Objective To investigate the effects of Mycobacterium vaccae vaccine on immunological function and clinical character in elderly patients with stable chronic obstructive pulmonary disease (COPD). MethodsA total of 100 elderly patients with stable COPD were randomly divided into immunotherapy group (group A, n= 50) and non-immunotherapy group (group B, n= 50), and normal control group (group C, n = 50). The levels of peripheral blood T-lymphocyte subsets (CD3+ , CD4+, CD8+ , CD4+/CD8+ ratio), natural killer cells (NK cells), immunoglobulins (IgG, IgA, IgM) and cytokines (IL-6, IL-8, TNF-a) were measured respectively before and after therapy. Group A and B were followed up for 1 year, then the times of acute outbreak and hospitalization of patients in the two groups were also compared. Results The levels of CD4 + ,CD4+/CD8+ ratio and NK cells in group A, B were significantly lower before therapy (P＜0. 05～0. 01＝, and the levels of IL-6, IL -8, TNF-a and IgA were significantly higher than in group C (P＜0. 01＝. After treatment with Mycobacterium vaccae vaccine in group A, the levels of CD4+ , CD4+/CD8+ ratio and NK cells were significantly higher (P＜0. 05-0. 01＝ and IL-6, IL-8, TNF-a and IgA were significantly lower than before treatment (all P＜0. 01＝. These levels showed no significant changes in group B after treatment (P＞0. 05). After 1-year follow-up, the times of acute outbreak and hospitalization on patients were statistically lower in group A than in group B (P＜ 0. 01 ).ConclusionsMycobacterium vaccae vaccine can improve cellular immunity function and reduce the times of acute outbreak and hospitalization in patients with stable COPD, so it has a higher clinical application value.

Objective Diabetic mice models were established.Hearts were separated from the body,reperfused after ischemia,and disposed of with the extraneous calcitonin gene-ralated peptide (CGRP),to prove if the CGRP had protective effect on the early-staged diabetic mice with cardiac ischemia.Method ICR mice were injected with Streptozocins intraperitoneally to establish diabetic model.The model mice and the normal mice were randomly divided into 4 groups:two diabetic groups,two control groups.Hearts of the experimental mice were taken out from the chest cavity alive,and hanged on the Langendorff steadily for 30min.Western blot and radioimmunoassay techniques were used to test expression of Vanilloid receptor(VR1) and CGRP in myocardic tissue;Madlab system was used to test the cardiac function,which including left ventricular end-diastolic pressure (LVEDP),left ventricular developed pressure (LVDP),heart rate (HR),and coronary artery flow (CF),in the process of ischemic reperfusion,And ELISA assay kit was used to measure the concentration of the lactate dehydrogenase (LDH) in perfusion fluid collected from the heart.Result Expressions of VR1 and CGRP in diabetic hearts were significantly lower than those in normal ones 2 weeks later(P＜0.01).By comparing with normal hearts,diabetic hearts had higher LVEDP and CF (P＜0.05),and lower LVDP and HR(P＜0.05).However,release of LDH were lower than normal ones (P＜0.05).Predisposition of normal and diabetic hearts with CGRP can improve the cardiac function after ischemie injury.And the beneficial effect was more profound in early-staged diabetic hearts than in normal ones.Conclusion The diabetes disease(DM) can impair the expression of CGRP in myocardiac tissue.The extraneous CGRP may exert more potent protective effect on cardiac function in the early-staged diabetic heart.

OBJECTIVETo build 3D-pharmacophore model of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors using distance comparisons method and design novel EGFR inhibitors.

METHODSThirteen typical EGFR inhibitors were selected, and their biologically active conformations were obtained by using DOCK5.0 program, then 3D-pharmacophore model of EGFR inhibitors was built using distance comparisons method.

RESULTSValidation of the 3D-pharmacophore model was carried out and novel structures with potential inhibitory activity were selected by means of 3D-searching and docking method.

CONCLUSIONThis method can improve hit rate of lead compounds discovery and can be used to design novel EGFR inhibitors.

Drug Design ; Enzyme Inhibitors ; Epidermal Growth Factor ; metabolism ; Models, Chemical ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; chemistry ; pharmacology ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; chemistry ; Structure-Activity Relationship

OBJECTIVETo investigate the effect of antidepressant on irritable bowel syndrome (IBS).

METHODSA self-control and follow-up study on subclinical dosage of antidepressants therapy (fluoxetine 10 mg/d, paroxetine 10 mg/d or doxepin 45 mg/d) for 9-12 wks in 46 patients with refractory IBS symptoms according to Rome II criteria was performed, the clinical outcomes were evaluated by scales changes of symptom-related-anxiety, severity index of symptom, and quality of life specific of IBS, as well as general psychiatric health by SCL-90 during treatment and follow-up periods.

RESULTSAll 46 cases completed therapy and first follow-up unit (12 wks after treatment) (FFU), at the end of FFU, clinical symptoms in all patients were improved (P < 0.01). Comparison of the scores of symptom-related-anxiety, index of symptom, and quality of life specific of IBS at the end of FFU with that at basal level, indexes of the severity (3.4 +/- 1.5 vs 1.8 +/- 0.84) and frequency (3.8 +/- 1.60 vs 2.0 +/- 0.76) of symptoms were subsided significantly (P < 0.01, respectively); the scores of symptom-anxiety questionnaire including body anxiety (16.04 +/- 1.65 vs 10.83 +/- 1.64, P < 0.001), cognitive anxiety (18.78 +/- 2.12 vs 11.17 +/- 1.89, P < 0.001), fear (15.80 +/- 1.76 vs 10.78 +/- 1.85, P < 0.001) and avoiding (15.47 +/- 1.53 vs 10.16 +/- 1.59, P < 0.001) were also subsided significantly. In the meantime, IBS-QoL improved significantly (P < 0.05), dysphoria, body image, interference with activity, health worry, social reaction and overall scores were improved significantly (P < 0.01, respectively). The status of general psychiatric health was also improved significantly (P < 0.01).

CONCLUSIONSTreatment of refractory IBS with subclinical dosage antidepressant is rational and effective, However a further study on its mechanisms is suggested.

Adult ; Antidepressive Agents ; administration & dosage ; Doxepin ; administration & dosage ; Female ; Fluoxetine ; administration & dosage ; Follow-Up Studies ; Humans ; Irritable Bowel Syndrome ; drug therapy ; Male ; Middle Aged ; Paroxetine ; administration & dosage ; Quality of Life

OBJECTIVETo investigate the effects of small interfering RNA targeting connective tissue growth factor (CTGF) on rat transforming growth factor beta (TGF beta)/Smads signal pathway.

METHODSChemically synthetic siRNA targeting CTGF was transfected into HSC T6 and then they were injected into rat livers through their intraportal veins. At the same time these rats also received CCl4 subcutaneously every three days for 6 consecutive weeks. Untreated HSC T6 or/and rats with random siRNA treatment served as controls. Total RNA or/and protein in HSC T6 and rat hepatic tissues were extracted. The expressions of CTGF and TGF beta 1, Smad2, 3 and 7 genes were detected by reverse transcription-polymerase chain reaction (RT-PCR) and/or Western blot.

RESULTSCTGF siRNA significantly reduced the expression of CTGF protein in HSC T6. At 48 h after CTGF siRNA treatment, the down-regulation of CTGF protein was the most significant, up to 94%+/-4% (t=46.196, P less than 0.01), but the expressions of TGF beta 1, Smad2, 3 and 7 mRNA showed no differences in HSC T6 compared with the blank controls. Six weeks after CCl4 injections, prominent up-regulations were observed in the gene expressions of CTGF and TGF beta 1 in saline control or siRNA-treated rat livers. Administering CTGF siRNA for six weeks markedly attenuated the induction of CTGF and TGF beta 1 genes; the expressions of CTGF and TGF beta 1 protein decreased by 95%+/-2% (F=21.234, P less than 0.01) and 74%+/-8% (F=13.464, P less than 0.05), respectively, whereas Smad2, 7 protein expressions were not affected.

CONCLUSIONSilencing the CTGF gene can suppress the TGF beta /Smads signal pathway in rat livers.

Animals ; Connective Tissue Growth Factor ; metabolism ; Gene Silencing ; Male ; RNA, Messenger ; genetics ; RNA, Small Interfering ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Smad Proteins ; metabolism ; Transfection ; Transforming Growth Factor beta ; metabolism

Objective: To observe the effects of angina pector is on severe ventricular arrhythmia and QTd in patients with first acute myocard ial infarction(AMI). Methods: One hundred and eight-four cases of first AMI were divided into 2 groups: PA group, angina pectoris occurred with in 24 h before AMI onset (n=58), NPA group, no preceeding angina pectori s occurred (n=126). Occurrence of complications and QTd were investigated du ring hospitalization. Results: The basic clinical characteristic s, coronary risk factors, medication before infarction, treatments after admissi on with antiarrhythmic agents, site of infarction, successful rate of thrombolys is and peak CK, CK-MB were not statistically different. Early QTd in PA group and NPA group were (56.22±18.40) ms vs (84.45±21.90) ms, respectively, P <0.05, late QTd in PA group and NPA group were (50.67± 16.34) ms vs (64.1 8(16.41) ms, respectively, P<0.05. Comparison with NPA group, incidence of severe ventricular arrhythmia, heart failure, cardiogenic shock and rate of car diac mortality in-hospital was lower in PA group. Conclusion: P reinfarction angina pectoris can significantly reduce the incidence of severe ve ntricular arrhythmia and QTd in the patients with first AMI, sugges ting that these favorable effects might be associated with protective effects of ischemic preconditioning on myocardium and ventricular pump function and improv ement of repolarizative asynchronism in ventricular myocardium.

AIMDesign, synthesis and evaluation of a series of 7-imidazolylalkanamido-1-carboxylalkylbenzodiazepine farnesyltransferase (FTase) inhibitors.

METHODS AND RESULTSCoupling of imidazolylalkylcarboxylic acids and 1-substituted 7-aminobenzodiazepines (5a-5c) yielded 10 new compounds (6-12, 16-18) which were biologically tested against FTase using scintillation proximity assay method.

CONCLUSIONFive target compounds were found to be potential farnesyltransferase inhibitors.

Alkyl and Aryl Transferases ; antagonists & inhibitors ; drug effects ; Benzodiazepines ; chemical synthesis ; chemistry ; pharmacology ; Farnesyltranstransferase ; Imidazoles ; chemical synthesis ; chemistry ; pharmacology ; Inhibitory Concentration 50 ; Molecular Conformation ; Molecular Structure ; Structure-Activity Relationship

OBJECTIVETo investigate the clinical manifestations, EB virus serology and treatment outcome of nasopharyngeal adenocarcinoma (NPAC).

METHODSClinical records of NPAC patients between 1964 and 2000 in Cancer Center of Sun Yat-sen University were retrospectively reviewed.

RESULTSAmong 48 patients with NPAC, 45.2% (7 cases of N1, 8 cases of N2 and 4 cases of N3) of them presented with cervical metastasis. Pathologically, common type and salivary gland type of NPAC accounted for 58.3% (28 cases) and 41.7% (20 cases) respectively. The positive rate of the EB virus antibody VCA-IgA was 56.7% in the whole group and only 23.7% in the salivary gland type of NPAC. The overall local control rate and the 5-year disease free survival rate by Kaplan-Meier method were 87.0% (40/46) and 65.2% respectively. Baseline data analysis showed that age, gender, N stage and M stage were not the significant factors, never the less the T stage was not balanced between the two groups (surgery plus radiotherapy vs radiotherapy alone, chi2 = 4.801, P = 0.045). The patients treated by surgery plus radiotherapy had significantly higher 5-year disease free survival rate than by radiotherapy alone (88.9% vs 74.7%, Log Rank test: chi2 = 4.272, P = 0.039). Cox's multivariate analysis showed treatment modality and N stage were the significant factors influencing survival (RR were 15.276 and 6.529, P < 0.05).

CONCLUSIONSNPAC is a distinct entity in all types of nasopharyngeal carcinoma. EB virus serology has limited value in its diagnosis. Surgery plus radiotherapy could be another choice of treatment for early lesions of NPAC.

Adenocarcinoma ; diagnosis ; pathology ; virology ; Adolescent ; Adult ; Aged ; Antibodies, Viral ; analysis ; Female ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnosis ; pathology ; virology ; Prognosis ; Retrospective Studies ; Young Adult

OBJECTIVETo analyze the clinical features of adrenal metastasis.

METHODSFrom January 1993 to December 2004, 103 cases of adrenal metastasis were reviewed.

RESULTSLung and hepatocellular carcinoma were the most common primary tumor of adrenal metastatic tumor, which about 36.9% (38/103) and 42.7% (44/103) of all cases, followed by renal carcinoma 6.8% (7/103), colorectal carcinoma 4.9% (5/103), stomach carcinoma 3.9% (4/103), breast cancer 1.9% (2/103), unknown primary tumor 2.9% (3/103). Most of these were low differentiation. The mean diameter of adrenal metastasis was 3.9 cm. The mean interval from detection of primary tumor to adrenal metastasis was 9.5 months. And 79.6% (82/103) were detected as a part of multiorgan metastasis. Only 5 cases (4.9%) were presented with pain in the back. There was little characterization of ultrasonography, CT and MRI, color-Doppler and selective arterial imaging showed little blood supply. All of patients were treated with synthetic methods, 16 cases (15.5%) who had undergone adrenalectomy for metastasis disease had a improved survival compared with those non-adrenalectomy.

CONCLUSIONSThere is no particular presentation of clinic and imaging, diagnosis depending on history, follow-up and the pathological presentation of primary tumor. There are no standard treatment guidelines for this group of patients. When the primary tumor could be resected or be well controlled, and there is no other evidence of metastasis, adrenalectomy is recommended. Transarterial chemoembolization (TACE) could not actually be performed.

Adrenal Gland Neoplasms ; diagnosis ; secondary ; therapy ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; pathology ; Combined Modality Therapy ; Female ; Humans ; Liver Neoplasms ; pathology ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Survival Analysis ; Treatment Outcome

Objective: To investigate the changes of myo cardial contractile function during myocardial stunning in calcium overload rats and the protective effects of tetrandrine. Methods: Forty-six rats were randomized into control, myocardial ischemia, myocardial stunning, low and high dose of tetrandrine groups. Another 10 rats were used to identify the calcium overload. vitamin D3 (0.3 million Unit/kg) and nicotinic acid were adm inistered. After 16 d when calcium overload occured, left anterior descending ar tery was ligated. Twenty minutes of myocardial ischemia followed by 60 min of re perfusion was induced. The contractile function parameters were determined dynam ically. At the end of experiment, myocardial cytosolic ［Ca2+］i was deter mined in various groups. In tetrandrine groups, tetrandrine (62.2 or 93.6 μmol/ kg ) was administered by gastrogavage daily.After 16 d, the rats undergone the e xperiments mentioned above. Results: Sixteen days after vitamin D3 , nicotinic acid were given, ［Ca2+］i increased by 2.6 folds (146.8±10.8 ) vs (368.5±22.6) nmol/L, (P<0.01). Whereas, ［Ca2+］i in tetrand rine groups were (210.8±16.4) and (198.6±15.3) nmol/L, which were significantl y lower than that of calcium overload group. Twenty minutes of myocardial ische mia resulted in the decrease of dp/dtmax and Vmax in all groups with the most si gnificant in stunning and calcium overload groups. The contractile function rest ored gradually after reperfusion. At all time points, dp/dtmax and Vmax in both tetrandrine groups were higher than those in both stunning and calcium overload groups. And effect with higher dose of tetrandrine were more significant than in low dose of tetrandrine. After 60 min of reperfusion, dp/dtmax in stunning, cal cium overload, low and high dose of tetrandrine groups were 49.7%, 51.5%, 71.0% and 83.4% of that in control, respectively， and Vmax were 55.0%, 49.8%, 73.9% and 77.5% of that in control, respectively. Conclusion: T he myocardial contractile function in vitamin D3-induced calcium overload gro up is impaired. On basis of myocardiocyte calcium overload, transient ischemia l eads to myocardial stunning. At the stage of ischemia, the impaired degree of my ocardial contractile function is similar to that in stunning group, suggesting a t this stage the effect of ischemia on myocardial function is greater than that of calcium overload. Tetrandrine chronically improves the myocardial function in Vitamin D3-induced calcium overload rats.