Pharmacokinetic-pharmacodynamic integration and modelling of florfenicol in calves.

Florfenicol was administered subcutaneously to 10 calves at a dose of 40 mg/kg. Pharmacokinetic-pharmacodynamic (PK-PD) integration and modelling of the data were undertaken using a tissue cage model, which allowed comparison of microbial growth inhibition profiles in three fluids, serum, exudate and transudate. Terminal half-lives were relatively long, so that florfenicol concentrations were well maintained in all three fluids. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration were determined in vitro for six strains each of the calf pneumonia pathogens, Mannhemia haemolytica and Pasteurella multocida. An PK-PD integration for three serum indices provided mean values for P. multocida and M. haemolytica, respectively, of 12.6 and 10.4 for Cmax /MIC, 183 and 152 h for AUC0-24 h /MIC and 78 and 76 h for T>MIC. Average florfenicol concentrations in serum exceeded 4 × MIC and 1.5 × MIC for the periods 0-24 and 48-72 h, respectively. Ex vivo growth inhibition curves for M. haemolytica and P. multocida demonstrated a rapid (with 8 h of exposure) and marked (6 log10 reduction in bacterial count or greater) killing response, suggesting a concentration-dependent killing action. During 24-h incubation periods, inhibition of growth to a bacteriostatic level or greater was maintained in serum samples collected up to 96 h and in transudate and exudate samples harvested up to 120 h. Based on the sigmoidal Emax relationship, PK-PD modelling of the ex vivo time-kill data provided AUC0-24 h /MIC serum values for three levels of growth inhibition, bacteriostatic, bactericidal and 4 log10 decrease in bacterial count; mean values were, respectively, 8.2, 26.6 and 39.0 h for M. haemolytica and 7.6, 18.1 and 25.0 h for P. multocida. Similar values were obtained for transudate and exudate. Based on pharmacokinetic and PK-PD modelled data obtained in this study and scientific literature values for MIC distributions, Monte Carlo simulations over 100 000 trials were undertaken to predict once daily dosages of florfenicol required to provide 50% and 90% target attainment rates for three levels of growth inhibition, namely, bacteriostasis, bactericidal action and 4 log10 reduction in bacterial count.

Spreader graft placement in endonasal rhinoplasty: Technique and a review of 100 cases.

BACKGROUND: Spreader grafts are widely considered to be the mainstay of treatment for insufficient internal nasal valve and are commonly placed preventively during rhinoplasty, after hump removal, to avoid middle vault collapse. Although the placement and suturing of spreader grafts in open rhinoplasty is fairly easy, their positioning and stabilization in endonasal rhinoplasty is associated with a learning curve. METHODS: A review of the technique with tips for the novice surgeon is presented, particularly as pertains to correct placement. The technique can be used to insert spreader grafts irrespective of whether the nasal dorsum is addressed. Suturing is usually unnecessary. A retrospective review of 100 patients in whom spreader grafts were placed was undertaken to evaluate complications such as poor placement, displacement or other complications. RESULTS: Although there is a learning curve to ensure the dorsal mucosal attachment is maintained while developing the pocket sufficiently dorsally for proper graft placement, the technique is easy to learn, effective, quick and technically simple to perform. Of 100 patients, three had a cartilaginous dorsal spur as the cephalic edge of the graft became visible. One patient developed an ecchymosis along the dorsum that caused a hump that resolved in two months. There were no other aesthetic or functional complications. CONCLUSION: The endonasal placement technique provides for simple, safe and easy placement, as well as stabilization of spreader grafts during endonasal rhinoplasty, with few complications.

HISTORIQUE: Les greffes d'écarteur sont largement considérées comme le pilier du traitement lorsque la valve nasale interne est trop étroite. Elles sont souvent implantées de manière préventive pendant la rhinoplastie, pour éviter l'affaissement du septum après la correction d'une bosse. Même si l'implantation et la suture des écarteurs sont plutôt simples lors d'une rhinoplastie ouverte, leur mise en position et leur stabilisation s'associent à une courbe d'apprentissage pour la rhinoplastie endonasale. MÉTHODOLOGIE: Une analyse de la technique avec des pinces pour le chirurgien novice est présentée, particulièrement pour garantir une bonne implantation. On peut utiliser la technique pour implanter des écarteurs, même si on ne touche pas l'arête du nez. En général, les sutures sont inutiles. Les chercheurs ont entrepris une analyse rétrospective de 100 patients qui se sont fait implanter des écarteurs, afin d'évaluer des complications comme une mauvaise implantation, un déplacement ou d'autres problèmes. RÉSULTATS: Même s'il y a une courbe d'apprentissage pour s'assurer que la muqueuse de l'arête du nez est bien rattachée et développer suffisamment la poche de l'arête pour bien implanter la greffe, la technique est facile à apprendre, efficace, rapide et simple sur le plan technique. Sur les 100 patients, trois ont présenté un éperon cartilagineux tandis que le bord céphalique de la greffe devenait visible. Un patient a présenté une ecchymose le long de l'arête du nez, laquelle a causé une bosse qui a disparu au bout de deux mois. Aucune autre complication n'a touché l'esthétisme ou la fonction du nez. CONCLUSION: La technique d'implantation endonasale est simple, sécuritaire et facile. Elle permet de bien stabiliser les écarteurs pendant la rhinoplastie endonasale et provoque peu de complications.

