Autoradiographic studies of cell dynamics in immunogenic granulomas transplanted into the skin of athymic nude mice

Summary Schistosome egg granulomas in the livers of thymus-intact (nu/+) mice are large and contain eosinophils and mast cells, while those in nude athymic (nu/nu) mice are small and devoid of eosinophils or mast cells. To investigate the cell sources and cell kinetics of hepatic granulomas of nu/+ mice isolated and grafted into the skin of nu/nu mice, biopsies taken after grafting were examined by light and electron microscopy and autoradiography after ³H-thymidine (TdR) injection of either the donor or recipient mice. At 1 week, the grafted granulomas appeared to be amorphous and were surrounded by leukocytes, and the ³H-TdR-labeled donor cells had disappeared. After 2 weeks, repopulation with macrophages began and by 3–5 weeks, the granulomas morphologically resembled hepatic lesions of nu/+ mice. Injection of recipients with ³H-TdR before grafting, showed that labeled macrophages, eosinophils, and mast cells repopulated in granulomas. No granulomas were seen when nu/nu mice were grafted with schistosome eggs alone, and organ culture of nu/+ granulomas before grafting reduced the number of repopulated granulomas. These findings indicate that nu/+cells in grafted granulomas are replaced by nu/nu cells. Granulomatous reaction of the grafted sites in nu/ nu mice is influenced by a substance in nu/+ granulomas, and cells of nunu mice locally acquire a nu/+ type response.     

Influence of cyproterone acetate and estradiol on cell kinetics in the sebaceous gland of the golden hamster ear

Summary The cell kinetics of the sebaceous gland of the hamster ear were analysed in untreated animals, in animals treated with cyproterone acetate, and in animals treated with estradiol. Both active substances lead to a reduction in the size of the sebaceous gland (measurement with the integration plate), to a reduction of mitoses (colcemide method), to a reduction in the ³H-thymidine labelling index, to a prolongation of the S-phase (double labelling technique with ³H-thymidine which remain in contact with the basal lamina of the sebaceous gland 6 days after application of the isotope. The results indicate that, like cyproterone acetate, estradiol reduces the effect of androgens on cell kinetics in the sebaceous gland under the test conditions chosen, even if in an entirely different way.Dedicated to Prof. Dr. W. Schneider on the occasion of his 70th birthday     

Topical tacalcitol (1,24-(R)-dihydroxyvitamin D3) induces a transient increase in thymidine incorporation and calmodulin content in pig epidermis following tape stripping in vivo

Tape stripping induces transient increase in keratinocyte proliferation in vivo. The effects of tacalcitol (l,24-(R)-dihydroxyvitamin D₃) ointment on the cell kinetics of pig epidermis after the tape stripping were investigated. The tacalcitol ointment (2 μg/g) was applied once to the back of pigs immediately after the tape stripping. The pig epidermal cell kinetics were analyzed at various times following the treatment. Tape stripping transiently increased thymidine incorporation of keratinocytes; the maximal effect was observed at 24 h. Tape stripping-induced increase in thymidine incorporation was markedly augmented by tacalcitol treatment. At 24 h following the tape stripping DNA-flow cytometry revealed an accelerated transition from G0/1 to S phase of cell cycle in tacalcitol treated epidermis. There was no significant difference, however, in mitotic counts and G2/M phase fractions between tape stripping-treated and tape stripping plus tacalcitol ointment-treated epidermis. We also measured calmodulin content of pig epidermis following the treatments. Although tape stripping slightly increased calmodulin content of pig epidermis, this was statistically not significant. Tape stripping plus tacalcitol ointment treatment resulted in a significant increase in calmodulin content at 24 h following the treatment. There was no significant difference in calmodulin content between tape stripping treated- and tape stripping plus tacalcitol-treated epidermis.     

基于改进遗传算法的Claus脱硫尾气加氢反应动力学

由于Claus反应在热力学上存在反应平衡,传统的Claus装置中尾气不能满足目前的排放要求。加氢还原吸收新工艺将尾气中的SO₂、有机硫、单质硫等硫化物转化为H₂S,提浓后再返回Claus装置,从而达到较高的总硫回收率。本文提出了一种幂指数型反应动力学模型,并采用改进遗传算法对动力学模型参数进行估值。统计检验和误差分析表明此模型计算值与实验值吻合良好,所建立的反应动力学模型适宜。     

Penciclovir solubility in Eudragit films: a comparison of X-ray, thermal, microscopic and release rate techniques

The solubility of penciclovir (C₁₀N₅O₃H₁₇) in a novel film formulation designed for the treatment of cold sores was determined using X-ray, thermal, microscopic and release rate techniques. Solubilities of 0.15–0.23, 0.44, 0.53 and 0.42% (w/w) resulted for each procedure. Linear calibration lines were achieved for experimentally and theoretically determined differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) data. Intra- and inter-batch data precision values were determined; intra values were more precise. Microscopy was additionally useful for examining crystal shape, size distribution and homogeneity of drug distribution within the film. Whereas DSC also determined melting point, XRPD identified polymorphs and release data provided relevant kinetics.     

Predicting the risk of bone metastasis in prostate cancer

The ability to identify prostate cancer patients at ‘high risk’ for bone metastasis development could allow early selection of those most likely to benefit from interventions to prevent or delay bone metastasis. This review is aimed to identify potential predictors of risk for bone metastasis in newly diagnosed patients and in those who have already received treatment.     

EFFECTS OF A MOVEMENT TRAINING PROGRAM ON HIP AND KNEE JOINT FRONTAL PLANE RUNNING MECHANICS

Background/Purpose:

Frontal plane running mechanics may contribute to the etiology or exacerbation of common running related injuries. Hip strengthening alone may not change frontal plane hip and knee joint running mechanics. The purpose of the current study was to evaluate whether a training program including visual, verbal, and tactile feedback affects hip and knee joint frontal plane running mechanics among females with evidence of altered weight bearing kinematics.

Methods:

The knee frontal plane projection angle of 69 apparently healthy females was determined during a single leg squat. The twenty females from this larger sample who exhibited the most acute frontal plane projection angle (medial knee position) during this activity were chosen to participate in this study (age = 20 ± 1.6 years, height = 167.9 ± 6.0 cm, mass = 63.2 ± 8.3 kg, Tegner Activity Rating mode = 7.0). Participants engaged in a 4‐week movement training program using guided practice during weight bearing exercises with visual, verbal, and tactile feedback regarding lower extremity alignment. Paired t‐tests were used to compare frontal plane knee and hip joint angles and moments before and after the training program.

Results:

After training, internal hip and knee abduction moments during running decreased by 23% (P=0.007) and 29% (P=0.033) respectively. Knee adduction and abduction excursion decreased by 2.1° (P = 0.050) and 2.7° (P=0.008) respectively, suggesting that less frontal plane movement of the knee occurred during running after training. Peak knee abduction angle decreased 1.8° after training (P=0.051) although this was not statistically significant. Contralateral peak pelvic drop, pelvic drop excursion, peak hip adduction angle, hip adduction excursion, and peak knee adduction angle were unchanged following training.

Conclusions:

A four week movement training program may reduce frontal plane hip and knee joint mechanics thought to contribute to the etiology and exacerbation of some running related injuries.

Level of Evidence:

Level 4     

Junior physician skill and behaviour in resuscitation: A simulation study

Introduction

Physicians are expected to manage their role as teamleader during resuscitation. During inter-hospital transfer the physician has the highest medical credentials on a small team. The aim of this study was to describe physician behaviour as teamleaders in a simulated cardiac arrest during inter-hospital transfer. Our goal was to pinpoint deficits in knowledge and skill integration and make recommendations for improvements in education.

Method

An ambulance was the framework for the simulation; the scenario a patient with acute coronary syndrome suffering ventricular fibrillation during transportation. Physicians (graduation age ≤5 years) working in internal medicine departments in Denmark were studied. The ambulance crew was instructed to be passive to clarify the behaviour of the physicians.

Results

72 physicians were studied. Chest compressions were initiated in 71 cases, ventilation and defibrillation in 72. The median times for arrival of the driver in the patient cabin, initiation of ventilation and chest compressions, and first defibrillation were all less than 1 min. Medication was administered in 63/72 simulations (88%), after a median time of 210 s. Adrenaline was the preferred initial drug administered (58/63, 92%). Tasks delegated were ventilations, chest compressions, defibrillation, and administration of medication (97%, 92%, 42%, and 10% of cases, respectively).

Discussion and conclusion

Junior physicians performed well with respect to the treatment given and the delegation of tasks. However, variations in the time of initiation it took for each treatment indicated lack of leadership skills. It is imperative that the education of physicians includes training in leadership.     

Identification of human multidrug resistance protein 1 (MRP1) mutations and characterization of a G671V substitution

The multidrug resistance protein 1 (MRP1) belonging to the ATP-binding cassette (ABC) superfamily of transport proteins can confer resistance to multiple natural product drugs and methotrexate in human tumor cells. In addition, MRP1 is expressed in normal tissues acting as an efflux pump for glutathione, glucuronate, and sulfate conjugates and may thus influence the pharmacokinetic properties of many drugs. Using polymerase chain reaction–single-strand conformation polymorphism analysis, we screened 36 Caucasian volunteers for mutations in the coding exons of the MRP1 gene, including the adjacent intron sequences. Among several mutations found, two are expected to cause amino acid substitutions. One of these mutations (G671V) was of special interest because it is located near the first nucleotide binding domain. To determine whether this mutation caused a change in the MRP1 phenotype, a mutant MRP1 expression vector was constructed and transfected into SV40-transformed human embryonic kidney cells (HEKSV293T) and the transport properties of the mutant protein were examined. Transport of the MRP1 substrates leukotriene C₄, 17β-estradiol 17β-(d)-glucuronide, and estrone sulfate by membrane vesicles prepared from transiently transfected HEKSV293T cells was comparable to that of wild-type MRP1. Received: July 16, 2001 / Accepted: August 21, 2001