A new direct compression mechanism of structural transition in Poria cocos extract composite particles.

The structural transition to generate amorphous translucent grains in Poria cocos dry extract (PCE) composite particles was found and studied as a new direct compression mechanism. The pressure and displacement sensing techniques were used to obtained stress-strain profiles during compression. The Exponential function, Kawakita model, Shapiro model and Heckel model were used to analysis mechanical properties of powders. 12 parameters derived from compression models and powder physical properties were applied to partial least squares method (PLS) for analyzing powder compression mechanism. It was found that only the oven-dried PCE composite particles undergoes the structural transition and generate translucent grains scattered and embedded in tablet, and these tablets have excellent mechanical stability. The structural transition in plant dry extract as the PCE composite particles could be exploited to improve powder compression and tabletability.

Antioxidative stress of oral administration of tea extract granule in chickens.

The present study was to evaluate antioxidative effect of tea extract granule (TEG) on oxidative stress induced by cyclophosphamide (Cy) in chickens. In experiment 1, chickens were randomly divided into 5 groups with 10 birds in each. Groups 3 to 5 were orally administered TEG in drinking water for 7 D at doses of 20, 40, and 80 mg/kg body weight, respectively. After that, groups 2 to 5 received intramuscular injection of Cy (100 mg/kg BW) for 3 D. Group 1 was not treated as a control. In experiment 2, chickens were grouped in the same way as in experiment 1. Groups 2 to 5 received intramuscular injection of Cy (100 mg/kg BW) for 3 D. After that, groups 3 to 5 were orally administered TEG in drinking water for 7 D at doses of 20, 40, and 80 mg/kg BW, respectively. Results showed that Cy injection induced significantly decreased body weight and oxidative stress. Oral administration of TEG before or after Cy injection increased body weight, the thymus, bursa, and spleen indices, total antioxidant capacity, and the levels of glutathione; elevated the activity of superoxide dismutase, catalase, and glutathione peroxidase; as well as decreased the protein carbonyl content, lipid peroxide, and malondialdehyde. In addition, TEG administration reduced intracellular reactive oxygen species. Therefore, TEG could be a promising agent against oxidative stress in the poultry industry.

Effects of dietary Enteromorpha powder supplementation on productive performance, egg quality, and antioxidant performance during the late laying period in Zi geese.

This study investigated the effects of dietary Enteromorpha powder supplementation on the productive performance, egg quality, and antioxidant performance of Zi geese during the late laying period. Three hundred twelve Zi geese (1 yr old) were randomly allocated into 2 cohorts to form a control group and an experimental group (with each cohort including 6 replicates and 21 female geese and 5 male geese in each replicate). The control group was fed a basal diet, and the experimental group was fed a diet containing 3% Enteromorpha powder. The data showed that Enteromorpha powder supplementation significantly improved egg production, laying rate, average daily egg weight (P < 0.01), and egg yolk color (P < 0.05). Supplementation decreased the ADFI and feed conversion rate (P < 0.01). Compared with the control group, glutathione peroxidase (GSH-Px) activity was significantly higher in serum and ovary tissue (P < 0.05), but GSH-Px activity was lower in liver tissue (P < 0.01). Malondialdehyde was reduced in liver and ovary tissue (P < 0.05) in the Enteromorpha powder supplementation group. Meanwhile, the expression of the CAT gene was significantly upregulated in the liver (P < 0.01) in the Enteromorpha group. These results indicate that dietary Enteromorpha powder supplementation improved productive performance and reduced the level of lipid peroxidation in Zi geese during the late laying period.

Association of use of Chinese herbal medicines and the risk of fracture in patients with osteoporosis: a population-based cohort study.

After utilizing a large population-based claims database and the application of propensity score match approach to reduce the confounding effects, we found that the use of Chinese herbal medicines (CHMs) was related to the lower risk of sequent osteoporotic fracture by 27% among the individuals with osteoporosis. The predominant effect was observed in those receiving CHMs for more than two years. INTRODUCTION: Osteoporosis (OS) is a highly disabling condition that can lead to fragility fracture, thus posing greater burdens of functional limitations for the affected individuals. It is unclear if the use of Chinese herbal medicines (CHMs) could reduce the risk of fracture due to OS. This study aimed to investigate the association of CHMs and the subsequent osteoporotic fracture risk among OS patients. METHODS: This longitudinal cohort study used the Taiwanese National Health Insurance Research Database to identify 250,699 newly diagnosed OS patients aged 20 years or older between 1998 and 2010. We recruited 103,325 CHM users following the onset of OS (CHM users) and randomly selected 103,325 subjects without CHM usage as controls (non-CHM users) by propensity score matching according to the demographic characteristics and comorbidities at enrollment. All enrollees were followed until the end of 2012 to record the incidence of osteoporotic fracture. We applied the Cox proportional hazard regression model to compute the hazard ratio (HR) of the risk of osteoporotic fracture. RESULTS: During the 15-year follow-up period, 7208 CHM users and 11,453 non-CHM users sustained osteoporotic fracture, with an incidence rate of 9.26 and 12.96, respectively, per 1000 person-years. We found that CHM users had a significantly reduced risk of osteoporotic fracture compared to non-CHM users (adjusted HR 0.73; 95% confidence interval [CI] = 0.70-0.75). Those treated with CHMs for longer than 730 days had a lower fracture risk by 54%. Some commonly used CHMs, such as Yan hu suo (Rhizoma Corydalis), Huang Qin (Scutellaria Baicale), Jie Geng (Platycodon grandifloras), Xiang Fu (Cyperus rotundus), Hai Piao Xiao (Cuttlebone Sepium), Jia-Wei-Xiao-Yao-San, Ge-Gen-Tang, Shao-Yao-Gan-Cao-Tang, and Du-Huo-Ji-Sheng-Tang, are related to the lower risk of fracture. CONCLUSIONS: The use of CHMs was associated with lower risk of osteoporotic fracture for OS patients, suggesting that it could be integrated into conventional therapy to prevent subsequent bone fracture.

Therapeutic effect of ginsenoside Rg1 on mastitis experimentally induced by lipopolysaccharide in lactating goats.

Escherichia coli is a cause of subclinical and clinical mastitis in dairy cattle and goats, and sometimes causes severe clinical disease that may result in death of the animal. Previous investigation showed that ginsenoside Rg1 extracted from Panax ginseng C.A. Meyer (Araliaceae) has an anti-inflammatory effect on the sepsis induced by E. coli lipopolysaccharide via competitive binding to toll-like receptor 4. We hypothesized that intravenous injection of Rg1 had therapeutic effect on mastitis experimentally induced by intramammary infusion of lipopolysaccharide in lactating goats. In this study, 9 lactating goats were randomly assigned to 1 of the 3 groups: (1) lipopolysaccharide intramammary infusion + saline intravenous injection, (2) lipopolysaccharide intramammary infusion + Rg1 intravenous injection, and (3) saline intramammary administration + saline intravenous injection. Because no adverse clinical signs were observed after intramammary infusion of saline and intravenous injection of Rg1 in a preliminary experiment, and available qualified goats were limited in this study, this treatment was not included in this study. One udder half of each goat received intramammary infusion of lipopolysaccharide (50 µg/kg of body weight; groups 1 and 2) or saline solution (group 3), and the other half was infused with 2 mL of saline solution at h 0. Afterward, intravenous injections of saline solution (groups 1 and 3) or Rg1 (2.5 mg/kg of body weight; group 2) were administered at h 2 and 4 post-lipopolysaccharide challenge. Blood and milk samples were collected 3, 6, 9, 12, 15, 18, 21, 24, 48, and 72 h post-lipopolysaccharide challenge, and clinical signs were monitored hourly after lipopolysaccharide challenge within the first 10 h and at the same time points as blood samples. The results showed that Rg1 treatment downregulated rectal temperature, udder skin temperature, udder girth, milk somatic cell count, and N-acetyl-ß-d-glucosaminidase and upregulated milk production, lactose, and recovered blood components, such as white blood cells, neutrophils, lymphocytes, total proteins, albumin, and globulin. Considering the positive therapeutic effect on lipopolysaccharide-induced mastitis in goats presented in this study as well as the anti-inflammatory activity found previously, the botanical Rg1 deserves further study as a therapeutic agent in the treatment of E. coli mastitis in dairy animals.

Effect of alpha-lipoic acid on relieving ammonia stress and hepatic proteomic analyses of broilers.