Determination of serum 25-hydroxyvitamin D(3) levels in early postmenopausal Iranian women: relationship with bone mineral density.

Serum levels of 25-hydroxyvitamin D(3) (25-OHD(3)) and bone mineral density (BMD) were determined in 73 selected, early postmenopausal women referred to the Bone Densitometry Center, Loghman-Hakim Hospital, Tehran, Iran. The relationship between them was also assessed. 25-OHD(3) levels were measured using high-performance liquid chromatography. BMD was measured with dual-energy X-ray absorptiometry of the lumbar spine and proximal femur regions. 25-OHD(3) levels ranged from 3.8 to 64.0 ng/mL (mean +/- SD: 17.1 +/- 11.3). Twenty-six subjects (36%) were vitamin D-deficient (<12 ng/mL). In the lumbar spine (L2-4) BMD measurements, 28 subjects (38%) were normal (T score > -1), 26 (36%) were osteopenic (T < or = -1 to >-2.5), and 19 (26%) were osteoporotic (T < -2.5). In the hip (total) BMD measurements, 41 subjects (56.1%) were normal, 31 (42.5%) were osteopenic, and 1 (1.4%) was osteoporotic. There was a significant correlation between spine BMD (Z score) and 25-OHD(3) (r = 0.23, p < 0.05), but the correlation was not significant for hip BMD. It was concluded that vitamin D deficiency was evident in early postmenopausal Iranian women, and serum 25-OHD(3) was weakly correlated with spine BMD, which may have physiological significance.

Determination of artemisinin in Artemisia sieberi and anticoccidial effects of the plant extract in broiler chickens.

Artemisinin has received much attention in the treatment of malaria in recent years, and it is now considered as a potential candidate to reduce coccidial infection in chickens. It is a sesquiterpene compound which has been isolated from Aretemisia annua for the first time. The present study aimed to investigate the occurrence of artemisinin in A. sieberi (AS) and to test the anticoccidial effects of plant extract in broiler chickens. The aerial parts of the plant were collected during different seasons from Yazd Province, in the centre of Iran. The artemisinin content of the AS was extracted with petrol ether and analysed by high-performance liquid chromatography using UV detection. Anticoccidial effects of the plant extract were tested on chicks challenged with various species of Eimeria. The infected chickens were treated with doses of 1 or 2.5 mg/kg per day artemisinin via oral administration of plant extract. The analytical results showed that the level of artemisinin in AS was 0.2% and 0.14% of dried weight (DW) of plant materials in summer and autumn, respectively. Treatment of experimentally infected chickens with AS extracts showed that artemisinin was able to reduce the severity of coccidial infection induced by Eimeria tenella and E. acervulina, but not E. maxima. The anticoccidial effects of artemisinin were shown by significant decrease in output of number of oocysts per gram of faeces in chickens challenged with different species of Eimeria. This study showed that the levels of artemisinin in AS were comparable with those in other species including A. annua, and that the extract of this plant can reduce coccidial infection in broiler chickens.

Generation of hydroxyl radicals during ascites experimentally induced in broilers.

Increased metabolic rates, pulmonary hypertension and cardiac dysfunction are the most important features of the ascites syndrome in broiler chickens. However, the mechanism of cell injury causing the pathogenesis of the syndrome is not clearly understood. Our study aimed to examine the generation of hydroxyl radicals (OH*) in broiler chickens experiencing ascites. The hundred and fifty 1-d-old chickens were purchased from a local hatchery and reared in an open poultry house for 46 d. They were divided at random into three groups and ascites was induced in two groups by exposing them to low temperature or administration of triiodothyronine (T(3)). The third group served as control and was reared normally. Haematological, biochemical and pathological tests were used to determine the incidence of ascites: including total red blood cell (RBC), packed cell volume (PCV), release of alanine transaminase (ALT) and aspartate transaminase (AST) and ratio of right ventricular weight to total ventricular weight (RV/TV). A salicylate hydroxylation method was used to examine the generation of hydroxyl radicals (OH*) in treated groups. TWo hydroxylated salicylic acid metabolites, 2,3- and 2,5-dihydroxy benzoic acid (2,3- and 2,5-DHBA), were measured by HPLC to detect the generation of OH*. An ascites syndrome was observed in T(3) and low-temperature treated groups, as shown by necropsy changes and increases in f RBC, PCV, ALT, AST and the ratio of RV/TV. Concentrations of 2,3- and 2,5-DHBA were increased in groups experiencing ascites compared to control group. It is suggested that reactive oxygen species that is OH* ions, may be involved in the pathogenesis of the ascites syndrome in broiler chickens.