Results and analysis of examination doses for paediatric CT procedures based on a nationwide survey in China.

OBJECTIVE: To report the results of a dose survey conducted across 31 provinces in mainland China from 2017 to 2018 and to analyse the dose level to determine the national diagnostic reference levels (DRLs) for paediatric CT procedures. METHODS: At least ten patients for each age group (0- < 1, 1- < 5, 5- < 10, 10- < 15 years) and each procedure (head, chest and abdomen) for each CT scanner were selected from four to eight hospitals in each province. The dose information (CTDIvol and DLP) was collected from the HIS or RIS-PACS systems. The median values in each CT scanner were considered the representative dose values for the paediatric patients in CT scanning. The national DRLs were estimated based on the 75th percentile distribution of the median values. RESULTS: A total of 24,395 patients and 319 CT scanners were investigated across 262 hospitals. For paediatric CT scanning in 4 different age groups, the median (P50) and the 75th percentile (P75) of CTDIvol and DLP for each scanning procedure were calculated and reported. National DRLs were then proposed for each procedure and age group. CONCLUSION: The dose level of CT scanning for children in mainland China was reported for the first time. The DRLs for paediatric CT in the present study are similar to those in some Asian countries but higher than those in European countries. CLINICAL RELEVANCE STATEMENT: The paediatric CT is an extensively used tool in diagnosing paediatric disease; however, children are more sensitive to radiation. Establishing the diagnostic reference level of paediatric CT examination is necessary to reduce the dose of CT in children and promote the optimisation of medical exposure. KEY POINTS: • The DRLs for 3 paediatric CT procedures (head, chest and abdomen) and 4 age groups (0- < 1, 1- < 5, 5- < 10, 10- < 15 years) were proposed in mainland China first time. • The examination parameter and dose for children need to be further optimised in China, especially to lower the tube voltage in paediatric CT.

CT evaluation of sigmoid plate dehiscence causing pulsatile tinnitus.

OBJECTIVES: To evaluate the characteristics of sigmoid plate dehiscence (SPD) causing pulsatile tinnitus (PT) on CT arteriography and venography (CTA + V). METHODS: Thirty PT patients treated successfully with SPD reconstruction were enrolled. Sixty asymptomatic patients were matched. The location, extent, number of SPD cases and concomitant signs, including venous outflow dominance, transverse sinus stenosis, high jugular bulb, temporal bone pneumatization, height of pituitary gland and pituitary fossa, abnormal mastoid emissary vein, were detected and compared using CTA + V. RESULTS: More than one SPD was found on the symptomatic side in 13/30 PT patients (43.3 %). The upper segment of the sigmoid plate was involved in 29/44 SPDs in the vertical direction (65.9 %); the lateral wall was involved in 38/44 SPDs in the horizontal direction (86.4 %). Singular SPD was detected in 3/60 asymptomatic patients (1.67 ± 0.35 mm(2)), less so in PT patients (7.97 ± 5.17 mm(2)). Compared with the control group, ipsilateral venous outflow dominance, high jugular bulb and bilateral transverse sinus stenosis were more common in the PT group, together with deeper pituitary fossa and flatter pituitary glands. CONCLUSION: SPD causing PT has characteristic CT findings. It may be generated by vascular or intracranial pressure abnormalities and act as a common key to triggering PT's perception. KEY POINTS: Pulsatile tinnitus (PT) caused by sigmoid plate dehiscence (SPD) may be cured. SPD causing PT has some characteristic findings on CT. SPD may be a common key to triggering PT's perception. Thin-slice high resolution CT venography is recommended for SPD assessment. The relationship between intracranial pressure and SPD causing PT should be studied.

Effects of Bafa Wubu and He-Style Tai Chi exercise training on physical fitness of overweight male university students: A randomized controlled trial.

