Measurement of the liver and spleen volume by single photon emission computed tomography

Organ volume was experimentally and clinically determined using single photon emission computed tomography (SPECT). In organ phantom filling with 99mTcO4-, the error was less than 3.3% in the volume over 400 ml but 11% at 200 ml. In 28 cases of patient, liver and spleen volume were measured by SPECT and X-CT. Good correlation was founded between SPECT volume and X-CT volume (r = 0.99, n = 49), although SPECT volume were 16% higher than X-CT volume (y = 1.16 x + 11.6, x: X-CT volume, y: SPECT volume).     

An evaluation of predicting postoperative residual liver function using 99mTc tin colloid

The rate of clearance (K value) of 99mTc tin colloid in the liver differentiates normal subjects from liver cirrhosis patients; so 99mTc tin colloid is as useful as 198Au colloid as a marker of liver function. There are several reports concerning volume estimation using liver scintigraphy. Our original method was devised to measure the effective liver volume by scintigraphy. By combining the K value with effective liver volume, a predictive index was obtained in order to predict the residual liver function before hepatic resection. The index in 24 patients with liver diseases was investigated before hepatic resection. Three of them died due to hepatic failure after hepatic resection. The indices were between 0.40 and 0.45 in two of these three patients and 0.338 in one. Among the patients without hepatic failure, the indices showed more than 0.45 in 19 patients and between 0.40 and 0.45 in two. These results indicate that the limitation of hepatic resection is between 0.40 and 0.45 of the predictive index.     

A cooperative group study of clinical efficacy of the liver SPECT

The purpose of this study is to evaluate the clinical efficacy of the liver SPECT about detectability of SOLs (space occupying lesion). The images were interpreted with the planar scintigram (PS) only and combination of PS and SPECT (single photon emission computed tomography) by 11 physicians. Changes of false positive and false negative rate were calculated to evaluate the influence of the diffuse parenchymal liver disease and the localization of the SOLs. Addition of SPECT to PS in the cases who are suspected SOLs is effective in right hepatic lobe (right anterior and posterior segment) to detect the SOLs, but not effective in left lateral segment. Addition of SPECT to PS in the cases with diffuse parenchymal liver disease and SOLs increases the false positive rate.     

SOL-detectability of liver SPECT--analysis of the structure of ROC-curve

The purpose of this study is to evaluate the clinical efficacy of liver SPECT (single photon emission computed tomography). The two examinations were performed in 76 cases with SOL (space occupying lesion) and 58 normal cases. The results of the image reading by the planar image only (PS) and that of the image reading by the combination of PS and SPECT (PS + SPECT) were analyzed by ROC (receiver operating characteristic) analysis. The ROC curves showed that SPECT appears to reduce the number of results which were equivocal by the image reading of PS only. The detectability of SPECT for SOL in the left lobe of liver was less than that of PS without statistical significance. However, the performance of SPECT for SOL in the right lobe of liver was significantly better than that of PS.     

The conjugative metabolism of 4-methylumbelliferone and deconjugation to the parent drug examined by isolated perfused liver and in vitro liver homogenate of rats

We examined the disposition of 4-methylumbelliferone (4-MU) and its conjugative metabolites, glucuronide (4-MUG) and sulfate (4-MUS), using a single-pass rat liver perfusion system. When 4-MU was delivered, the steady-state hepatic extraction ratio for 4-MU was very high (approximately 1.0) and its conjugative metabolites, 4-MUG and 4-MUS, appeared to a large extent in the effluent perfusate. The biliary excretion rate of the 4-MUG conjugated from 4-MU was 44% of the infusion rate at the steady-state, whereas those of 4-MU and 4-MUS were less than 1% of the infusion rate. When 4-MUG was delivered, the steady-state hepatic extraction ratio for 4-MUG was very low (less than 0.05) and the removal rate of 4-MUG from the perfusate was almost identical to the excretion rate of 4-MUG into the bile, while 4-MU and 4-MUS were slightly excreted into the bile (1% of the total biliary excretion rate), suggesting that a little deconjugation of 4-MUG to 4-MU occurred in the liver. Similarly, 4-MU and 4-MUS were not detectable in the effluent perfusate. The apparent extraction ratio (Eapp) for the intracellularly conjugated 4-MUG was approximately twenty times higher than that for the pre-conjugated 4-MUG. This discrepancy between the values of Eapp for the intracellularly conjugated and pre-conjugated 4-MUG might be attributed mainly to the diffusional barrier for the metabolite between the blood and hepatocytes, as suggested in the previous simulation (J. Pharmacokin, Biopharm., 15, 399 (1987].(ABSTRACT TRUNCATED AT 250 WORDS)     

