Glycyrrhizin is a major bioactive component of liquorice, which exerts multiple biochemical and pharmacological activities and is frequently used in combination with other drugs in the clinic. Mycophenolate mofetil (MMF), an immunosuppressant widely used in transplant patients, is metabolized by UDP-glucuronyltransferases (UGTs). Although significant evidence supports that glycyrrhizin could interact with the cytochrome P450s (CYPs), few studies have addressed its effects on UGTs. The present study aimed at investigating the regulatory effects of diammonium glycyrrhizinate (GLN) on UGTs in vitro and in vivo. We found that long-term administration of GLN in rats induced overall metabolism of MMF, which might be due to the induction of UGT1A protein expression. Hepatic UGT1A activity and UGT1A mRNA and protein expression were significantly increased in GLN-treated rats. UGT1A expression levels were also increased in the intestine, contradicting with the observed decrease in intestinal UGT1A activities. This phenomenon may be attributed to different concentrations of glycyrrhetinic acid (GA) in liver and intestine and the inhibitory effects of GA on UGT1A activity. In conclusion, our study revealed that GLN had multiple effects on the expression and activities of UGT1A isoforms, providing a basis for a better understanding of interactions between GLN and other drugs.
Animals ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Glucuronosyltransferase ; chemistry ; metabolism ; Glycyrrhizic Acid ; chemistry ; pharmacology ; Herb-Drug Interactions ; Intestines ; chemistry ; drug effects ; enzymology ; Kinetics ; Liver ; chemistry ; drug effects ; enzymology ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the expression and clinical pathological significance of EB virus (Epstein-Barr virus, EBV), PTEN and VEGF in angioimmunoblastic T -cell lymphoma (AITL).

METHODSThe EBV -encoded small RNA (EBER) expression in 21 cases of AITL was detected by in situ hybridization. The expressions of PTEN and VEGF were detected in 21 cases of AITL and 20 cases of lymph node reactive hyperplasia by immunohistochemical EnVision two-steps method. The expression and clinicopathological significance of EBV, PTEN and VEGF in AITL were analyzed.

RESULTSThe positive expression rate of EBER in 21 cases of AITL was 61.9%; the expressions of PTEN and VEGF in AITL and lymph node reactive hyperplasia were significantly different (P<0.05). The expressions of EBER and PTEN negatively correlated (P<0.05). The EBER positive expression rates of male patients in AITL group and the progressed group was 80% and 78.6% respectively, which were significantly higher than that in female patients and patients in non- advanced group (P<0.05); the PTEN expression rates in the AITL group accompanying B symptoms and progressed group were 31.3% and 21.4%, respectively, which were significantly lower than those in patients without B symptoms and non-progressed group (P<0.05). Survival analysis showed that the PTEN expression negatively correlated with the overall survival rate of patients (P<0.05).

CONCLUSIONEBV infection and low expression of PTEN may indicate the deterioration of angioimmunoblastic T-cell lymphoma. Whether the EBV involved in the ocurring of T-cell angioimmunoblastic lymphoma by down-regulating PTEN expression is unclear, further research is needed.

Epstein-Barr Virus Infections ; Female ; Herpesvirus 4, Human ; Humans ; Immunoblastic Lymphadenopathy ; In Situ Hybridization ; Lymphoma, T-Cell ; Male ; PTEN Phosphohydrolase ; Survival Analysis ; Survival Rate ; Vascular Endothelial Growth Factor A

OBJECTIVETo study the expression of nNOS and ultrastructural changes in the penile tissue of rats with prolactinoma-induced erectile dysfunction (ED).

METHODSWe established the model of prolactinoma in 20 male Westar rats by peritoneal injection of diethylstilbestrol (DES) and treated the control rats with normal saline (n = 10) or sterilized arachis oil (n = 10). After 8 weeks, we performed the apomorphine test and measured the weight of the pituitary gland and the levels of serum prolactin (PRL) and testosterone (T) to confirm the successful construction of the prolactinoma-induced ED model. Then we determined the expression of nNOS in the penile tissue by immunohistochemistry and examined the ultrastructural changes of the penile cavernosum under the transmission electron microscope.

RESULTSThe prolactinoma-induced ED model was successfully established in 15 rats. The weight of the pituitary gland was significantly increased in the rats treated with DES as compared with the normal saline and sterilized arachis oil controls ([46.7 ± 15.5] vs [11.7 ± 2.4] and [12.4 ± 2.3] mg, both P < 0.05). The level of serum PRL was markedly higher while that of T remarkably lower in the former than in the latter two groups ([1,744.9 ± 304.5] vs [11.5 ± 2.4] and [10.6 ± 1.9] ng/ml, both P < 0.0l; [1.54 ± 0.46] vs [3.11 ± 1.08] and [3.04 ± 1.11] ng/ml, both P < 0.05). The rate of penile erection was significantly reduced in the prolactinoma-induced ED model rats in comparison with the normal saline and arachis oil controls (16.7% vs 100% and 87.5%, both P < 0.05), and so was the expression of nNOS in the penile tissue (0.024 ± 0.011 vs 0.066 ± 0.019 and 0.058 ± 0.021, both P < 0.05). Transmission electron microscopy manifested significant ultrastructural changes in the endothelial and smooth muscle cells of the cavernous tissue in the prolactinoma-induced ED models.

CONCLUSIONThe ultrastructural changes of the penile cavernous tissue and the reduced expression of nNOS in penile tissue may be the most important mechanisms of prolactinoma-induced ED in rats.

Animals ; Apomorphine ; Carcinogens ; Diethylstilbestrol ; Erectile Dysfunction ; etiology ; Humans ; Male ; Myocytes, Smooth Muscle ; ultrastructure ; Nitric Oxide Synthase Type I ; metabolism ; Organ Size ; Penile Erection ; Penis ; enzymology ; ultrastructure ; Pituitary Neoplasms ; chemically induced ; complications ; Prolactin ; blood ; Prolactinoma ; chemically induced ; complications ; Rats ; Rats, Wistar ; Testosterone ; blood

OBJECTIVETo study the effectiveness of waist circumference cut-off values in predicting the prevalence of metabolic syndrome (MetS) and risk factors in adults in China.

METHODSA cross-sectional survey was condcuted in 14 provinces (autonomous region, municipality) in China. A total of 47,325 adults aged⋝20 years were selected by multistage stratified sampling, and questionnaire survey and physical and clinical examination were conducted among them. MetS was defined according to the International Diabetes Federation (IDF) criteria and modified IDF criteria.

RESULTSThe age-standardized prevalence of MetS was 24.2% (22.1% in men and 25.8% in women) and 19.5% (22.1% in men and 18.0% in women) according to the IDF criteria and modified IDF criteria respectively. The age-standardized prevalence of pre-MetS was 8.1% (8.6% in men and 7.8% in women) according to the modified IDF criteria. The prevalence of MetS was higher in urban residents than rural residents and in northern China residents than in southern China residents. The prevalence of central obesity was about 30% in both men and women according to the ethnicity-specific cut-off values of waist circumference for central obesity (90 cm for men and 85 cm for women). Multivariate regression analysis revealed no significant difference in risk factors between the two MetS definitions.

CONCLUSIONUsing both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China. Conclusion Using both the modified IDF criteria and ethnicity-specific cut-off values of waist circumference can provide more useful information about the prevalence of MetS in China.

Adult ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Metabolic Syndrome ; diagnosis ; epidemiology ; Middle Aged ; Obesity ; epidemiology ; Prevalence ; Risk Assessment ; Risk Factors ; Waist Circumference

In vitro amplified human leukocyte antigen (HLA)-haploidentical donor immune cell infusion (HDICI) is not commonly used in children. Therefore, our study sought to evaluate its safety for treating childhood malignancies. Between September 2011 and September 2012, 12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer Center. The median patient age was 5.1 years (range, 1.7-8.4 years). Of the 12 patients, 9 had high-risk neuroblastoma (NB) [7 showed complete response (CR), 1 showed partial response (PR), and 1 had progressive disease (PD) after multi-modal therapies], and 3 had Epstein-Barr virus (EBV)-positive lymphoproliferative disease (EBV-LPD). The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×10(8) immune cells/kg body weight: 71 infusions with natural killer (NK) cells, 8 with cytokine-induced killer (CIK) cells, and 13 with cascade primed immune cells (CAPRIs); 83 infusions with immune cells from the mothers, whereas 9 with cells from the fathers. Twenty cases (21.7%) of fever, including 6 cases (6.5%) accompanied with chills and 1 (1.1%) with febrile convulsion, occurred during infusions and were alleviated after symptomatic treatments. Five cases (5.4%) of mild emotion changes were reported. No other adverse events occurred during and after the completion of HDIDIs. Neither acute nor chronic graft versus host disease (GVHD) was observed following HDICIs. After a median of 5.0 months (range, 1.0-11.5 months) of follow-up, the 2 NB patients with PR and PD developed PD during HDICIs. Of the other 7 NB patients in CR, 2 relapsed in the sixth month of HDICIs, and 5 maintained CR with disease-free survival (DFS) ranging from 4.5 to 11.5 months (median, 7.2 months). One EBV-LPD patient achieved PR, whereas 2 had stable disease (SD). Our results show that HDICI is a safe immunotherapy for childhood malignancies, thus warranting further studies.
Child ; Child, Preschool ; Cytokine-Induced Killer Cells ; immunology ; Epstein-Barr Virus Infections ; therapy ; Female ; Follow-Up Studies ; Graft vs Host Disease ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Immunotherapy, Adoptive ; Infant ; Killer Cells, Natural ; immunology ; Lymphoproliferative Disorders ; therapy ; virology ; Male ; Neuroblastoma ; therapy ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo determine occupational hazards in work sites of a large solid waste landfill and analyze their adverse health effects.

METHODThe national standardized detection methods were used to determine dust concentration, harmful gas and physical factors in worksites. Routine physical examination, pulmonary function, hearing tests and nervous system test were performed in workers for 2 consecutive years. Urine lead, cadmium and mercury contents were detected. The comet assay was use to measure DNA damage in peripheral blood lymphocytes among workers.

RESULTThe main occupational hazard factors in this solid landfill are dust, harmful gas, high temperature and noise. The oxides, carbon monoxide, and noise and high temperatures in summer at some work sites exceeded the national occupational exposure limits. The prevalence of respiratory inflammation and rate of pulmonary function decrease among front-line workers and on-site technical managers are 21.2% and 11.5%, which are significantly higher than those among administrative staff (7.1% and 0) (P < 0.05). Nervous system abnormalities rate of front-line workers and on-site technical managers was 50.0%, which is significantly higher than that (26.7%) of administrative staff (P < 0.05). Because of long-term exposure to high intensity noice, hearing loss rate of bulldozer drivers was 10.3%. In addition, about 75% of workers with DNA damage in peripheral blood lymphocyte are front-line workers.

CONCLUSIONAdverse health effects from occupational hazards were observed among workers in this solid waste landfill.

Adult ; Female ; Humans ; Male ; Middle Aged ; Occupational Diseases ; epidemiology ; Occupational Exposure ; Refuse Disposal ; Respiratory Tract Infections ; epidemiology ; Risk Factors ; Workplace