BACKGROUND: Regeneration of type Ⅱ furcation defects of periodontal tissues is still a great clinical challenge. OBJECTIVE: To compare different densities of autologous bone marrow mesenchymal stem cells (auto-BMSCs) for repairing canine experimental class Ⅱ furcation defects of periodontal tissues. DESIGN: A randomized controlled trial. SETTING: Laboratory in Stomatological Hospital Affiliated to Fujian Medical University and Department of Animal Experiment in Fuzhou General Hospital. MATERIALS: Experiments were performed at the Laboratory in Stomatological Hospital Affiliated to Fujian Medical University and Department of Animal Experiment in Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA from July 2005 to September 2006. Six 18-month Beagle dogs were provided by Department of Animal Experiment in Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA. Animal intervention met animal ethical standards. Bio-Gide collagen membrane and BME-10X collagen membrane were used in the study.METHODS: Class Ⅱ furcation defects were induced surgically on the buccal side of canine mandibular second and third premolar (P2, P3) and first molar (M1). The ex vivo expanded auto-BMSCs from six 18-month Beagle dogs were seeded in BME-10X collagen membranes at cell density of 5×108 L-1，5×109 L-1，5×1010 L-1, and delivered into experimental class Ⅱ furcation defects, underneath a Bio-Gide membrane. Bio-Gide membrane alone was used as a control. The percentage of new cementum length and percentage of new alveolar bone area were measured on OLYPUS IX 71 inverted research microscope and OLYSIA BioAutoCell software in a computer.MAIN OUTCOME MEASURES: Each specimen was stained with hematoxylin and eosin. The lengths of new cementum and the area of new alveolar bone were calculated.RESULTS: The percentage of newly formed cementum length and the percentage of newly formed alveolar bone area were (51.5±5.6)% and (27.1±7.7)% in the control group,（84.8±8.9）% and（30.6±7.7）% in the 5×108 L-1 BMSCs group, (91.8±5.2)% and (68.3±11.4)% in the 5×109 L-1 BMSCs group and (88.8±7.2)% and (78.5±12.7)% in the 5×1010 L-1 BMSCs group. There were significant differences when comparing the BMSCs groups to the control group (P < 0.01), but there was no significant difference in each BMSCs group. There were significant differences in the percentage of newly formed alveolar bone when comparing the 5×109 L-1 and 5×1010 L-1 BMSCs groups to 5×108 L-1 BMSCs group and control group (P < 0.05), but there was no significantly difference between the first two groups, and neither was the later.CONCLUSION:Periodontal regeneration can be induced by BMSCs transplantation. The mechanism of regeneration is associated with inoculated density.

Chronic cerebral hypoperfusion is a common pathological state. Cognitive impairment is its main manifestation in early stage, and it will eventually result in persistent or progressive cognitive impairment and neurological deficits. Chronic cerebral hypoperfusion caused neuronal damage, synapse abnormity, energy impairment and the function defects of central cholinergic system and monoaminergic system are its pathophysiological mechanisms resulting in cognitive impairment.

To study the metabolite excretion of theophylline, a rapid and specific method by liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) method for simultaneous determination of theophylline, 1, 3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX) and 1-methyluric acid (1-MU) in human urine was developed using theophylline-d6 and 5-fluorouracil as internal standards. Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the negative mode for mass spectrometric detection. After diluted with methanol and centrifuged, the analytes and ISs were separated on a XDB-Phenyl (150 mm x 4.6 mm, 5 microm) column with a mixture of water-methanol-formic acid (30 : 70 : 0.15) as mobile phase at a flow rate of 0.6 mL x min(-1). The linear calibration curves for theophylline, 1, 3-DMU, 3-MX and 1-MU were obtained in the concentration range of 1.0-250 microg x mL(-1), separately. The method herein described is effective and convenient, and can be used for determination of theophylline and its three metabolites. The results showed that urinary excretion ratio of theophylline, 1,3-DMU, 3-MX and 1-MU is approximately 1 : 3 : 1 : 2 in Chinese subjects, which is similar to the reported excretion pattern in Caucasian.
Administration, Oral ; Asian Continental Ancestry Group ; Calibration ; Chromatography, Liquid ; Delayed-Action Preparations ; metabolism ; Healthy Volunteers ; Humans ; Spectrometry, Mass, Electrospray Ionization ; Tablets ; Tandem Mass Spectrometry ; Theophylline ; metabolism ; urine ; Uric Acid ; analogs & derivatives ; urine ; Xanthines ; urine

The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.
Administration, Oral ; Adolescent ; Adult ; Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Antihypertensive Agents ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; Cross-Over Studies ; Drug Liberation ; Humans ; Hydrochlorothiazide ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Male ; Tablets ; Tandem Mass Spectrometry ; Therapeutic Equivalency ; Valsartan ; administration & dosage ; adverse effects ; blood ; pharmacokinetics ; Young Adult

Cerebral Infarction ; etiology ; Dextrocardia ; etiology ; Female ; Humans ; Infant ; Spleen ; abnormalities ; Syndrome

OBJECTIVEParkinson's disease (PD), a neurodegenerative disorder, has been reported to be associated with brain neuroinflammation in its pathogenesis. Herein, changes in peripheral immune system were determined to better understand PD pathogenesis and provide possible target for treatment of PD through improvement of immune disorder.

METHODS1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was intraperitoneally injected into mice to prepare PD model. Expression levels of pro-inflammatory and anti-inflammatory cytokines and transcription factors of CD4+ T lymphocyte subsets in spleen and mesenteric lymph nodes and concentrations of the cytokines in serum were examined on day 7 after MPTP injection. Percentages of CD4+ T lymphocyte subsets were measured by flow cytometry.

RESULTSMPTP induced PD-like changes such as motor and behavioral deficits and nigrostriatal impairment. Expression levels of the pro-inflammatory cytokines including interferon (IFN)-γ, interleukin (IL)-2, IL-17 and IL-22, in spleen and mesenteric lymph nodes were upregulated and their concentrations in serum were elevated in PD progression. But, the concentrations of the anti-inflammatory cytokines including IL-4, IL-10 and transforming growth factor (TGF)-β were not altered in the two lymphoid tissues or serum of PD mice. In addition, expression of T-box in T cells (T-bet), the specific transcription factor of helper T (Th) 1 cells, was downregulated, but expression of transcription factor forkhead box p3 (Foxp3), the transcription factor of regulatory T (Treg) cells, was upregulated. In support of the results, the numbers of IFN-γ-producing CD4+ cells (Th1 cells) were reduced but CD4+CD25+ cells (Treg cells) were elevated in both the lymphoid tissues of PD mice.

CONCLUSIONPD has a dysfunction of peripheral immune system. It manifests enhancement of proinflammatory response and CD4+ T cell differentiation bias towards Treg cells away from Th1 cells.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; CD4-Positive T-Lymphocytes ; pathology ; Cell Differentiation ; Cytokines ; blood ; Disease Models, Animal ; Flow Cytometry ; Forkhead Transcription Factors ; metabolism ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-17 ; blood ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Interleukins ; blood ; Lymph Nodes ; cytology ; Lymphocyte Activation ; Mice ; Parkinson Disease ; immunology ; physiopathology ; Spleen ; cytology ; T-Box Domain Proteins ; metabolism ; T-Lymphocytes, Regulatory ; Th1 Cells ; Transforming Growth Factor beta ; blood

ObjectiveTo investigate the clinical characteristics of the inpatients suffering from dengue fever in order to provide references for better diagnosis and treatment.Methods The clinical data of 158 dengue fever patients admitted to the First Affiliated Hospital of Sun Yat-Sen University from July 23rd to October 31st, 2014 during the 2014 epidemic in Guangzhou area were retrospectively analyzed, including general clinical manifestations, conventional examinations, pathogenesis, and prognosis.Results The mean age of the 158 patients was (56±20) years, with half of them over 60 years old (79 cases). Among them, 94 (59.49%) were male.① The common manifestations included fever (100%), headache (70.89%), myalgia/bone soreness (62.03%), and skin rash (54.43%). Bleeding and plasma leakage were found in 25.95% and 14.56% of the patients respectively.② Laboratory examination:leucopenia (75.32%) and thrombocytopenia (77.85%) were found, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated in 57.59% and 77.85% of the patients respectively. However, elevation of blood hematocrit was rare (1.27%).③ It was found that in the acute phase (0 - 5 days of the onset), serum dengue virus antibody IgM (DF-IgM) was positive in 63.54% of the patients (61/96), and 92.62% (113/122) of patients were dengue virus RNA (DENA-RNA) positive.④ The rate of comorbidity in this study was 55.06% (87/158), including hypertension (27.22%) and type 2 diabetes (15.82%), which were the two most common co-morbidities.⑤ All the patients were given supportive therapy to prevent complications. They were also isolated for more than 5 days after onset, and at least for 24 hours after subsidence of fever in addition.⑥ The criteria for the diagnosis of severe dengue were fulfilled in 18 patients (11.39%). One patient died of massive hemorrhage from gastro-intestinal tract, and 1 patient voluntarily left hospital with untreated multiple organ dysfunction syndrome (MODS). Another 2 patients of dengue fever died from primary cardio-cerebrovascular disease, and the remaining 154 patients (97.47%) fully recovered with supportive therapy and complication prevention measures.Conclusions The clinical manifestations of inpatients with dengue fever in this study were typical, and they manifested a higher incidence of severe illness. DENA-RNA could be a sensitive indicator for early pathogenic diagnosis. With symptomatic and supportive therapy, most patients had a good outcome. However, early diagnosis and clinical interventions of severe dengue still need further studies.

Objective To evaluate the quality of Radix et Caulis Ilicis Asprellae from Pingyuan planting base and Chinese herbal medicine market. Methods The water- and alcohol-soluble extracts from 19 batches of Radix et Caulis Ilicis Asprellae medicinal materials were detected according to Appendix ⅨH, ⅩA of the Chinese Pharmacopoeia ( 2010 edition). And the quality of the medicinal materials was evaluated by microscopic identification technology according to the method for Radix et Caulis Ilicis Asprellae recorded in Guangdong Provincial Chinese Medicine Standard, and then thin layer chromatography ( TLC) was optimized to establish the high performance liquid chromatography (HPLC) fingerprint. The HPLC was performed on Waters XBridgeTM C18 column (250 mm × 4.6 mm, 5μm) with acetonitrile(A)-0.2% (v/v) phosphorus acid (B) as the mobile phase by gradient elution, flow rate was 1.0 mL/min, and detection wavelength was 220 nm. Results The results of sample characters, TLC and microscopic identification showed that the samples of Radix et Caulis Ilicis Asprellae in Chinese herbal medicine markets were certified products, but stems and roots were blended. Seven common peaks were showed by HPLC and confirmed by similarity analytical software. The similarity of 15 batches of planting base samples was all above 0.9. Of 19 batches of the commercial samples, the similarity of 11 batches was above 0.9. The alcohol-soluble extract contents were in the range of 64.55 mg/g to 186.18 mg/g. Conclusion The medicinal materials of Radix et Caulis Ilicis Asprellae from Chinese herbal medicine market are certified products, but the qualities vary greatly for the blending of stems and roots and inadequate growth years. The quality of materials from planting base is better. The established method is helpful for the quality evaluation and control of Radix et Caulis Ilicis Asprellae.

Objective To investigate the metabolism and function of the intestinal microbiota from liver cirrhosis patients.Methods Sixteen cases of liver cirrhosis and twenty normal individuals were selected , whose intestinal microbiota metagenomic DNA was extracted , followed by high-throughput Solexa sequencing and the bioinformatics analysis of metabo-lism and function annotation to compare the differences between the patients and normal subjects and find out about the cir -rhosis-related functions .Results The functional diversity was significantly reduced in the intestinal microbiota of cirrhotic patients.At the module or pathway level , the intestinal microbiota of patients showed an enrichment in metabolisms of drugs, essential amino acid , propanoate metabolism and inflammatory reaction , whereas an opposite tendency was observed in the metabolic ability of butyrate , bile acid and cell cycle .Conclusion Under the influence of liver cirrhosis , the growth environment in the intestine is destroyed , causing, the intestinal microbiota the exhibit some compensation to adapt to the changed intestinal micro-environment .

Poly ( aspartic acid-co-leucine) was synthesized, modified via ethylenediamine, conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and finally chelated with gadoliniumⅢ, yielding PL-A2-DOTA-Gd. The T1-relaxivity (15. 3 mmol-1 ·L·s-1 ) of PL-A2-DOTA-Gd was 2. 6 times than that of Gd-DOTA (5. 8 mmol-1·L·s-1) in D2O. The results of magnetic resonance imaging experiments showed significant enhancement in the rat liver after intravenous administration of PL-A2-DOTA-Gd, which persisted longer than Gd-DOTA. The mean percentage enhancements of liver parenchyma were 65. 1%±5. 2%and 21. 3%±4. 9%, for PL-A2-DOTA-Gd and Gd-DOTA, respectively.