Activity of ginsenoside Rh<Subscript>2</Subscript> on the growth of mice splenic lymphocytes investigated by microcalorimetry and factor analysis

The power–time curves of mice splenic lymphocytes growth at 37 °C affected by ginsenoside Rh₂ were determined by microcalorimetry using a 3114/3236 TAM air bioactivity monitor with ampoule mode. Then, the minimal inhibitory concentration (MIC) of Rh₂ on splenic lymphocytes growth was determined by serial dilution method. From factor analysis (FA) on six quantitative thermokinetic parameters from the power–time curves, the activity of Rh₂ on splenic lymphocytes could be quickly evaluated by analyzing the changes in the two main parameters: growth rate constant k, and maximum heat-output power, P _m. The results showed that Rh₂ had strong inhibitory activity on splenic lymphocytes growth, and this inhibitory activity was strengthened with increasing concentration of Rh₂ in the concentration range of 1.0–32.0 μg mL⁻¹. This strong inhibitory also could be confirmed from the MIC of 50.0 μg mL⁻¹ of Rh₂ on splenic lymphocytes growth in RPMI-1640 culture medium. This study illustrated that microcalorimetry could not only offer a useful method for evaluating the activity of drugs, but also serve as a quantitative, sensitive, and simple analytic tool for the evaluation of drugs on cell growth.     

Detection efficiency improvement of a large volume scintillation cell

A large volume scintillation cell (LVSC) for radon activity concentration measurements has been reported at MARC-IV. The present paper describes improvements in the detection efficiency of the LVSC and results of the radon activity concentration measurements for indoor air that were performed using the improved LVSC. The cell is a cylindrical shape and has two photomultiplier tubes that are attached to a condensing lens on the photocathode so as to provide good light collection. Individual counting efficiencies were determined to be 0.48 for ²²²Rn, 0.55 for ²¹⁸Po, and 0.61 for ²¹⁴Po. The average counting efficiency per alpha-particle from the radon and its short half-life progenies was 0.55. This value is smaller than the original value reported by LUCAS of 0.86. However, the sensitivity is approximately eight times higher than that of the Lucas cell, which has a smaller volume. A background counting rate of 0.015 cps was obtained. The lower limit of detection (LLD) for the measurements was estimated using the average background counts, the detection efficiency and measurement time. The LLD at 80% statistics confidence limits was less than 10 Bq/m³ when counted within two hours.     

Molecular Modification of Benzophenone Derivatives for Lower Bioenrichment and Toxicity Through the Pharmacophore Model

In this study, we used the improved extreme-difference normalization method to calculate the comprehensive evaluation values of bioenrichment and toxicity of benzophenone UV light absor-bers(BPs). Based on this parameter, a 3D-QSAR(QSAR=quantitative structure activity relationship) pharmacophore model was constructed using Discovery Studio software and applied to the mole-cular modification of BPs. With three commonly used ingredients in sunscreen 2-hydroxy-4-methoxybenzophenone(BP-3), 2,2'-dihydroxy-4,4'-dimethoxybenzophenone(BP-6) and 2,2'-dihydroxy-4-methoxybenzophenone(BP-8) as target molecules, we performed BPs substitution reaction based on the binding positions of characteristic elements of the pharmacophore model and designed BP derivatives with reduced bioenrichment and toxicity. Stability and function evaluation showed that while the stability of 6 BP derivatives was enhanced, the light absorption capacity was also significantly enhanced(from 9.16% to 43.16%). Molecular dynamics simulation results showed that the binding ability of BP-609 molecule with serum albumin was reduced by 16.37% compared with BP-6, and the binding with collagen could not occur spontaneously, which could be used as an explanation for the simultaneous reduction of its bioenrichment and toxicity. Besides, through the simulation of human metabolism, it was found that the liver metabolites of BP-609 were less toxic, which reduced the potential risk of human metabolism. It proved that the molecular modification scheme of BPs was environment-friendly.     

甘草次酸修饰海藻酸钠纳米给药系统的肝靶向性评估

通过EDC/NHS偶联反应将疏水性肝靶向小分子甘草次酸(GA)连接到天然多糖海藻酸钠(ALG)上,制备了具有双亲性肝靶向药物载体材料(GA-ALG).采用乳化法对广谱抗癌药物阿霉素(DOX)进行包载,得到肝靶向载药纳米粒子( DOX/GA-ALG NPs).利用单光子发射型计算机断层成像技术(SPECT)和药物体内分布...     

Development of <Superscript>111</Superscript>In labeled insulin for receptor imaging/therapy

In order to target insulin receptors in various diabetic and insulinoma conditions, human recombinant insulin was successively labeled with [¹¹¹In]-indium chloride after conjugation with freshly prepared cyclic DTPA-dianhydride (ccDTPA). The best results of the conjugation were obtained by addition of 0.5 mL of an insulin pharmaceutical solution (5 mg/mL, in phosphate buffer, pH 8) to a glass tube pre-coated with DTPA-dianhydride (0.01 mg) at 25 °C with continuous mild stirring for 30 minutes. Radio-thin layer chromatography (RTLC), instant thin layer chromatography (ITLC) and high performance liquid chromatography (HPLC) have shown an overall radiochemical purity of higher than 93% at optimized conditions (specific activity = 550–750 MBq/mg, radiochemical yield =81%). The white blood cell labeling capacity of the tracer was determined up to 4 hours at 37 °C. Preliminary in vivo studies in normal rat model was performed to determine the biodistribution of the radiotracer up to 48 hours. It showed a high liver and spleen uptake of the tracer which is consistent with other reported radiolabeled insulins. SPECT images have also shown high liver accumulation of the tracer.     

金银花的毛细管电泳指纹图谱研究

采用毛细管区带电泳法,以50 mmol/L硼砂(含20 mmol/L β-环糊精(CD),用磷酸调pH 8.0)为背景电解质,运行电压12 kV,紫外检测波长254 nm,重力进样15 s（高度8.5 cm）,建立了金银花药材水提取液的毛细管电泳指纹图谱(CEFP)。将13个不同产地的金银花药材供试液的CEFP进行比较,以电泳峰出现率100%计,确定金银花的共有指纹峰为18个。该CEFP具有较好的精密度和重现性,分离效能高且成本低廉。提出了指纹图谱宏观含量相似度R、投影含量相似度C和定量相似度P的概念,可从总体上评价药材化学组分的整体含量情况。从两个方面评价各产地药材与对照CEFP间的总体相似性,合格药材应具备以下两个条件：(1)代表化学成分分布相似性的定性相似度(S)≥0.90;(2)描述药材整体化学成分含量的定量相似度(R,C,P,Q)应在80%～120%。以此二类相似度指标控制金银花的质量,建立了指纹图谱评价的又一新方法。     

The impact of endotrophin on the progression of chronic liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and can lead to multiple complications, including non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. The fibrotic liver is characterized by the pathological accumulation of extracellular matrix (ECM) proteins. Type VI collagen alpha3 (Col6a3) is a biomarker of hepatic fibrosis, and its cleaved form, endotrophin (ETP), plays a critical role in adipose tissue dysfunction, insulin resistance, and breast cancer development. Here, we studied the effects of the Col6a3-derived peptide ETP on the progression of chronic liver diseases, such as NASH and liver cancer. We used a doxycycline (Dox)-inducible liver-specific ETP-overexpressing mouse model on a NAFLD-prone (liver-specific SREBP1a transgenic) background. For this, we evaluated the consequences of local ETP expression in the liver and its effect on hepatic inflammation, fibrosis, and insulin resistance. Accumulation of ETP in the liver induced hepatic inflammation and the development of fibrosis with associated insulin resistance. Surprisingly, ETP overexpression also led to the emergence of liver cancer within 10 months in the SREBP1a transgenic background. Our data revealed that ETP can act as a “second hit” during the progression of NAFLD and can play an important role in the development of NASH and hepatocellular carcinoma (HCC). These observations firmly link elevated levels of ETP to chronic liver disease.Subject terms: Metabolic syndrome, Biological techniques     

Fundamental study for SPECT imaging with 123I produced by (p, 5n) reaction

The effects of higher-energy photon from 123I (p, 5n) on the SPECT image quality were evaluated. The quality was evaluated by image contrast and %rms. Image contrast had similar tendency to planar and SPECT FWHM value. %rms was affected by septal penetration. Using 140 keV high resolution collimator (140 keV HR), image contrast was superior to that for 300 keV medium energy collimator (300 keV ME), but septal penetration rate (SPR) was 18% and %rms was 10.5. When quantitation is required, the collimator with less SPR than 18% is recommended for SPECT imaging. Using 300 keV ME, SPR was 0.05%, but spatial resolution and image contrast were inferior to that for 140 keV HR.     

Scintigraphic imaging of autotransplanted splenic grafts by 99mTc-labeled heat-damaged erythrocytes

Splenectomy is known to increase the risk of bacterial infection. Recently splenic autotransplantation has been suggested as a method of preserving splenic function. In order to demonstrate the viability of transplanted tissue, spleen scintigraphy using 99mTc labeled heat damaged erythrocytes were carried out. So far 21 studies have done in 12 patients. Spleen scans were positive 1 month after surgery, though images showed poor contrast against considerable background of bone marrow and blood pool. The quality of the images much improved five to twelve months after surgery. Functioning splenic autografts could be also shown by scintigraphy using 99mTc sulfur colloid, but the image quality was poorer, particularly within the early stage after operation. Labeling yields were 79.8% on the average, ranging from 45.6-92.3%, that affected little the quality of images. Important techniques in the splenic autotransplantation imaging include a thorough elimination of free 99mTcO4- before injection and to use comparatively small volume of damaged erythrocytes.     

Flow injection-capillary electrophoresis system with contactless conductivity detection and hydrostatic pressure generated flow. Application to the quantitative analysis of inorganic anions in water samples

A simple and inexpensive flow injection-capillary electrophoresis (FI-CE) system with contactless conductivity detection (CCD) for automated quantitative analysis of chloride, nitrate, and sulfate in various water samples is demonstrated. A glass bottle containing the background electrolyte that is raised above the FI-CE interface generates a pulse-free, highly reproducible flow of the electrolyte through the FI-CE interface. The system operates at a flow rate of 300 microLmin(-1) with an injection volume of only 4 microL. The repeatability of peak areas (n = 18) was better than 0.81% RSD and the sample throughput was 90 samples per hour using the background electrolyte containing 12 mM L-histidine adjusted to pH 4.00 with acetic acid. The limits of detection were better than 125 microgL(-1) and were comparable to those obtained by conventional CE systems with CCD. Various calibration methods for FI-CE system with electrokinetic injection were tested and their suitability for the analysis of anions in real samples was evaluated.     

Determination of interferon-gamma in Chinese hamster ovary cell culture supernatant by coupled-column liquid chromatography

A robust tandem HPLC method coupling size-exclusion (Shodex Asahipak GS-320HQ) and reversed phase (Vydac 218TP54) columns with ultraviolet detection was developed for quantitative determination of interferon-gamma (IFN-gamma) in Chinese hamster ovary cell culture supernatant. The 2D-HPLC system was linked up by a 6-port 2-position low hold-up volume switch valve. Compared to a commercial ELISA kit for IFN-gamma, the coupled column LC approach was able to detect and quantify soluble IFN-gamma, regardless of the glycoprotein's molecular/conformational variability and sample background. Each LC-LC analysis took 90 minutes inclusive of column regeneration. The relative standard deviation of measurements (n = 5) was less than 3%. The limit of detection (LOD) was determined to be 0.35 microg IFN-gamma.     

