DNA Replication ; physiology ; Epstein-Barr Virus Infections ; virology ; Herpesvirus 4, Human ; genetics ; metabolism ; physiology ; Humans

BACKGROUND: Apoptosis in the skeletal muscle leads to a variety of skeletal muscle diseases, but there are ideal no therapies so far. OBJECTIVE: To analyze the effects of different intensities of exercises on the morphology and apoptosis of the skeletal muscle in rats. METHODS: Thirty healthy male 3-month-old Sprague-Dawley rats were randomly allocated into three groups (n=10 per group): control group (no swimming), aerobic exercise and high-intensity exercise groups. The rats in the exercise groups underwent swimming for consecutive 10 weeks. Then, the gastrocnemius muscle was isolated from all rats under anesthesia. The morphology and cell apoptosis were detected by hematoxylin-eosin staining and TUNEL test. At the same time, the levels of superoxide dismutase and malondialdehyde in skeletal muscle tissue were tested and the correlation of malondialdehyde with integrated optical density (IOD) was analyzed. RESULTS AND CONCLUSION: The results of hematoxylin-eosin staining showed that the muscle fibers were in disorder arrangement with obscure structure in the high-intensity exercise group. Compared with the control group, the content of malondialdehyde was increased in the exercise groups, especially in the aerobic exercise group (P < 0.05). The level of superoxide dismutase in the high-intensity exercise group was significantly lower than that in the aerobic exercise group (P < 0.05). The results of TUNEL test showed that the IOD values in the high-intensity exercise group were significantly higher than those in the aerobic exercise and control groups (P < 0.05). There was a positive correlation of malondialdehyde with IOD. These results indicate that the long-term and high-intensity exercise can increase the content of malondialdehyde in the skeletal muscle, resulting in an aggravation of fatigue. Aerobic exercise can obtain the adaptation of the skeletal muscle, but damage the morphology and structure of the skeletal muscle because of excessive exercise load, thus accelarating the cell apoptosis. With the exercise intensity increasing, the balance between malondialdehyde production and clearance is broken, and the IOD value is increased.

OBJECTIVETo see the change of capillary of heart in Athlete's Heart, so that to discover the mechanism of pathologic change.

METHOD18 male SD rats were separated randomly into control group (without any exercise), aerobic exercise group (swimming for 75 min every day), and overload group (swimming for 180 min with 5% weight of its body every day). After 5 days per week, 12 weeks, exercise training stopped and heart of rats were observed under Transmission Electron Microscope.

RESULTSIn aerobic exercise group, the capillary cavities in heart expand, the walls of capillary become thick; the number of mitochondrion increases; endothelium cells become active in growth. However, after overload exercise, the walls of capillary cockle and protuberances appear. The mitochondrion swell and the cristae become disorder. Most of endosomes expand and their number increases. The karyons become abnormity in shape and uniformity in electronic density, besides the nuclear envelope cockle. The basilar membranes become thick and unclear.

CONCLUSIONAfter exercise training, both physical and pathologic changes in heart capillary are found. In suitable exercises group, the capillaries change physically; the pathologic changes are becoming visible after overload exercise however.

Animals ; Capillaries ; ultrastructure ; Cardiomegaly ; etiology ; pathology ; Male ; Physical Conditioning, Animal ; adverse effects ; Physical Endurance ; Rats ; Rats, Sprague-Dawley ; Sports

OBJECTIVEThis study is to see the pathologic change of cardiac myocyte in Athlete's Heart, and explore the mechanism of the pathologic change.

METHODSFifteen male SD rats were separated randomly into control group (without any exercise), aerobic exercise group (Ae group, swimming for 75 min every day), and overloading exercise group (Oe group, swimming for 180 min with a loading of 5 percent of body weight every day). After 5 days per week for 12 weeks, swimming stopped, the rat hearts were prepared to specimens and examined under Transmission Electron Microscope.

RESULTSThe Ae group, the number and volume of mitochondria increased, and the membrane of mitochondria remained entire. Few of dense bodies were found in cytoplasm. The nucleus envelopes of expansion nucleus appear as dentition. These changes were considered as the adaptation to exercises. At the same time, some pathologic changes of the cardiac myocytes similar to senescence also appeared, such as mitochondria expanse, the crista disorder or disappearance, unclear mitochondria membrane, many dense bodies in cytoplasm, nucleus disfiguration and chromatin collection at edge.

