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.     

Sequences from higher primates orthologous to the human Xp/Yp telomere junction region reveal gross rearrangements and high levels of divergence

A high level of sequence polymorphism combined with linkage disequilibrium has created a limited number of highly diverged haplotypes across the human Xp/Yp telomere junction region. To gain insight into the unusual genetic characteristics of this region, we have examined the orthologous sequences in the common chimpanzee (Pan troglodytes ), the gorilla (Gorilla gorilla) and the orang-utan (Pongo pygmaeus). Divergence from the human Xp/Yp sequence is higher (average 2.6-fold) than that observed at other loci. The position of the human Xp/Yp telomere is unique, as additional sequences are present at this location in the other three species. These included an array of subterminal satellite in the chimpanzee and, in the gorilla a small interstitial array of telomere-like repeats followed by sequences with strong homology to the human 18p subterminal region. In the orang-utan, two alleles with different structures were identified. These differ by the presence or absence of a short interspersed nuclear element (SINE) sequence just proximal to long arrays of telomere-like repeat sequences that probably represent the proximal end of the orang-utan Xp/Yp telomere. In addition, a high level of sequence divergence between the two orang-utan structures was identified. This divergence is similar to that observed between the human Xp/Yp telomere-adjacent haplotypes. The high sequence divergence and evidence of gross rearrangements indicate that the Xp/Yp telomeric region has evolved faster than the rest of the genome.      

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.     

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.     

Working profiles of dental hygienists in public and private practice in Finland and Norway

Abstract: Aim: The aim was to compare the working profiles of Finnish and Norwegian dental hygienists in public and private practice. To this end, we compared the procedures performed, the type of patients and the time devoted to different tasks. Subjects and methods: A questionnaire survey was originally conducted among a representative sample of dental hygienists in Finland (n = 595) and all authorized dental hygienists in Norway (n = 1 138) in 2004. The questionnaires collected data on the dental hygienists’ age, gender, year of graduation, working experience, work sector (private or public), working time spent on different activities and patient groups. The questionnaire also assessed how frequently the dental hygienists performed 25 different treatment measures. Results: The Norwegian dental hygienists spent 45.4% of their clinical time on check‐ups, whereas the Finns spent 49.9% of their time scaling. Dental hygienists in Finland and Norway working in the public sector spent 42.9% and 74.6% of their working time dealing with children and youth respectively. Conclusions: The working profiles of dental hygienists in Finland and Norway were quite similar, although differences in distribution by activities, type of patients and treatment measures do exist. The main activity of the dental hygienists was clinical work. The most commonly practised clinical activity among Finnish dental hygienists was scaling, and among Norwegians, check‐ups. Public dental hygienists in both countries dealt mainly with children and youths. Oral hygiene instruction was the most commonly reported treatment measure among both Finns and Norwegians.