Ammonia in poultry houses not only affects worker health but also induces a variety of poultry diseases. Alpha-lipoic acid (LA) is an effective antioxidant that protects cells against oxidative injury during various toxic and pathological processes. This study was designed to evaluate the mitigating effects of LA supplementation on ammonia stress and hepatic proteome changes in broilers. Male broilers (22 d old) were allocated to 3 groups: (1) a control group without ammonia stress (CTRL); (2) exposure to 70 ppm ammonia (AM); and (3) exposure to 70 ppm ammonia and dietary administration of 300 mg/kg LA (AM+LA). Ammonia exposure significantly decreased broiler growth performance and plasma glutathione peroxidase activity (P < 0.05), and increased plasma malondialdehyde content and glutamic-pyruvic transaminase activity (P < 0.05). These negative effects were eliminated by LA supplementation. Comparative proteomic analyses revealed 291 differentially expressed proteins in the AM group compared to the CTRL and AM+LA groups. A total of 30 proteins were differentially expressed between the AM/CTRL and (AM+LA)/AM groups. The addition of LA restored 24 of these proteins to control levels; these proteins were mainly related to transcription regulation, detoxification, protein translation and degradation, and immune and stress responses. The differentially expressed proteins included the high mobility group box (HMGB) and glutathione S-transferase (GST), which is closely related to immune response and oxidative stress, and collagens, which are implicated in liver injury. The addition of LA to broiler diet may reduce ammonia toxicity by maintaining the antioxidant system, xenobiotic metabolism, and metabolic pathways.

Higher all-cause hospitalization among patients with chronic hepatitis C: the Chronic Hepatitis Cohort Study (CHeCS), 2006-2013.

In the United States, hospitalization among patients with chronic hepatitis C virus (HCV) infection is high. The healthcare burden associated with hospitalization is not clearly known. We analysed data from the Chronic Hepatitis Cohort Study, an observational cohort of patients receiving care at four integrated healthcare systems, collected from 2006 to 2013 to determine all-cause hospitalization rates of patients with chronic HCV infection and the other health system patients. To compare the hospitalization rates, we selected two health system patients for each chronic HCV patient using their propensity score (PS). Propensity score matching was conducted by site, gender, race, age and household income to minimize differences attributable to these characteristics. We also compared primary reason for hospitalization between chronic HCV patients and the other health system patients. Overall, 10 131 patients with chronic HCV infection and 20 262 health system patients were selected from the 1 867 802 health system patients and were matched by PS. All-cause hospitalization rates were 27.4 (27.0-27.8) and 7.4 (7.2-7.5) per 100 persons-year (PY) for chronic HCV patients and for the other health system patients, respectively. Compared to health system patients, hospitalization rates were significantly higher by site, gender, age group, race and household income among chronic HCV patients (P < 0.001). Compared to health system patients, chronic HCV patients were more likely to be hospitalized from liver-related conditions (RR = 24.8, P < 0.001). Hence, patients with chronic HCV infection had approximately 3.7-fold higher all-cause hospitalization rate than other health system patients. These findings highlight the incremental costs and healthcare burden of patients with chronic HCV infection associated with hospitalization.

[Basal cell carcinoma of prostate: a report of three cases].

To explore the clinical pathological characteristics and improve the recognition in the diagnosis and treatment of basal cell carcinoma (BCC) of prostate. Three cases of BCC of prostate were reported and the relevant literature was reviewed to investigate the diagnosis and treatment of this disease. We analyzed three cases of prostatic BCC. Their ages were within a range of 57 to 83 years. One of them complained of hematuria and two complained of dysuria. All of them presented with prostatic hyperplasia. Two of them presented with high prostate specific antigen (PSA) and one with normal PSA. Case 1 had prostate cancer invasion of bladder, rectal fascia, with lymph node metastasis, bone metastasis and lung metastases. The patient received bladder resection+bilateral ureteral cutaneous ureterostomy+lymph node dissection on November 2, 2014 . Postoperative pathological diagnosis showed BCC. Reexamination of pelvic enhanced MRI in January 8, 2015 suggested pelvic recurrence. Abdominal enhanced CT showed multiple liver metastases and pancreatic metastasis on July 11, 2015. Prostate cancer specific death occurred in October 2015. Case 2 was diagnosed as BCC in prostate biopsy on March 27, 2015. Positron emission tomography and computed tomography (PET-CT) showed pulmonary metastasis and bone metastasis. Then the patient received chemotherapy, endocrine therapy and local radiation therapy. Reexamination of PET-CT on January 11, 2016 showed that the lung metastase tumors and bone metastase tumors were larger than before. Up to January 10, 2016, the patient was still alive. Postoperative pathological changes of transurethral resection of prostate (TURP) in case 3 showed BCC might be considered. The PET-CT suggested residual prostate cancer, which might be associated with bilateral pelvic lymph node metastasis. In April 20, 2016, the review of PET-CT showed pelvic huge irregular hybrid density shadow, about 14.5 cm×10.0 cm×12.9 cm in size, and tumor recurrence was considered. Then the patient received local radiation therapy. The patient survived in the followed upon January 10, 2016. BCC of prostate is a rare subtype. Due to the local infiltrative and distant metastatic potentiality, active management is preferred and a life-long follow-up is necessary.

