ObjectiveTo observe the effect and safety of continuous epidural analgesia with sufentanil in different concentrations combined with 0.125% bupivacaine on pain after thoracotomy.Methods30 patients with ASA grade Ⅱ～Ⅲ and underwent thoracotomy were randomly divided into 3 groups treated with 0.125% bupivacaine combined with sufentanil 0.25 μg/ml (group A), 0.50 μg/ml (group B) and 0.75 μg/ml (group C) respectively. Before operation starting, epidural puncture was performed at T7～T8 and a catheter was put in. After operation, continuous epidural analgesia was performed by connecting the catheter and a analgesic pump. Analgesia effect was evaluated by visual analogous score (VAS) at sixth, twelfth, twenty-fourth and forty-eighth hours after operation. Dosage of assistant drug and side effects such as calmness, nausea, vomiting, skin pruritus and respiratory inhibition were also recorded.ResultsVAS scores and dosage of assistant drug of group B and group C were not different, but they were all lower than that of group A (P<0.05). Scores of skin pruritus of group A and group B were lower than that of group C (P<0.05), but there was no significant difference between group A and group B. No respiratory inhibition occurred in patients of all three groups.ConclusionContinuous epidural analgesia of 0.50 μg/ml sufentanil combined with 0.125% bupivacaine is safe and effective for patients after thoracotomy.

Objective To investigate the role of cathepsin G in photoaged fibroblasts. Methods Human fibroblasts were cultured and induced to premature senescence using UVA + MOP methods. Senescence-associated-β-galactosidase (SA-β-gal) stain was used to evaluate the positive rate of aged cells. The mRNA and protein expression of cathepsin G in photoaged fibroblasts were detected by real-time RT-PCR and Western blot techniques. Results Over 98 % induced cells presented a positive SA-β-gal straining. The expression of cathepsin G, detected by Western blot, was increased to (1. 70±0. 028) times of the control. And RT-PCR revealed that the synthesis of cathepsin G mRNA was also up-regulated to 1. 42±0. 09. Conclusion The results of our study demonstrates a significant correlation between photoaged fibroblasts and cathepsin G. The up-regulation of cathepsin G may play an important role in the damages of extracellular matrix and activation of MMPS in photoaged human skin.

Objective To investigate the expression changes of aspartic proteinase (cathepsin D) and cysteine proteinase (cathepsin K) in photoaged fibroblasts. Methods The senescence of human fibroblasts was induced via culture in the presence of 8-methoxypsralen (MOP) of 50 mg/L in darkness for 24 hours followed by irradiation with UVA of 80 kJ/m~2. Then, aged fibroblasts were confirmed by senescence-associated β-galactosidase (SA-β-gal) staining. Real-time RT-PCR and Western blot were carried out to detect the mRNA and protein expressions of cathepsin D and cathepsin K in photoaged and normal control fibroblasts, respectively. Results Western blot showed a significant difference between photoaged and control fibroblasts in the grey scale of cathepsin D and cathepsin K (3.25 ± 0.33 vs 14.18 ± 2.25, f = 30.61, P < 0.01; 2.39 ± 0.66 vs 29.38 ± 4.62, t = 12.63, P< 0.01). The △Ct values for cathepsin D and cathepsin K mRNA were 2.79 ± 0.17 and -0.92 ± 0.06, respectively, in photoaged fibroblasts, significantly lower than those in the control fibroblasts (4.54 ± 0.34, 2.57 ± 0.13, t = 20.78, 28.50, respectively, both P < 0.01). According to the value of 2~(-△△Ct), the expression of cathepsin D and cathepsin K mRNA decreased 0.24 ± 0.021 and 0.09 ± 0.005 folds, respectively, in photoaged fibroblasts compared with the control fibroblasts. Conclusion The expression of cathepsin D and cathepsin K is decreased in photoaged fibroblasts.

In recent years, the incidence and mortality rate of invasive fungal infection have increased dramatically, and it is of great significance to develop novel antifungal agents with new chemical structure and new mode of action. In this review, novel antifungal lead compounds reported from 2007 to 2009 are reviewed. Moreover, their chemical structures, antifungal activities and structure-activity relationships have been summarized, which can provide useful information for future study of antifungal agents.
Antifungal Agents ; chemical synthesis ; chemistry ; pharmacology ; therapeutic use ; Fungi ; drug effects ; Heterocyclic Compounds ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Lipopeptides ; chemistry ; pharmacology ; therapeutic use ; Molecular Structure ; Mycoses ; drug therapy ; Nitriles ; chemistry ; pharmacology ; therapeutic use ; Plant Extracts ; chemical synthesis ; chemistry ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Pyridines ; chemistry ; pharmacology ; therapeutic use ; Quinazolines ; chemistry ; pharmacology ; therapeutic use ; Quinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; Thiazoles ; chemistry ; pharmacology ; therapeutic use ; Triazoles ; chemistry ; pharmacology ; therapeutic use

To study the pharmacokinetic process of Danshensu in cerebal ischemia injury model rats and the correlation with its anti-cerebral ischemia effect. In this study, the middle cerebral artery occlusion (MCAO) model was established, in which all of the rats were intravenously injected of Danshensu at a single dose of 40 mg x kg(-1). The HPLC-DAD method was applied to determine the plasma concentration of Danshensu at different time points and draw the drug-time curve. Meanwhile, the superoxide dismutase (SOD) and the lactate dehydrogenase (LDH) activity were determined to draw the time-effect curve. The DAS 3.2. 6 software was used to process the data, analyze their correlation, compare the pharmacokinetic difference between model and normal rats after the administration of the same doses of Danshensu and the changes in pharmacodynamic indicators of model rats after the administration, and evaluate the effect of Danshensu in treating the cerebral ischemia disease. According to the results, the pharmacokinetic processes of Danshensu in the cerebral ischemia-reperfusion and normal rats were consistent to the two-compartment model. The main pharmacokinetic parameters were: t1/2alpha were (0.267 +/- 0.026), (0.148 +/- 0.020) h;t1/2beta were (1.226 +/- 0.032), (1.182 +/- 0.082) h; AUC0-infinity were (42.168 +/- 4.007), (26.881 +/- 1.625) mg x L(-1) x h. After the cerebral ischemia-reperfusion, the activity of SOD decreased and the activity of LDH increased. Danshensu could inhibit the decrease in the SOD activity and the increase in the LDH activity within a certain period of time. This indicated that Danshensu could stay longer in cerebral ischemia-reperfusion rats than in normal rats and eliminated more slowly, which reflected the rationality of Danshensu in the clinical treatment of cerebral ischemia diseases. Danshensu's effect against the cerebral ischemic injury may be related with its level in vivo. Its plasma concentration is positively related to the SOD activity and negatively related to the LDH activity.
Animals ; Brain Ischemia ; drug therapy ; Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry

[Objective]To investigate the effects of ghrelin on inflammatory signaling protein kinase B(Akt),nuclear factor-κB(NF-κB)and inducible nitric oxide synthase(iNOS)in alveolar macrophage(AM).[Methods]24 Male SD rats were randomly divided into Sham,CLP,CLP+ghrelin,and Sham+ghrelin groups. Cecal ligation and puncture(CLP)was used to induce sepsis. Ghrelin(20 nmol/kg)was administered by intraperitoneal injection at 3 h and 15 h post-operation. Histopathological changes of lungs were observed and scored.AM were extracted from bronchoalveolar lavage fluid(BALF). Interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in BALF were detected by ELISA. IL-1β,TNF-α,and IL-6 mRNA in AM were detected by qPCR.NF-κB p65,IκBα,p-IκBα,Akt,p-Akt and iNOS in AM were detected by immunofluorescence(IF)and Western blotting.[Results]The histologic score(6.7±0.8),BALF IL-1β[(146±12)pg/mL]and IL-6[(182±10)pg/mL]from CLP+ghrelin group were respectively 35.4%,44.5% and 46.42% lower than those from CLP group[(10.3±0.7),(263±17)pg/mL,and(273±5)pg/mL],P<0.05.No significant difference was found in BALF TNF-α between CLP group and CLP+ghrelin group.The IL-1β,TNF-α and IL-6 mRNA in AM from CLP+ghrelin group were respectively 54.38%,53.6% and 46.42% lower than those from CLP group,P<0.05. The nuclear NF-κB p65 and cytoplasmic p-IκBα,p-Akt and iNOS from CLP+ghrelin group were respectively 32.58%,45.42%,27.6% and 48.33% lower than those from CLP group,P<0.05. There was no significant difference in all data between Sham group and Sham+ghrelin group.[Conclusion]Ghrelin can decrease the activity of inflammatory signaling proteins Akt,NF-κB and iNOS in AM,therefore restricts AM expressing pro-inflammatory cytokines IL-1β,TNF-α,and IL-6,thus alleviates sep-sis-induced acute lung injury(ALI).

Objective To analyze the clinical practice ofmicrosurgical operation in intracranial ruptured aneurysms of anterior circulation via lateral supraorbital approach and pterional approach.Methods A retrospective analysis was performed on the clinical data of 74 patients with intracranial ruptured aneurysms of anterior circulation,admitted to our hospital from June 2011 to December 2011;38 patients were assigned to neurosurgical treatment via lateral supraorbital approach,while the other 36 were performed neurosurgical treatment via pterional approach.Statistical analysis was performed on the clinical data.Results In the patients performed neurosurgical treatment via lateral supraorbital approach,the average operation time was (142±32) min,average length of incision was (9.2± 1.5) cm,and the mean hospital stay was (11.9±4.3) d.Two months after discharge,33 got recovery and 5 had light disability; no severe disability or PVS was observed.No significant difference was noted in good recovery rate and clipping success rate between the two group patients (P＞0.05),but significant differences were observed in the operation time,length of incisions,and mean hospital stay between the two group patients (P＜0.05).Conclusion Neurosurgical treatment via lateral supraorbital approach is a safe and mini-invasive method for intracranial ruptured aneurysms of anterior circulation,which is more suitable for extensive promotion.

OBJECTIVETo explore the correlation between the polyomavirus DNA load and the dose of immunosuppressant in patients with allogene bone marrow transplantation (allo-BMT) for preventing the development of post-transplantational hemorrhagic cystitis.

METHODSSerial blood and urine samples from 122 cases of allo-BMT recipients were obtained and DNA was extracted from urine samples. Polyomavirus DNA-specific probe was synthesized and Fluorescence quantitative polymerase chain reaction was used for detecting the polyomavirus DNA loads and Fluorescence polarization immunoassay (FPIA) was performed for determining the dose of immunosuppressant Cyclosporin A (CsA) in blood.

RESULTSThe altered polyomavirus DNA load in urine was followed by concentration of CsA in blood. When the concentration of CsA in blood was higher than 86-105 ng/ml, the positive rate of polyomavirus DNA load was significantly increased and both presented the linable correlation.

CONCLUSIONIn immunosuppression condition, polyomavirus DNA load correlated to the dose of immunosuppressant, which increased the risk of post-transplantational hemorrhagic cystitis.

Bone Marrow Transplantation ; adverse effects ; Cyclosporine ; adverse effects ; blood ; Cystitis ; prevention & control ; virology ; DNA, Viral ; genetics ; urine ; Dose-Response Relationship, Drug ; Humans ; Immunosuppressive Agents ; adverse effects ; blood ; Polyomavirus ; genetics ; isolation & purification ; Polyomavirus Infections ; prevention & control ; virology ; Transplantation, Homologous ; adverse effects ; Viral Load

IgA nephropathy is one of the most common forms of primary glomerulonephritis in adults, and the pathogenetic mechanisms seem to be diverse. Proinflammatory cytokines, Th1/Th2 cytokines, and chemokines would be involved in the pathogenetic pathways and would affect the functional and histologic consequences. To evaluate this hypothesis, we tried to quantify the magnitude of intrarenal gene expression of various cytokines(TNF-alpha, IL-1beta, IL- 6, IL-15, IFN-gamma, IL-2, IL-10) and chemokines(IL-8, RANTES) in 61 renal core biopsy specimens confirmed as IgA nephropathy by immunofluorescent microscopy. Semiquantitative reverse-transcriptase polymerase chain reactions(RT-PCR) using the internal competitors were done for the quantification of gene transcripts. And using the immunohistochemistry (IHC), we tried to determine the degree of expression and the location of various cytokines and chemokines in renal tissues in 29 patients among the above patients. The IFN-gamma/IL-10 ratio was higher in patients with renal dysfunction than that in patients with normal renal function(p=0.0483). Gene transcript levels of proinflammatory cytokines(TNF-alpha, IL-1beta) were high in patients with significant proteinuria. In patients with severe glomerular sclerosis, the ratio of IFN-gamma/IL-10 gene transcripts was high(p=0.0363). IL-10 gene transcript level was related to the severity of tubulointerstitial damage. The levels of gene expression of TNF-alpha(p=0.0026), IL-10(p=0.0092) and IFN-gamma(p=0.0188) were related to the degree of mesangial matrix expansion, and the extent of intrarenal arteriolar lesions correlated with the expression of the IL-8 genetranscript(r=0.3828, p=0.0033). The cellular infiltration in glomeruli was related with chemokine(IL-8) gene expression, but the relation was not significant statistically. The degree of IgA deposition in glomeruli was related with the expression of IL-6 and IL-15. The expression of intrarenal gene transcripts of various cytokines and chemokines were closely interrelated. Th1 or Th2 cytokine polarization was not present in IgA nephropathy. In IHC, TNF-alpha, IFN-gamma and IL-2 were immunostained dominantly in mesangial region, but not in tubulointerstitial region. In contrast, positive reactions for IL-10 were observed mainly in tubules. The significant reactions for IL-8 were noted in the periarteriolar and arteriolar areas. The results of RT- PCR and IHC showed positive relationships, but those were not significant statistically. This study suggests that proinflammatory, Th1/ Th2 cytokines and chemokines are involved in the specific processes of inflammation and immunologic injury, and their predominance and the level of expression could determine the pathogenetic processes and the severity of the clinical manifestations in IgA nephropathy.
Adult ; Biopsy ; Chemokines* ; Cytokines* ; Gene Expression ; Glomerulonephritis ; Glomerulonephritis, IGA* ; Humans ; Immunoglobulin A* ; Immunohistochemistry ; Inflammation ; Interleukin-10 ; Interleukin-15 ; Interleukin-2 ; Interleukin-6 ; Interleukin-8 ; Microscopy ; Polymerase Chain Reaction ; Proteinuria ; Sclerosis ; Tumor Necrosis Factor-alpha

This study was aimed to investigate the effects of different stimulatory factors on proliferation and function of cytokine induced killer (CIK) cells. Peripheral blood mononuclear cells (PBMNC) were separated by Ficoll-Hypacue gradient. According to supplement of different stimulatory factors (CD28 mAb, IL-15 and IL-21), the experiment was divided into five groups:control group (CIK), CB28+IL-15+IL-21 group, IL-15+IL-21 group, CD28+IL-15 group and CD28+IL-21 group. Effects of different stimulatory factors on the proliferation of CIK cells were assayed by an automated hematology analyzer. Changes of granzyme B,perforin and CD107a were detected by flow cytometry. IL-10, IL-12, INF-γ and TNF-α were quantified by ELISA. Cytotoxicities on lung cancer cell line A549, breast adenocarcinoma cell line MFC-7 and human melanoma cell line HME1 were examined by lactate dehydrogenase release method. The results showed that there were significant differences among different groups. The highest proliferation index on days 10 was observed in group CD28mAb, IL-15 and IL-21(255.3 ± 6.3), which was higher than control group, IL-21+IL-15 group and CD28 mAb+IL-21 group (166.6 ± 13.5, 199.4 ± 15.0 and 228.8 ± 16.6) (P < 0.05). The expression of perforin in CD28 mAb+IL-15 group was higher than the other groups. The expression of perforin,GranB and CD107a of costimulatory groups was higher than control group. The cytotoxicities of CD28 mAb+IL-15 group on A549, MFC-7 and HME1 cells (82.2%, 59.3% and 70.6%) were much higher than that of control group (60.9%, 49.6% and 48.4%) (P < 0.05). The highest IFN-γsecretion was found in CD28 mAb, IL-15 and IL-21 groups. It is concluded that there are significant difference of proliferative capacity, cytokine secretion and cytotoxicity after being activated by different stimulatory factors. Adding corresponding stimulatory factors into the culture system displays a great value for target cells culture.
Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cytokine-Induced Killer Cells ; cytology ; drug effects ; Humans ; Interferon-gamma ; metabolism ; Interleukin-10 ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-15 ; pharmacology ; Interleukins ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism