An Aersol-OT (AOT) included microemulsion containing fluorouracil was prepared by using appropriate proportion of oil, co-surfactant and water for increasing the drug transdermal delivery ability. According to the area of microemulsion basing on the pseudo-tertiary phase diagrams, the optimum formulation was screened initially. And the permeation flux of fluorouracil across excised mice skin was determined in vitro using Franz diffusion cell to optimize the formulation further. The effect of the kind of co-surfactant, the content of water, the content of mixed surfactant, the mass ratio of surfactant/cosurfactant (Km) and the drug load on skin permeation of fluorouracil were evaluated. The optimum formulation was composed of 0.5% (w/v) fluorouracil, 30% water, 20% mix-surfactant (AOT/Tween 85, Km = 2) and 49.5% oil (IPM). The cumulative amount permeated of fluorouracil in 12 hour was 1 355.5 microg x cm(-2), 19.1 folds and 7 folds more than 0.5% fluorouracil aqueous solution and 2.5% (w/w) fluorouracil cream, respectively. The permeation of this microemulsion accorded with first-order model. The water/AOT/Tween 85/IPM microemulsion system promoted the permeation of fluorouracil greatly, which may be a promising vehicle for the transdermal delivery of fluorouracil and other hydrophilic drug.
Administration, Cutaneous ; Animals ; Antimetabolites, Antineoplastic ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Delivery Systems ; methods ; Emulsions ; Fluorouracil ; administration & dosage ; pharmacokinetics ; Male ; Mice ; Myristates ; chemistry ; Oils ; chemistry ; Polysorbates ; chemistry ; Skin Absorption ; Succinates ; chemistry ; Surface-Active Agents ; chemistry ; Water ; chemistry

OBJECTIVETo understand the characteristics of pncA gene in multidrug-resistant Mycobacterium tuberculosis isolates and its correlation with drug resistance to pyrazinamide.

METHODSA total of 127 clinical isolates of multidrug-resistant mycobacterium tuberculosis were collected from Shenzhen from year 2007 to 2009. PZA susceptibility was determined by the BACTEC MGIT 960 PZA method. Pyrazinamidase (PZase) activity testing and pncA gene sequencing were performed in all the isolates. The type and frequency of mutations in pncA were determined. Correlation analysis among PZA susceptibility and PZase activity, pncA mutation was performed.

RESULTSAmong the 127 isolates, 62 isolates (48.8%) were found resistance to PZA. Among the 62 PZA resistant isolates, 45 isolates which had various pncA mutations were negative for PZase. Mutation rate was 77.4% (48/62) in total PZA resistance isolates. Different types of 48 resistant isolates were identified in the pncA gene, including base substitution (33 isolates), frame shift mutation (12 isolates) and codon mutation (3 isolates). No mutations except one isolate (N11D) existed in all PZA-susceptibility isolates which were positive for PZase. A total of 5 mutations which have not been described previously were found as follows: H57P, P62Q, G108R, D110Y and G162V. The correlation among the PZA susceptibility and the PZase activity (r = 0.895, P < 0.05), the pncA mutation (r = 0.779, P < 0.05) were significant in 127 multidrug-resistant isolates.

CONCLUSIONA high diversity of pncA gene mutation was found among PZA resistant strains of MTB. This study revealed five new mutations of the pncA gene that were not previously described, which scattered in the hot-spot regions located in the metal coordination site and active site of the enzyme. Mutations had a high correlation with the PZA resistance.

Antitubercular Agents ; pharmacology ; DNA, Bacterial ; genetics ; Humans ; Mutation ; Mycobacterium tuberculosis ; drug effects ; genetics ; isolation & purification ; Pyrazinamide ; pharmacology ; Tuberculosis, Multidrug-Resistant ; genetics ; microbiology

Currently, there are limited strategies for convenient and rapid wound repair in clinical practice. In recent years, in-situ cell electrospinning (IS-CE) technology, developed from in-situ electrospinning (IS-E) technology, has emerged. IS-CE technology involves encapsulating living cells within micro-nanofibers to construct living fibrous tissue scaffolds in situ, making some progress in wound repair applications. However, this technology still faces limitations such as low cell survival rate and poor fiber stability. This article provides a comprehensive review on the current status of both IS-E and IS-CE technologies, as well as the application of IS-CE technology in wound repair. In addition, the advantages, limitations, and improvement methods of IS-CE technology applied in wound treatment are emphatically discussed, aiming to provide insights for its application in tissue engineering and wound repair.

OBJECTIVETo investigate the clinicopathological features and the immunohistochemical phenotype of perianal Paget's disease (PPD) associated with internal anorectal adenocarcinoma, with emphasis on the histogenesis of Paget's cells.

METHODSThe clinical and pathologic features of three cases of PPD with rectal adenocarcinoma were investigated. Periodic-acid-Schiff (PAS), alcian-blue and mucicarmine staining with and without diastase digestion were performed. The immunohistochemical study was performed on selected sections by a panel of antibodies including carcinoembryonic antigen (CEA), CK7, CK8, CK10/13, CK20 and gross cystic disease fluid protein 15 (GCDFP15).

RESULTSAll three cases occurred in middle to old age male patients complaining of anal bleeding. Digital physical examination revealed ulcerated or cauliflower-like masses in the anus just distal to the dentate line. Perianal skin erythematous patches were found in two cases, and small discrete granules in one case. Histologically, the anorectal neoplasm was either a moderately or poorly differentiated adenocarcinoma. Two types of Paget's cells were noted, namely the classical type characterized by a polygonal shape with vesicular nuclei and abundant pale cytoplasm, and the signet ring type characterized by eccentrically displaced nucleus. Both the rectal adenocarcinoma cells and Paget's cells showed strong positivity for PAS, AB and mucicarmine, which were resistant to the diastase digestion. Immunohistochemically, they were both positive for CEA, CK7, CK8 and CK20, but negative for CK10/13 and GCDFP15.

CONCLUSIONSThe CK20(+)-GCDFP15(-) type Paget's cells in PPD were derived from the direct intraepithelial Pagetoid spread of anorectal adenocarcinomas. PPD was more frequently associated with internal carcinomas than any other type of extramammary Paget's disease. It is recommended that clinicians should carefully examine the anus or rectum in the presence of PPD to ascertain if it is associated with an internal carcinoma.

Aged ; Aged, 80 and over ; Apolipoproteins ; Apolipoproteins D ; Carrier Proteins ; analysis ; Diagnosis, Differential ; Glycoproteins ; analysis ; Humans ; Immunohistochemistry ; Intermediate Filament Proteins ; analysis ; Keratin-20 ; Male ; Membrane Transport Proteins ; Middle Aged ; Paget Disease, Extramammary ; chemistry ; diagnosis ; pathology ; Rectal Neoplasms ; chemistry ; diagnosis ; pathology

OBJECTIVETo research on the main pattern of hepatic cells death during hepatic ischemia/ reperfusion (I/R) injury in cirrhotic rat.

METHODSCirrhotic rat model was established by carbon tetrachloride replication. These rats were randomly divided into sham operation group and I/R group. In the I/R group, 70% i/R injury model was established and then the liver samples were taken 0, 1, 6, 24, and 48 hours after reperfusion. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, Na+ - K+ ATPase, and Ca2+ ATPase were compared. the percentage of apoptotic/oncotic hepatic cells was measured with flow cytometry, and the changes in hepatic cellular structures were observed under transmission electron microscope.

RESULTSCompared with the sham operation group, the levels of serum AST and ALT significantly increased in the I/R group (P < 0.05), reaching their peak levels at the 6th hour. The activities of Na+ - K+ ATPase and Ca2+ ATPase dramatically decreased one hour after reperfusion and then gradually recovered (P < 0.05). Hepatic cells mainly suffered oncosis at the early stage after reperfusion (within 6 hours); at the late stage (around 24 hours after reperfusion), apoptosis became the main death pattern.

CONCLUSIONOncosis is the main pattern of hepatic cells death during I/R injury in cirrhotic rat, and the severity of hepatic injury correlates with the oncosis.

Alanine Transaminase ; blood ; Animals ; Apoptosis ; Aspartate Aminotransferases ; blood ; Disease Models, Animal ; Humans ; Liver Cirrhosis ; blood ; physiopathology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Reperfusion Injury ; blood ; physiopathology

OBJECTIVETo detect the expression of Per2 in non-small cell lung cancer (NSCLC), and analyze its clinical significance.

METHODSThe expression of Per2 was determined in 60 NSCLC and 20 normal lung tissues by immunohistochemical assay, and the relationship between Per2 expression and clinicopathological features was analyzed.

RESULTSThe positive expression rates of Per2 in NSCLC and normal lung tissues were 71.7% and 95.0%, respectively (P < 0.05). The expression of Per2 in NSCLC was correlated with pathological differentiation and TNM stage (P < 0.05).

CONCLUSIONThe expression of Per2 in NSCLC is decreased. The negative expression of Per2 may contribute to the development and invasion in NSCLC.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; surgery ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms ; metabolism ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Period Circadian Proteins ; metabolism ; Smoking

OBJECTIVE: To study the changes of electrocardiograms (ECG) and myocardial ultrastructure in heroin dependence in rats, in order to reveal the mechanisms of the myocardial injury by heroin. METHODS: Establish heroin addict model in SD mice, investigate the changes in electrocardiograms, HE staining and myocardial ultrastructure. RESULTS: The electrocardiograms of the addict group had prominently changes, main expressions: heart rate decreased, P wave and T wave amplitude reduced and duration increased, S-T reduced and duration increased, QT interval prolongation, these changes indicated that myocardium had been injured, myocardial ischemia, ventricle function declined. These difference was significant (P<0.05) between before inject heroin and after inject heroin. Transformations in the ultrastructure: nuclear concentrate, reduce, nuclear membrane shrink, chromatin agglutinate, mitochondria cristal had disorder formation, disappeared or hollowed, these indicated that heroin could cause pathological changes in myocardial ultrastructure. CONCLUSION Above-mentioned changes indicated that heroin can injure myocardium, and the changes of myocardial ultrastructure suggested that myocardial apoptosis may be one of the mechanisms of the myocardial injury by heroin.
Animals ; Disease Models, Animal ; Electrocardiography ; Heart Rate ; Heroin Dependence/physiopathology* ; Myocardial Ischemia/physiopathology* ; Myocardium/ultrastructure* ; Rats ; Rats, Sprague-Dawley

The heroin abuses can seriously damage human body system, among them the damage of cardiovascular system is various. In this paper those damages involved heart rate, blood pressure, electrocardiogram, heart function, blood circulation, the changes of some material inside, and complications of cardiovascular system are reviewed.
Arrhythmias, Cardiac/etiology* ; Blood Circulation ; Blood Pressure ; Cardiovascular Diseases/physiopathology* ; Death, Sudden/etiology* ; Electrocardiography ; Heart Rate ; Heroin Dependence/physiopathology* ; Humans ; Myocardial Ischemia/etiology*

OBJECTIVETo investigate the feasibility and efficacy of treating atrial fibrillation (AF) with circumferential pulmonary vein (PV) linear ablation guided by 3 dimensional mapping system and single circular mapping catheter.

METHODSFrom April 2004 to January 2005, PV isolation with circumferential PV linear ablation guided by CARTO system (in 76 patients) or EnSite-NavX system (in 24 patients) was performed in 100 consecutive patients with significantly symptomatic, drug refractory AF. The procedural end-point was complete electrical isolation of bilateral PV.

RESULTSUp to 200 linear circles were produced around each ipsilateral PVs in all 100 cases, and 95.0% (190/200) of PV isolation rate was achieved with a mean procedure time of 150-365 (240 +/- 65) min and a mean fluoroscopy time of 23-61 (37 +/- 12) min, respectively. Eight cases with recurrent AF (8.0%) underwent second session. Cumulative atrial tachyarrhythmias-free rate was 85.0% (85/100) during a mean follow-up of 5.5-12 (10.2 +/- 5.7) months. Atrial tachyarrhythmias-free rate was 66.0% (66/100), 82.0% (82/100), 87.0% (87/100), 85.0% (85/100), 85.0% (85/100), and 88.6% (70/79) during the follow up at 1 month, 2 months, 3 months, 4 months, 5 months and 6 months, respectively. There were 2 complications (1 tamponade and 1 PV stenosis), which were rehabilitated after conservative treatment.

CONCLUSIONPV isolation with circumferential PV linear ablation guided by 3 dimensional mapping system is safe and effective for treating AF.

Adolescent ; Adult ; Aged ; Atrial Fibrillation ; surgery ; Catheter Ablation ; methods ; Feasibility Studies ; Female ; Humans ; Imaging, Three-Dimensional ; Male ; Middle Aged ; Pulmonary Veins ; surgery ; Treatment Outcome ; Young Adult

OBJECTIVETo study the genetic diversity and genetic relationship in different species and populations of Curcuma by ISSR-PCR marker technique.

METHODEighty populations and 37 samples of Curcuma including C. phaeocaulis, C. kwangsiensis and C. wenyujin were studied by ISSR-PCR markers. The systematic diagram of Similar coefficient and genetic distance were set up by POPGEN32 software and clustered by UPGMA method.

RESULTA total of 65 loci were scored by 5 primers, among which 34 were polymorphic loci. The percentage of polymorphic loci was 52.3%. Genetic similarity coefficient changed from 0.6864 to 0.9997. Nei's gene diversity index (H), and Shannon information index (I) were 0.1521 and 0.2338. The inner genetic diversity of Curcuma species was lower than the outer.

CONCLUSIONThe genetic variation of different populations Curcuma was big. The inherited differentiation of inner populations was low. Different populations of Curcuma were related to character of species and geological distribution.

Genetic Variation ; genetics ; Polymerase Chain Reaction ; methods ; Polymorphism, Genetic ; genetics ; Species Specificity ; Zingiberaceae ; classification ; genetics