This study aimed to compare the effects of 12-week Bafa Wubu Tai Chi (BW-TC) and traditional He-style Tai Chi (TH-TC) exercise training on physical fitness parameters in overweight university students and to compare the differences in their effects. A total of 81 overweight male university students were randomly assigned to the BW-TC group (N = 27), the TH-TC group (N = 27), and the control group (CG, N = 27). Upper limb grip strength, wall squat, sitting and reaching, 6-minute walk, single-leg stance, and Y-balance were measured at baseline and after 12 weeks of Tai Chi training. There were no significant differences in demographic characteristics and assessment parameters among the groups at baseline (p>0.05). Both BW-TC and TH-TC performed Tai Chi exercise program training lasting 12 weeks, with three sessions per week, each lasting 60 minutes intervention. The changes in mean scores for the sit-and-reach test were 3.11 cm and 4.52 cm, for the wall squat test were 27.56 s and 36.85 s, and for the 6-minute walk test were 22.93 m and 63.22 m, and Y-balance (p<0.05) significantly increased in both BW-TC and TH-TC groups, while the mean score of single-leg stance significantly decreased (p<0.05). Additionally, compared to the BW-TC group, the TH-TC group showed a significant increase in lower limb strength (13.89 s, p = 0.048) and the distance of the Y-balance test in the left posterior medial direction (4.04 cm, p = 0.031). BW-TC and TH-TC interventions effectively improved physical fitness in overweight university students. However, TH-TC showed superior results in lower limb strength improvement. Trial registration number: ChiCTR2200059427 (https://www.chictr.org.cn).

A Survey of Mean Glandular Doses and Suggestions on National Diagnostic Reference Levels for Digital Mammography in China.

ABSTRACT: The primary purpose of this study was to report the mean glandular doses and to determine the national diagnostic reference levels for digital mammography based on data between 2016 and 2018 in China. The data from 19,076 mammograms (4,769 examinations) by random sampling from 118 digital mammography systems were compiled. Exposure factors included age, compressed breast thickness, kVp, mAs, target/filter combination, entrance surface air kerma, and mean glandular doses, which were retrospectively surveyed and recorded from the monitor. The national diagnostic reference levels (75th percentiles) in mean glandular dose were calculated across median value obtained for all included data and stratified to specific compressed breast thickness ranges. The patients' ages ranged from 22 to 88 y, with a median age of 45. The applied voltage and output medians were 28 kVp and 75.1 mAs for all exposure, respectively. The median CBTs were 45 mm and 48 mm for craniocaudal views and mediolateral oblique views, and the corresponding median mean glandular doses were 1.32 mGy and 1.40 mGy, respectively. The national diagnostic reference level at compressed breast thickness of 40-50 mm was 1.67 mGy for CC views and 1.71 mGy for MLO views. The median mean glandular doses varied significantly and increased with compressed breast thickness, demonstrating the necessity of establishing DRL according to breast thickness and optimizing the clinic's digital mammography practice in China.

Comparing the Effects of Bafa Wubu Tai Chi and Traditional He-Style Tai Chi Exercises on Physical Health Risk Factors in Overweight Male College Students: A Randomized Controlled Trial.

The aim of this study was to evaluate the effects of Bafa Wubu Tai Chi (BW-TC) and traditional He-style Tai Chi (TH-TC) exercises on physical health risk factors in overweight male college students and to compare the effectiveness of the two Tai Chi exercise forms in improving these risk factors. METHODS: Eighty-one overweight male university students between the ages of 18 and 23 were randomly assigned in a 1:1:1 ratio to the BW-TC group, TH-TC group, and control group (CG). The Tai Chi exercise training consisted of 12 weeks, three times a week, for 60 min per session. The CG attended three health lectures and maintained their normal study routine. The outcomes were body composition and blood lipids. Data were collected at baseline and post-intervention and analyzed using one-way ANOVA and mixed-design ANOVA. RESULTS: At baseline, there were no significant differences in demographic characteristics and assessed parameters (p > 0.05) among the groups. The BW TC and TH TC groups both significantly decreased their body weight (2.69 kg, 2.04 kg, respectively), body mass index (0.90 kg/m2, 0.67 kg/m2, respectively), body fat percentage (1.46%, 1.10%, respectively), low-density lipoprotein cholesterol (8.82 mg/dL, 9.27 mg/dL, respectively), total cholesterol (8.57 mg/dL, 9.34 mg/dL, respectively) and triglycerides (10.14 mg/dL, 10.63 mg/dL, respectively); and increased their muscle mass (-0.56 kg, -1.13 kg, respectively) and high-density lipoprotein cholesterol (-5.77 mg/dL, -6.37 mg/dL, respectively). Multiple comparisons showed that both Tai Chi groups were significantly better than the CG in improving the evaluated parameters. CONCLUSIONS: Two types of Tai Chi interventions were effective in improving body composition and blood lipids in overweight university students, without significant differences between the two.

