Endoscopes ; Humans ; Nasal Cavity ; surgery ; Nasal Septum ; surgery ; Reconstructive Surgical Procedures ; Rhinoplasty ; Surgical Flaps

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; radiotherapy ; Esophageal Neoplasms ; metabolism ; pathology ; radiotherapy ; Female ; Follow-Up Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Inhibitor of Apoptosis Proteins ; Lymphatic Metastasis ; Male ; Microtubule-Associated Proteins ; metabolism ; Middle Aged ; Neoplasm Staging ; Paraffin Embedding ; Survival Rate ; Vascular Endothelial Growth Factor A ; metabolism

Objective To study changes of phosphorylated cyclic adenosine monophosphate(c-AMP) response element binding protein in hippocampus(CA1) of neonatal rats after cerebral hypoxic-ischemia(HI)and effects of gangliosides (GM1)on the p-CREB.Methods An animal model of neonatal hypoxic-ischemia brain damage was established. Changes of p-CREB in hippocampal CA1 was detected with immunohistochemical methods.Results The p-CREB levels in the CA1 of HI and GM1 groups increased transiently and then decreased quickly, but there was no significant difference between HI and GM1 group.Conclusion The p-CREB levels in the CA1 of HI group increase transiently and then decrease quickly after HI ;GM1 has little effect on p-CREB in the CA1 after HI.

OBJECTIVETo evaluate the effect of Tongnao Huoluo Acupuncture (THA) therapy on acute cerebral infarction (ACI).

METHODSAdopting multi-centered, randomized and controlled method, 397 ACI patients from 10 hospitals subjected to the study were treated according to the initiating time (IT) of disease during hospitalization: the 138 patients of stage-1 with IT < or =6 h, were randomly assigned to three groups, treated respectively with THA (Group A), thrombolysis with urokinase (Group B) and Batroxobin (Group C); the 140 patients of stage-2 with IT within 6-48 h, and 119 patients of stage-3 with IT within 48 h-14 d were randomly assigned to three groups, treated respectively with THA (Group D) body acupuncture (Group E), and conventional treatment (Group F). Therapeutic effect was evaluated by NIHSS scores estimated at the day 1, 3, 7, 14, 28 and 90 of treatment, and the Barthel Index (BI) measured at day 14, 28 and 90.

RESULTSEffect in Group A was insignificantly different from that in Group B (P > 0.05), but was different from that in Group C significantly (P < 0.01). At day 90, the percentage of patients with high BI (HBI%, patients with BI >95%) was insignificantly different in Group A vs. B (P > 0.05), but was significantly different in Group A vs. C (P < 0.01). Comparisons between Group D, E and F showed that the therapeutic effect in Group D was equivalent to that in Group E (P < 0.05), but better than that in Group F (P < 0.01), and HBI% in Group D was superior than that in the other two groups (P < 0.01).

CONCLUSIONSTHA therapy shows favorable effects in reducing the crippling rate and improving the living capacity of ACI patients.

Acupuncture Therapy ; methods ; Adult ; Aged ; Cerebral Infarction ; therapy ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome

The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium chanmel blocker nimodipine (NLMO) and their combination on cadmium (Cd) poisoning of mice were studied.A series of biochemical parameters including urinary enzyme activities, blood and urine Cd levels, metallothionein (MT) contents in liver and kidney, hepatic ultrastructure and Ca2+ -Mg2- AT Pase activitv in erythrocyte membrane were determined. Animal models for Cd poisoning were established by peritoneal injection of 1/5 LD50 CdCl2. The experimental groups were protected by administration of CPZ, NIMO and CPZ and NIMO in combination I h before the injection of CdCl2. Five days later, samples were collected for analysis. The data showed that CPZ could protect kidney tissue against Cd-induced damage, as the urinary y-glutamyl-traspeptidase (γ-GT) and N-acetyl-β-D-glucosaminidase (NAG) activities were reduced significantly. There was neither evidence of the protective effect of NIMO on kidney tissue nor an indication of a synergistic effecf of CPZ and NIMO.Both CPZ and NIMO showed a considerable protective effect against the decrease in Ca2+ -Mg2+ AT-Pase activity, and a synergistic action was observed. Cd content in blood was reduced significantly by CPZ or the combination of CPZ and NIMO, but elevated by NIMO. Both CPZ and NIMO considerably increased MT contents in livers and kidneys and ameliorated damaged to the hepatic ultrastructures caused by Cd. The results indicated that these inhibitors could protect mice against the toxic effects of Cd in liver and kidney tissues, while CPZ was more efficient than NIMO. The combination of CPZ and NIMO excrted a synergistic action. The protective action of these two drugs might be relevent to the function of MT.

To clarify the important functional residues in the active site of N-myristoyltransferase (NMT), a novel antifungal drug target, and to guide the design of specific inhibitors, multiple sequence alignments were performed on the NMT family and thus evolutionary trace was constructed. The important functional residues in myristoyl CoA binding site, catalytic center and inhibitor binding site of NMT family were identified by ET analysis. The trace residues were mapped onto the active site of CaNMT. Trpl26, Asn175 and Thr211 are highly conserved trace residues and do not interact with current NMT inhibitors, which are potential novel drug binding sites for the novel inhibitor design. Pro338, Leu350, Ile352 and Ala353 are class-specific trace residues, which are important for the optimization of current NMT inhibitors. The trace residues identified by ET analysis are of great importance to study the structure-function relationship and also to guide the design of specific inhibitors.
Acyl Coenzyme A ; metabolism ; Acyltransferases ; chemistry ; genetics ; metabolism ; Amino Acid Sequence ; Animals ; Binding Sites ; Conserved Sequence ; Enzyme Inhibitors ; chemistry ; pharmacology ; Evolution, Molecular ; Humans ; Imidazoles ; chemistry ; pharmacology ; Models, Molecular ; Molecular Sequence Data ; Oligopeptides ; chemistry ; pharmacology ; Phylogeny ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid

Ketamine (KTM), a N-methyl-D-aspartate (NMDA) receptor antagonist, was found to has an anti-inflammatory effect, but some patients suffered from exacerbated pro-inflammatory reactions after anesthesia with KTM. The present study was aimed to examine the underlying mechanism of pro-inflammatory effects of KTM. In this study, RAW264.7 cells were exposed to KTM and NMDA alone or combined for 30 min before lipopolysaccharide (LPS) stimulation. The expression levels of IL-6 and TNF-α were detected by RT-PCR and ELISA, and those of NMDA receptors by RT-PCR in RAW264.7 cells. Additionally, the TLR4 expression was determined by RT-PCR and flow cytometry, respectively. The results showed that in RAW264.7 cells, KTM alone promoted the TLR4 expression, but did not increase the expression of IL-6 or TNF-α. In the presence of LPS, KTM caused a significantly higher expression of IL-6 and TNF-α than LPS alone. NMDA could neither alter the IL-6 and TNF-α mRNA expression, nor reverse the enhanced expression of IL-6 and TNF-α mRNA by KTM in LPS-challenged cells. After TLR4-siRNA transfection, RAW264.7 cells pretreated with KTM no longer promoted the IL-6 and TNF-α expression in the presence of LPS. In conclusion, KTM accelerated LPS-induced inflammation in RAW264.7 cells by promoting TLR4 expression, independent of NMDA receptor.
Anesthetics, Dissociative ; pharmacology ; Animals ; Cell Survival ; drug effects ; Gene Expression Regulation ; Inflammation Mediators ; pharmacology ; Interleukin-6 ; genetics ; Ketamine ; pharmacology ; Lipopolysaccharides ; pharmacology ; Macrophages ; drug effects ; metabolism ; Male ; Mice ; N-Methylaspartate ; pharmacology ; RAW 264.7 Cells ; Signal Transduction ; drug effects ; Toll-Like Receptor 4 ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; genetics

AIMA series of triazole antifungal agents were synthesized to search for novel triazole antifungal agents with more potent activity, less toxicity and broader spectrum.

METHODSTwenty-one 1-(1H-1, 2, 4-triazolyl)-2-(2, 4-diflurophenyl)-3-(4-substituted-1-piperazinyl)-2-propanols were synthesized, on the basis of the three dimensional structure of P450 cytochrome 14alpha-sterol demethylase (CYP51) and their antifungal activities were also evaluated.

RESULTSResults of preliminary biological tests showed that most of title compounds exhibited activity against the eight common pathogenic fungi to some extent and the activities against deep fungi were higher than that against shallow fungi. In general, phenyl and pyridinyl analogues showed higher antifungal activity than that of the phenylacyl analogues.

CONCLUSIONSeveral title compounds showed higher antifungal activities than fluconazole and terbinafine. Compound VIII-1, 4, 5 and IX-3 showed the best antifungal activity with broad antifungal spectrum and were chosen for further study.

Antifungal Agents ; chemical synthesis ; chemistry ; pharmacology ; Aspergillus fumigatus ; drug effects ; Candida albicans ; drug effects ; Cryptococcus neoformans ; drug effects ; Fluconazole ; pharmacology ; Microbial Sensitivity Tests ; Molecular Structure ; Naphthalenes ; pharmacology ; Structure-Activity Relationship ; Triazoles ; chemical synthesis ; chemistry ; pharmacology

OBJECTIVETo explore the effect and the mechanism of yifei jianpi recipe (YFJPR) on patients with chronic obstructive pulmonary disease (COPD).

METHODSForty patients with COPD in stable phase were randomly divided into two groups, the treated group and the control group. Indexes including the total and differential count of inflammatory cell in sputum, levels of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha), as well as the percentage of forced expiratory volume in one second in its predicted value (FEV1%) and ratio of FEV1/forced vital capacity (FVC) in patients were measured before and after treatment, and compared with those in 20 healthy subjects.

RESULTSAll the indexes measured in patients before and after treatment were significantly different from those in healthy subjects (P < 0.01). Differential count of polymorphonuclear neutrophil (PMN) and levels of IL-8 and TNF-alpha in sputum in the treated group significantly decreased after treatment (P < 0.01), while the non-PMN differential count and levels of FEV1% and FEV1/FVC significantly increased (P < 0.01). But in the control group, changes only showed in increasing of FEV1% and FEV1/FVC (P < 0.05 or P < 0.01). And the effects in the treated group were better than those in the control group (P < 0.01).

CONCLUSIONYFJPR can play a therapeutic role on patients with COPD by way of reducing the airway inflammatory reaction.

Adult ; Aged ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interleukin-8 ; metabolism ; Leukocyte Count ; Male ; Middle Aged ; Neutrophils ; pathology ; Phytotherapy ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; metabolism ; pathology ; Respiratory Function Tests ; Sputum ; cytology ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism