were inferior. Dietary OEO supplementations could not support growth to a level comparable with the MON (100 mg/kg). The MON programs were more efficacious in reducing fecal oocyst numbers compared to CNT and OEO treatments (P < 0.05). Serum malondialdehyde and nitric oxide concentrations were decreased (P < 0.01), whereas superoxide dismutase (P < 0.05) and total antioxidant status (P < 0.01) were increased in response to dietary medication with MON and OEO. All MON and OEO treatments conferred intestinal health benefits to chickens by improving their morphological development and enzymatic activities. The results suggest that OEO supported the intestinal absorptive capacity and antioxidant defense system during Eimeria infection; however, it displayed little direct activity on the reproductive capacity of Eimeria This might be the reason for inferior compensatory growth potential of OEO compared to that MON following the challenge. Combination MON with OEO was not considered to show promise for controlling chicken coccidiosis because of the lack of a synergistic or additive effect.

Effects of selenium on ischaemia-reperfusion injury in a rat testis model.

Selenium is shown to have beneficial effects on ischaemia-reperfusion (IR) injury. Our aim was to assess the effects of selenium on IR-induced testicular damage in terms of biochemical and histopathological evaluation. A total of 32 rats were randomised into four groups: control, IR, IR + selenium (IR + S) and S. Detorsion was applied after 3 h of torsion. Testicular tissue superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), total antioxidant capacity (TAC) and DNA fragmentation levels were determined. Testicular tissue samples were examined by histopathological examination and terminal deoxynucleotidyl transferase dUTP nick end-labelling staining. The control, IR and IR + S groups had higher SOD values compared with the S group; SOD levels of the control and IR + S groups were higher than those of the IR group (P < 0.05). Further, MDA levels of the IR group were higher than those in the other three groups (P < 0.05). The IR group revealed lower TAC levels than the three groups (P < 0.05 for all). GSH levels of the IR group were significantly lower than those in the other three groups (P < 0.05 for all). In contrast, GSH levels of the IR + S group increased compared with those of the S group. The IR group had more DNA fragmentation than the control and S groups (P < 0.05). It is concluded that selenium possibly reduces oxidative stress and apoptosis caused by testicular IR injury in rats. The testicular protective effect of selenium appears to be mediated through its anti-apoptotic and antioxidative effects. However, selenium does not affect DNA fragmentation.

Plasma disposition and faecal excretion of eprinomectin following topical and subcutaneous administration in non-lactating dairy cattle.

AIMS: To investigate the plasma disposition and faecal excretion of eprinomectin (EPM) in non-lactating dairy cattle following topical and S/C administration. METHODS: Holstein dairy cows, 3.5-5 years-old, were selected 20-25 days after being dried off and were randomly allocated to receive EPM either topically (n=5) or S/C (n=5) at dose rates of 0.5 and 0.2 mg/kg bodyweight, respectively. Heparinised blood and faecal samples were collected at various times between 1 hour and 30 days after treatment, and were analysed for concentrations of EPM using high performance liquid chromatography with a fluorescence detector. RESULTS: The maximum concentration of EPM in plasma (Cmax) and the time to reach Cmax were both greater after S/C administration (59.70 (SD 12.90) ng/mL and 1.30 (SD 0.27) days, respectively) than after topical administration (20.73 (SD 4.04) ng/mL and 4.40 (SD 0.89) days, respectively) (p<0.001). In addition, S/C administration resulted in greater plasma availability (area under the curve; AUC), and a shorter terminal half-life and mean residence time (295.9 (SD 61.47) ng.day/mL; 2.95 (SD 0.74) days and 4.69 (SD 1.01) days, respectively) compared with topical administration (168.2 (SD15.67) ng.day/mL; 4.63 (SD 0.32) days, and 8.23 (SD 0.57) days, respectively) (p<0.01). EPM was detected in faeces between 0.80 (SD 0.45) and 13.6 (SD 4.16) days following S/C administration, and between 1 (SD 0.5) and 20.0 (SD 3.54) days following topical administration. Subcutaneous administration resulted in greater faecal excretion than topical administration, expressed as AUC adjusted for dose (1188.9 (SD 491.64) vs. 311.5 (SD 46.90) ng.day/g; p<0.05). Maximum concentration in faeces was also higher following S/C than topical administration (223.0 (SD 63.96) vs. 99.47 (SD 43.24) ng/g; p<0.01). CONCLUSIONS: Subcutaneous administration of EPM generated higher plasma concentrations and greater plasma availability compared with topical administration in non-lactating cattle. Although the S/C route provides higher faecal concentrations, the longer faecal persistence of EPM following topical administration may result in more persistent efficacy preventing establishment of incoming nematode larvae in cattle.

Evaluation of oxidative stress via total antioxidant status, sialic acid, malondialdehyde and RT-PCR findings in sheep affected with bluetongue.

INTRODUCTION: Bluetongue (BT) is a non-contagious infectious disease of ruminants. The disease agent bluetongue virus (BTV) is classified in the Reoviridae family Orbivirus. AIMS AND OBJECTIVES: The aim of this study was to determine serum malondialdehyde (MDA), total antioxidative stres (TAS), total sialic acid (TSA), ceruloplasmin, triglyceride, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), cholesterol, creatinine, albumin, and total protein levels in sheep with and without bluetongue (BT). MATERIALS AND METHODS: The study included 13 Sakiz crossbreed sheep, aged 1-4 years and usually in the last stage of pregnancy, as the BT group and a control group consisting of 10 healthy sheep. All sheep were clinically examined before collecting blood samples. Serum ALT, AST, cholesterol, triglyceride, albumin, GGT, total protein, creatinine and TAS levels were measured using commercially available kits as per manufacturer's recommendations using a Biochemistry Auto Analyzer (Sinnowa D280, China). Serum lipid peroxidation was estimated through a previously described method in which MDA reacts with thiobarbituric acid (TBA) to form a coloured complex at a maximum absorbance of 535 nm. The TSA value was measured at 549 nm using the method described by Warren (1959): sialic acid was oxidised to formyl-pyruvic acid, which reacts with TBA to form a pink product. The ceruloplasmin concentration was measured according to Sunderman and Nomoto (1970): ceruloplasmin and p-phenylenediamine formed a coloured oxidation product that was proportional to the concentration of serum ceruloplasmin. Real time RT-PCR and conventional RT-PCR were performed as described by Shaw and others (2007). RESULTS: Biochemistry analysis of serum showed that in the BT group, TSA, MDA, triglyceride and ALT and AST were higher and that ceruloplasmin and TAS were lower than in the control group. Serum albumin, cholesterol, creatinine, total protein and GGT did not differ significantly between the two groups. CONCLUSIONS: Serum triglyceride, ceruloplasmin, TSA, MDA and TAS concentrations may prove beneficial to the diagnosis, prognosis and biochemical analysis of BT.

The effects of different ages and dosages on the plasma disposition and hair concentration profile of ivermectin following pour-on administration in goats.

The effects of different ages and dosages on the plasma disposition and hair concentration profile of ivermectin following pour-on administration in goats. J. vet. Pharmacol. Therap.34, 70-75. The effects of different ages and dosages on the plasma disposition and hair degradation of ivermectin (IVM) were investigated following pour-on administration in goats. Twenty-eight female Saanen goats allocated into two groups of 14 animals according to their ages as young (5-6 months old) and old (12-24 months old) groups. Each age group was divided into two further of seven goats and administered pour-on formulation of IVM topically at the in recommended dosage rate of 0.5 mg/kg bodyweight The recommended cattle dosages rate of 0.5 mg/kg or at the higher dosage of 1.0 mg/kg. Blood samples were collected at various times between 1 h and 40 days. In addition, hair samples (>0.01 g) were collected using tweezers from the application sites and far from application sites of the all animals throughout the blood sampling period. The plasma and hair samples were analyzed by high performance liquid chromatography (HPLC) using fluorescence detection following solid and liquid phase extractions, respectively. Dose- and age-dependent plasma disposition of IVM were observed in goats after pour-on administration. In addition, relatively high concentration and slow degradation of IVM in hair samples collected from the application site and far from the application site were observed in the present study. The differences between young and old goats are probably related to differences in body condition and/or lengths of haircoat. The systemic availability of IVM following pour-on administration is relatively much lower than after oral and subcutaneous administrations but the plasma persistence was prolonged. Although, the longer persistence of IVM on hairs on the application site may prolong of efficacy against ectoparasites, the poor plasma availability could result in subtherapeutic plasma concentrations, which may confer the risk of resistance development in for internal parasites after pour-on administration in goats.

