As a novel transdermal drug delivery technology of minimally invasive, safe and efficient, microneedles have received increasing attention. The microchannels formation by microneedles onto the skin is a prerequisite and key for microneedles to deliver drugs. However, there is still a lack of systematic evaluation in skin microchannels. This review summarized influencing factors and evaluation methods in microchannels formation and healing by microneedles, including geometric parameters, materials for preparation, drugs, penetration parameters, differences among the skin of subjects, and presence or absence of occlusion. This review provides reference for other scholars to further study the effectiveness and security of microneedle applications.

ABSTRAC: The therapeutic course of an aciclovir-induced acute renal dysfunctional patients was summarized. This had been relieved through a 15-day treatment with Western medicine but with a two-week protracted low fever that was cured by the authors using Chinese medicinal herbs for supplementing qi to support essence, nourishing yin to depress fire, clearing heat, and detoxicating. For the sake of providing a reference to clinical medication, the materials used for the disease were recorded and analyzed to explore the clinical characteristics of Chinese medicine treatment and prevention of anaphylaxis responses, such as the protracted low fever after acute renal dysfunction induced by overinfused aciclovir.
Acyclovir ; administration & dosage ; adverse effects ; Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; Drug-Related Side Effects and Adverse Reactions ; therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Infusion Pumps ; Medicine, Chinese Traditional ; methods ; Phytotherapy ; Remission Induction

The present study investigated the influence of the methyl jasmonate and salicylic acid elicitors on the formation of phenylethanoid glycosides (PeG) in the suspension cultures of Cistanche deserticola. The results showed that methyl jasmonate and salicylic acid enhanced greatly the accumulation of PeG and echinacoside (Echin), but their optimum elicitation dosage and addition time were different. The yields of PeG and Echin were significantly increased in the presence of 5 micromol/L methyl jasmonate on day 14 (up to 2.59-fold and 3.82-fold, respectively), whereas treated with 50 micromol/L salicylic acid on day 28, the maximum content of them were, respectively, 2.71 and 3.16-fold higher than the untreated cell cultures.
Acetates ; pharmacology ; Cell Culture Techniques ; Cistanche ; drug effects ; metabolism ; Culture Media ; Cyclopentanes ; pharmacology ; Glycosides ; biosynthesis ; Oxylipins ; pharmacology ; Phenylethyl Alcohol ; metabolism ; Salicylic Acid ; pharmacology

OBJECTIVETo set up a method for the drainage of lymph fluid and explore the change of active materials in lymph fluid and serum after rat ischemia-reperfusion injury.

METHODSThe method of the drainage of lymph fluid was well established. Sixteen healthy male rats of SPF grade were selected and randomly divided into 2 groups: intestinal ischemia-reperfusion + drainage group (I/R + drainage group) and drainage group. All the rats were subjected to superior mesenteric artery occlusion for 60 minutes, followed by 120 minutes of reperfusion. We compared the change of high mobility group box-1 (HMGB1) protein, endotoxin tumor necrosis factor alpha (TNF-alpha), interleukin (IL) -1 beta, IL-6, and soluble vascular cell adhesion molecular-1 (sICAM-1) by draining lymph fluid and collecting serum in 2 groups.

RESULTSThe drainage of lymph fluid was successfully performed. The HMGB1, endotoxin, and cytokines in serum and lymph fluid were significantly higher in ischemia-reperfusion group than in drainage group (P < 0. 05).

CONCLUSIONSThe method for drainage of lymph fluid is simple and feasible. Endotoxin, HMGB1, and some cytokines in serum and lymph fluid may mediate the ischemia-reperfusion injury.

Animals ; Disease Models, Animal ; Drainage ; methods ; Endotoxins ; metabolism ; HMGB1 Protein ; metabolism ; Interleukin-6 ; metabolism ; Intestines ; blood supply ; metabolism ; Lymph ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Fatigue is a common complication of type 2 diabetes mellitus (T2DM). We examined the relationship between T2DM fatigue and the skeletal muscle 5-hydroxytryptamine (5-HT) system. In animal experiments, a T2DM model was established in mice by feeding a high-fat diet with intraperitoneal injection of streptozotocin. The mice were treated with the 5-HT_2A receptor antagonist sarpogrelate hydrochloride (SH) and the 5-HT synthesis inhibitor carbidopa (CDP) (separately and in combination). In cell culture experiments, C2C12 cells were stimulated with D-glucose, palmitic acid or 5-HT. 5-HT_2AR, 5-HT synthesis and 5-HT degradation were inhibited by SH, CDP, or monoamine oxidase A (MAO-A) inhibitor. The animal experiments were in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. The results showed that 5-HT_2AR, 5-HT synthase and MAO-A were expressed in mouse skeletal muscle and C2C12 cells. The expression of these proteins was significantly up-regulated in T2DM mice or when C2C12 cells were exposed to palmitic acid and D-glucose; palmitic acid was a stronger stimulant of their expression than D-glucose. Rotating rod experiments and biochemical index tests have shown that T2DM fatigue is associated with an increase in skeletal muscle 5-HT_2AR, 5-HT synthesis and 5-HT degradation. 5-HT_2AR mediates the expression of MAO-A and the synthesis of 5-HT, which indirectly regulates the degradation of 5-HT. MAO-A regulates cell inflammation, mitochondrial ROS production and membrane potential depolarization by mediating 5-HT degradation. MAO-A also inhibits the expression of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1), carnitine palmitoyltransferase-1 (CPT1) and ATP synthase-6 (ATP6), thus inhibiting mitochondrial functions such as fatty acid β oxidation and ATP synthesis. SH and CDP can effectively treat T2DM fatigue, and can also reduce blood glucose and blood lipid, and the combination of SH and CDP has a clear synergistic effect.

A pairs of primers were designed according to the fusion protein(F)gene sequences of canine distemper virus(CDV)in GenBank.A 369 bp fragment aimed signal peptide fragment of F gene was amplified.The PCR products from viscera samples,blood,urine of fur animals including foxes,minks and raccoon dogs,which collected in the years 2005-2007,were cloned to pMD18-T Vector and sequenced.We obtained 13 positive signal peptide fragments from wild-type strains.The results indicated there was obviously genetic diversity between the wild-type strains and CDV3 and other vaccine strains.The homology with CDV3 is 80.7%-83.2%in nucleotide,and 64.8%-71.3%in amino acid.The analysis for the hydrophobic regions indicated the function of signal peptide fragment may be changed.This study can offer aca- demic data to research of CDV genetic variation and epidemiology.

OBJECTIVETo investigate the prognostic factors and to analyze the efficacy of chemotherapy and/or radiotherapy for Barrett's esophageal adenocarcinoma after radical surgical resection.

METHODSThe clinical data of 108 patients with adenocarcinoma Barrett's esophagus picking out from 783 esophageal adenocarcinoma patients surgically treated between June 1978 to June 2001 in the Shandong Provincial Hospital and Shandong Qianfoshan Hospital were analyzed retrospectively. 60Co gamma-irradiation or 6MVX-ray with conventional fraction were used for radiotherapy with a total volume dosage of 55-70 Gy. The chemotherapy was either FAM (iv infusion of 5-Fu 500 mg, d1-d5; ADM 50 mg d1; MMC 12 mg, d1) or CMF regimen (iv infusion of CTX 800 mg d1, d8; MTX 30 mg d1; 5-Fu 500 mg, d1-d5) for 4-6 cycles. The Kaplan-Meier amalysis was used to estimate the survival rate. Log rank test was used for comparison of the survival difference among different groups.

RESULTSIn this series, 76 of 92 patients who underwent radical surgical resection received postoperative radiotherapy alone, and 16 received radiotherapy plus chemotherapy. Twelve of the other 16 patients who underwent palliative surgical resection received chemotherapy plus radiotherapy, the remaining 4 patients died of operative complications during surgery. The overall 1-, 3- and 5-year survival rate of this series was 81.5%, 51.9% and 22.2%, respectively. In the radical resection group, it was 15.8% for the patients received radiotherapy alone versus 75.0% for those treated by chemotherapy plus radiotherapy. The 5-year survival rate was 33.3% for the patients without extra-esophageal infiltration and 33.3% for the patients without lymph node metastasis, respectively. However, it was only 9.1% for the patients with extra-esophageal infiltration and 14.3% for those with lymph node metastasis, respectively. For the patients who had palliative surgical resection, though they received chemotherapy plus radiotherapy postoperatively, none of them survived longer than 5-year. Statistically significant difference among these groups was demonstrated by Log rank test (P < 0.05).

CONCLUSIONChemotherapy plus radiotherapy after radical surgical resection may improve the survival of patients with adenocarcinoma in Barrett's esophagus adenocarcinoma patient. The pathological stage, extra-esophageal infiltration, lymph node metastasis and postoperative chemotherapy plus radiotherapy are important prognostic factors.

