Limonin existed in citrus fruits has been shown to have anti-bacterial, anti-viral, anti-feedant, anti-nociceptive, anti-inflammatory activities and anti-carcinogenic activities. But the clinical use is limited by its low bioavailability. The aim of this study is to observe the absorption and secretion transport mechanisms of limonin in intestine which can pave the way for the further study and clinical use. The transport characteristics and mechanisms of limonin in rat were studied by in situ intestine perfusion and in vitro Caco-2 cells method. The intestinal absorption of limonin was probably via a facilitated diffusion pathway which was poor and without segment-selection. Verapamil and ketoconazole improved the absorption remarkably according to the result of in vitro Caco-2 cells study; however, probenecid had no significant effect on the absorption. The P-gp efflux and CYP3A4 metabolism were involved in the poor intestinal absorption and low bioavailability of limonin. The exploration of the intestinal absorption mechanism is crucial to the design of dosage form and clinical use of limonin.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Biological Availability ; Biological Transport ; drug effects ; Caco-2 Cells ; Cytochrome P-450 CYP3A ; metabolism ; Dose-Response Relationship, Drug ; Humans ; Intestinal Absorption ; drug effects ; Ketoconazole ; pharmacology ; Limonins ; administration & dosage ; pharmacokinetics ; Male ; Perfusion ; Probenecid ; pharmacology ; Rats ; Verapamil ; pharmacology

OBJECTIVETo examine the association between Ponderal index (PI) at birth and metabolic syndrome during middle age.

METHODSTotally, 975 adults (494 men and 481 women) aged 41-52 from the study cohort of Fetal Origin of Adult Disease were recruited in the study for clinic examinations, involving anthropometry and measurements of blood pressure, fasting and 2 hr plasma levels of glucose and insulin, serum lipid profile. Their HOMA-insulin resistance (IR) index was estimated. Metabolic syndrome (MS) was diagnosed according to 1999 WHO definition. Multivariate logistic regression analysis was used to estimate the effect of PI on MS and the interaction between PI at birth and body mass index (BMI) in adulthood.

RESULTSPrevalence of MS was 18.7% in this mid-aged population, 24.8%, 19.4%, 16.3% and 14.0% in those with less than the 25th percentile, the 25th to less than the 50th percentile, the 50th to less than the 75th percentile and more than 75th percentile of PI at birth, respectively, in a decreasing trend (chi2 M-H for trend=9.938 adjusted for gender, P=0.002). Logistic regression analysis showed that both PI at birth and BMI during adulthood could influence their occurrence of MS (beta=-0.125, P=0.002, for PI; and beta=0.430, P=0.000, for BMI). A synergistic effect between PI at birth and BMI in adulthood was observed in this population. Persons who were thin at birth with PI less than the 25th percentile, and became overweight with BMI greater than or equal to 24 kg/m2 later in their life, were at higher risk of suffering from metabolic syndrome (OR=29.1, 95% CI=13.6-62.1), in comparison with those who became overweight during adulthood from a higher PI at birth (OR=16.0, 95% CI=7.9-32.3) and those who were thin at birth and remained a appropriate BMI during their adulthood (OR=2.0, 95% CI=0.7-5.7). Attributable fraction of the interaction to MS was 34.6%.

CONCLUSIONSThin at birth was a predictor for later occurrence of metabolic syndrome, as well as an effect modifier for the association between of later BMI and metabolic syndrome, i.e., overweight later in his life was most deleterious for a person with growth retardation at birth.

Adult ; Birth Weight ; Blood Glucose ; metabolism ; Body Mass Index ; China ; epidemiology ; Cohort Studies ; Female ; Humans ; Insulin Resistance ; physiology ; Lipids ; blood ; Logistic Models ; Male ; Metabolic Syndrome ; epidemiology ; Middle Aged ; Prevalence ; Risk Factors

BACKGROUNDThe most critical mechanism governing drug resistance in Candida albicans (C. albicans) involves efflux pumps, the functionality of which largely depends on energy metabolism. Alcohol dehydrogenase I (ADH1) plays an important role in intracellular energy metabolism. The aim of this study was to explore the relationship between ADH1 and drug resistance in C. albicans.

METHODSTwenty clinical C. albicans samples isolated from individual patients diagnosed with vulvovaginal candidiasis, and two C. albicans strains obtained from a single parental source (the fuconazole (FLC)-sensitive strain CA-1S and the FLC-resistant strain CA-16(R)) were included in our study. In accordance with the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines, we used the microdilution method to examine the FLC minimum inhibitory concentrations (MICs) and real-time reverse transcription polymerase chain reaction (RT-PCR) to measure the mRNA expression levels of ADH1 and the azole resistance genes CDR1, CDR2, MDR1, FLU1 and ERG11 in all the isolates.

RESULTSA highly significant positive correlation between the mRNA levels of ADH1 and the MICs (rs = 0.921, P = 0.000), as well as positive correlations between the mRNA level of ADH1 and those of CDR1, CDR2 and FLU1 (rs of 0.704, 0.772 and 0.779, respectively, P < 0.01), were observed in the 20 clinical C. albicans samples. The relative expression of ADH1 was upregulated 10.63- to 17.61-fold in all of the drug-resistant isolates. No correlations were found between the mRNA levels of ADH1 and those of MDR1 or ERG11 (P > 0.05). The mRNA levels of the examined drug resistance genes were higher in the CA-16(R) strain than in CA-1(S), and the mRNA levels of ADH1 in CA-16(R) were 11.64-fold higher than those in CA-1(S) (P < 0.05).

CONCLUSIONSThese results suggest that high levels of ADH1 transcription are implicated in FLC resistance in C. albicans and that the mRNA expression levels of ADH1 are positively correlated with those of CDR1, CDR2 and FLU1.

ATP-Binding Cassette Transporters ; genetics ; Alcohol Dehydrogenase ; genetics ; Candida albicans ; drug effects ; Candidiasis, Vulvovaginal ; microbiology ; Drug Resistance, Fungal ; genetics ; Drug Resistance, Multiple ; genetics ; Female ; Fluconazole ; pharmacology ; Fungal Proteins ; genetics ; Humans ; Membrane Transport Proteins ; genetics ; RNA, Messenger ; analysis

OBJECTIVETo analyze the outcome and prognosis of autologous hematopoietic stem cell transplantation (AHSCT) combined with high dose radiotherapy/chemotherapy in 22 patients with nasal NK/T cell lymphoma.

METHODSFrom July 1992 to December 2005, 22 patients with nasal NK/T cell lymphoma were diagnosed pathologically. Immunophenotyping was performed in 13 cases. The patients were classified by Ann Arbor staging system and international prognosis index (IPI). The patients received cycles of chemotherapy every other two weeks or combined with radiotherapy for remission induction, followed high dose radiotherapy/chemotherapy, combined with autologous peripheral blood stem cell transplantation (APBSCT), or autologous bone-marrow transplantation (ABMT). Patients were given complementary radiotherapy after transplantation if they did not have it before. Twelve patients of IPI 3 -4 received consolidation chemotherapy, and one of them received the second transplantation.

RESULTSThe median follow-up duration was 64 (12 - 168) months. The 5 and 8-year overall survivals (OS) were 79.3% and 64.1%, and disease free survivals (DFS) were 36.4% and 27.3%, respectively. The 5-year OS were as follows: for stage I - II and III - IV disease were 90.0% and 70.0% (P = 0. 041); for patients without and with B symptom were 100.0% and 70.7% (P = 0.045); and for IPI 1 - 2 and 3 - 4 were 100.0% and 60.0% (P = 0.035), respectively. Multivariate analysis by COX regression revealed that disease stage, B symptom and IPI were independent prognostic factors.

CONCLUSIONAHSCT combined with high dose radiotherapy/chemotherapy is an effective treatment for patients with poor prognosis nasal NK/T cell lymphoma.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Extranodal NK-T-Cell ; diagnosis ; radiotherapy ; therapy ; Male ; Middle Aged ; Nose Neoplasms ; diagnosis ; radiotherapy ; therapy ; Prognosis ; Transplantation, Autologous ; Treatment Outcome

OBJECTIVETo evaluate the efficacy of three categorized formulas for tonifying Shen yang, i.e. Shenqi Pill (SP), Yougui Pill (YP), and Yougui Drink (YD) based on rough set, thus exploring the law of compatibility between the core herbs and the edge herbs as well as the law of compatibility between the yang-tonifying herbs and the yin-tonifying herbs in the core herbs.

METHODSThe rats were divided into the normal group, the Shen-yang deficiency model group, and the original prescription group, the core herbs group, and the edge herbs group of this three categorized formulas for tonifying Shen yang, 11 groups altogether. Thyroxine (T4), cortisol (CORT), and testosterone (T) were detected respectively. The decision rules model based on rough set was set up, the interactions between various herbs were analyzed according to the decision rules.

RESULTSThere were synergies between yam and cinnamon, yam and aconite, as well as yam and wolfberry. Poria alisma, Cortex Moutan, and oriental waterplantain tuber had no effect themselves, but they had synergistic effects with the core herbs in SP. Angelica had a certain effect itself, but its functions were different to different core herbs in YP. Licorice had no effect itself, and it was antagonistic with the core herbs in YD.

CONCLUSIONSThe compatibility of core herbs of categorized formula for tonifying Shen yang should focus on benefiting both yin and yang, as well as mutual rooting of yin-yang. Appropriate edge herbs should be chosen for compatibility according to different core herbs. The decision rules model based on rough set has a good prospect in exploring the law of compatibility of the categorized formulas.

Animals ; Drug Incompatibility ; Drugs, Chinese Herbal ; administration & dosage ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the key indicators in the pituitary-target gland axes in the animal model of Shen-yang deficiency syndrome (SYDS).

METHODSThe 8 biological indicators [thyroid stimulating hormone (TSH), 3, 3', 5-triiodothyronine (T3), thyroxine (T4), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), adrenocorticotropic hormone (ACTH), and cortisol (CORT)] in the pituitary-target gland axes were grouped using factor analysis. Then the sensitivity of every indicator was calculated according to the sensitivity function defined in this paper, so as to find all the most sensitive indicators in every group as key indicators of SYDS.

RESULTSThe key indicators in the early period of SYDS were T, LH, T4, and CORT. The key indicators in the middle period were LH,T, CORT, and ACTH. The key indicators in the late period were LH, T, CORT, and FSH.

CONCLUSIONST, LH, and CORT were the common key indicators of the three periods, and other different key indicator of SYDS in the early, middle and late period were T4, ACTH, and FSH respectively, which changed from the thyroid axis to the adrenal axis and then to the gonadal axis as the period changed. The key indicators in the late period were mainly in the gonadal axis, showing gonadal dysfunction in the late period.

Animals ; Disease Models, Animal ; Estradiol ; analysis ; Factor Analysis, Statistical ; Follicle Stimulating Hormone ; analysis ; Hydrocortisone ; analysis ; Luteinizing Hormone ; analysis ; Male ; Pituitary-Adrenal System ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Testosterone ; analysis ; Thyrotropin ; analysis ; Thyroxine ; analysis ; Yang Deficiency ; physiopathology

OBJECTIVETo investigate the influence of mutual interactions between FasL expressed by colon carcinoma cells and endogenous cytokines interleukin-18 on liver metastasis and invasion of human colon cancer cells.

METHODSUsing immunohistochemical streptavidin-biotin complex (SABC) method, the expressions of Fas receptor and Fas ligand in SW620 colon carcinoma cells and Chang liver cells were observed so as to provide morphological evidence for the functions of Fas receptor and Fas ligand. In an effort to examine the cytotoxicity of effector cells, CytoTox(96) Non-Radioactive Cytotoxicity Assay was adopted to measure the LDH releasing value after the SW620 cells were co-cultured with Chang liver cells.

RESULTSIt was shown that the Fas ligand of colon carcinoma SW620 cells was positive and the positive substances were distributed in the cell membrane and cytoplasm, and the Fas receptor of colon carcinoma SW620 cells was negative. The Fas receptor of Chang liver cells turned out to be positive and the positive substances were distributed in the cell membrane, and the Fas ligand of Chang liver cells was negative. At 6 hours after co-culture of IFN-γ-stimulated Chang liver cells with interleukin-18-stimulated (for 36 h) SW620 cells or unstimulated SW620 cells, the cytotoxicity of SW620 cells to IFN-stimulated Chang liver cells at effector-to-target ratios of 10:1, 5:1, 2.5:1 and 1.25:1 was 68.3%, 49.8%, 21.1%, 9.7% (F = 76.87, P < 0.05) and 32.7%, 21.8%, 11.1%, 6.7% (F = 7.27, P < 0.05), respectively. The non-radioactive cytotoxicity assay showed that the apoptotic rate of Chang liver cells was remarkably increased with the increase of planting concentration of SW620 after the SW620 cells were co-cultured with Chang liver cells. The cytotoxicity was significantly enhanced by interleukin-18.

CONCLUSIONThe FasL expression of human colon cancer cells may be regulated by endogenous interleukin-18 in the host microenvironment and enhance the liver colonization competence of colon cancer cells through induction of apoptosis in the Fas-expressing hepatocytes.

Apoptosis ; Cell Line, Tumor ; Cells, Cultured ; Coculture Techniques ; Colonic Neoplasms ; immunology ; metabolism ; pathology ; Cytotoxicity, Immunologic ; Fas Ligand Protein ; metabolism ; Hepatocytes ; cytology ; metabolism ; Humans ; Interferon-gamma ; pharmacology ; Interleukin-18 ; pharmacology ; L-Lactate Dehydrogenase ; metabolism ; fas Receptor ; metabolism

OBJECTIVETo estimate the impact of autologous transfusion on the status of perioperative immune activation in malignant tumor patients. The Serum Neopterin and Interleukin-2 (IL-2) were measured.

METHODSSixty patients undergoing elective radical resection for malignant stomach tumor were enrolled in the prospective study and assigned to the following groups: (1) Group A received autologous transfusion. (2) Group H received allogeneic transfusion. The perioperative course (Before induction of anesthesia, after operation and 5 d after operation) of Neopterin and IL-2 was compared.

RESULTSIn group A, Serum Neopterin was significantly lower than baseline after operation and IL-2 had no significant changes. In group H, both Serum Neopterin and IL-2 were significantly lower than baseline after operation and 5 d after operation. Compared with group A, Serum Neopterin was significantly lower than baseline after operation and 5 d after operation and IL-2 was significantly lower than baseline 5 d after operation.

CONCLUSIONAutologous transfusion decreased the perioperative immune suppression in malignant stomach tumor patients.

Adult ; Aged ; Blood Transfusion, Autologous ; adverse effects ; methods ; Female ; Humans ; Interleukin-2 ; blood ; immunology ; Male ; Middle Aged ; Neopterin ; blood ; immunology ; Perioperative Care ; adverse effects ; methods ; Postgastrectomy Syndromes ; blood ; etiology ; immunology ; Stomach Neoplasms ; blood ; immunology ; surgery ; Treatment Outcome

Objective To study the relationship between emotional,physical abuse and internet addiction disorder(IAD)among middle school students.in order to lay foundation for the development of prevention and control programs on IAD.Methods Students selected from 76 classes in Grade One and Grade Two,filled out the anonymous questionnaire,which including demographic characteristics of students,Young's Intemet Addiction Scale,Parent-Child Conflict Tactics Scales.etc.Non-conditional multivariate logistic regression model was employed to explore the relationship between child abuse and IAD.Independent variable was child abUSe while dependent variable was IAD.Covariant variables would include demographic characteristics,as sex,age,style of household,et al.Results Among 3798 students,the overail prevalence of emotional abuse was 81.1%.with 55.1% of them reported having experienced physical abuse.Among 3507 intemet users,5.2%was diagnosed as IAD.Results from the nonconditional multivariate Iogistic regression model showed that odds ratio of severe physical abuse and moderate physical abuse were 3.02(1.63-5.58)and 4.00(2.01-7.93).Conclusion Moderate physical abuse and severe physical abuse were possible risk factors of IAD.

OBJECTIVETo determine whether tanycytes be able to support the regeneration of completely transected spinal cord in adult rats.

METHODSSubcultured tanycytes was transplanted into completely T8 transected spinal cord using the untranslated completely transected rats as control. After transplantation the rubrospinal motor evoked potentials were recorded below the injury level at the end of 12th week, assistant by Basso-Beatie-Bresnahan locomotor rating scale and histology method.

RESULTSAt the end of 12th week the total peak amplitude of rubrospinal motor evoked potentials (MD = 133.2 microV, P < 0.01) and BBB locomotor rating scale (MD = 5.0000, P < 0.01) were both significantly improved in cell transplanted group compared with that in the untranslated control group, while the latency of the first peak was shortened (MD = 0.061 ms, P = 0.040). HE staining showed more integrity in transected spinal cords in cells transplanted groups.

CONCLUSIONTransplanted tanycytes can support the regeneration of transected spinal cords in rats.

Animals ; Cell Transplantation ; Cells, Cultured ; Evoked Potentials, Motor ; Male ; Neuroglia ; cytology ; transplantation ; Rats ; Rats, Wistar ; Recovery of Function ; Spinal Cord Injuries ; physiopathology ; surgery