A study of variations of transverse foramens of cervical vertebras in human: accessory foramina in shape and number.

Transverse foramens of 250 cervical vertebras were examined. There were accessory foramina and variations in shape and number in 10 out of 250 cervical vertebras. Since such a variation of foramens, through which the vertebral artery passes, has not been detected in the literature, these ten cases are to be considered.

A variation of the median nerve at the level of brachial plexus.

We report a variation of the median nerve at the level of brachial plexus in a 38 years old male cadaver. The median nerve was formed by the fusion of three branches; two of them coming from the lateral cord, and one from the medial cord. The abnormal root coming from the lateral cord had a very close oblique course over the axillary artery. These kinds of variations are more prone to injury in radical neck dissections and in other surgical operations of the axilla. Secondly, the very close course of the unusual branch with the axillary artery may lessen the blood supply of the upper extremity by compressing the vessel.

Morphometric analysis of the foot in adult Turkish men.

It is now well known that anthropometric measures of the foot differ in different communities. This research is a descriptive study to determine the foot measures collected from 1956 personnel working at a communication school. The results of this study are statistically different from the values of Paris system that is accepted by Turkish National Institute for Standardization (abbreviated as TSE). It is found that Turkish men's feet are shorter and wider as compared to the standards accepted by TSE.

The configuration of prepubertal hymen in Turkish population and its clinical aspect.

The importance of the hymenal configuration lies in the fact that it is accepted as an important sign of the virginity in many countries and also it needs a clearcut definition for the forensic evaluation of child abuse and rape. To improve understanding of configuration of the normal hymen we studied 100 prepubertal hymens. In addition to the most commonly seen types we found the fimbriated hymen at a high rate especially in adolescents. There was another configuration the appearance of which differed on each half of the vaginal orifice; one half had a labium while the other had fimbriae. The tagged type hymen was also encountered.

[Appropriate concentrations of antimicrobial agents in used cadaver pools]. / Kadavra havuzlarinda kullanilan antimikrobiyal ajanlarin uygun konsantrasyonlarinin arastirilmasi.

Samples for microbiologic culture were taken from 17 cadaver and 4 cadaver pools in the Department of Anatomy of Gülhane Military Medical Academy (GMMA), Military Faculty of Medicine. Samples were inoculated on bacteriologic and mycologic media and were incubated in aerobic and 10% CO2 atmosphere conditions. From 3 of 4 pools containing different concentration of phenol and formalin, pathogenic bacteria that might be present in normal flora and saprophytic fungi were isolated. In the guidance of these results, in order to keep the cadavers for a long time and laboratory safety, use of formalin and phenol not less than 5% and 4% concentrations of the cadavers respectively and the pools should be taken into consideration.

[Herpes simplex type I virus observed in the superior cervical ganglion from human cadavers and autopsy materials]. / Insan kadavra ve otopsi materyallerinden elde edilen ganglion cervicale superius'larda herpes simplex tip I virusunun arastirilmasi.

Herpes Simplex Type I (HSV I) causes some infections such as herpes labialis, encephalitis, keratoconjunctivitis and also some cranial nerve syndromes such as acute vestibular neuritis, migraine and Meniere's disease in human. We used 4 fixated and 16 fresh cadavers to isolate HSV I virus from the Superior Cervical Ganglia. The ganglia materials are inoculated to PRK (primary rabbit kidney), VERO (African Green Monkey Kidney) and BHK 21 (Baby Hamster Kidney) cell lines in order to isolate the virus. We isolated HSV I virus from 12 fresh cadavers' cervical ganglia (75%) and neutralisation test is performed in order to characterize HSV I. But we could not isolate the virus from any of the fixated cadavers.