In vitro and in vivo antimicrobial efficacy of essential oils and individual compounds against Phytophthora parasitica var. nicotianae.

AIM: To evaluate the antimicrobial effects of essential oils (EOs) from cassia, basil, geranium, lemongrass, cumin and thyme, as well as their major components, against Phytophthora parasitica var. nicotianae; to investigate morphological changes in hyphae and sporangia in response to treatment with cinnamaldehyde; and to further evaluate potential biocontrol capacities against tobacco black shank under greenhouse conditions. METHODS AND RESULTS: The results revealed that the extent of mycelial growth inhibition was primarily dependent on the composition and concentration of the EOs and the structure of individual compounds. Cinnamaldehyde had a significantly higher inhibitory effect on mycelial growth, formation of sporangia, and production and germination of zoospores in P. parasitica var. nicotianae in vitro, achieving complete inhibition of these phenotypes at 72, 36, 36 and 18 mg l(-1), respectively. Scanning electron microscopic observations revealed that cinnamaldehyde can cause considerable morphological degenerations of hyphae and sporangia such as cytoplasmic coagulation, shrivelled mycelia and sporangia aggregates and swelling and lysis of mycelia and sporangia walls. In vivo assays with cinnamaldehyde demonstrated that this compound afforded protective effect against tobacco black shank under greenhouse conditions in susceptible tobacco plants. CONCLUSIONS: The results of in vitro and in vivo bioassays, together with SEM imaging of the microstructure of P. parasitica var. nicotianae supported the possibility of using cinnamaldehyde as a potent natural biofungicide in the greenhouse. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a theoretical basis for the potential use of cinnamaldehyde as commercial agents or lead compounds that can be exploited as commercial biofungicides in the protection of tobacco plants from P. parasitica var. nicotianae infection.

Cardiac iron measurement and iron chelation therapy in patients with ß thalassaemia major: experience from Taiwan.

BACKGROUND: The aims of our study were to evaluate (i) the relationship between cardiac T2* values and cardiac complications in Asian ß-thalassaemia major (TM) patients, and (ii) the association between cardiac T2* values and other parameters currently used to predict cardiac complications as a result of transfusion iron overload. METHODS: We examined the myocardial iron loads of 88 TM patients from Taiwan with cardiac T2* magnetic resonance imaging (MRI) and assessed the correlation between cardiac T2* values and serum ferritin levels, liver iron concentration and left ventricular ejection fraction (LVEF). We also determined the predictive value of these measurements for the development of arrhythmia. RESULTS AND CONCLUSION: In our group of Taiwanese patients, the relative risk for arrhythmia was 10·36 when cardiac T2* values were less than 10 ms (compared with ≥10 ms) and 1·98 when serum ferritin levels increased >2500 ng mL(-1) (compared with ≤2500 ng mL(-1) ). Serum ferritin levels correlated with cardiac T2* values in patients with abnormal myocardial iron loads (T2* < 20 ms, r = -0·48, P = 0·004, n = 34), but LVEF (measured by echocardiography) gave no indication of excess myocardial iron deposition (r = -0·07, P = 0·52) or of the risk of developing arrhythmia.

TU-E-BRB-07: An EPID Based Dosimetric Verification Tool for SBRT with High Dose Rate FFF Beams.

PURPOSE: The increasing use of unflattened high dose rate and/or small sized fields in stereotactic body radiosurgery (SBRT) presents a significant challenge and calls for new tools for dosimetric measurements and quality assurance (QA). The purpose of this work is to investigate a high spatial resolution (0.2mm) and high frame rate (50Hz) amorphous silicon flat-panel electronic portal imaging device (EPID) from Perkin Elmer for SBRT. METHODS: A Monte Carlo N-Particle eXtended (MCNPX) simulation and convolution based calibration procedure has been developed to derive a voxel-based response function specific to the EPID construct and beam characteristics. Both standard photon beams and flattening filter free (FFF) beams of all energies from Varian TrueBeam STX were studied and the linearity and dose rate dependence were tested. EPID with detailed materials composition was simulated using the MCNPX to generate a scatter kernel composed of dose deposition in the EPID phosphor, and optical photon spreading and to deconvolve the EPID images to high spatial resolution photon fluence map. The fluence map was convolved with MCNPX generated kernels to the 3D dose distribution in the phantom and compared with pinpoint ion chamber and film measurements. RESULTS: EPID response showed excellent linearity (R2>0.9998) and dose rate dependence less than 1.8% for up to 2400MU/min. Output factors for field sizes ranging from 1×1 to 20×20cm2 were measured and used to fit the optical photon glare kernel. Fluence profiles deconvolved using MCNPX scattering kernel agrees with the measurements to within 2%. Results of typical pre-treatment QA test exhibit excellent spatial resolution required for SBRT. CONCLUSIONS: The high spatial resolution and high frame rate EPID proved to be an accurate and efficient tool for SBRT QA. Through convolution with MCNPX scattering core and comprehensive EPID calibration, accurate 3D dose maps can be generated for independent dosimetric verification of SBRT treatments.

Improvement of natural microbial remediation of petroleum-polluted soil using graminaceous plants.

A 150-day pot experiment was conducted with graminaceous plants grown in natural soil contaminated with petroleum. The relationships among microbial activity, dehydrogenase activity, catalase activity, soil moisture, and the petroleum degradation rate were analyzed. All three plants accelerated the degradation of petroleum compared with unplanted soil. Plant roots improved the soil moisture by about 5% (from 15% in unplanted soil to 20% in soil containing plant roots), and the number of microorganisms in the rhizosphere increased by more than three orders of magnitude. The induction of the rhizosphere environment and the intimidation of the petroleum changed the abundance and activity of the microorganisms. Dehydrogenase activity in the rhizosphere was 1.54 to 1.87 times the value in the unplanted soil, but catalase activity was 0.90 to 0.93 times the value in unplanted soil. The petroleum degradation rates in the rhizosphere were 2.33 to 3.19 times higher than in the unplanted soil. The effect of rhizosphere degradation clearly changed the hydrocarbon composition, increasing the degradation of alkane hydrocarbons with low and moderate carbon contents. The rhizosphere environment promoted degradation of the high-carbon-content hydrocarbons into low-carbon-content hydrocarbons. At the same time, the Pr/nC(17), Ph/nC(18), and Pr/Ph values increased by 0.99 and 2.69 units, and decreased by 1.25 units, respectively, compared with the undegraded oil. The plants also accelerated the isomerization of alkane hydrocarbons.

Cytotoxicity, apoptosis and DNA damage induced by Alpinia galanga rhizome extract.

Alpinia galanga, or galangal, has been a popular condiment used in Thai and Asian cuisine for many years. However, relatively little is known of the potential beneficial or adverse health effects of this spice. This study was conducted to analyze the capacity of galangal extract to induce cytotoxicity and DNA damage in six different human cell lines including normal and p53-inactive fibroblasts, normal epithelial and tumour mammary cells and a lung adenocarcinoma cell line. We deliberately focused on treatment with the crude aqueous extract of galangal rhizomes, rather than compounds extracted into an organic solvent, to more closely reflect the mode of dietary consumption of galangal. The cell lines displayed a broad range of cytotoxicity. There was no evidence for preferential cytotoxicity of tumour cells, but there was an indication that p53-active cell lines may be more sensitive than their p53-inactive counterparts. The contribution of apoptosis to total cell killing was only appreciable after exposure to 300 microg/mL of extract. Apoptosis appeared to be independent of p53 expression. Exposure to as little as 100 microg/mL galangal extract generated a significant level of DNA single-strand breaks as judged by the single-cell gel electrophoresis technique (comet assay). The three major UV-absorbing compounds in the aqueous extract were identified by mass spectrometry as 1'-acetoxychavicol acetate and its deacetylated derivatives. However, when tested in A549 human lung adenocarcinoma cells, these compounds were not responsible for the cytotoxicity induced by the complete aqueous extract.

