Multi-target drugs attract increasing attentions for the therapy of complicated neurodegenerative diseases. In this study, a computer-assisted strategy was applied to search for multi-target compounds by the pharmacophore matching. This strategy has been successfully used to design dual-target inhibitor models against both the acetylcholinesterase (AChE) and poly (ADP-ribose) polymerase-1 (PARP-1). Based on two pharmacophore models matching and physicochemical properties filtering, one hit was identified which could inhibit AChE with IC50 value of (0.337 +/- 0.052) micromol x L(-1) and PARP-1 by 24.6% at 1 micromol x L(-1).
Acetylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; pharmacology ; Computer-Aided Design ; Drug Discovery ; methods ; Poly(ADP-ribose) Polymerase Inhibitors

10.3969/j.issn.2095-4344.2013.25.023

An investigation on the chemical constituents of the 90% EtOH extract of Perovskia atriplicifolia led to the isolation of fifteen compounds from the EtOAc fraction. Based on the detailed spectral analysis (MS, 1D and 2D NMR), as well as comparison with the literatures, the structures of compounds 1-15 were determined as cirsimaritin (1), salvigenin (2), syringaldehyde (3), vinyl caffeate (4), 2α, 3α-dihydroxyolean-12-en-28-oicacid (5), 2α, 3α-dihydroxyurs-12-en-28-oicacid (6), niga-ichigoside F1 (2α, 3β, 19α, 23- tetrahydroxyurs - 12-en-28-oicacid- O-β-D- glucopyranoside, 7), sericoside (8), 4-epi-niga-ichigoside F1 (2α, 3β, 19α, 24-tetrahydroxyurs-12-en-28-oicacid O-β-D-glucopyranoside, 9), 2α, 3β, 24-trihydroxyolean-12-en-28-oicacid O-β-D-glucopyranosyl-(1 --> 2) - β-D-glucopyranoside (10), pruvuloside A (11), asteryunnanoside A [2α, 3β, 23-trihydroxyolean-12-en-28-oicacid O-β-D-glucopyranosyl-(1 --> 2)-β- D- glucopyranoside,12], rosmarinic acid methyl ester (13), β-sitosterol (14), and daucosterol (15), respectively. Compounds 1-13 were isolated from the Perovskia genus for the first time. All the compounds were obtained from P. atriplicifolia for the first time.
Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Lamiaceae ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization

BACKGROUNDSmall acoustic neuromas seldom result in typical vestibular symptoms, despite the tumor arising from the vestibular nerve. In this study, we have shown that abnormal gait in eleven patients with small acoustic neuroma could be detected in gait analysis by the use of tactile sensor. Patients displayed no oculomotor abnormality and had tumors less than 10 mm from the porus acoustics.

METHODSGait related parameters including the coefficients of variations (CV) of stance, swing, double support, area ratio of trajectories of center of force (TCOF), in addition to the foot pressure difference between both feet, were used for assessment of gait.

RESULTSThe CV of swing and the area ratio of TCOF were greater in patients than those in the control group (P < 0.05). The values of these two parameters became greater under an eyes closed condition compared to eyes open (P < 0.05) in the patient group.

CONCLUSIONThese results indicate that gait analysis may be helpful to assess vestibulospinal function of patients with small acoustic neuroma, the slight vestibular deficits of which can not be detected by visual observation.

Adult ; Aged ; Female ; Gait Disorders, Neurologic ; diagnosis ; etiology ; Humans ; Male ; Middle Aged ; Neuroma, Acoustic ; physiopathology

OBJECTIVE: By detecting the myelin structure in acoustic tumor tissues, the cell origin and state of acoustic tumor tissues were investigated. METHOD: Immunofluorescence labeling, immunoblot analysis and electron microscopic study were performed to identify myelin structure and myelin protein in acoustic tumor tissues. RESULT: In this work, we found some early stage of myelin forming in acoustic tumor tissues, but there were no axon nor compact myelin formed and the myelin basic protein whose expression indicates the beginning of myelination was negative detected. We also found that the cell of acoustic tumor express p75,a marker for immature Schwann cells and mature non-myelin-forming Schwann cells. CONCLUSION The date shown in this experiment indicates that the cell of acoustic tumor is in a remyelinating state.
Humans ; Microscopy, Electron ; Myelin Sheath ; pathology ; ultrastructure ; Neuroma, Acoustic ; pathology ; Schwann Cells ; pathology

OBJECTIVETo evaluate technique aspects of video-assisted thoracoscopic lobectomy for benign diseases.

METHODSRetrospective review of 24 patients with benign pulmonary disease underwent thoracoscopic lobectomy from September 2006 to September 2008. One patient had bilateral bronchiectasis received concurrent bilateral lobectomy. The patients included 11 males and 13 females with mean age of 49.0 years. Fifteen cases were diagnosed as benign diseases preoperatively consisted 10 bronchiectasis as the primary indication. The other 9 cases were pulmonary nodules pathologic diagnosed intra-operatively. Inflammation changes including dense plural adhesions, pulmonary artery adhesions and calcified lymph nodes were managed endoscopically.

RESULTSAll 25 thoracoscopic procedures were completely with no conversion to thoracotomy. The mean operation time was (163 +/- 52) min, blood loss was (163 +/- 130) ml. There was no hospital death or major morbidity. Postoperative drainage was (5.8 +/- 2.8) d. No long-term complications were noticed during a mean follow-up of 7.3 months.

CONCLUSIONChronic inflammation induced adhesions is the key limiting factor for thoracoscopic lobectomy for benign diseases.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Lung Diseases ; surgery ; Male ; Middle Aged ; Pneumonectomy ; methods ; Retrospective Studies ; Thoracoscopy ; Young Adult

BACKGROUNDThe feasibility of completing a lobectomy by completely video-assisted thoracoscopic surgery (cVATS) in the management of bronchiectasis is unclear. By retrospectively comparing the outcomes from the lobectomies that used thoracotomy vs. cVATS, we determined the appropriateness of the minimally invasive cVATS approach in the management of bronchiectasis.

METHODSBetween June 2001 and October 2010, 60 patients with bronchiectasis underwent surgery, of which 56 lobectomies were performed. All lobectomies were carried out by either thoracotomy or cVATS approach. Pulmonary vessels and bronchi were manipulated by ligation or stapler in the thoracotomy group, while they were dissected by endo-cutters in the cVATS group.

RESULTSThere were 21 patients in the thoracotomy group and 35 patients in the cVATS group. Two cVATS patients (5.7%) converted. The difference in operation time, chest tube duration, lengths of hospitalization, and morbidity were not significantly different between the two groups (P > 0.05). The blood loss was less in the cVATS group (P = 0.015). A total of 52.4% and 62.9% of patients were postoperatively asymptomatic in the thoracotomy and cVATS groups respectively, and symptomatic improvement was obtained in 38.1% patients by thoracotomy vs. 31.4% patients by cVATS.

CONCLUSIONcVATS lobectomy is safe and effective for the management of bronchiectasis, especially for the patients with localized lesions.

Adult ; Bronchiectasis ; surgery ; Female ; Humans ; Male ; Middle Aged ; Thoracic Surgery, Video-Assisted ; methods

BACKGROUNDHigh peritoneal transport status was previously thought to be a poor prognostic factor in peritoneal dialysis (PD) patients. However, its effect on diabetic nephropathy PD patients is unclear in consideration of the adverse impact of diabetes itself. The purpose of this study was to investigate the influence of peritoneal transport characteristics on nutritional status and clinical outcome in diabetic nephropathy patients on PD.

METHODSOne hundred and two diabetic nephropathy patients on PD were enrolled in this observational cohort study. According to the initial peritoneal equilibration test result, patients were divided into two groups: Higher transport group (HT, including high and high average transport) and lower transport group (LT, including low and low-average transport). Demographic characteristics, biochemical data, dialysis adequacy, and nutritional status were evaluated. Clinical outcomes were compared. Risk factors for death-censored technique failure and mortality were analyzed.

RESULTSCompared with LT group (n = 37), serum albumin was significantly lower and the incidence of malnutrition by subjective global assessment was significantly higher in HT group (n = 65) (P < 0.05). Kaplan-Meier analyses showed that death-censored technique failure and mortality were significantly increased in HT group compared with that in LT group. On multivariate Cox analyses, higher peritoneal transport status and lower residual renal function (RRF) were independent predictors of death-censored technique failure when adjusted for serum albumin and total weekly urea clearance (Kt/V). Independent predictors of mortality were advanced age, anemia, hypoalbuminemia, and lower RRF, but not higher peritoneal transport status.

CONCLUSIONSHigher peritoneal transport status has an adverse influence on nutrition for diabetic nephropathy patients on PD. Higher peritoneal transport status is a significant independent risk factor for death-censored technique failure, but not for mortality in diabetic nephropathy patients on PD.

Aged ; Aged, 80 and over ; Biological Transport ; Cohort Studies ; Diabetic Nephropathies ; metabolism ; therapy ; Female ; Humans ; Kidney ; metabolism ; pathology ; Male ; Middle Aged ; Nutritional Status ; Peritoneal Dialysis

OBJECTIVETo study the inhibitory effect of mutant K-ras gene depletion by small interfering RNA on the growth of lung cancer cell line-H441 cells in vitro and in vivo.

METHODSOne pair of 63 bp reverse repeated sequence targeting mutant K-ras(V12) mRNA spaced by 9 bp nucleotide were synthesized and inserted into plasmid pSilencer3.1 eukaryotic expression vector. After transient and stable transfection into H441 cells, the mutant K-ras mRNA and protein level were measured by RT-PCR and Western blotting, and the H441 cells proliferation was measured by MTT method, and the apoptosis rate was detected by flow-cytometry. H441 cells treated with pSilencer3.1-K-ras(V12) were transplanted subcutaneously in nude mice and their tumorigenesis ability was observed.

RESULTSThe recombinant plasmid pSilencer3.1-K-ras(V12) was successfully constructed by sequencing. The introduction of pSilencer3.1-K-ras(V12) was showed to efficiently and specifically inhibit the expression of K-ras(V12) gene according to the results of RT-PCR and Western blotting (P < 0.01, as compared with controls). The inhibitory effect on cell proliferation was confirmed by MTT test (P < 0.05, as compared with controls). Apoptosis rate of H441 cells treated with pSilencer3.1-K-ras(V12) was significantly higher than that of the control cells (P < 0.01). The test in vivo showed that downregulation of K-ras(V12) expression in H441 cells apparently affected their ability to form tumors in nude mice.

CONCLUSIONSsiRNA targeting mutant K-ras mRNA can specifically suppress the expression of mutant K-ras gene in H441 cells, and therefore has a substantially inhibitory effect on cell proliferation in vitro and in vivo, it provides a new method and material to the gene therapy of lung cancer.

Adenocarcinoma ; genetics ; pathology ; therapy ; Animals ; Apoptosis ; Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; Gene Silencing ; Genetic Therapy ; Genetic Vectors ; Humans ; Lung Neoplasms ; genetics ; pathology ; therapy ; Mice ; Mice, Nude ; Plasmids ; genetics ; Point Mutation ; RNA, Messenger ; genetics ; metabolism ; RNA, Small Interfering ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection ; Xenograft Model Antitumor Assays ; ras Proteins ; genetics ; metabolism

OBJECTIVEThe prevalence of obesity and of type 2 diabetes mellitus in children have increased in the Chinese population over the past two decades, and thus diabetes prevention has become a major concern of public health agencies. Identification of individuals at risk for diabetes is an essential first step in designing and implementing intervention programs. Insulin resistance is the hallmark of the pathophysiology of type 2 diabetes mellitus. Subjects with hyperinsulinemia and impaired glucose tolerance are well accepted as being at high risk for diabetes. Acanthosis nigricans (AN) has been proposed as a reliable marker of hyperinsulinemia, but its utility for predicting hyperinsulinemia has not been systematically evaluated in obese children. In order to further explore the relationship between obese childhood with benign acanthosis nigricans and insulin resistance and type 2 diabetes mellitus, we examined 19 obese children with benign acanthosis nigricans.

METHODSNineteen of seventy six obese children (25%) with BMI over 25 enrolled in the Children' Hospital of Zhejiang University School of Medicine fromJune 1st to September 1st in 2003 were studied. Skin biopsies were performed in these 19 obese children with acanthosis nigricans for final diagnosis. Levels of glucose, insulin, and glucose/insulin ratio were measured on fasting blood specimens and anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index were examined. Oral glucose tolerance tests were also performed in these 19 children with benign acanthosis nigricans.

RESULTSAnthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index as well as fasting insulin level in acanthosis nigricans group were significantly higher than that of healthy controls (P < 0.01). Fasting glucose to insulin ratio (FGIR) of these 19 obese children with benign acanthosis nigricans was 4.27 +/- 0.53, indicating apparent insulin resistance. One of them was diagnosed as type 2 diabetes mellitus and ten of them showed impaired oral glucose tolerance.

CONCLUSIONChildhood benign acanthosis nigricans is tightly associated with obesity, hyperinsulinemia, insuline resistance and type 2 diabetes mellitus, and may be used as a reliable index of insulin resistance.

Acanthosis Nigricans ; complications ; physiopathology ; Child ; Diabetes Mellitus, Type 2 ; complications ; physiopathology ; Humans ; Hyperinsulinism ; complications ; physiopathology ; Insulin Resistance ; Obesity ; complications ; physiopathology