Adenocarcinoma ; pathology ; surgery ; therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Barrett Esophagus ; pathology ; surgery ; therapy ; Combined Modality Therapy ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Esophageal Neoplasms ; pathology ; surgery ; therapy ; Esophagectomy ; methods ; Female ; Fluorouracil ; therapeutic use ; Humans ; Lymphatic Metastasis ; Male ; Methotrexate ; therapeutic use ; Middle Aged ; Mitomycin ; therapeutic use ; Neoplasm Staging ; Postoperative Period ; Prognosis ; Radiotherapy, High-Energy ; methods ; Retrospective Studies ; Survival Analysis ; Treatment Outcome

OBJECTIVETo study the effects of benzo[a]pyrene (B[a]P) on capability of learning and memory and the content of amino acid neurotransmitters in hippocampus of rats.

METHODSThirty-two healthy, male SD rats were randomly divided into 4 groups according to their weights after intubated into ventricles: the solvent control group, 2.5, 5.0 and 10.0 mmol/L groups. 10 microl of B[a]P olive oil solutions, of different concentrations 2.5, 5.0 and 10.0 mmol/L, were injected into rats' lateral ventricles, respectively. Rats in the solvent control group were injected into the same volume of olive oil as that in B[a]P group. Rats' capability of learning and memory was tested by Morris water maze. The content of amino acid neurotransmitters in rats' hippocampus were determined by high performance liquid chromatogram with a fluorescence detector.

RESULTSCompared with the controls, the performances of learning and memory of rats decreased significantly in B[a]P treated groups (P<0.01). Levels of glutamate (Glu) were lower significantly in treated groups than that in controls (P<0.01). No significant differences were found in contents of aspartic acid (Asp), glycine (Gly) and aminobutyric acid (GABA) among the four groups.

CONCLUSIONB[a]P can damage rats' spatial learning and memory, and which could be related to decreased contents of excitatory amino acids in hippocampus.

Amino Acids ; metabolism ; Animals ; Benzo(a)pyrene ; toxicity ; Hippocampus ; drug effects ; metabolism ; Male ; Maze Learning ; drug effects ; Memory ; drug effects ; Neurotransmitter Agents ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo probe into the situation and significance of p16 gene CPG island methylation in patients with arseniasis caused by coal-burning pollution.

METHODSDNA was extracted using the Phenol-Chloroform method from leukocytes of 51 patients suffered from coal-burnt arsenism and 52 healthy volunteers. The quantity of the DNA was determined by UV spectrophotometry. Target DNA was denatured by NaOH, then the single strand DNA was modified by sodium bisulfite, converting all unmethylated (but not the methylated) cytosines to uracil. Subsequently a nested amplification with primers specific for methylated versus unmethylated DNA was performed, and PCR products were detected by gel electrophoresis.

RESULTSHypermethylation of the p16 CPG island was presented in 94.1% of the patients suffering from coal-burnt arsenism and in 73.1% of the healthy volunteers. There was statistical difference (P < 0.05) between them.

CONCLUSIONSMethylation of p16 gene CPG island should have important pertinence in the metabolism of coal-burnt arsenism.

Arsenic Poisoning ; blood ; genetics ; China ; Coal ; CpG Islands ; DNA Methylation ; Genes, p16 ; Humans

OBJECTIVETo evaluate the relationship between PAR1 (Protease-Activated Receptor 1) expression and the clinicopathologic features and to investigate the prognostic value of PAR1 expression in hepatocellular carcinoma (HCC) in early stage after curative resection.

METHODSReal-time PCR was used to detect PAR1 expression in 41 pairs of tumors and matched peritumoral samples of HCC in early stage. Prognostic value of PAR1 mRNA expression was evaluated. Meanwhile, another 49 tissue paraffin slices of HCC were tested using immunohistochemistry (Envision) and the prognostic value of PAR1 expression and other clinicopathologic factors were evaluated.

RESULTSPeritumoral PAR1 mRNA expression was significantly increased in HCCs from the patients with tumor recurrence as compared with those without recurrence (P < 0.05). Peritumoral PAR1 protein expression was related to tumor differentiation (P < 0.05). Kaplan-Meier analysis showed that Peritumoral PAR1 protein expression was associated with the overall survival (OS) (P < 0.05) of HCC patients and the time to recurrence (TTR) (P < 0.05). The 1, 3 and 5 -year overall survival time and the cumulative recurrence time in the high PAR1 protein expression group were significantly lower as compared to the low PAR1 expression group in the peritumoral liver tissue.

CONCLUSIONSPeritumoral PAR1 expression is closely associated with the prognosis of early stage HCC patients after curable surgery. PAR1 may be involved in thrombin-mediated invasion process and may be used as a prognostic marker for HCC.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Female ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Postoperative Period ; Prognosis ; Receptor, PAR-1 ; metabolism