Antigens, CD20 ; metabolism ; CD5 Antigens ; metabolism ; Colonic Neoplasms ; complications ; metabolism ; pathology ; surgery ; Cyclin D1 ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Ileal Diseases ; complications ; pathology ; surgery ; Ileocecal Valve ; Intestinal Neoplasms ; complications ; metabolism ; pathology ; surgery ; Intestinal Polyps ; complications ; metabolism ; pathology ; surgery ; Intussusception ; complications ; pathology ; surgery ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; pathology ; Lymphoma, Mantle-Cell ; complications ; metabolism ; pathology ; surgery ; Middle Aged

The association rate constant and dissociation rate constant are important parameters of the drug-cyclodextrin supermolecule systems, which determine the dissociation of drugs from the complex and the further in vivo absorption of drugs. However, the current studies of drug-cyclodextrin interactions mostly focus on the thermodynamic parameter of equilibrium constants (K). In this paper, a method based on quantitative high performance affinity chromatography coupled with mass spectrometry was developed to determine the apparent dissociation rate constant (k(off,app)) of drug-cyclodextrin supermolecule systems. This method was employed to measure the k(off,app) of meloxicam and acetaminophen. Firstly, chromatographic peaks of drugs and non-retained solute (uracil) on β-cyclodextrin column at different flow rates were acquired, and the retention time and variance values were obtained via the fitting the peaks. Then, the plate heights of drugs (H(R)) and uracil (H(M,C)) were calculated. The plate height of theoretical non-retained solute (H(M,T)) was calculated based on the differences of diffusion coefficient and the stagnant mobile phase mass transfer between drugs and uracil. Finally, the k(off,app) was calculated from the slope of the regression equation between (H(R)-H(M,T)) and uk/(1+k)2, (0.13 ± 0.00) s(-1) and (4.83 ± 0.10) s(-1) for meloxicam and acetaminophen (control drug), respectively. In addition, the apparent association rate constant (k(on,app)) was also calculated through the product of K (12.53 L x mol(-1)) and k(off,app). In summary, it has been proved that the method established in our study was simple, efficiently fast and reproducible for investigation on the kinetics of drug-cyclodextrin interactions.
Acetaminophen ; chemistry ; Chromatography, Affinity ; Drug Interactions ; Kinetics ; Mass Spectrometry ; Thermodynamics ; Thiazines ; chemistry ; Thiazoles ; chemistry ; beta-Cyclodextrins ; chemistry

Objective To improve the level of early detection and treatment of pyonephrosis. Methods This study included 41 cases(17 men and 24 women;mean age,49 years)of pyonephrosis.A variety of examinations,including urinary analysis,blood analysis,kidney nuclear medicine scan,ultrasonog- raphy,intravenous urography(IVU),and CT were used for the early diagnosis of pyonephrosis.Pereutaneous nephrostomy(PCN)drainage was done for the interim management of pyonephrosis,then phase 2 operation was performed in 28 cases.The double-J tube was placed in ureter by ureteroscope for drainage,and then phase 2 operation was done in 2 cases.Emergency operation was done in 10 cases.The remaining 1 case un- derwent ESWL after anti-infective therapy.Results Definite diagnosis of pyonephrosis before operation was made by invasive examinations in 31 cases(75.6%),and by percutaneous drainage in 4 cases;the other 6 cases were detected during operation.Only 6 cases(14.6%)underwent nephrectomy;the other 35 cases (85.4%)underwent kidney-sparing operation.Follow-up of 3 months to 9 years was available in 37 cases. No nephrectomy was needed in 33 cases with spared kidney.Serum creatinine was normal in the 4 cases un- dergoing nephrectomy.Conclusions The key to the treatment of pyonephrosis by kidney-sparing surgery is early diagnosis,timely drainage and relief of obstruction.Ultrasonography plays an important role in the early diagnosis of pyonephrosis,and CT has a high sensibility in the diagnosis.Pereutaneons nephrolithotomy (PCNL)secondary to drainage through pereutaneous nephrostomy was beneficial to the patients with kidney stones or upper ureter stones.

Objective The detection of malignant lymphoma with invasion in liver and spleen using PET/CT has not been well documented in the literature. This study aimed to investigate the usefulness of PET/CT in this regard and to compare it with plain CT. Methods Forty-one pathologically confirmed malignant lymphoma patients with liver and spleen invasion were recruited into this study. Among all patients, there were 38 non-Hodgkin's lymphoma (NHL), 2 Hodgkin's lymphoma (HL) and 1 gastric mucosa associated lymphoma. PET/CT imaging was recorded 1h after injection of 296～444 MBq 18F-fluorodeoxyglucose (FDG). Results (1) There were 30(30/41) patients with liver invasion, including hepatic nodules, mass and portal nodes. The mass was large to invade surrounding liver parenchyma. (2) There were 23(23/41) patients with spleen invasion. The spleen was enlarged and demonstrated diffused hyper-metabolism. (3) Other invasion included: lung (n=13), cortical bone and marrow (n=12), stomach (n=9), pleural (n=6), and subcutaneous soft tissue (n=5) and so on. Conclusion PET/CT could accurately diagnose the invasion in liver and spleen of malignant lymphoma, which was of potential role on the diagnosis and staging of lymphoma.

OBJECTIVETo observe the expressions of caspase-8 and caspase-9 mRNA, and explore the changes of apoptosis of bone marrow hematopoietic cells in patients with chronic mountain sickness (CMS).

METHODSOf 18 CMS patients and 16 controls were enrolled in this study. The apoptotic index (AI) of bone marrow mononuclear cells (BMMNC) was measured by TUNEL technique, the levels of caspase-8 and caspase-9 mRNA in BMMNC of CMS patients and controls were determined by RT-PCR. Results (1)The AI of BMMNC in patients with CMS (8.51 ± 3.35)% was lower than that in controls (16.00 ± 4.28)% (P < 0.01); (2) The values of caspase-8 and caspase-9 mRNA were (0.28 ± 0.07) and (0.23 ± 0.08) respectively, in CMS patients, which were significantly lower than those of (0.45 ± 0.09) and (0.41 ± 0.09) respectively, in the controls (both P < 0.01); (3) Hemoglobin (Hb) value was negatively correlated with levels of caspase-8 and caspase-9 mRNA (r values were -0.52 and -0.61 respectively, both P < 0.05) in CMS patients. There was a negative correlation between AI and Hb (r value was -0.89, P < 0.01) in CMS patients. However, the significant relationship was not found between AI and level of caspase-8 or caspase-9 mRNA (P > 0.05).

CONCLUSIONSThe results showed a decrease apoptosis of BMMNCs and reduced levels of caspase-8 and caspase-9 mRNA in CMS patients, the latter might be involved in the change of BMMNCs apoptosis.

Adult ; Altitude Sickness ; metabolism ; pathology ; Apoptosis ; Bone Marrow Cells ; metabolism ; Case-Control Studies ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Humans ; Male ; Middle Aged

The release behavior of single pellet was investigated by LC/MS/MS method with tamsulosin hydrochloride (TSH) as the model drug of the research and then the pellets were divided into four groups according to the drug loading. Comparison of dissolution profiles of each group and capsule were performed using f1 and f2 factor methods to study the difference and similarity. The release profiles of single pellet, each group and capsule were analyzed using principle component analysis (PCA). The particle system was built through Matlab to get the target release profile. The result of this research demonstrated the release behavior of single pellet correlated well with the drug loading. While the dissolution profile of capsule as a reference, the similarity factor of dissolution profiles of the lower drug loading groups were 62.2, 67.1, 53.9, respectively and, 43.3 for highest drug loading group. The particle systems with different pellet distribution and same release profiles were built through release behavior of single pellet. It is of significance to investigate the release behavior of single pellets for studying the release regularity of multiple-unit drug delivery system.
Capsules ; Chemistry, Pharmaceutical ; Chromatography, Liquid ; Delayed-Action Preparations ; Drug Delivery Systems ; Drug Liberation ; Principal Component Analysis ; Sulfonamides ; administration & dosage ; chemistry ; Tandem Mass Spectrometry ; Technology, Pharmaceutical

AIMTo investigate effect of ginkgo biloba extract (GBE) on N-methyl-D-aspartate (NMDA)-activated currents (I(NMDA)) and evaluate further the modulatory effects of Micro-GBE/Nano-GBE.

METHODSBy means of whole-cell patch clamp technique, NMDA-activated currents from acutely isolated rat hippocampal neurons were recored.

RESULTSThe majority of the neurons examined (81.8%, 90/110) were sensitive to NMDA (1 mmol/L) and its co-agonist Gly (10 micromol/L). NMDA activated an inward current, which manifested apparent desensitization and could be blocked by its specific antagonist MK-801. After the neurons were treated with Micro/Nano GBE (0.1 mg/ml) followed by the application of NMDA (1 mmol/L) and Gly (10 micromol/L) for 30 s, it was show that NMDA-activated currents were obviously inhibited (P < 0.01, n = 8). The inhibitory rate were 40% +/- 17% and 64% +/- 15% respectively. It showed that the modulatory effect of Nano-GBE (dissolved in the stander extracellular solution) on NMDA-activated current was significantly higher than that of Micro-GBE (dissolved in DMSO) (P < 0.05).

CONCLUSIONThe inward currents activated by NMDA could be depressed by Micro-GBE and Nano-GBE. The modulatory effects of GBE on NMDA-activated current are expected to contribute to the neuroprotective effects of ginkgo biloba extracts. In addition, at the same concentration, the modulatory effect of Nano-GBE on NMDA-activated current is better than that of Micro-GBE.

Animals ; Cells, Cultured ; Ginkgo biloba ; Hippocampus ; drug effects ; physiology ; N-Methylaspartate ; pharmacology ; Neurons ; drug effects ; physiology ; Patch-Clamp Techniques ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; drug effects

OBJECTIVEChronic myocardial ischemia (CMI) has become the most important cause of heart failure (HF) all over the world. The aim of the current study was to investigate the effects of Sarco-endoplasmic reticulum calcium ATPase 2a (SERCA2a) gene transfer on cardiac function and endoplasmic reticulum stress (ERS) associated myocardial apoptosis in a minipig HF animal model induced by CMI.

METHODSHF was induced in minipigs by implantation of ameroid constrictor in the initial segment of left anterior descending (LAD) branch of coronary artery. After confirmation of myocardial perfusion defects and cardiac function impairment by myocardial perfusion imaging and echocardiography, animals were divided into 4 groups (n = 4 each): HF group, HF + enhanced green fluorescent protein (EGFP) group, HF + SERCA2a group, and shamed animals as control group. A total amount of 1 × 10(12) v.g. of rAAV1-EGFP or rAAV1-SERCA2a were injected intramyocardially to each animal of HF + EGFP and HF + SERCA2a groups. Sixty days after gene transfer, protein level and activity of SERCA2a were examined, cardiac functions and changes of serum inflammatory and neuro-hormonal factors were determined. Apoptotic index of the ischemic myocardium, protein levels of ER stress marker glucose regulated protein 78 (GRP 78) and ER stress specific apoptotic marker caspase-12 were also assayed.

RESULTSAt the study end, echocardiographic and hemo dynamic measurements indicated a significant improvement of both cardiac systolic and diastolic function in HF + SERCA2a group compared with HF/HF + EGFP groups [LVEF (60.2 ± 8.6)% vs (44.2 ± 7.1)% and (46.8 ± 6.7)%, Ev/Av 1.28 ± 0.24 vs 0.77 ± 0.17 and 0.80 ± 0.21, +dp/dt(max) (2713.9 ± 434.0) mm Hg/s (1 mm Hg = 0.133 kPa) vs (1892.3 ± 434.2) mm Hg/s and (1931.2 ± 397.4) mm Hg/s, -dp/dt(max) (1422.1 ± 334.4) mm Hg/s vs (848.3 ± 308.3) mm Hg/s and (849.5 ± 278.3) mm Hg/s, P < 0.05], along with increase in both SERCA2a protein level (1.13 ± 0.26 vs 0.73 ± 0.17 and 0.64 ± 0.18, P < 0.05) and activity [(16.2 ± 5.5) IU/ml vs (7.9 ± 3.1) IU/ml and (7.5 ± 2.8) IU/ml, P < 0.05] compared with HF/HF + EGFP groups. Serum concentrations of inflammatory factor tumor necrotic factor α [(382.3 ± 114.4) ng/L vs (732.3 ± 201.4) ng/L and (689.8 ± 192.5) ng/L, P < 0.05], neural-hormonal factors brain natriuretic peptide [(142.6 ± 45.3) ng/L vs (422.3 ± 113.6) ng/L and (393.7 ± 103.3) ng/L, P < 0.01], endothelin-1 [(111.4 ± 37.5) ng/L vs (193.5 ± 54.3) ng/L and (201.0 ± 72.1) ng/L, P < 0.05] and angiotensin II [(189.7 ± 65.2) µg/L vs (538.3 ± 135.2) µg/L and (525.5 ± 144.1) µg/L, P < 0.01] were also significantly decreased in HF + SERCA2a group compared with HF/HF + EGFP groups. The apoptotic index [(12.71 ± 4.11)% vs (23.22 ± 7.23)% and (24.31 ± 6.38)%, P < 0.05], protein levels of GRP 78 (1.27 ± 0.33 vs 3.23 ± 1.14 and 4.18 ± 1.13, P < 0.05) and protein level ratios of cleaved caspase-12 to total caspase-12 [(4.62 ± 1.93)% vs (9.71 ± 2.70)% and (10.14 ± 2.81)%, P < 0.05] were also significantly reduced in the ischemic myocardium of HF + SERCA2a group compared with the HF/HF + EGFP groups.

CONCLUSIONOverexpression of SERCA2a significantly improved cardiac systolic and diastolic function in this HF model partly through attenuation of ER stress related myocardial apoptosis, suggesting its therapeutic potential for CMI related heart failure.

Animals ; Chronic Disease ; Disease Models, Animal ; Genetic Therapy ; Heart Failure ; therapy ; Myocardial Ischemia ; therapy ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; genetics ; Swine ; Swine, Miniature

Objective To compare the histologic grade between biopsy and postoperative specimen in bladder urothelial carcinoma,and approach the state and the reasons of underestimate the histologic grade preoperative.Methods We retrospectively 82 cases of urothelial carcinoma at the Third Affiliated Hospi- tal of the Sun Yat-Sen University.For all the cases in this study,the histologic grade,using the 1998 World Health Organization and International Society of Urological Pathologists(WHO/ISUP)classification,was i- dentical when the biopsy specimen and postoperative specimen were compared.Results In this study,35 cases,28 cases and 19 cases were G_1、G_2、G_3 by biopsy preoperative,respectively;while 22 cases,32 cases、28 cases were G_1、G_2、G_3 postoperative,respectively.There were 24 cases(29.3%)underestimate the histo- logic grade by biopsy preoperative in the 82 cases,while 4 cases(4.9%)overestimate preoperative.The state of underestimate the histologic grade is correlated with the location of biopsy,tissue dose and the conser- vation of pathology judgment.Conclusions There were 24 cases(29.3%)underestimate the histologic grade by biopsy preoperative.We should pay more attention to this state of underestimate the histologic grade preoperative in the treatment of bladder urothelial carcinoma.

Objective To study the clinical value of serum cytokeratin 19 fragment (CYFRA21-1) as a biomarker in evaluating its prognosis,monitoring and follow-up of the postoperative patients with non- small cell lung cancer (NSCLC).Methods Serum CYFRA21-1 was determined by radioimmunoassay for 207 patients with NSCLC before and after surgical operation at Tongji Hospital,Shanghai.Relationship between serum CYFRA21-1 and the prognosis,recurrence and metastasis of lung cancer was analyzed retrospectively.Results The patients were followed-up for 37 months in average.Preoperative serum CYFRA21-1 was positive in 42.0% (87/207) of all the cases,48.8% (60/123) of squamous cell earcinama and 34.6% (27/78) of adenocarcinoma,with statistical significance (X~2=3.901,P