A semi-supervised learning-based quality evaluation system for digital chest radiographs.

BACKGROUND: Digital radiography is the most commonly utilized medical imaging technique worldwide, and the quality of radiographs plays a crucial role in accurate disease diagnosis. Therefore, evaluating the quality of radiographs is an essential step in medical examinations. However, manual evaluation can be time-consuming, labor-intensive, and prone to interobserver differences, making it less reliable. PURPOSE: To alleviate the workload of radiographic technologists and enhance the efficiency of radiograph quality evaluation, it is crucial to develop rapid and reliable quality evaluation methods and establish a set of quantitative evaluation standards. To address this, we have proposed a quality evaluation system for digital radiographs that utilizes deep learning techniques to achieve fast and precise evaluation. METHODS: The evaluation of frontal chest radiograph quality involves assessing patient positioning through semantic segmentation and foreign body detection. For lung, scapula, and clavicle segmentation in digital chest radiographs, a residual connection-based convolutional neural network π-ResUNet, was proposed. Criteria for patient positioning evaluation were established based on the segmentation and manual evaluation results. A convolutional neural network, FasterRCNN, was utilized to detect and localize foreign bodies in digital chest radiographs. To enhance the performance of both neural networks, a semi-supervised learning (SSL) strategy was implemented by incorporating a consistency loss that leverages a large number of unlabeled digital radiographs. We also trained the network using the fully supervised learning (FSL) strategy and compared their performance on the test set. The ChestXRay-14 and object-CXR datasets were used throughout the process. RESULTS: By comparing with the manual annotation, the proposed network, trained using the SSL method, achieved a high Dice similarity coefficient (DSC) of 0.96, 0.88, and 0.88 for lung, scapula, and clavicle segmentation, respectively, outperforming the network trained with the FSL method. In addition, for foreign body detection, the proposed SSL method was superior to the FSL method, achieving an AUC (Area under receiver operating characteristic curve, Area under ROC curve) of 0.90 and an FROC (Free-response ROC) of 0.77 on the test dataset. CONCLUSIONS: The experimental results show that our proposed system is well-suited for radiograph quality evaluation, with the semi-supervised learning method further improving the network's performance. The proposed method can evaluate the quality of a chest radiograph from two aspects-patient positioning and foreign body detection-within 1 s, offering a promising tool in radiograph quality evaluation.

Higher Iodine Concentration Enables Radiation Dose Reduction in Coronary CT Angiography.

RATIONALE AND OBJECTIVES: To test whether higher iodine concentration together with higher noise level could lead to a further dose reduction in an already low dose coronary CT angiography (CCTA) protocol without comprising image quality. MATERIALS AND METHODS: One hundred eighty patients with suspected coronary artery disease (CAD) were randomly assigned into three groups: (a) conventional dose (CD) group, 100 kV with a noise index (NI) of 25 and iohexol (350 mg I/ml); (b) low dose (LD) group, 80 kV with a NI of 25 and iohexol (350 mg I/ml); (c) further low dose (FLD) group, 80 kV with a NI of 30 and iomeprol (400 mg I/ml). The volume and injection rate of contrast medium were fixed at 60 ml and 5 ml/s. The radiation dose (volume CT dose index [CTDIvol], dose length product [DLP], and effective dose [ED]) were recorded. For image quality, both quantitative (enhancement, noise, signal-to-noise ratio [SNR], and contrast-to-noise ratio [CNR]) and qualitative indices were assessed. RESULTS: Compared to the CD group, ED was reduced by 16% and 42% in the LD and FLD groups, respectively (p < 0.05). Qualitative analysis showed no significant difference among the 3 groups (p > 0.05), while quantitative analysis revealed significantly higher attenuation in the LD and FLD groups. Signal-to-noise ratios and CNRs of the LD and FLD groups were significantly higher except for the CNR at the left circumflex branch of the FLD group (p < 0.05). CONCLUSION: Increasing iodine concentration and noise level may further reduce the radiation dose by 26% on top of a 16% reduction from 100 kV to 80 kV without image quality compromise.