ECT脑血流灌注显像、CT和MRI在难治性癫痫中的诊断价值分析

选择2013年10月~2018年12月于我院收治的53例经临床确诊的难治性癫痫患者临床资料，所有患者均于发作间期分别行常规CT、MRI、SPECT检查，观察3种方法对致痫病灶检出和定位准确率，探讨单光子发射计算机断层成像术（SPECT）、CT和MRI在难治性癫痫中的诊断价值。结果显示，SPECT检测患侧rCBF低于健侧[（46.05±7.62）vs（54.51±9.39），P<0.05]，MRI检测患侧NAA（cho+Cr）低于健侧[（0.47±0.05）vs（0.69±0.11），P<0.05]。SPECT对致痫灶检出率、定位准确率分别为81.13%、73.58%，均高于MRI和常规CT（P<0.05）。联合SPECT、CT、MRI对致痫灶检出率、定位准确率达94.34%、92.45%，高于单独诊断（P<0.05），联合rCBF+NAA（cho+Cr）预测致痫病灶位置的AUC达0.923，灵敏度和特异度达82.26%、98.91%，高于rCBF、NAA（cho+Cr）（P<0.05）。结论：PET-CT、MRI对难治性癫痫术前定位均有较高临床应用价值，PET-CT在致痫灶检率、定位定侧方面更有优势，联合诊断更有助于提高定位准确率。     

Preparation and evaluation of <Superscript>131</Superscript>I-quercetin as a novel radiotherapy agent against dedifferentiated thyroid cancer

Here we reported the radiolabeling and evaluation of a novel ¹³¹I-radiolabeled quercetin for the treatment of dedifferentiated thyroid cancers. The human thyroid cancer cell lines (FTC-133, TT and DRO) experienced much higher uptake of ¹³¹I-quercetin as compared to the free ¹³¹I. And the proliferation inhibition rate of ¹³¹I-quercetin on in vitro DRO cell line was 86.87 ± 7.15%. Biodistribution and SPECT analysis demonstrated that the injected radioactivity mainly accumulated in tumors. The tumor volume in the treatment group was dramatically inhibited in comparison with the control group.     

A quantitative study of continuous flow-counterbalanced capillary electrophoresis for sample purification

A systematic evaluation of continuous flow-counterbalanced capillary electrophoresis for microscale preparative applications is presented. The success of the technique was found to depend on the specific nature of the analyte and background electrolyte and was most heavily influenced by factors such as solution conductivity and rate of buffer depletion. The performance of the technique for the system studied was ultimately limited by contamination arising from changes in analyte mobilities during extended run times. Marked improvements in both purification rate and yield were observed using the zwitterionic buffer 2-(N-cyclohexylamino)ethanesulfonic acid when compared to similar runs carried out using a borate background electrolyte. A quantitative evaluation of the technique was performed for the analytes studied and the performance of the technique has been compared to fraction collection methods. The highest recovery achieved was 5.2% of the fastest migrating component present in the original sample with a resolution of 9 to the adjacent peak and required 100 min under optimized conditions. Recovery could be further increased to 9.0% in 120 min for the same analyte using pressure-ramped flow-counterbalanced capillary electrophoresis.     

Quantitation of human leukocyte proteins after silver staining: a study with two-dimensional electrophoresis.

The quantitative attributes of human leukocyte proteins detected by silver staining two-dimensional electrophoresis (2-DE) gels were studied by using computer-assisted data analysis. Experiments included (a) analysis of replicate patterns of the same sample, (b) analysis of different dilutions of the same sample, and (c) analysis of samples from different individuals. Over 200 proteins were observed to have coefficients of variation (CV) less than or equal to 15% when data from replicate patterns were analyzed. In contrast, 8 proteins had CV values of less than or equal to 15% when data from different samples were analyzed. The dilution experiment showed that a majority of the proteins detected with some consistency (i.e., observed in at least 80% of the patterns) have a linear relationship between the amount of protein loaded onto a 2-DE gel and the spot volume in the final 2-DE pattern. The slope of the curves and the deviation from linearity were found to be quite protein-specific. These results indicate that optimization of sample purity and minimization of staining protocol variables are required to limit the background quantitative variability between and within 2-DE runs to a level that will allow detection of quantitative changes indicative of biological responses.