Interaction between anandamide and sphingosine-1-phosphate in mediating vasorelaxation in rat coronary artery

Background and purpose:

This study establishes a pharmacokinetic/pharmacodynamic (PK/PD) model to describe the time course and in vivo mechanisms of action of the antinociceptive effects of lumiracoxib, evaluated by the thermal hyperalgesia test in rats.

Experimental approach:

Female Wistar fasted rats were injected s.c. with saline or carrageenan in the right hind paw, followed by either 0, 1, 3, 10 or 30 mg·kg⁻¹ of oral lumiracoxib at the time of carrageenan injection (experiment I), or 0, 10 or 30 mg·kg⁻¹ oral lumiracoxib at 4 h after carrageenan injection (experiment II). Antihyperalgesic responses were measured as latency time (LT) to a thermal stimulus. PK/PD modelling of the antinociceptive response was performed using the population approach with NONMEM VI.

Results:

A two-compartment model described the plasma disposition. A first-order model, including lag time and decreased relative bioavailability as a function of the dose, described the absorption process. The response model was: LT=LT₀/(1 +MED). LT₀ is the baseline response, and MED represents the level of inflammatory mediators. The time course of MED was assumed to be equivalent to the predicted profile of COX-2 activity and was modelled according to an indirect response model with a time variant synthesis rate. Drug effects were described as a reversible inhibition of the COX-2 activity. The in vivo estimate of the dissociation equilibrium constant of the COX-2-lumiracoxib complex was 0.24 µg·mL⁻¹.

Conclusions:

The model developed appropriately described the time course of pharmacological responses to lumiracoxib, in terms of its mechanism of action and pharmacokinetics.     

输液中注射用头孢米诺钠的稳定性

1材料和方法 1.1材料日本岛津10-Arp高效液相色谱仪,C18柱(5 μm,4.6 mm×150 mm),PHS-3C型pH计(上海雷磁仪器厂);注射用头孢米诺钠(南昌立健药业有限公司,批号:20040701),50 g/L葡萄糖注射液(四川科伦大制药有限公司,批号:040912-091),100 g/L葡萄糖注射液(湖南科伦大制药有限公司,批号:040710-07),9 g/L氯化钠注射液(湖南科伦大制药有限公司,批号:040926-06),葡萄糖氯化钠注射液(湖南科伦大制药有限公司,批号:040929-06),甲硝唑注射液(安徽双鹤药业有限公司,批号:040926-2E);甲醇、冰醋酸、四氢呋喃均为分析纯.     

Cystoid macular oedema following cataract surgery: A review

Pseudophakic cystoid macular oedema (PCMO) remains a significant cause of compromised postoperative vision in contemporary cataract surgery. Well‐established risk factors include intraoperative complications such as posterior capsule rupture and preoperative factors including: diabetes mellitus, uveitis, retinal vein occlusion, epiretinal membrane. The role of topical glaucoma medications in PCMO continues to be debated. Current treatment strategies largely target suppression of inflammation. Topical NSAIDs remain the mainstay in prophylaxis and treatment of PCMO. Topical corticosteroids are commonly used as monotherapy or in combination with NSAIDs. Unfortunately, high‐quality trials are notably lacking for other PCMO treatment modalities such as: periocular corticosteroids, orbital floor triamcinolone, intravitreal triamcinolone, corticosteroid implants, intravitreal bevacizumab and pars‐plana vitrectomy. A lack of consistency in defining PCMO and resolution of PCMO explains why even large systematic reviews may come to contradictory conclusions. This review explores the varied contemporary evidence‐base in relation to the aetiology, diagnosis, prophylaxis and treatment of PCMO.     

Over expression of vascular endothelial growth factor in correlation to Ki-67, grade, and stage of breast cancer

OBJECTIVE: To assess the significance of vascular endothelial growth factor (VEGF) protein over expression in human breast cancer, and its possible correlation with cell proliferation marker (Ki-67), grade and stage of breast cancer. METHODS: We carried out this study at the Department of Pathology, Kufa University, between November 2006 and September 2007. A retrospective study was employed on paraffin-embedded blocks from 52 female patients with breast cancer. A group of 21 patients with benign breast lesions was included for comparison and 14 cases of normal breast tissue as a control group. This investigation designed to employ immunohistochemistry using Avidin-Biotin Complex (ABC) method for detection of both VEGF and Ki-67. RESULTS: A total of 87 samples was included. Vascular endothelial growth factor immunoexpression was considered as positive in 61.5% of malignant and in 19% of benign breast lesions. No over expression sign has been noticed in normal breast tissue (p<0.005). No significant difference in VEGF over expression among different histological types of breast cancer (p>0.05). Vascular endothelial growth factor immunostaining was positively correlated with Ki-67, grade, stage, lymph node metastasis, and recurrence of breast cancer (p<0.05). No such correlation has been seen when the age of the patients has been considered. CONCLUSION: Vascular endothelial growth factor Vascular endothelial growth factor plays an important role in pathogenesis of breast cancer evolution, and supports the evidence of its role in angiogenesis and cell survival. This study recommended that the blocking of VEGF may be a target for blocking angiogenesis and hence improving the efficacy of anti-cancer therapy.     

Combination of ECMO and cytokine adsorption therapy for severe sepsis with cardiogenic shock and ARDS due to Panton–Valentine leukocidin—positive <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> pneumonia and H1N1

Sepsis-induced cardiogenic shock in combination with severe acute respiratory failure represents a life-threatening combination that is often refractory to the conventional methods of treatment. We describe the case of a 33-year-old patient who developed acute cardiovascular collapse and ARDS secondary to superinfection of Panton–Valentine leukocidin—positive Staphylococcus aureus and H1N1 pneumonia who underwent successful combination therapy for severe sepsis-related cardiomyopathy and respiratory failure using extracorporeal membrane oxygenation and cytokine adsorption therapy.