Optimization of imaging parameters in chest CT for COVID-19 patients: an experimental phantom study.

BACKGROUND: With the global outbreak of coronavirus disease 2019 (COVID-19), chest computed tomography (CT) is vital for diagnosis and follow-up. The increasing contribution of CT to the population-collected dose has become a topic of interest. Radiation dose optimization for chest CT of COVID-19 patients is of importance in clinical practice. The present study aimed to investigate the factors affecting the detection of ground-glass nodules and exudative lesions in chest CT among COVID-19 patients and to find an appropriate combination of imaging parameters that optimize detection while effectively reducing the radiation dose. METHODS: The anthropomorphic thorax phantom, with 9 spherical nodules of different diameters and CT values of -800, -630, and 100 HU, was used to simulate the lesions of COVID-19 patients. Four custom-simulated lesions of porcine fat and ethanol were also scanned at 3 tube potentials (120, 100, and 80 kV) and corresponding milliampere-seconds (mAs) (ranging from 10 to 100). Separate scans were performed at pitches of 0.6, 0.8, 1.0, 1.15, and 1.49, and at collimations of 10, 20, 40, and 80 mm at 80 kV and 100 mAs. CT values and standard deviations of simulated nodules and lesions were measured, and radiation dose quantity (volume CT dose index; CTDIvol) was collected. Contrast-to-noise ratio (CNR) and figure of merit (FOM) were calculated. All images were subjectively evaluated by 2 radiologists to determine whether the nodules were detectable and if the overall image quality met diagnostic requirements. RESULTS: All simulated lesions, except -800 HU nodules, were detected at all scanning conditions. At a fixed voltage of 120 or 100 kV, with increasing mAs, image noise tended to decrease, and the CNR tended to increase (F=9.694 and P=0.033 for 120 kV; F=9.028 and P=0.034 for 100 kV). The FOM trend was the same as that of CNR (F=2.768 and P=0.174 for 120 kV; F=1.915 and P=0.255 for 100 kV). At 80 kV, the CNRs and FOMs had no significant change with increasing mAs (F=4.522 and P=0.114 for CNRs; F=1.212 and P=0.351 for FOMs). For the 4 nodules of -800 and -630 HU, CNRs had no statistical differences at each of the 5 pitches (F=0.673, P=0.476). The CNRs and FOMs at each of the 4 collimations had no statistical differences (F=2.509 and P=0.125 for CNRs; F=1.485 and P=0.309 for FOMs) for each nodule. CNRs and subjective evaluation scores increased with increasing parameter values for each imaging iteration. The CNRs of 4 -800 HU nodules in the qualified images at the thresholds of scanning parameters of 120 kV/20 mAs, 100 kV/40 mAs, and 80 kV/80 mAs, had statistical differences (P=0.038), but the FOMs had no statistical differences (P=0.085). Under the 3 threshold conditions, the CNRs and FOMs of the 4 nodules were highest at 100 kV and 40 mAs (1.6 mGy CTDIvol). CONCLUSIONS: For chest CT among COVID-19 patients, it is recommended that 100 kV/40 mAs is used for average patients; the radiation dose can be reduced to 1.6 mGy with qualified images to detect ground-glass nodules and exudation lesions.

Management of infection control and radiological protection in diagnostic radiology examination of COVID-19 cases.

Since the COVID-19 outbreak, diagnostic imaging has been providing valuable radiological support for disease diagnosis and prognosis prediction. Radiological staff, especially radiographers working on the front line in the battle against the COVID-19 outbreak. They are in direct contact with the patients, bearing the responsibility and pressure of both the infection prevention and control and the radiation protection. A number of relevant professionals and experts reached a consensus, which clarifies the detailed implementing rules with respective to infection control and protection of the radiation workers, disinfection of diagnostic radiology equipment and workplace, and radiological protection. The aim is to further normalize the clinical procedures of radiological staff, reduce the infection risk, especially the radiation risk to medics and patients.

DOSE DISTRIBUTION IN A BREAST UNDERGOING MAMMOGRAPHY BASED ON A 3D DETAILED BREAST MODEL FOR CHINESE WOMEN.

Not only the mean glandular dose (MGD) but also the glandular dose distribution is important in describing the radiation exposure to breast in mammography. For a more precise knowledge of the absorbed dose distribution in the breast, experimental measurements with thermoluminescence dosemeter and Monte Carlo simulations with Geant4 were performed in this study. The experimental measurements with homogeneous physical breast phantoms were used to validate Monte Carlo simulations of homogeneous mathematical breast models undergoing mammography. Then a 3D detailed breast model with a compressed breast thickness of 4 cm and a glandular content of 50%, which has been constructed in previous work, was used to study the absorbed dose distribution inside the breast undergoing mammography. Furthermore, the effects of the glandular tissue distribution on MGD were studied by reversing the breast model in head-toe direction to get a breast model with a different distribution of glandular tissues.

Monte Carlo calculation of conversion coefficients for dose estimation in mammography based on a 3D detailed breast model.

PURPOSE: At present, the Chinese specification for testing of quality control in x-ray mammography is based on a simple breast model, and does not consider the glandular tissue distribution in the breast. In order to more precisely estimate the mean glandular dose (MGD) in mammography for Chinese women, a three-dimensional (3D) detailed breast model based on realistic structures in the breast and Chinese female breast parameters was built and applied in this study. METHODS: To characterize the Chinese female breast, Chinese female breast parameters including breast size, compressed breast thickness (CBT), and glandular content were investigated in this study. A mathematical model with the detailed breast structures was constructed based on the Chinese female breast parameters. The mathematical model was then converted to a voxel model with voxels. The voxel model was compressed in craniocaudal (CC) view to obtain a deformation model. The compressed breast model was combined with the Chinese reference adult female whole-body voxel phantom (CRAF) to study the effects of backscatter from the female body. Monte Carlo simulations of the glandular dose in mammography were performed with Geant 4. The glandular tissue dose conversion coefficients for breasts with different glandular contents (5%, 25%, 50%, 75%, and 100% glandularity) and CBTs (3 cm, 4 cm, 5 cm, and 6 cm) were calculated, respectively, at various x-ray tube voltages (25 kV, 28 kV, 30 kV, 32 kV, and 35 kV) for various target/filter combinations (Mo/Mo, Mo/Rh, Rh/Rh, and W/Rh). RESULTS: A series of glandular tissue dose conversion coefficients for dose estimation in mammography were calculated. The conversion coefficients calculated in this study were compared with those estimated with the simple breast model. A discrepancy of 5.4-38.0% was observed. This was consistent with the results obtained from the realistic breast models in the literature. CONCLUSIONS: A 3D detailed breast model with realistic structures in the breast was constructed based on the Chinese female breast parameters. It was used to calculate glandular tissue dose conversion coefficients for mammography. Although the accuracy of the proposed model could not be directly assessed, the consistency of the obtained results with previously performed analyses increases the confidence in the applicability of the proposed model. The proposed model could be used in dose estimation and dose optimization for mammography of Chinese women.

The citrus flavonoid naringenin stimulates DNA repair in prostate cancer cells.

As part of a systematic study of the effects of phytochemicals beyond antioxidation on cancer prevention, we investigated whether naringenin (NR), a citrus flavonoid, stimulates DNA repair following oxidative damage in LNCaP human prostate cancer cells. The 8-hydroxydeoxyguanosine (8-OH-dG) to deoxyguanosine (dG) ratio was measured after cells were treated with 200 micromol/L of ferrous sulfate in serum-free medium followed by NR exposure for 24 h in growth medium. The results demonstrated that exposure to 10-80 micromol/L of NR led to a significant decrease in the ratio of 8-OH-dG to 10(6) dG. Because cells were treated with NR after ferrous sulfate was removed, we conclude that we demonstrated an effect on DNA repair beyond antioxidation. In support of this conclusion, we determined the induction of mRNA expression over time after oxidative stress followed by NR administration of three major enzymes in the DNA base excision repair (BER) pathway: 8-oxoguanine-DNA glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease and DNA polymerase beta (DNA poly beta). hOGG1 and DNA poly beta mRNA expression in cells after 24-h exposure to NR was increased significantly compared with control cells without NR. The intracellular concentration of NR after exposure to 80 micromol/L was 3 pmol/mg protein, which is physiologically achievable in tissues. In conclusion, the cancer-preventive effects of citrus fruits demonstrated in epidemiological studies may be due in part to stimulation of DNA repair by NR, which by stimulating BER processes may prevent mutagenic changes in prostate cancer cells.

Catechin and caffeine content of green tea dietary supplements and correlation with antioxidant capacity.

The health benefits associated with tea consumption have resulted in the wide inclusion of green tea extracts in botanical dietary supplements, which are widely consumed as adjuvants for complementary and alternative medicines. Tea contains polyphenols such as catechins or flavan-3-ols including epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate (EGCG), as well as the alkaloid, caffeine. Polyphenols are antioxidants, and EGCG, due to its high levels, is widely accepted as the major antioxidant in green tea. Therefore, commercial green tea dietary supplements (GTDS) may be chemically standardized to EGCG levels and/or biologically standardized to antioxidant capacity. However, label claims on GTDS may not correlate with actual phytochemical content or antioxidant capacity nor provide information about the presence and levels of caffeine. In the current study, 19 commonly available GTDS were evaluated for catechin and caffeine content (using high-performance liquid chromatography) and for antioxidative activity [using trolox equivalent antioxidant capacity (TEAC) and oxygen radical antioxidant capacity (ORAC) assays]. Product labels varied in the information provided and were inconsistent with actual phytochemical contents. Only seven of the GTDS studied made label claims of caffeine content, 11 made claims of EGCG content, and five specified total polyphenol content. Caffeine, EGCG, and total polyphenol contents in the GTDS varied from 28 to 183, 12-143, and 14-36% tablet or capsule weight, respectively. TEAC and ORAC values for GTDS ranged from 187 to 15340 and from 166 to 13690 mumol Trolox/g for tablet or capsule, respectively. The antioxidant activities for GTDS determined by TEAC and ORAC were well-correlated with each other and with the total polyphenol content. Reliable labeling information and standardized manufacturing practices, based on both chemical standardization and biological assays, are recommended for the quality control of botanical dietary supplements.

Pistachio skin phenolics are destroyed by bleaching resulting in reduced antioxidative capacities.

Pistachio shells split naturally prior to maturity leading to their unique crack-shell form. Within 24 h of harvest, hull-trapped moisture may cause shell staining. The illegal process of bleaching has been used to restore a desirable white color to pistachio shells. It is not known whether bleaching adversely affects phytochemical levels in pistachios. Therefore, we identified for the first time multiple pistachio skin phenolics as quercetin (14.9 microg/g), luteolin (10.0 microg/g), eriodictyol (10.2 microg/g), rutin (1.6 microg/g), naringenin (1.2 microg/g), apigenin (0.2 microg/g), and the anthocyanins, cyanidin-3-galactoside (696 microg/g) and cyanidin-3-glucoside (209 microg/g). We investigated the effects of bleaching (0.1-50% hydrogen peroxide) on phenolic levels and antioxidative capacities in raw and roasted nuts. Because of their flavylium cation structures, anthocyanins were the most sensitive to bleaching. Bleaching decreased total anthocyanin levels [mug/g of skins (% hydrogen peroxide)]: 905 and 549 (0%); 653 and 145 (0.1%); 111 and 18.4 (5%); 6.1 and 3.2 (25%); 0 and 0 (50%) for raw and roasted nuts, respectively. Bleaching also reduced antioxidative capacity [microM/g of Trolox (% hydrogen peroxide)]: 945 and 725 (0%); 940 and 472 (0.1%); 930 and 455 (5%); 433 and 370 (25%); 189 and 173 (50%), for raw and roasted nuts, respectively. Raw nuts preserved phenolic levels and antioxidant capacity better than roasted nuts, suggesting contributing effects of other substances and/or matrix effects that are destroyed by the roasting process. The destruction of bioactive phenolics in pistachio skins may negatively impact the potential health benefits arising from pistachio consumption.

In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice.

Pomegranate (Punica granatum L.) fruits are widely consumed as juice (PJ). The potent antioxidant and anti-atherosclerotic activities of PJ are attributed to its polyphenols including punicalagin, the major fruit ellagitannin, and ellagic acid (EA). Punicalagin is the major antioxidant polyphenol ingredient in PJ. Punicalagin, EA, a standardized total pomegranate tannin (TPT) extract and PJ were evaluated for in vitro antiproliferative, apoptotic and antioxidant activities. Punicalagin, EA and TPT were evaluated for antiproliferative activity at 12.5-100 microg/ml on human oral (KB, CAL27), colon (HT-29, HCT116, SW480, SW620) and prostate (RWPE-1, 22Rv1) tumor cells. Punicalagin, EA and TPT were evaluated at 100 microg/ml concentrations for apoptotic effects and at 10 microg/ml concentrations for antioxidant properties. However, to evaluate the synergistic and/or additive contributions from other PJ phytochemicals, PJ was tested at concentrations normalized to deliver equivalent amounts of punicalagin (w/w). Apoptotic effects were evaluated against the HT-29 and HCT116 colon cancer cell lines. Antioxidant effects were evaluated using inhibition of lipid peroxidation and Trolox equivalent antioxidant capacity (TEAC) assays. Pomegranate juice showed greatest antiproliferative activity against all cell lines by inhibiting proliferation from 30% to 100%. At 100 microg/ml, PJ, EA, punicalagin and TPT induced apoptosis in HT-29 colon cells. However, in the HCT116 colon cells, EA, punicalagin and TPT but not PJ induced apoptosis. The trend in antioxidant activity was PJ>TPT>punicalagin>EA. The superior bioactivity of PJ compared to its purified polyphenols illustrated the multifactorial effects and chemical synergy of the action of multiple compounds compared to single purified active ingredients.

Bioavailability and antioxidant effect of epigallocatechin gallate administered in purified form versus as green tea extract in healthy individuals.

Tea polyphenols have strong in vitro antioxidant activity. Due to their limited bioavailability, however, their contribution to in vivo antioxidant activity may depend on the form of administration. A human intervention study was performed to evaluate the bioavailability and antioxidant capacity of (-)-epigallocatechin-3-gallate (EGCG) administered as a single large dose in the form of either purified EGCG or as green tea extract (Polyphenon E). Plasma concentrations of tea polyphenols were determined by high-performance liquid chromatography (HPLC) analysis combined with coulometric array electrochemical detection (ECD). We found no differences in plasma EGCG concentrations and trolox equivalents determined by the trolox equivalent antioxidant capacity assay after administration of either form of EGCG. However, we found that the plasma antioxidant activity was significantly affected by changes in the plasma urate concentration, which may have interfered with the effect of tea polyphenols on the antioxidant activity. In addition, lymphocyte 8-hydroxydeoxyguanosine to deoxyguanosine (8-OHdG/10(6)dG) ratios were determined by HPLC with ECD. The 8-OHdG/10(6)dG ratios did not change significantly during the 24 h following both EGCG interventions but correlated significantly within individuals determined during the two interventions separated by 1 week. In summary, changes in plasma uric acid due to dietary intake were significantly correlated to the plasma antioxidant activity and exerted a stronger influence on the plasma antioxidant activity compared with the EGCG intervention. In future studies of dietary effects on the plasma antioxidant capacity, changes in plasma uric acid will need to be closely monitored.

Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement.

BACKGROUND: Green and black tea polyphenols have been extensively studied as cancer chemopreventive agents. Many in vitro experiments have supported their strong antioxidant activity. Additional in vivo studies are needed to examine the pharmacokinetic relation of absorption and antioxidant activity of tea polyphenols administered in the form of green or black tea or tea extract supplements. OBJECTIVE: The purpose of this study was to compare the pharmacokinetic disposition of tea polyphenols and their effect on the antioxidant capacity in plasma 8 h after a bolus consumption of either green tea, black tea, or a green tea extract supplement. DESIGN: Thirty healthy subjects were randomly assigned to 3 different sequences of green tea, black tea, or a green tea extract supplement in a 3 x 3 crossover design with a 1-wk washout period in between treatments. RESULTS: Flavanol absorption was enhanced when tea polyphenols were administered as a green tea supplement in capsule form and led to a small but significant increase in plasma antioxidant activity compared with when tea polyphenols were consumed as black tea or green tea. All 3 interventions provided similar amounts of (-)-epigallocatechin-3-gallate. CONCLUSIONS: Our observations suggest that green tea extract supplements retain the beneficial effects of green and black tea and may be used in future chemoprevention studies to provide a large dose of tea polyphenols without the side effects of caffeine associated with green and black tea beverages.

Sustained delivery of cytarabine-loaded vesicular phospholipid gels for treatment of xenografted glioma.

This study described the development of vesicular phospholipid gels (VPGs) for sustained delivery of cytarabine (Ara-C) for the treatment of xenografted glioma. Ara-C-loaded VPGs in the state of a semisolid phospholipid dispersion looked like numerous vesicles tightly packing together under the freeze-fracture electron microscopy (FF-TEM), their release profiles displayed sustained drug release up to 384 h in vitro. The biodistribution of Ara-C in the rat brain showed that Ara-C-loaded VPGs could maintain therapeutic concentrations up to 5mm distance from the implantation site in brain tissue within 28 days. At the same time, fluorescence micrograph confirmed drug distribution in brain tissue visually. Furthermore, after single administration, Ara-C-loaded VPGs group significantly inhibited the U87-MG glioma growth in right flank in comparison with Ara-C solution (p<0.01). It was explained that the entrapped drug in VPGs could avoid degradation from cytidine deaminase and sustained release of drug from Ara-C-loaded VPGs could maintain the effective therapeutic levels for a long time around the tumor. In conclusion, Ara-C-loaded VPGs, with the properties of sustained release, high penetration capacity, nontoxicity and no shape restriction of the surgical cavity, are promising local delivery systems for post-surgical sustained chemotherapy against glioma.

A stable and practical etoposide-containing intravenous long-/medium-chain triglycerides-based lipid emulsion formulation: pharmacokinetics, biodistribution, toxicity, and antitumor efficacy.

OBJECTIVES: This work aimed to evaluate pharmacokinetics, biodistribution, toxicity, and antitumor activities of a highly stable long-/medium-chain triglycerides (LCT/MCT)-based etoposide parenteral emulsion (EPE) in comparison to etoposide parenteral solution (EPS). METHODS: Using high-pressure homogenization method, EPE was prepared and sterilized at 121°C for 10 min by autoclaving. The biological samples were analyzed using the UPLC-ESI-MS/MS method. RESULTS: Superior stability of EPE was verified with no significant changes in physicochemical properties in the accelerating and long-term stability tests. Similar pharmacokinetic behavior in beagle dogs was obtained and the AUC 0 - 12h values were 1196.73 ± 320.85 and 1505.56 ± 617.93 µg.h/L for EPE and EPS (p > 0.5), respectively. Likewise, no remarkable difference in biodistribution profiles in mice was found for both formulations. Safety assessment studies including hemolysis test, rabbit ear vein test and injection anaphylaxis were undertaken and the EPE was proven to be safe for intravenous administration. Specifically, after consecutive 12 weeks administration in rats, systematic and local toxicity induced by EPE were alleviated relative to that of EPS. Furthermore, significant and comparable antitumor activities to EPS were also demonstrated by EPE with tumor suppression rate (TSR) of 66.63, 55.94, and 60.16% against H460, Hep G2, and BCAP-37 human cancer cell lines in nude mice at the dose of 15 mg/kg, respectively. CONCLUSION: These results suggest that this LCT/MCT-based lipid emulsion is a promising alternative intravenous carrier for etoposide with high stability, improved convenience, alleviated toxicity, and noncompromised antitumor efficacy.