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.     

OUR EXPERIENCE WITH DIAGNOSTIC AND THERAPEUTIC CHOLEDOCHOSCOPY

Flexible choledochoscope was used in 16 patients undergoing common bile duct (CBD) exploration for suspected stones. Stones were found in the CBD in 4 patients in whom introperative cholangiogram was normal. T-tube cholangiogram done between the 10th and 14th postoperative days was normal in all 16 patients. None of the patients had symptoms suggestive of retained stones during follow-up ranging from 6 to 19 months. We feel that the use of choledochoscopy in patients undergoing CBD exploration will help reduce the incidence of retained stones.KEY WORDS: Cholangiography, Choledocholithiasis, Choledochoscopy     

HIV INFECTION IN HERPES ZOSTER

The interaction of Herpes zoster and Human Immunodeficiency Virus (HIV) was evaluated in 120 cases of herpes zoster admitted to our hospital and in 157 HIV positive cases detected in the hospital during the same period. The incidence of HIV seropositivity was 22.5 per cent in cases of herpes zoster without AIDS defining disease conditions. Whereas the incidence of Herpes zoster in cases detected to be HIV positive in the same period was 17.2 per cent. A large number of herpes zoster cases found to be HIV positive were in the sexually active age group viz. 21-30 years. Thoracic dermatomal segments were most frequently involved. None of the cases had severe complications or showed evidence of progression to symptomatic HIV disease.KEY WORDS: Herpes zoster, HIV infection     

Role of oestrogen therapy in the management of short stature in Turner syndrome

It is now clear that parenteral growth hormone (GH) therapy stimulates growth and increases the adult stature of girls with Turner syndrome. In addition, oestrogens are given to almost all girls with this syndrome because of primary hypogonadism. Oestrogens influence both growth and maturation of the epiphyseal growth plates. Therefore, the form and timing of oestrogen therapy may have an important impact on the outcome of other growth-promoting therapies. To examine the impact of the timing of oestrogen initiation on growth, a randomized trial was conducted in patients with Turner syndrome who were receiving GH. Some patients received oestrogen at 12 years of age, while in others this treatment was not started until 15 years of age. Those girls that received oestrogen later were significantly taller as adults. The single most important factor in determining height gain appeared to be the number of years of GH therapy prior to the initiation of oestrogen treatment.     

Medical treatment of hepatic amebic abscess: rare need for percutaneous drainage

Although amebic liver abscess can virtually always be successfully treated medically, percutaneous drainage has been advocated recently. In 96 recently treated patients, therapeutic aspiration and percutaneous drainage were rarely needed. Most cases were correctly diagnosed by means of clinical, laboratory, and sonographic findings. Abscesses in only 13 (13.5%) patients were diagnostically aspirated. An abscess in one patient was therapeutically aspirated because the patient was responding slowly to medical therapy. No patient required catheter drainage. The key to successful amebic abscess management is medical therapy. Therapeutic drainage is rarely needed. Successfully treated patients occasionally respond slowly to medical therapy, and successfully treated amebic abscesses may enlarge or become bizarre-appearing on sonograms. This should not prompt therapeutic drainage. Diagnostic aspiration is appropriate when amebic and pyogenic abscesses are indistinguishable using clinical and imaging findings. Rare indications for therapeutic aspiration or drainage include pyogenic superinfection and large, juxtacardiac abscesses (potential intrapericardial rupture).     

Digital beam attenuator technique for compensated chest radiography

The feasibility of producing patient-specific beam attenuators for chest radiography has been investigated using an anthropomorphic phantom and a human volunteer. A low-dose test exposure is digitized, processed, and used to print a small cerium filter, which is placed in the x-ray beam near the collimator. The final radiograph is recorded on film. The technique results in relatively uniform film exposure, so that structures in all regions of the chest are simultaneously displayed with optimal film contrast. The equalized exposure improves image quality in the normally underpenetrated regions and reduces the role of cross-scatter from the lungs. The image is analogous to optical or computer-processed unsharp masking techniques, but the processing is accomplished in the x-ray beam and results in an improved exposure distribution, giving advantages that cannot be achieved with image processing techniques alone.     

图形翻转视觉诱发电位在视神经管减压后视神经损伤不同时期的变化特征

目的:观察视神经损伤动物模型在损伤后和不同时期视神经管减压后视觉诱发电位的变化,了解创伤性视神经损伤的手术时机与疗效的关系。方法:实验于2005-03/05在解放军南京军区南京总医院动物实验中心完成。①实验分组:30只新西兰白兔随机分为正常对照组、术后2d减压组、术后7d减压组、术后14d减压组、术后不减压组,每组6只。②造模:除正常对照组外,其余各组在视神经孔中塞入一细端为2mm直径的圆锥软硅胶,阻塞视神经孔,造成视神经的挤压伤。③指标检测:采用图形翻转视觉诱发电位检测损伤前、损伤后1h、减压前1h、减压后2周视功能变化,记录NPN曲线主波(P波)的绝对潜伏期、绝对波幅。正常对照组仅采集一组数据作为对照。结果:30只实验动物均进入结果分析。①正常对照组家兔图形翻转视觉诱发电位检查均引出典型NPN波型曲线,视神经挤压伤后1hNPN波形低阔扁平,P波潜伏期延长,波幅降低。②P波潜伏期:术后2d减压组减压后短于减压前[(71.25±8.51),(86.47±14.28)ms,P<0.05];术后7d减压组减压前后比较差异无显著性(P>0.05);术后14d减压组减压后明显长于减压前[(158.73±15.16),(116.35±17.13)ms,P<0.05]。术后2d减压组和术后7d减压组短于术后不减压组(P<0.01)。术后7,14d减压组和术后不减压组明显长于正常对照组(P<0.01)。③P波波幅:术后2d减压组减压后高于减压前[(5.25±0.78),(4.42±0.42)μV,P<0.05]。术后2d减压组减压后低于术后7d减压组、术后14d减压组(P<0.01),术后14d减压组低于术后7d减压组(P<0.05);术后7d减压组、术后14d减压组、术后不减压组低于正常对照组(P<0.01)。结论:神经元继发性损伤是视功能进行性下降的重要原因,视神经减压术有利于减轻视神经间接损伤,较早期(损伤后48h以内)减压可阻止轴突继发性损伤,避免视功能进一步下降,并在一定程度上逆转视功能的损害。     

Face shape of unaffected parents with cleft affected offspring: combining three‐dimensional surface imaging and geometric morphometrics

Authors – Weinberg SM, Naidoo SD, Bardi KM, Brandon CA, Neiswanger K, Resick JM, Martin RA, Marazita ML Objective – Various lines of evidence suggest that face shape may be a predisposing factor for non‐syndromic cleft lip with or without cleft palate (CL/P). In the present study, 3D surface imaging and statistical shape analysis were used to evaluate face shape differences between the unaffected (non‐cleft) parents of individuals with CL / P and unrelated controls. Methods – Sixteen facial landmarks were collected from 3D captures of 80 unaffected parents and 80 matched controls. Prior to analysis, each unaffected parent was assigned to a subgroup on the basis of prior family history (positive or negative). A geometric morphometric approach was utilized to scale and superimpose the landmark coordinate data (Procrustes analysis), test for omnibus group differences in face shape, and uncover specific modes of shape variation capable of discriminating unaffected parents from controls. Results – Significant disparity in face shape was observed between unaffected parents and controls (p < 0.01). Notably, these changes were specific to parents with a positive family history of CL / P. Shape changes associated with CL / P predisposition included marked flattening of the facial profile (midface retrusion), reduced upper facial height, increased lower facial height, and excess interorbital width. Additionally, a sex‐specific pattern of parent‐control difference was evident in the transverse dimensions of the nasolabial complex. Conclusions – The faces of unaffected parents from multiplex cleft families displayed meaningful shape differences compared with the general population. Quantitative assessment of the facial phenotype in cleft families may enhance efforts to discover the root causes of CL /P.