Improved treatment results for childhood acute myeloid leukemia in Taiwan.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.

Two novel mutations of the glycine receptor gene in a Taiwanese hyperekplexia family.

The authors report a Taiwanese family with autosomal recessive hyperekplexia. Two novel mutations, W96C (from the paternal allele) and R344X (from the maternal allele), which are located in exon 4 and exon 7 of the GLRA1 gene, were identified in this family. A series of electrophysiologic investigations were conducted in one of the probands, and the results suggest that the "startle center" is located subcortically.

Hyperbaric oxygen attenuates lipopolysaccharide-induced acute lung injury.

OBJECTIVES: To study the effect of hyperbaric oxygen therapy in alleviating acute lung injury induced by lipopolysaccharide (LPS) in rats. DESIGN AND INTERVENTIONS: The rats received an intraperitoneal injection of LPS (15 mg/kg). Animals were either breathing air at 1 ATA or subjected to hyperbaric oxygen (HBO(2)) therapy. The HBO(2) therapy was carried out in a hyperbaric chamber at a pressure of 3 ATA for 90 min. In another two groups, LPS-treated rats also received intraperitoneal injection of N(omega)-nitro-L-arginine (LNAME, 25 mg/kg) or L-N(6)-(iminoethyl)lysine (LNIL, 10 ml/kg). Another two groups of LPS-treated rats were subjected to HBO(2) exposure after the injection of L-NAME or L-NIL. MEASUREMENTS AND MAIN RESULTS: The bronchoalveolar lavage (BAL) was done into the left lung at 7.5 h after intraperitoneal injection of LPS. Parts of the right lung were excised for myeloperoxidase measurement, whereas the rest was collected for wet/dry ratio determination. LPS significantly increased the nitrite/nitrate (NO(x)(-)) concentration (34.4+/-15.7 vs 4.5+/-3.1 microM), LDH activity (66+/-17 vs 46+/-15 mAbs/min), and protein concentration (373+/-119 vs 180+/-90 mg/l) in the BAL fluid. Treatment with HBO(2) immediately after the injection of LPS enhanced the increase of NO(x)(-) production, but reduced the LDH and protein in BAL fluid to the control levels. Pretreatment with either L-NAME or L-NIL abolished the increase of NO(x)(-) in the BAL fluid and further elevated the LDH level and protein concentration. CONCLUSION: Our results suggested that HBO(2) alleviates the LPS-induced acute lung injury, which may be related to the enhancement of nitric oxide production.

Danggui shaoyao san improve colchichine-induced learning acquisition impairment in rats.

AIM: To investigate the effects of the water extracts of Danggui Shaoyao San (DGSYS) in rats used the passive avoidance task. METHODS: Impairment in learning acquisition in rats was induced by colchicines, and the level of superoxide dismutase in the brain and the effects of DGSYS on the locomotor activity and pain threshold induced by colchicines were detected. RESULTS: DGSYS (0.1-1.0 g/kg) attenuated the impairment of learning acquisition induced by colchicine (15 microg) and DGSYS (0.5 and 1.0 g/kg) increased the level of SOD (141 +/- 3 and 135.4 +/- 2.0) in the brain. However, DGSYS (0.1 - 1.0 g/kg) did not affect the locomotor activity and pain threshold in the rats treated with colchicines. CONCLUSION: DGSYS can improve the learning acquisition deficit induced by colchicine in rats. The action mechanism of DGSYS may be involved in the increase in the level of superoxide dismutase.

Intratumoral injection of boiling carboplatin (BCBP) solution for treatment of liver cancer in the animal model.

BACKGROUND/AIMS: To develop a new modality of local hyperthermal chemotherapy for liver cancer. METHODOLOGY: Carboplatin solutions of various concentrations were heated at 60 degrees C, 80 degrees C and 100 degrees C, and carboplatin content, pH value and ultraviolet absorption spectrum were assayed before and after heating. By establishing BALB/c murine model of subcutaneous transplant liver cancer, intratumoral injection of boiling carboplatin solution (group A), 45 degrees C carboplatin solution (group B), room-temperature carboplatin solution (group C), boiling distilled-water (group D) and room-temperature distilled-water (control group) was carried out, and tumor growth curve, tumor regression rate and pathohistological features following treatment were evaluated. RESULTS: Carboplatin content remained stable, ultraviolet absorption spectrum presented no remarkable changes and pH value showed a slight decline after being heated for up to 20 min. Following treatment, all 16 tumors in group A were completely regressed up to day 21. In groups B, C and control group, no tumors became fully regressed and a size of 1.98 +/- 1.11 cm2, 1.50 +/- 0.58 cm2 and 4.83 +/- 0.37 cm2 was presented on day 21, respectively. In group D, though all tumors grossly disappeared during the early post-treatment days, 12 out of 16 recurred on day 21. The tumor regression rate in group A was significantly lower as compared with that of groups B, C, D and control group (all P < 0.01). Histological examination revealed massive necrosis with some degenerated tumor cells at the tumor margin in groups A and D, and only focal necrosis with more viable tumor cells at the center and margin in groups B and C on post-treatment day 1 and 3. Twenty-one days after injection, all tumors in group A presented complete necrosis and were partly replaced by fibrotic tissue. Except for 4 regressed tumors in group D which had the same histological features as those in group A, all other tumors in groups B, C, D and control group presented the same histological features as those untreated. CONCLUSIONS: Carboplatin solution remained stable at boiling status. Intratumoral injection of boiling carboplatin solution could completely devitalize liver cancer tissue via synergistic effects of direct tumoricidal role of heat and the heat-enhanced tumoricidal role of carboplatin.

Isolation of praeruptorins A and B from Peucedanum praeruptorum Dunn. and their general pharmacological evaluation in comparison with extracts of the drug.

The root of Peucedanum praeruptorum Dunn. was extracted with solvents at different polarity obtaining three chemical fractions: aqueous (H2O), n-butanol (BuOH) and ethyl acetate (AcOEt). From AcOEt praeruptorins A and B were isolated by column chromatography on silica gel, using toluene/ethyl acetate as eluent, and identified by 1H and 13C NMR analysis. The extracts and the praeruptorins were tested for gross behavioural effects and acute toxicity in mice; the cytotoxicity on Artemia salina Leach and the antimicrobial activity were also evaluated. None of the tested substances evoked behavioural effects or acute toxicity after oral administration in mice; delayed mortality was observed with AcOEt and praeruptorin A only after intraperitoneal administration of high doses (1 g/kg). In Artemia salina test AcOEt, and praeruptorins A and B had LC50 values of 40.2, 121.2 and 34.5 microg/ml, respectively. AcOEt and praeruptorin A showed antimicrobial activity on Streptococcus agalactiae; their MIC values were 250 and 100 microg/ml, respectively.

Monitoring expression of genes involved in drug metabolism and toxicology using DNA microarrays.

Oligonucleotide DNA microarrays were investigated for utility in measuring global expression profiles of drug metabolism genes. This study was performed to investigate the feasibility of using microarray technology to minimize the long, expensive process of testing drug candidates for safety in animals. In an evaluation of hybridization specificity, microarray technology from Affymetrix distinguished genes up to a threshold of approximately 90% DNA identity. Oligonucleotides representing human cytochrome P-450 gene CYP3A5 showed heterologous hybridization to CYP3A4 and CYP3A7 RNAs. These genes could be clearly distinguished by selecting a subset of oligonucleotides that hybridized selectively to CYP3A5. Further validation of the technology was performed by measuring gene expression profiles in livers of rats treated with vehicle, 3-methylcholanthrene (3MC), phenobarbital, dexamethasone, or clofibrate and by confirming data for six genes using quantitative RT-PCR. Responses of drug metabolism genes, including CYPs, epoxide hydrolases (EHs), UDP-glucuronosyl transferases (UGTs), glutathione sulfotransferases (GSTs), sulfotransferases (STs), drug transporter genes, and peroxisomal genes, to these well-studied compounds agreed well with, and extended, published observations. Additional gene regulatory responses were noted that characterize metabolic effects or stress responses to these compounds. Thus microarray technology can provide a facile overview of gene expression responses relevant to drug metabolism and toxicology.