CONCLUSIONAfter exercise training, some pathologic changes of cardiac myocyte also occur with physiological changes. With the raise of exercise intension, the pathologic changes become more obvious, even appearance of cardiac myocyte death.

Animals ; Cardiomegaly ; etiology ; pathology ; Exercise Tolerance ; Male ; Microscopy, Electron ; Mitochondria, Heart ; ultrastructure ; Myocardial Contraction ; Myocytes, Cardiac ; ultrastructure ; Rats ; Rats, Sprague-Dawley ; Swimming

OBJECTIVE: To explore the inhibitive effects of 1,3,8-trihydroxy-5-methoxyxanthone (TMX) on cytochrome P450s (CYP450s) in human liver microsomes. METHODS: Probe drugs were incubated with and without adding TMX to determine the changes of enzyme activities. The concentration ratio of metabolites to probe drugs was used to present enzyme activities. Concentrations of the probe drugs and their metabolites in the incubated mixture were detected by high performance liquid chromatography. RESULTS: The variations (mean, 95%CI) of the activities of CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 were 2.95 x 10(-3) (2.03 x 10(-3), 3.88 x 10(-3)), 3.14 x 10(-2) (1.87 x 10(-2), 4.42 x 10(-2)), 2.27 x 10(-3) (-1.4 x 10(-2),1.81 x 10(-2)), 7.72 x 10(-2) (-0.83 x 10(-2), 0.2374), and -0.2548 (-2.9802, 2.4707), respectively. The activities of CYP1A2 and CYP2C9 were significantly reduced in the present of TMX. CONCLUSION TMX (10 micromol/L) has significant inhibitive effect on the activities of CYP1A2 and CYP2C9, but no significant inhibitive effect on the activities of CYP2C19, CYP2E1 and CYP3A4.
Cytochrome P-450 Enzyme System ; metabolism ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; Xanthones ; pharmacology

In order to explore the application of real-time quantitative reverse-transcription polymerase chain reaction (Q-PCR) for detecting PML/RARalpha gene transcripts in patients with acute promyelocytic leukemia (APL), the bone marrow samples from 46 newly diagnosed APL patients were collected for analysis. Three plasmids containing cDNA fragments of the bcr1-, bcr3-form PML/RARalpha and ABL control gene were constructed respectively. The ABI Prism 7500 Sequence Detection System using Taqman fluorogenic probes was used to quantify target gene. PML/RARalpha mRNA was detected by Q-PCR in 46 APL patients and 40 non-APL patients. The normalized quotient (NQ) of PML/RARalpha mRNA was calculated as followings: NQ = PML/RARalpha mRNA copy numbers/ABL mRNA copy numbers. Immunophenotype of acute promyelocytic leukemia was determined by four-color flow cytometry. The results showed that the coefficients of variation (CV) of inter-day assay and intra-day assay by using Q-PCR were 1.58% and 0.88% respectively. Q-PCR could detect reproducibly 5 copies of target gene per 100 ng RNA and no pseudopositive results were found. The median NQ of PML/RARalpha mRNA was 0.450 (0.084 - 1.082) in 46 APL patients. There was no indication of any correlation of PML/RARalpha mRNA type with age, sex, hemoglobin, platelet count, percentage of promyelocytes in bone marrow detected by morphology or flow cytometry, PML/RARalpha NQ, or signs of clinically diagnosed coagulation/bleeding disorders. Compared with bcr1-form cases, bcr3-form cases had more M(3v) phenotype (42.9% vs 9.4%, P = 0.015) and higher WBC count (9.35 x 10(9)/L vs 2.15 x 10(9)/L, P = 0.038). APL cells could be classified into large side scatter population (L-SSC) and non-large side scatter population (NL-SSC) in CD45/SSC histogram of flow cytometry. 87.50% patients with bcr1-form showed L-SSC phenotype and 64.29% patients with bcr3-form showed NL-SSC phenotype. It is concluded that a sensitive Q-PCR method is established. The median NQ of PML/RARalpha mRNA was 0.450 in newly diagnosed APL patients. There was no significant difference about PML/RARalpha mRNA expression of both bcr3-form and bcr1-form APL patients. Type of PML/RARalpha transcripts is related with the morphology and immunophenotype.
Adolescent ; Adult ; Aged ; Child ; Female ; Genes, abl ; genetics ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics ; metabolism ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; analysis ; genetics ; Phenotype ; RNA, Messenger ; analysis ; genetics ; Receptors, Retinoic Acid ; analysis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods

This study was aimed to investigate the relationship of immunophenotypic features with minimal residual disease (MRD) detection and gene types in APL patients. Immunophenotypes were analyzed in 221 newly diagnosed APL patients by using four-color flow cytometry. Among of them, CD123 antibody was examined in 87 patients and the fused gene pml-raralpha were detected by PCR in 196 specimens simultaneously. The results of immunophenotyping demonstrated that the positive percentages of CD123, CD33 and CD9 in newly diagnosed APL patients were 100%, 99.1% and 96.0% respectively, and mean percentages of positive cells in positive patients were all around 90%. Although the positive rates of CD117, CD13, CD38 and CD64 were all above 96%, but the mean percentages of positive cells in different positive patients were diverse and average percentages of positive cells were about 70%. CD15, CD56 and CD11b were expressed in some patients, but CD34 and HLA-DR were rarely expressed in the majority of patients, and average positive percentages were all lower. Among 196 newly diagnosed APL patients, bcr1, bcr2 and bcr3 expressions were 63.3%, 4.6% and 32.1% respectively. The results showed a strong correlation of positive expression of CD34 with bcr3 isoform. When cut-off value was chosen as 20%, the proportions of CD34 positive patients in bcr3 and bcr1 cases were 15.4% (10/65) and 3.3% (4/121) separately, which had a significant difference (p < 0.05). When cut-off value was 10%, bcr3 cases had a significantly higher percentage of CD34 positive, compared with bcr1 cases (p < 0.001), which was 47.7% (31/65) and 5.8% (7/121) respectively. However, there was no statistically significant difference on the other antigens between the two groups. Bcr3 isoform was highly indicated when CD34 was positive and non- large side scatter (NL-SSC) was shown in APL cells. It is concluded that there is a unique characteristics of immunophenotyping, and antigens such as CD123, CD33 and CD9 are more applicable to the detection of MRD in APL patients. The positive expression of CD34 and NL-SSC are associated with bcr3 isoform, and the relationship between gene type and antigen expression can be suggested more accurately when the cut-off value is chosen as 10%.
Adolescent ; Adult ; Aged ; Antigens, CD ; genetics ; Child ; Female ; Flow Cytometry ; Humans ; Immunophenotyping ; Leukemia, Promyelocytic, Acute ; diagnosis ; genetics ; immunology ; Male ; Middle Aged ; Neoplasm, Residual ; diagnosis ; genetics ; Young Adult

OBJECTIVETo analyze the in-hospital mortality and factors affecting in-hospital mortality for patients with transposition of the great arteries (TGA) undergoing arterial switch operation (ASO).

METHODSBetween January 2004 and December 2007, ASO was performed in 169 patients [129 male, 40 female; mean age (11.71 ± 26.3) months] with TGA. The patients were divided in intact ventricular septum group (n = 56): TGA with intact ventricular septum and ventricular septal defect group (n = 113): TGA with ventricular septal defect. Multiple logistic regression analysis was performed to identify the risk factors of in-hospital mortality.

RESULTSThe overall in-hospital mortality was 11.24% (19/169). The yearly in-hospital mortality was similar between intact ventricular septum group and ventricular septal defect group. With the improvement of perioperative treatment, the in-hospital mortality decreased from 16.67% in 2004 to 3.92% in 2007. The multivariate analysis revealed that body weight ≤ 3 kg (OR: 4.571, P = 0.0409), complicating ventricular septal defect (OR: 4.444, P = 0.0406), complex TGA (OR: 4.321, P = 0.0140), coronary anomalies (OR: 4.867, P = 0.0104) and non-type A coronary arteries (OR: 3.045, P = 0.0243) were independent predictors for poor early postoperative survival.

CONCLUSIONBody weight ≤ 3 kg, complicating ventricular septal defect, complex TGA, coronary anomalies are independent predictors for increased in-hospital mortality in patients with transposition of TGA and undergoing arterial switch operation.

