Pharmacokinetics of Moxifloxacin in Rabbits After Intravenous,Subcutaneous and a Long‐acting Poloxamer 407 Gel Formulation Administration

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long‐acting poloxamer 407 gel formulation (SC‐P407). Moxifloxacin concentrations were determined by high‐performance liquid chromatography assay with fluorescence detection. Mean half‐life for IV, SC and SC‐P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C_max was 1.61 ± 0.49 mg/l. After SC‐P407 administration, the bioavailability was 44% and the C_max 1.83 was ±0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC‐P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC‐P407 formulation and the favourable PK behaviour such as the long half‐life, acceptable bioavailability and excellent PK–PD ratios achieved indicate that it is likely to be effective in rabbits.     

降钙素防治骨质疏松模型兔的人工假体无菌性松动的实验研究

[目的]探讨降钙素对已行人工假体植入骨质疏松模型免的假体无菌性松动防治作用的实验研究。[方法]将30只假体植入模型的骨质疏松症兔随机分成实验组和对照组，各15只。实验组给予鲑鱼降钙素治疗（6U／kg，肌注，隔日1次），而对照组给予等量的生理盐水肌注，持续治疗半年。两组均分别于术前、术后4、8、12和24周检测假体周围感应区（ROI）骨密度（BMD）；于术前及术后4、12、24周行血清骨代谢指标检测：骨特异性碱性磷酸酶（BALP）、骨钙素（BGP）、抗酒石酸酸性磷酸酶-5b（TRAP-5b）；所有动物于术后24周处死，分别行假体拔出实验与扭转实验测定和假体周围骨组织形态计量学分析。[结果]术后24周，实验组假体周围局部感兴趣区BMD增加近5％，而对照组假体周围局部感兴趣区BMD下降了6％，两组比较有显著性差异（P〈0．01）；骨代谢指标中，术后24周实验组的BALP、BGP稍有下降，但组内无显著性差异（P〉0．05），而TRAP-5b有明显下降（P〈0．05），这些指标与对照组比较差异显著（P〈0．05或P〈0．01）；生物力学检测显示，实验组的假体拔出实验较对照组提高了约50％，扭转实验提高近1倍，且两组比较差异显著（P〈0．01）；骨组织形态计量学显示，实验组中反映骨吸收的Oc．No／Tb．Pm、ES／BS明显减少；反映骨量和微结构的％Tb．Ar、Tb．N明显增多，而Tb．Sp明显变窄：反映骨形成与骨矿化的OS／BS、MAR、BFR／TV及％L．Pm也均明显增多；这些指标与对照组比较差异显著（P〈0．01或P〈0．05）。[结论]鲑鱼降钙素能明显减少人工假体周围骨量的丢失和抑制骨溶解；并加快假体周围的骨形成，提高骨密度，促进生理性骨矿化；还能改善骨质量，促进骨微结构改变，提高骨的生物力学特性并增加假体四周的支撑力。其对骨质疏松症兔的假体松动有明显的预防和治疗作用。这对临床预防和治疗人工关节的无菌性松动有很好的指导意义。     

Right aortic arch detected in fetal life.

OBJECTIVE: To evaluate the prenatal distribution, associated conditions and outcome of the different types of right aortic arch (RAA) detected in fetal life. METHODS: This was a retrospective review of all cases of RAA detected prenatally between 1998 and 2005 in two tertiary referral centers. RESULTS: In the study period 71 cases of RAA were detected; 26 (37%) had RAA with aberrant left subclavian artery, 23 (32%) had RAA with mirror-image branching, 20 (28%) had RAA of unknown type and two (3%) had double aortic arch. While 20/26 cases with RAA and aberrant left subclavian artery were isolated findings, all 23 cases with RAA and mirror-image branching were associated with cardiac defects, namely tetralogy of Fallot (43%) or pulmonary atresia with ventricular septal defect (22%). Of the 20 cases with RAA, 19 of unknown type were associated with heterotaxy syndromes and had additional cardiac malformations and ambiguities of the situs. The two cases with DAA were isolated findings. Seven cases in our series (10%) had a microdeletion 22q11 and these were significantly associated with extracardiac malformations. The outcome in our series depended solely on the associated cardiac and extracardiac malformations, with the exception of one infant with isolated DAA, in whom a surgical correction was warranted. CONCLUSIONS: RAA detected in fetal life is associated frequently with other cardiac/non-cardiac malformations, heterotaxy syndromes and microdeletions 22q11. The associated conditions vary depending on the branching type of the brachiocephalic vessels and the presence of extracardiac malformations.     

Autoimmune hepatitis: a study of 50 patients.

INTRODUCTION: Autoimmune hepatitis (AIH) is a well-defined entity in the West but there are sparse Indian data on this disease. AIM: To study the clinical profile and response to treatment of Indian patients with AIH. METHODS: This is a part retrospective and part prospective study of 50 patients (median age 48 years, range 11-82; 43 women) seen between 1995 to 2001, diagnosed to have AIH as per the revised scoring system. Clinical and laboratory profile, response to treatment, and complications of treatment were analyzed. RESULTS: AIH accounted for 6% of all patients with liver disease seen during the period. The presenting symptoms were gastrointestinal in 43 and non-gastrointestinal in 7, with median symptom duration of 6 months (range 2 weeks to 40 years). Forty patients (80%) had chronic liver disease. Associated illnesses were present in 28 patients. Twenty-six patients were classified as definite and the rest as probable AIH. Forty-nine patients had Type 1 AIH. Five patients had overlap syndrome. Forty-five patients (90%) received immunosuppressive therapy. Twelve of 18 patients receiving only prednisolone and 21 of 27 patients receiving prednisolone and azathioprine combination responded. Thirteen (26%) patients had therapy-related complications (infectious 5, non infectious 8) with two treatment-related deaths. CONCLUSION: Type 1 AIH was the predominant type of AIH. The majority of patients with AIH presented with chronic liver disease. There was good response to immunosuppressive therapy. Therapy-related complications occurred in one-fourth of patients.     

Semi-empirical systematics of (n,3He) reaction cross-section at 14.6 and 20 MeV.

A new semi-empirical formula for the evaluation of (n,(3)He) reaction cross-sections at the energy of 14.6 and 20 MeV is presented. Formula was derived using the analytical expression for the evaluation of the (3)He spectrum within the frame of pre-equilibrium exciton model. The systematics obtained is compared with the empirical formula for the (n,(3)He) reaction cross-section.