Chalone-induced inhibition in DNA synthesis of human psoriatic epidermal cells cultured in diffusion chambers in mice.

Pieces of human psoriatic skin and suspensions of mouse bone marrow cells as non-epidermal control tissue were cultured for four days in diffusion chambers implanted intraperitoneally in 40 mice. The mice were divided into three groups. On the second and third day of the culture partially purified epidermal extract containing epidermal chalone, granulocyte extract containing granulocyte chalone, and Hanks' solution were injected intraperitoneally into the mice of the three groups, respectively. On the fourth day, incorporation of 3H-TdR into the diffusion chamber cultures and various epithelia and several non-epidermal tissues of the host animal was studied autoradiographically and radiochemically. The results showed that the epidermal chalone induced a marked, statistically significant, depression in the labelling index of the cultured psoriatic epidermal cells and in the number of labelled cells in the host ear epidermis (31% and 62%, respectively); the other host epithelia were not significantly inhibited. A crude granulocyte extract used in most experiments was clearly toxic; the semipurified granulocyte chalone used in one experiment had no effect on the psoriatic and cultures, but affected weakly the cultured bone marrow cells. Neither the epidermal nor the granulocyte extract had any inhibitory effect on the non-epidermal tissues studied.     

Non-Gaussian diffusion in human brain tissue at high b-factors as examined by a combined diffusion kurtosis and biexponential diffusion tensor analysis

Diffusion tensor imaging (DTI) permits non-invasive probing of tissue microstructure and provides invaluable information in brain diagnostics. Our aim was to examine approaches capable of capturing more detailed information on the propagation mechanisms and underlying tissue microstructure in comparison to the conventional methods. In this work, we report a detailed in vivo diffusion study of the human brain in an extended range of the b-factors (up to 7000 s mm(-2)) performed on a group of 14 healthy volunteers at 3T. Combined diffusion kurtosis imaging (DKI) and biexponential diffusion tensor analysis (BEDTA) were applied to quantify the attenuation curves. New quantitative indices are suggested as map parameters and are shown to improve the underlying structure contrast in comparison to conventional DTI. In particular, fractional anisotropy maps related to the slow diffusion tensor are shown to attain significantly higher values and to substantially improve white matter mapping. This is demonstrated for the specified regions of the frontal and occipital lobes and for the anterior cingulate. The findings of this work are substantiated by the statistical analysis of the whole slice histograms averaged over 14 subjects. Colour-coded directional maps related to the fast and slow diffusion tensors in human brain tissue are constructed for the first time and these demonstrate a high degree of axial co-alignment of the two tensors in the white matter regions. It is concluded that a combined DKI and BEDTA offers a promising framework for monitoring tissue alteration during development and degeneration or as a consequence of the neurological disease.     

Effect of prolonged fluconazole treatment on Candida albicans in diffusion chambers implanted into mice

Fluconazole is an azole agent with primarily fungistatic activity in standard in vitro susceptibility tests. The present study was undertaken to develop a diffusion chamber model system in mice in order to study the in vivo effects of prolonged fluconazole treatment on Candida albicans. Chambers containing 100 C. albicans yeast cells were implanted subcutaneously on the flanks of C57BL/6 mice and were then retrieved 6 or 14 weeks later (after fluconazole treatment for 4 or 12 weeks, respectively). Leukocyte counts demonstrated that implantation of the chambers did elicit an inflammatory response but that only small numbers of inflammatory cells were able to enter the chamber interior. Treatment with fluconazole at 10 mg/kg of body weight/day for 12 weeks not only reduced the numbers of viable organisms within the chambers compared to those in untreated mice (mean +/- standard deviation of log(10) CFU of 0.7 +/- 1.2 versus 2.3 +/- 2.0; P < 0.001 by the Bonferroni test) but also increased the numbers of chambers that became sterile over the treatment period (14 of 16 versus 6 of 19; P = 0.0009 by the chi-square test). However, treatment for only 4 weeks had minimal effects on the numbers of chamber CFU, and none of the chambers became sterile during this period. Distribution of retrieved organisms between interior fluid and the chamber filters was approximately equal in all the treatment groups. This model system appears to be useful for evaluating the effects of antifungal drugs over prolonged periods in vivo. Its use in the present study demonstrates that fluconazole can increase the rate of sterilization of C. albicans foci that are protected from the host's inflammatory response.     

The utility of diffusion chambers as models for the description of drug disposition

Tissue cages were employed to explore the diffusion processes of several cephalosporins into extravascular fluids. Concentrations of cefotaxime in serum and in subcutaneous chambers increased proportionally to the amount of the drug injected. Administration of single equal doses of cephalothin, cephaloridine and cefotaxime resulted in different concentration-time courses in the serum and in diffusion chambers. These observations suggest that diffusion chambers are linked to the tissue at the implantation site. None of the classical compartmental approaches can be applied to evaluate the kinetics of drug diffusion into tissue cages. Correlations of total or non-protein bound drug concentrations in tissue cages to those in the peripheral compartment assumed concentration and time dependent diffusion processes. No specific diffusion constant based on the law of Fick could be derived for the diffusion chambers used in this study. Concentration-time courses in serum and interstitial fluid can be simultaneously evaluated according to pharmacokinetic-pharmacodynamic models. Based on the equation describing the effect site this model can be used to simulate drug concentrations in tissue cages by varying the dose size or the dose interval.     

Comparative studies of humoral factors stimulating granulopoiesis in agar in vitro and in diffusion chambers.

The factor stimulating granulopoiesis in diffusion chambers (DCF) was compared with the CSA in post-EMS in two ways: (1) Mouse bone marrow cells were maintained in suspension cultures, containing DCF or EMS, which were assayed at intervals for colony-forming cells, both in agar in vitro and in diffusion chambers. (2) The enhanced growth seen in chambers incubated in pretreated mice was compared with the CSA of serum and DCF recovered from these animals. The results show that the cells forming granulocytic colonies in agar in vitro and in diffusion chambers are closely related, if not identical, and that different sources of CSA may differ in their ability to maintain precursor cell numbers in suspension culture. The CSA of DCF did not correlate with growth enhancement in diffusion chambers or with the levels of CSA in the serum.     

实时组织弹性成像弥散定量分析技术诊断甲状腺弥漫性病变

目的 探讨实时组织弹性成像弥散定量分析技术在甲状腺弥漫性病变中的应用价值。方法 纳入甲状腺弥漫性病变患者165例,包括甲状腺功能亢进56例(甲亢组)、桥本甲状腺炎81例(桥本组)和亚急性甲状腺炎28例(亚甲炎组),另收集健康志愿者81名作为正常对照组,对所有研究对象行超声弹性成像,采用实时组织弹性成像技术获得弹性声像图,计算应变均值与蓝色区域所占百分比(蓝色区域%)。结果 正常对照组甲状腺弹性声像图均为Ⅰ级(81/81,100%),甲亢组Ⅱ级多见(39/56,69.64%),桥本组病Ⅲ级多见(54/81,66.67%),亚甲炎组Ⅳ级多见(21/28,75.00%)。正常对照组、甲亢组、桥本组、亚甲炎组应变均值依次下降,分别为121.06±14.58、101.31±17.16、89.73±17.57和56.00±23.29,蓝色区域%依次升高,分别为(19.14±11.23)%、(32.42±11.70)%、(39.03±12.66)%和(67.00±18.18)%,两两比较差异均有统计学意义(P均<0.01)。结论 不同甲状腺弥漫性病变硬度不同,实时组织弹性成像弥散定量分析技术能定量其硬度,有助于鉴别诊断。     

Rat, ovine and bovine Peyer's patches mounted in horizontal diffusion chambers display sampling function.

Freshly excised rat, ovine and bovine ileal Peyer's patch (PP) and non-Peyer's patch tissues (NPP) were mounted in modified horizontal polyethylene diffusion chambers with a range of window areas. Rat tissue was initially used to establish that barrier function and histology were maintained for up to 60 min. Horse-radish peroxidase (HRP) fluxes and S. Typhimurium adherence and invasion were significantly higher in rat PP over NPP. Particle uptake was shown to be a rapid, energy-, time-, and size-dependent process, occurring more readily in PP than NPP tissue in each species. In a kinetic analysis, particles were localized initially in the follicle-associated epithelium and then in the dome region. For NPP uptake, particles were initially localized to villous epithelium, and were then detected in the crypts and lamina propria. Electrophysiological parameters including pharmacologically-stimulated inward short-circuit current responses were determined in isolated PP and NPP from each species mounted under identical conditions in Ussing chambers. In conclusion, comparative functional and histological characteristics of PP from several species were demonstrated in horizontal diffusion chambers. Horizontal diffusion chambers are therefore a useful in vitro model in which a range of functions including transport of particulate formulations by PP may be examined.     

Concentrations of various antibiotics in serum and fluids accumulated in diffusion chambers implanted in various sites in rabbits.

Diffusion chambers with Millipore membranes were implanted in soft tissue, kidneys, and peritoneal and pleural cavities of rabbits. Single doses of azlocillin, cefazolin, and gentamicin were injected intramuscularly and ampicillin was administered orally 2--5 weeks after implantation. The concentrations of the respective drugs in simultaneously collected samples of fluid from each diffusion chamber were measured and compared with concentrations found at the same time in serum. All chambers were tolerated well, and the method proved to be effective for collecting data on the distribution of drugs throughout the body.     

Methodology for measuring diversity in human populations

A population is considered diverse if it contains individuals with a wide variety of demographic and cultural characteristics or attributes. However, it is often difficult to compare the relative diversity of two groups. It is even more difficult to specifically measure or quantify the diversity of any single group. In this paper a three step process for measuring and quantifying diversity in a human populations is described. The measurement methodologies illustrated in an example using this process are based upon fractionalization techniques and mathematical information theory.     

正常人脑弥散定量研究

目的确立标准化的正常人脑各部位ADC参考值,探讨ADC值与脑内不同结构部位的关系.方法选择健康男女各30名,所有对象进行MR检查,包括常规MRI和EPI弥散加权成像,弥散敏感系数分别为b=0,b=1000 s/mm2;测定双侧半球的34个感兴趣区的平均ADC值.结果灰质的平均ADCAv最高(0.80±0.05)×10-3mm2/s,其次是白质的平均ADCAv(0.77±0.05)×10-3mm2/s,丘脑的平均ADCAv(0.75±0.07)×10-3mm2/s,基底节的平均ADCAv最低(0.73±0.06)×10-3mm2/s.双侧半球相同部位之间经配对t检验,双侧脑室间平均ADCAv存在差异(P＜0.05),其余结构之间差异无显著性意义(P＞0.05).结论正常人脑各部位ADC值的定量研究为弥散成像的临床应用提供了依据和指导.     

MR扩散加权成像在软组织肿瘤中的应用进展

磁共振扩散加权成像是反映水分子扩散特性、检测组织微观结构变化的功能成像技术,包括单指数扩散加权成像(diffusion weighted imaging,DWI)、体素内不相干运动(intravoxel incoherent motion,IVIM)模型、扩散张量成像(diffusion tensor imaging,DTI)和扩散峰度成像(diffusion kurtosis imaging,DKI),目前已用于软组织肿瘤临床评估.本文就上述四种技术类型做简要介绍,并就其在软组织肿瘤的良恶性鉴别诊断、组织学分级预测、浸润评估、术后复发监测以及放化疗疗效评价或预测中的应用进展进行综述.     

Intraoperative positive fluid balance improves tissue diffusion of ceftizoxime

AIM OF STUDY: To demonstrate that administration of fluids and the consequent improvement of fluid balance during a surgical procedure can modify the tissue diffusion of ceftizoxime. METHODS: Twenty-eight patients (30-79 years) undergoing major abdominal surgery of the colon were administered ceftizoxime 30 mg/kg i.v. at induction of anesthesia. A sample of arterial blood was taken before administration of the drug (t0) and then again at the time of vascular occlusion of the colon segment to be removed (t1). A sample of the segment of removed colon was taken. The patients were divided into two groups on the basis of the fluid balance between t0 and t1: group A (n = 17) with a fluid balance <1,000 ml and group B (n = 11) with a fluid balance >1,000 ml. The parameters evaluated in each group were: weight, height and age of the patients, serum and tissue antibiotic concentration, percent ratio of serum and tissue concentration, time elapsed between t0 and t1, volume of administered fluids between t0 and t1, diuresis and hourly diuresis between t0 and t1 and body fluid distribution, obtained using a bioelectrical impedance analyzer. The mean results obtained in the two groups were then compared using Student's t test. RESULTS: The balance of fluids calculated up to t1 was 675 +/- 308 ml for group A and 1,411 +/- 405 ml for group B (p < 0.01). The means of the recorded values that showed statistically significant differences were: mean percent concentration ratio (43.6 +/- 8.4 vs. 84 +/- 16%; p < 0.05), concentration in the colonic segment (16.3 +/- 7.9 vs. 37.2 +/- 25.9 mg/ml; p < 0.05), urinary volume gathered up to t1 (538 +/- 557 vs. 169 +/- 104 ml; p < 0.05), hourly urinary volume up to t1 (311.1 +/- 296 vs. 97.6 +/- 77.9 ml/h; p < 0.05), percent variation of resistance (95.1 +/- 5.1 vs. 89.7 +/- 8.6; p < 0.05). The other means did not show any significant statistical differences. CONCLUSIONS: A higher tissue water level seems to facilitate the penetration of the antibiotic into the tissue according to the pharmacokinetic characteristics of ceftizoxime: high amount of free drug (not bound to plasma proteins) and high hydrosolubility.     

软组织肿瘤MR弥散加权成像量化研究初探

目的:探讨MR弥散加权成像(DWI)ADC值和EDC在软组织肿瘤定性诊断中的价值。材料和方法:研究了23例软组织肿瘤DWI。DWI采用SE-EPI序列,弥散敏感系数b分别取0、300s/mm²,同时在3个方向施加弥散敏感梯度场,获得其ADC值和EDC值。结果:①在b=300s/mm²时,良性肿瘤组的ADC值为(1.64±0.15)×10^-3mm²/s,恶性肿瘤的ADC值为(1.86±0.19)×10^-3mm²/s,恶性肿瘤组的ADC值大于良性肿瘤的ADC值,良、恶性肿瘤组间的ADC值差异有显著性;②在b=300s/mm²时,良性肿瘤组的EDC值为(136.89±44.60)×10^-3,恶性肿瘤的EDC值为(160.02±83.23)×10^-3,恶性肿瘤组的EDC值大于良性肿瘤的EDC值,良、恶性肿瘤组间的EDC值差异无显著性。结论:在b=300s/mm²时,恶性软组织肿瘤的ADC值大于良性软组织肿瘤的ADC值,良、恶性肿瘤组间的ADC值差异有显著性;恶性肿瘤组的EDC值大于良性肿瘤的EDC值,良、恶性肿瘤组间的EDC值差异无显著性。     

Relationship between tissue tension and thermal diffusion to peripheral tissue using an energy device

The aim of the study was to assess the relationship between tissue tension and thermal diffusion to peripheral tissues using an electric scalpel, ultrasonically activated device, or a bipolar sealing system. The mesentery of pigs was excised with each energy device (ED) at three tissue tensions (0, 300, 600 g). The excision time and thermal diffusion area were monitored with thermography, measured for each ED, and then histologically examined. Correlations between tissue tension and thermal diffusion area were examined. The excision time was inversely correlated with tissue tension for all ED (electric scalpel, r = 0.718; ultrasonically activated device, r = 0.949; bipolar sealing system, r = 0.843), and tissue tension was inversely correlated with the thermal diffusion area with the electric scalpel (r = 0.718) and bipolar sealing system (r = 0.869). Histopathologically, limited deep thermal denaturation occurred at a tension of 600 g with all ED. We conclude that thermal damage can be avoided with adequate tissue tension when any ED is used.     

Immunoreactive tissue kallikrein in human serum

Human urinary kallikrein and an antiserum to it raised in the rabbit were used to detect and quantitate immunoreactive tissue kallikrein in human serum. Both 125I-labeled kallikrein and the unlabeled purified enzyme appear complexed to higher molecular weight entities in serum, but specific binding between radiolabeled enzyme and antiserum was unaffected by the presence of serum or plasma. Parallelism to standard displacement curves was always seen with radioimmunoassay of normal sera as well as with human mixed saliva or pancreatic extracts. Assay sensitivity is 160 pg/ml of serum, or 16 pg per tube. Purified plasma kallikrein or prekallikrein in concentrations up to 10 micrograms/ml showed no displacement. Acetone-kaolin activation of plasma produced the expected 30-fold increase in Tos-Arg-OMe esterase activity but no change in immunoreactive tissue kallikrein levels. Serum concentrations were 3.8 +/- 0.7 (mean +/- SE) ng/ml in 21 normal volunteers, and were similar in patients with Fletcher trait or Hageman factor deficiency. Significantly increased serum concentrations were seen with long-term low dietary sodium intake or acute forms of pancreatitis. Although the relation of this immunoreactive material to any active tissue kallikrein within the circulation remains to be determined, our studies provide a new parameter for the assessment of a system repeatedly suggested to have some role in regulation of vascular resistance.     

Trace-element concentrations in human autopsy tissue

In this report on trace-element concentrations (As, Ca, Cd, Cl, Co, Cr, Cu, Fe, Hg, K, Mg, Mn, Mo, Na, Ni, Pb, Rb, Sb, Se, Zn) in human heart, liver, kidney, aorta, and rib obtained from 200 autopsied patients, we give special attention to sampling procedure, analysis technique, and various sources of error (autolysis, contamination with blood, and lack of sample homogeneity). We present the concentration data (averages, standard deviations, and ranges) obtained by neutron activation analysis, and we analyze the distribution of the data. The three types of distribution we distinguished are relevant to considerations of the importance of processes of storage of certain elements in specific organs.     

Brain tissue water comes in two pools: evidence from diffusion and R2' measurements with USPIOs in non human primates

Diffusion-weighted MRI of non-human primates revealed that USPIO Bulk Magnetic Susceptibility (BMS) T2' effects of Ultrasmall Superparamagnetic Particles with Iron Oxide (USPIO) in the brain cannot be explained by a single compartment model, as diffusion and T2' effects appear coupled: Apparent Diffusion Coefficient (ADC) values depend on USPIO concentration and relaxivity effects of USPIO decrease with the b value. On the other hand, USPIO and diffusion effects could be well uncoupled using a model consisting in a fast and a slow diffusion pool with different relaxivities. Diffusion-weighting acts as a filter which emphasizes the contribution of the slow pool when increasing b values (apparent decrease in ADC and R2'). Those results have implications for human studies using BMS contrast agents, as well as BOLD and diffusion fMRI.