Arteries ; surgery ; Body Weight ; Cardiac Surgical Procedures ; mortality ; Child, Preschool ; Female ; Heart Septal Defects, Ventricular ; complications ; mortality ; surgery ; Hospital Mortality ; Humans ; Infant ; Logistic Models ; Male ; Risk Factors ; Transposition of Great Vessels ; mortality ; surgery

This study was aimed to explore prognostic significance of minimal residual disease (MRD) detection in patients with acute myeloid leukemia (AML) by multiparameter flow cytometry (MCF). Leukemia-associated immunophenotype (LAIP) of newly diagnosed AML patients were determined by 4-color 5 antibody panels and patients with sensitive LAIP were chosen for MRD detection. 601 bone marrow samples from 95 patients were acquired after treatment and MRD were considered positive by the critical normal value plus twice standard deviation in normal bone marrow specimen. The patients were divided into three groups and the clinical significance was analyzed every 2 months within initial 6 months after induction treatment. The results showed that the relapse rate and relapse-free survival (RFS) rate were all significantly different between MRD positive and MRD negative patients in the three groups (p < 0.05). Patients with MRD positive had a median relapse-free survival time of 11 months, 11.5 months and 11 months at 1 - 2, 3 - 4 and 5 - 6 months respectively, while all patients with MRD negative were not observed to reach median release-free survival time (p < 0.05). Furthermore, the clinical significance was analyzed after induction and one course of consolidate treatment, the relapse rate of MRD positive and MRD negative patients were 57.14% versus 0% and 91.67% versus 2.27% respectively (p = 0.000 and p = 0.000). It is concluded that MRD detection by multi-parameter flow cytometry can predict outcome of AML patients, which should be continuously monitored after treatment.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Flow Cytometry ; methods ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; Male ; Middle Aged ; Neoplasm, Residual ; diagnosis ; Prognosis ; Young Adult

BACKGROUND AND OBJECTIVELetrozole is an aromatase inhibitor that is used in the treatment of estrogen-sensitive tumors such as endometrial carcinoma, however, its therapeutic effect is still to be further improved. It is reported that curcumin has antitumor capability and can enhance the sensitivity of tumor cells to anticancer agents. This study was to investigate the inhibitory effect of letrozole combination with curcumin on the implanted endometrial tumor growth.

METHODSNude mice were implanted with endometrial carcinoma RL-952 cells. All tumor-bearing mice were randomly divided into 5 groups: control(without treatment), Let(1) (letrozole, 1 microg/d), Let(10) (letrozole, 10 microg/d), Cur [ curcumin, 300 mg/kg.d)], and Let + Cur group [10microg/d letrozole + 50mg/ (kg.d) curcumin]. The tumor growth was monitored. Tumor cells apoptosis was detected in both control and treated groups. The expressions of bcl-2 mRNA and bcl-2 protein were detected using RT-PCR and Western blot, respectively.

RESULTSFifty mice were successfully implanted with the endometrial tumor. Treatment with letrozole markedly inhibited tumor growth; the inhibitory effect was further enhanced by the combination of letrozole and curcumin. The inhibitory rates in Let (1), Let (10), the Cur, and the Let + Cur groups were 15.95%, 22.49%, 21.57%, and 35.89%, respectively. Treatment with curcumin inhibited the expression of bcl-2 in tumor cells at the mRNA and protein levels. The apoptosis rates in the control group and the four experimental groups mentioned above were 16.97%, 32.90%, 35.80%, 34.16%, and 47.24%, respectively. Tumor cells apoptosis were observed in mice treated with either letrozole or curcumin; however, combination of letrozole and curcumin further enhanced the inhibitory rate in tumor growth.

CONCLUSIONSTreatment with letrozole or curcumin could inhibit the xenografted endometrial tumor growth by inducing apoptosis in tumor cells. Combination of letrozole and curcumin further enhanced the inhibitory effect of tumor growth.

Adenocarcinoma ; metabolism ; pathology ; Animals ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Curcumin ; administration & dosage ; pharmacology ; Drug Synergism ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Nitriles ; administration & dosage ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Random Allocation ; Receptors, Estrogen ; metabolism ; Triazoles ; administration & dosage ; pharmacology ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays