Electrocardiography ; Humans ; Myocardial Ischemia ; physiopathology

The design space of the high shear wet granulation process was established and validated within the framework of quality by design (QbD). The system of microcrystalline cellulose-de-ioned water was used in this study. The median granule size and bulk density of granules were identified as critical quality attributes. Plackeet-Burmann experimental design was used to screen these factors as follows: dry mixing time, the impeller and chopper speed of dry mixing, water amount, water addition time, wet massing time, the impeller and chopper speed of wet massing and drying time. And the optimization was implemented with the central composite experimental design based on screened critical process parameters. The design space of the high shear wet granulation process was established based on the quadratic polynomial regression model. Since the P-values of both models were less than 0.05 and values of lack of fit were more than 0.1, the relationship between critical quality attributes and critical process parameters could be well described by the two models. The reliability of design space, illustrated by overlay plot, was improved with the addition of 95% confidence interval. For those granules whose process parameters were in the design space, the granule size could be controlled within 250 to 355 μm, and the bulk density could be controlled within a range of 0.4 to 0.6 g x cm(-3). The robustness and flexibility of the high shear wet granulation process have been enhanced via the establishment of the design space based on the QbD concept.
Cellulose ; chemistry ; Reproducibility of Results ; Technology, Pharmaceutical ; methods ; Water

Objective This study was to understand the structure characteristics of prophages in the genome of Enterococcus hirae R17,and also to analyze their interaction relationships with the host bacterium.Methods The gene distribution and gene encoding characteristics of prophages in the genome of Enterococcus hirae R17 were identified using the PHAST software.The virulence gene,antimicrobial resistance genes,and environmental resistance genes in the prophages were also analyzed.Results Three prophages were found on the chromosome of Enterococcus hirae,including two incomplete prophage elements (Prophage-1 and Prophage-2) and one complete prophage (Prophage-3).Some function genes of bacteria were found in the sequence of three prophages,including nucleotide transportation and metabolism related genes.One incomplete prophage carrying erythromycin-and bacitracin-resistance genes was identified in the plasmid,which suggested that prophage induced gene horizontal transfer caused erythromycin-and bacitracin-resistance of Enterococcus hirae R17.Conclusion This study laid a solid foundation for the diversity analysis of prophages of Enterococcus hirae.Prophages played an important role in promotion of antimicrobial resistance of enterococci.Scientists should pay more attention to the spread of antimicrobial resistance and pathogenicity induced by prophages.

Objective To investigate the life quality in infants with food allergy before and after treatment by using of Food Allergy Quality of Life Questionnaire - Parent Form(FAQLQ - PF). Methods The severity of eczema in 46 children with food allergy was determined by eczema area and severity index(EASI). The life quality of such infants was assessed by the FAQLQ - PF after 2 - months treatment. Results (1)Among the 50 subjects,46(92% )respon-ded to the tests;the average age was(4. 78 ± 1. 48)months. Twenty - nine(63. 04% )subjects had family history of allergic disease. Egg(73. 91% )was the most common allergen,followed by cow milk(43. 48% ),fish and shrimp (8. 70% ),and carrot(4. 35% ).(2)The scores of EASI,FAQLQ - PF in children with food allergy before treatment were 13. 20 ± 12. 86 and 2. 12 ± 1. 33,respectively,the scores after treatment declined(2. 02 ± 4. 40 and 1. 33 ± 1. 08, respectively),there was a statistical significance(t = 28. 070,4. 014,all P ﹤ 0. 05).(3)Compared with pre - treat-ment,the scores of emotional impact subscale and food anxiety subscale declined,from 2. 10 ± 1. 47 and 2. 63 ± 1. 83 to 1. 30 ± 1. 09 and 1. 68 ± 1. 37,respectively,and there were statistically significant differences(t = 5. 204,8. 818,all P ﹤ 0. 05).(4)There was a positive correlation between the EASI and FAQLQ - PF scores(ρ = 0. 205,P ﹤ 0. 05). Conclusions Food allergy adversely affects the quality of life in infants. The poor life quality is associated with more severe symptoms. The life quality in infants and parents can be improved by standardized treatment.

This study plans to prepare lipid bilayer-coated mesoporous silica nanoparticles (LMSNs) which are pH sensitive with core-shell structure to improve the tumor cell lethality of antitumor drug. The lipid coated mesoporous silica nanoparticles loaded with irinotecan (CPT-11) (CPT-11-LMSNs) were prepared by hot water-film hydration method, and the characterized its morphology, particle size and release in vitro. Meanwhile, the intracellular uptake and cell toxicity of CPT-11-LMSNs and intracellular accumulation of CPT-11 were evaluated on human breast carcinoma cell line (MCF-7). The results indicated that the mean diameter of the spherical LMSNs was (120.27 +/- 5.91) nm. The slow release in simulated normal physiological conditions and a rapid release under simulated intracellular condition demonstrated the pH sensitivity of CPT-11-MSNs in vitro. Moreover, the CPT-11-LMSN could improve the intracellular CPT-11 cumulant 2.1 times and reduce half maximal inhibitory concentration (IC50) values of CPT-11 1.4 times compared with CPT-11-MSNs, demonstrating a stronger cell lethality.
Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Camptothecin ; administration & dosage ; analogs & derivatives ; pharmacology ; Cell Proliferation ; drug effects ; Drug Carriers ; Humans ; Hydrogen-Ion Concentration ; Lipid Bilayers ; administration & dosage ; chemistry ; MCF-7 Cells ; Nanoparticles ; Particle Size ; Porosity ; Silicon Dioxide ; administration & dosage ; chemistry

In this work, we developed PEO-PPO-PEO micelles loaded with irinotecan hydrochloride (CPT-11) using breast cancer resistance protein (BCRP) inhibitory material PEO20-PPO70-PEO20, and studied its mechanism of decreasing CPT-11 induced delayed diarrhea and intestinal toxicity. BCRP-overexpressing MDCKII (MDCKII/BCRP) cells were used to evaluate the effect of PEO20-PPO70-PEO20 and PEO-PPO-PEO micelles on transmembrane transport of CPT-11 in vitro. The biliary excretion, delayed diarrhea and intestinal damage of CPT-11 loaded PEO-PPO-PEO micelles of rats were investigated. The results showed that the obtained micelles could decrease the biliary excretion of CPT-11, ameliorate delayed diarrhea and intestinal toxicity of rats through inhibiting BCRP-mediated CPT-11 efflux. PEO-PPO-PEO micelles were promising carriers to reduce intestinal toxicity of CPTs.
ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; adverse effects ; pharmacokinetics ; Bile ; secretion ; Biological Transport ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; pharmacokinetics ; Cells, Cultured ; Diarrhea ; chemically induced ; drug therapy ; Dogs ; Drug Carriers ; Intestines ; drug effects ; Madin Darby Canine Kidney Cells ; Male ; Micelles ; Neoplasm Proteins ; metabolism ; Polyethylene Glycols ; administration & dosage ; chemistry ; Propylene Glycols ; administration & dosage ; chemistry ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo trace magnetically labeled MSCs transplanted into the rat livers by magnetic resonance imaging (MRI).

METHODSFeridex and DAPI labeled rat mesenchymal stem cells (MSCs) were injected via portal veins into carbon tetrachloride treated rats. MRI was performed with a clinical 1.5 T MRI machine immediately before the MSCs injection and at h 1, d 3, d 7, and d 14 after the injection, and then the signal-to-noise ratio (SNR) was measured. MRI findings were compared with the liver histopathologies after the slides were stained with fluorescence dye and Prussian blue.

RESULTSThe SNR for liver was 1.10+/-0.26 at hour 1, 8.18+/-1.55 at day 3, 11.08+/-1.30 at day 7, and 14.15+/-1.02 at day 14 respectively. Within 7 days after the MSCs transplantation, the SNRs of the livers were significantly lower than those before the transplantation (P less than 0.05). Histologically, the blue fluorescent particles under the fluorescence microscopy matched in distribution with the iron particles on the Prussian blue stained slides.

CONCLUSIONThe magnetically labeled MSCs transplanted into livers give rise to an obvious signal decrease, and can be tracked with a 1.5 T clinical MRI machine for up to 7 days after MSCs transplantation.

Animals ; Image Enhancement ; methods ; Liver ; pathology ; Magnetic Resonance Imaging ; Male ; Mesenchymal Stem Cell Transplantation ; Radioactive Tracers ; Rats ; Rats, Wistar

The concept of J wave syndromes was first proposed in 2004 by Yan et al for a spectrum of electrocardiographic (ECG) manifestations of prominent J waves that are associated with a potential to predispose affected individuals to ventricular fibrillation (VF). Although the concept of J wave syndromes is widely used and accepted, there has been tremendous debate over the definition of J wave, its ionic and cellular basis and arrhythmogenic mechanism. In this review article, we attempted to discuss the history from which the concept of J wave syndromes (JWS) is evolved and current controversies in JWS.
Brugada Syndrome ; Death, Sudden, Cardiac ; Electrocardiography ; Ventricular Fibrillation

OBJECTIVETo investigate the effects of chronic amiodarone therapy on L-type calcium current recovery and action potential duration of rabbit ventricular myocytes.

METHODSHealthy rabbits (1.6-1.8 kg) were treated with amiodarone (80 mg x kg(-1) x d(-1)) for four weeks. Action potential duration (APD) was recorded under isolated arterially perfused left ventricular wedge preparation, then single myocytes were isolated using enzyme digestion. L-type calcium current recovery (time constant, tau) were determined by fitting data with monoexponential. Tau/APD90 were compared in cells treated with saline, amiodarone and sotalol (3 x 10(-5) mmol/L).

RESULTSIn chronic amiodarone treated myocytes, tau [(164 +/- 8) ms vs. (98 +/- 8) ms, P<0.05], APD90 [(321 +/- 12) ms vs. (220 +/- 10) ms, P<0.05] and tau/APD90 (0.51 +/- 0.03 vs. 0.44 +/- 0.03, P<0.05) were significantly increased than those in control myocytes. Sotalol significantly increased tau [(128 +/- 7) ms vs. (98 +/- 8) ms, P<0.05] and ADP90 [(405 +/- 13) ms vs. (220 +/- 10) ms, P<0.05] while reduced the tau/APD90 (0.32 +/- 0.05 vs. 0.44 +/- 0.03, P<0.05) compared to control myocytes.

CONCLUSIONThe differential effect of amiodarone and sotalol on ventricular myocytes tau/APD90 ratio might be responsible for the safety profile of these two drugs.

Action Potentials ; Amiodarone ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Calcium Channels, L-Type ; drug effects ; physiology ; Myocytes, Cardiac ; drug effects ; physiology ; Patch-Clamp Techniques ; Rabbits ; Sotalol ; pharmacology

OBJECTIVETo evaluate whether or not administration of folic acid and resveratrol have preventive effects on cleft palate formation as well as the comparison of the two drugs' s effects.

METHODSPregnant mice were randomly divided into 9 groups, with 8 mice in each group. The TCDD group mice were dosed with TCDD 28 microg/kg body weight on gestation day 10 (GD 10) animals in folic acid group were respectively dosed with folic acid 15, 10, 5 mg/kg and TCDD 28 microg/kg; resveratrol treated mice were divided into 3 groups: resveratrol 50 mg/kg were orally administered for 6 consecutive days, from gestational day GD 8 to GD13 in resveratrol (GD8-13 ) group; resveratrol 50 mg/kg were orally administered for 6 consecutive days, from gestational day GD 8 to GD13, followed hy an oral administered with TCDD on GD10 in resveratrol (GD8-13) + TCDD group; resveratrol 50mg/kg and TCDD 28 microg/kg were used by gavage administration at GD10 in resveratrol (GD10) + TCDD group. Control mice were treated with the same volume of water for 6 consecutive days from GD8 to GD13 and were given a single dose of corn oil on GD10. The pregnant mice weight and embryos, the number of live, cleft palate, dead and resorption fetal mice were recorded on GD 17.5. The coronal sections of the fetal mice heads were prepared at GD 17.5 and observed by microscopy.

RESULTSTotal frequency of clefts was 92.86% in TCDD group, 84.00% (15 mg), 73.08% (10 mg), 84.00% (5 mg) in folic acid + TCDD groups, 0% in resveratrol (GD10) group, 74.51% (GD10), 57.78% (GD8-13) in resveratrol + TCDD groups. The frequency of cleft was 0% in the control group. Compared with the control and the TCDD groups, there were significant differences in the number of live, dead and resorption fetal mice in TCCD + resveratrol (GD8-13) group (P < 0.05). No significant differences in embryonic weight, live fetuses weight, the number of live, dead and resorption fetal mice were found in the other groups (P > 0.05).

CONCLUSIONTest dose of folic acid and resveratrol both had certain antagonistic effect on cleft palate in mice induced by TCDD, with folic acid 10 mg/kg, resveratrol 50 mg/kg GD8-13 doses having stronger antagonistic action. Effects of both the two drugs have no significant difference, but resveratrol (50 mg/kg, GD8-13) significantly affects the fetal mice's growth and development under TCDD exposure in utero.

Abnormalities, Drug-Induced ; prevention & control ; Animals ; Cleft Palate ; chemically induced ; prevention & control ; Female ; Fetus ; Folic Acid ; administration & dosage ; pharmacology ; Humans ; Mice ; Mice, Inbred C57BL ; Polychlorinated Dibenzodioxins ; antagonists & inhibitors ; Pregnancy ; Random Allocation ; Stilbenes ; administration & dosage ; pharmacology ; Teratogens