Objective To investigate the role of nentrophils in the pathogenesis of psoriasis vulgaris. Methods Neutrophils were isolated from venous blood samples of 25 patients with psoriasis vulgaris (including 13 cases of active psoriasis and 12 cases of inactive psoriasis) as well as 25 normal human con-trols, and cultured. Then, these neutrophils were grouped and treated with lipopolysaccharide (LPS, 100 g/L),CpG-A (50 mg/L), CpG-B (50 mg/L), and RPMI 1640 culture medium, respectively, for 24 hours followed by the collection of culture supematants. Human keratinocytes (HaCaT) were cultured in the presence of su-pematants of treated or untreated nentrophils for 72 hours followed by the detection of cell proliferation with MTT assay. To determine the role of proinflammatory factors, SOD/CAT and monoclonal antibody to IL-8 and TNF-alpha of 400 u/mL were used to pretreat HaCaT cells 1 hour prior to the stimulation with super-natants of neutrophils. Results Compared with culture medium, the supematant of unstimulated neutrophils from normal controls or patients with inactive psoriasis had no significant effect on the proliferation of HaCaT cells (P ＞ 0.05), but that from patients with active psoriasis markedly promoted the proliferation of HaCaT cells (t = 2.41, P < 0.05). ARe, stimulation by LPS, CpG-A and CpG-B, the supematant of active patient-derived neutrophils significantly promoted the proliferation of HaCaT cells compared with that of normal control-derived nentrophils (t = 3.11, 2.89, 2.29, respectively, all P < 0.05). In comparison with tmstimulated neutrophils, the supematant from LPS- and CpG-A stimulated nentrophiles significantly accelerated the pro-liferation of HaCaT cells. Furthermore, the proliferation of HaCaT cells induced by the supematants of LPS-,CpG-A-, CpG-B-stimulated neutrophils from psoriatic patients was statistically suppressed by the pretreat-ment with the monoclonal antibody to IL-8, TNF-alpha and SOD/CAT (all P < 0.05). Conclusions In patients with psoriasis vulgaris, there is an abnormal secretion of IL-8, TNF-alpha and superoxide by neutrophils in peripheral blood, and these proinflammatory factors could promote the proliferation of HaCaT cells.

To provide insights into the mechanism for the attenuate-synergistic effect of Zuota to Tibetan medicine Renqing Mangjue, a contrasted study was carried out on the pharmacokinetics of brucine and strychnine in mice plasm, which are active and toxicant ingredient in the Tibetan medicine Renqing Mangjue. LC-MS/MS was used to detect simultaneously the concentrations of brucine and strychnine in mice plasm at-different time intervals after administration parallelly and randomly, and the pharmacokinetic software Kinetica 5. 0 was selected to non-compartmental analysis (NCA) for data, and statistical analysis software SPSS 19. 0 was used for significance test on the pharmacokinetic parameters. A reliable LC-MS/MS method was established for the determination of brucine and strychnine in blood plasma, which are consistent with the requirements of the preclinical pharmacokinetic study confirmed by the methodology. The linear concentration ranges of brucine and strychnine were 0.301-104.4 µg · L(-1) (r = 0.999 5) and 0.305-106 µg · L(-1) (r = 0.999 7), respectively; The intra-day and inter-day variable coefficients were both less than 10.0% with good precision; The average extraction recoveries of brucine and strychnine were 116.23% and 112.82%, and RSD were 3.2% and 2.3% separately;The average matrix effects of brucine and strychnine were 122.48% and 116.36%, and RSD were 7.7% and 4.4%, respectively. The pharmacokinetic results showed that AUCtot of brucine and strychnine in Zuota group were both increased remarkably (P < 0.05), and the Cmax of brucine in Zuota group was about 5.25-fold higher than that of brucine in non-Zuota group (P < 0.05). The Tmax of brucine and strychnine reduced to one-eighth and one-quarter respectively compared with those in Non-Zuota group. In addition, the eliminations of brucine and strychnine in vivo were accelerated after the compatibility of Zuota. A significant difference (P < 0.05) occurred at the MRT0-t, of brucine, while the MRT0-∞ and Lz of strychnine were statistically significant upon the inspection level α = 0.1. It was found that the absorption degree of brucine and strychnine in Zuota group increased in the range of the safe dose (or concentration), while their elimination rates were accelerated, which may be one of the mechanisms for attenuate-synergistic effect of Zuota to Tibetan medicine Renqing Mangjue.
Animals ; Female ; Male ; Medicine, Tibetan Traditional ; Mice ; Strychnine ; analogs & derivatives ; pharmacokinetics

Aged, 80 and over ; Heart Valve Prosthesis Implantation ; methods ; Humans ; Male ; Prosthesis Failure

Animals ; Antihypertensive Agents ; pharmacology ; Blood Pressure ; drug effects ; Cold Temperature ; Hypertension ; etiology ; physiopathology ; Hypolipidemic Agents ; pharmacology ; Isoflavones ; pharmacology ; Kidney ; pathology ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Male ; Mice ; Mice, Inbred ICR

AIMTo study the enhancing effect of electroporation and iontophoresis on the permeation of insulin through human cadaver skin in vitro.

METHODSUsing side by side two-chamber diffusion cells, the flux of insulin achieved with iontophoresis and electrophoration were compared.

RESULTSThe application of high-voltage pulse combined with iontophoresis resulted in higher flux transdermal permeation of insulin than either one technique alone (P < 0.05). Pulsing at a higher voltage increased the flux of insulin more dramatically than pulsing at a lower voltage (P < 0.01). The transdermal transport of insulin by 90 pulse of 500 V (exponential pulse generater, pulse time: 20-24 ms, pulse frequency: 3 pulse.min-1) followed by iontophoresis led to a quick input and a high steady flux.

CONCLUSIONElectroporation combined with iontophoresis can enhance the permeation of insulin significantly.

Electroporation ; methods ; Humans ; In Vitro Techniques ; Insulin ; administration & dosage ; pharmacokinetics ; Iontophoresis ; methods ; Permeability ; Skin ; metabolism ; Skin Absorption

AIMTo inspect the effects of cold-stress on filial growth and development of pregnant mice.

METHODSPregnant mice were divided into pregnant control group(PN) and pregnant cold-stress group (PC). The PC were kept in (4 +/- 2) C from 8:00 to 12:00 every day and the PN were kept in 25 degrees C. After 18 days, the blood pressure of pregnant mice were measured, and the weight of fetus, placenta and amniotic fluid were recorded. The natal mice visceral organs weight, visceral organs weight and body weight ratio were also measured. Growth curve and increment ratio curve of body weight were protracted every day from 1 st day to 44th day. Blood pressure of all filiality were measured in 8 weeks after they were born.

RESULTSThe blood pressure in PC was increased than that in PN (P < 0.05), the weight of fetus, placenta and amniotic fluid of PC decreased significantly compared with PN (P < 0.01). The filial visceral organ weight of PC reduced obviously compared with PN (P < 0.05), while the visceral organs weight and body weight ratio had no statistical meanings between the offspring of PC and PN (P > 0.05). Obvious difference of growth curve of the two filial groups was also existed until sexual maturity, but increment ratio curve of body weight of the two filial groups was basically fitted close. Filial blood pressure of PC was evidently higher than that in PN.

CONCLUSIONCold-stress stimulations seriously affect filial growth and development of pregnant mice.

Animals ; Cold Temperature ; adverse effects ; Female ; Fetal Growth Retardation ; etiology ; Hypertension, Pregnancy-Induced ; etiology ; Male ; Mice ; Pregnancy ; Prenatal Exposure Delayed Effects ; Stress, Physiological ; physiology

Aortic Aneurysm, Abdominal ; surgery ; Endovascular Procedures ; adverse effects ; Humans ; Intestinal Fistula ; diagnosis ; etiology ; Male ; Middle Aged

Totally 79 obese children and 64 children with normal body weight were included in the present study.Serum apolipoprotein A5 (ApoA5) and leptin levels were determined by ELISA and fasting insulin by RIA.The clinical data including height,body weight,waist circumference,blood pressure,blood lipid,blood glucose,etc,were collected.Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated.The results showed that compared with normal weight children,both serum leptin and insulin levels were significantly raised in obese children [19.15 (13.01 ～ 25.08) ng/ml vs 3.29 (1.45 ～ 6.02) ng/ml and 15.44 (12.05 ～ 20.26) μg/L vs 10.12 (8.60 ～ 12.60) μg/L,both P＜0.01],while ApoA5 level was significantly lowered [134.5 (105.9 ～ 172.7) ng/ml vs 2005.9(164.3 ～ 265.3) ng/ml,P＜0.01].Serum ApoA5 was negatively correlated with serum leptin and insulin (both P＜0.01).

Objective This study aimed at exploring the causative genes and summarizing the clinical characteristics in two Chinese families with thoracic aortic aneurysm and dissection ( TAAD ) .Methods The whole exome capture and high throughput sequencing were applied to identify the causative gene.Family members were examined for features of syndromic ge-netic diseases by clinician and geneticist.Results Four known TAAD candidate genes were identified in family TAA01:rs140598(FBN1), rs185661462(MYH11), rs77620762(MYLK3), and rs111426349(TGFBR1).The TGFBR1 mutation (c.1459C>T) had been confirmed to co-segregate with the TAAD phenotype in all affected family members.Early onset of aortic root dilatation was significant in this family , and the average age at diagnosis of aortic root dilatation or aneurysm was23. 2 years.ACTA2(c.445C>T) was proved in family TAA02, and livedo reticularis was confirmed.Conclusion The causa-tive genes were identified via whole exome capture and high throughput sequencing in two TAAD families .Early onset of aortic root aneurysm was proved in TAA01, while livedo reticularis was found in TAA02.

Objective Optimal detection of deep hypothermic circulatory arrest (DHCA)-induced early brain injury is important but the effective technique is still not available in the present.The relationship between diffusion wcighted imaging (DW1) and histopathological changes in DHCA-induced piglet brain injury model were analyzed.Methods Eighteen pigs underwent deep hypothermic circulatory arrest and were divided into three groups:group A (n =6) served as control,only underwent anesthesia and thoracotomy,without extracorporeal circulation.Group B (n =6) served as underwent deep hypothermic circulatory arrest at 20 ℃ for 120 min,survived for 1 day.Group C (n =6) served as underwent deep hypothermic circulatory arrest at 20 ℃ for 120 min,survived for 2 days.Diffusion-weighted imaging and histopathology were used to study the brain injury.Results There were hematoxylin-eosin (+) and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (+) cells in cerebral cortex and hippocampus.Hyperintensity was most evident in the cerebral cortex in group B and group C with diffusion-weighted imaging,but it was not seen in hippocampus in both groups.There were 5 and 6 piglets can be seen hyperintensity with diffusion-weighted imaging sequence in group B and group C respectively.Hyperintensity was also seen in T2WI sequence in 3 and 5 piglets in group B and group C respectively.Conclusion The study demonstrates the feasibility of diffusion-weighted imaging on evaluation of brain injury after deep hypothermic circulatory arrest and cerebral cortex was selectively vulnerable to cell injury.It is superior to conventional imaging.