Objective To evaluate the effect of BML-111 on NF-κB pathway during acute lung injury induced by hemorrhagic shock and resuscitation in rats.Methods Thirty-two adult male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 4 groups (n =8 each) using a random number table:sham operation group (group S),hemorrhagic shock and resuscitation group (group HSR),BML-111 group,and BML-111 + BOC-2 (lipoxin A4 receptor antagonist) group (group BOC-2).The animals were anesthetized with intraperitoneal pentobarbital sodium.Hemorrhagic shock was induced by blood letting and maintained for 30 min.The animals were then resuscitated for 30 min by infusion of the shed blood and lactated Ringer's solution.In group BOC-2,BOC-2 (50 μg/kg) was injected intraperitoneally before blood letting.In BML-111 and BOC-2 groups,BML-111 (1 mg/kg) was injected intraperitoneally at the beginning of resuscitation.The rats were sacrificed at 2 h after the end of resuscitation and lungs were removed for determination of pathological changes,myeloperoxidase (MPO) activity,intercellular adhesion molecule-1 (ICAM-1) expression (by immunohistochemistry),tumor necrosis factor-alpha (TNF-α) content (by ELISA),and NF-κB p65 and IκB-α expression (by Western blot).Results Compared with group S,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and IκB-α expression was down-regulated in group HSR.Compared with group.HSR,the MPO activity,ICAM-1 expression,and TNF-α content were significantly decreased,NF-κB p65 expression was down-regulated,IκB-α expression was up-regulated,and pathological changes of lung were attenuated in group BML-111.Compared with group BML-111,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and lκ:B-α expression was down-regulated,and pathological changes of lung were aggravated in group BOC-2.Conclusion BML-1 11 inhibits activation of NF-κB pathway and inflammatory responses,thus mitigating acute lung injury induced by hemorrhagic shock and resuscitation in rats.

Objective To evaluate the effect of lipoxin A4 receptor agonist BML-111 on acute lung injury induced by hemorrhagic shock and resuscitation in rats.Methods Thirty-two healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 200-250 g,were randomized into 4 groups (n =8 each) using a random number table:sham operation group (S group),hemorrhagic shock/resuscitation group (HSR group),BML-111 group,and BML-111 plus BOC-2 (lipoxin A4 receptor antagonist) group (BOC-2 group).The animals were anesthetized with 2％ pentobarbital sodium 80 mg/kg,tracheostomized and mechanically ventilated.Left common carotid artery was cannulated for blood-letting and fluid infusion.Hemorrhagic shock was induced according to the method described by Kochanek et al.MAP was reduced to 35-45 mmHg and maintained at this level for 30 min.The animals were then resuscitated for 30 min with infusion of the blood withdrawn and lactated Ringer' s solution 2 times the volume of blood withdrawn.In BML-111 and BOC-2 groups,BML-111 (1 mg/kg) was injected intraperitoneally at the beginning of resuscitation.In BOC-2 group,BOC-2 (50 μg/kg) was injected intraperitoneally before blood-letting.The rats were sacrificed at 2 h after completion of resuscitation.Bronchoalveolar lavage fluid (BALF) was collected for determination of neutrophil count.Lungs were excised for microscopic examination of the pathological changes and for determination of wet/dry lung weight ratio (W/D ratio),contents of interleukin-1 (IL-1β) and IL-6,and phosphorylation of mitogen-activated protein kinase (MAPK).Results Compared with group S,the neutrophil count in BALF,W/D ratio,contents of IL-1β and IL-6,and phosphorylation of MAPK were significantly increased in HSR group (P ＜ 0.05).The neutrophil count in BALF,W/D ratio,contents of IL-1β and IL-6,and phosphorylation of MAPK were significantly lower in BML-111 group than in HSR group,and higher in BOC-2 group than in BML-111 group (P ＜ 0.05).Conclusion BML-111 can attenuate acute lung injury induced by hemorrhagic shock and resuscitation in rats and inhibition of activation of MAPK pathways and reduction of inflammatory responses in lung tissues are involved in the mechanism.

To evaluate the effects of p-octyl polyethylene glycol phenyl ether (Triton X-100), polyoxyl 35 caster oil (EL35) and polyoxyl 40 hydrogenated caster oil (RH40) on the activity of Cytochrome P450 3A (CYP3 As) in vivo. Rats were administered with saline, ketoconazole (75 mg x kg(-1) x d(-1)), Triton X-100 (30 mg x kg(-1) x d(-1)), EL35 (150 mg x kg(-1) x d(-1)) and RH40 (150 mg x kg(-1) x d(-1)) intragastrically for 5 consecutive days, and then given midazolam 10 mg x kg(-1) 20 min after the last treatment of ketoconazole or three surfactants with the same dose through duodenal administration. Pharmacokinetics parameters for midazolam and its metabolite 1'-hydroxymidazolam were estimated from the plasma concentration-time data by a noncompartmental approach. The results showed that multiple dose administration of Triton X-100, EL35 and RH40 decreased the ratios of 1'-hydroxymidazolam and midazolam AUC0-infinity from 1.14 to 0.90, 1.03 and 0.64, respectively. In contrast, multiple dose administration of ketoconazole caused the ratios of 1'-hydroxymidazolam and midazolam a significant decrease to 0.50. This study indicated that Triton X-100 and EL35 would have no inhibition on CYP3A, while RH40 had significant inhibition on CYP3A. Therefore, RH40 might be used to prepare drug formulations in pharmaceutical industry and would increase the bioavailability of some drugs transformed by CYP3As and further lead to significant clinical pharmacologic effects.
Animals ; Area Under Curve ; Biological Availability ; Biotransformation ; Cytochrome P-450 CYP3A ; metabolism ; Ketoconazole ; pharmacology ; Male ; Midazolam ; analogs & derivatives ; pharmacokinetics ; Octoxynol ; pharmacology ; Polyethylene Glycols ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Surface-Active Agents ; pharmacology

OBJECTIVETo investigate the expression of translationally controlled tumor protein (TCTP) in human breast cancer tissues and its clinical significances.

METHODSThe expression of TCTP in 94 human breast cancer and the corresponding adjacent normal mammary tissues were detected using immunohistochemistry.

RESULTSThe expression rate of TCTP was 64.89% in human breast cancer tissues, significantly higher than that in normal benign mammary tissues (39.36%, P<0.001). TCTP overexpression was positively correlated to the tumor size, clinical stage, lymph node metastasis and histological grade of breast cancer (P<0.05). Patients with positive TCTP expression had a significantly shorter mean survival time than those with negative expression (P<0.001).

CONCLUSIONTCTP may play an important role in the tumorigenesis and development of breast cancer, and can be an important prognostic factor for this malignancy.

Rutin deca (H-) sulfate sodium (RDS) possesses very good activity as an inhibitor of the complement system of warm-blooded animals and HIV. An ion-pair coupled with solid-phase extraction technique (IP-SPE) was developed to extract RDS from rat plasma, urine, bile and protein solution samples. The assay was applied to pharmacokinetics of RDS, including plasma pharmacokinetics, excretion and protein binding studies. After i.v. 5, 20 and 100 mg x kg(-1) RDS via tail vein in rats, the plasma concentration-time profiles were fitted using 3P97 software. The average terminal half-life (t(1/2)) was 3.432 +/- 0.185 2 h. The relationship of dose and AUC of RDS was linear within the dosage range. This suggested that the disposition of RDS in rats belong to linear kinetics and the pharmacokinetic parameters of RDS were dose independent. After iv RDS 20 mg x kg(-1) in rats, the biliary excretion amount of parent drug amount was only 0.3181% +/- 0.2087% of given dosage, and the urinary excretion was 86.0% +/- 6.1% in 36 h. Ultrafiltration techniques were applied to determine the protein binding of RDS in plasma (from SD rat, Beagle dog and human), human serum albumin (HSA) and human alpha1-acid glycoprotein (AGP). The mean protein binding rate in plasma of SD rat, Beagle dog and human plasma of RDS were 80%-90%, in which the range of concentration of RDS was 5 to 100 microg x mL(-1). The protein binding to HSA was 85.7% +/- 1.3% and 14.0% +/- 3.2% to AGP.
Animals ; Area Under Curve ; Bile ; metabolism ; Dogs ; Half-Life ; Humans ; Injections, Intravenous ; Kinetics ; Male ; Orosomucoid ; metabolism ; Protein Binding ; Rats ; Rats, Sprague-Dawley ; Rutin ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics ; urine ; Serum Albumin ; metabolism ; Solid Phase Extraction ; methods

Objective To investigate the clinical effect of endoscopic treatment of carpal tunnel syndrome (CTS) with subsynovial hyperplasia. Methods 37 cases (total 41 wrists) of CTS with subsynovial hyperplasia who accepted endoscopic treatment in our hospital were retrospectively analysised, all the transverse ligament of wrist were cutted off under endoscope and the hyperplastic subsynovial membrane arounding the superficial flexor tendon of finger. The changes of clinical symptoms and signs before and after operation were compared. Results According to Kelly classification, the overall excellent and good rate was 95.12%. After operation, the feel of numb and pain during night disappeared in all patients, the positive rate of Tinel and Phalen sign was both reduced to 2.44% (P < 0.05), and the mean value of two-point discrimination was reduced to (3.5 ± 0.9) mm. No serious complication occurred during treatment. Conclusion For the patients of CTS with subsynovial hyperplasia, to cut the transverse ligament tendon under endoscope and remove the subsynovial around the flexor tendon at the same time is a new and feasible surgical procedure with notable curative effect, which deserves clinical popularization.

Objective:To observe the clinical efficacy of Tongxie Yaofang on irritable bowel syndrome-D (IBS-D) of liver-stagnation and spleen-deficiency type, in order to explore its mechanism in regulating brain-intestine interaction by changing the intestinal flora before and after treatment. Method:Totally 116 patients with IBS-D with liver stagnation and spleen deficiency who were diagnosed from July 2016 to December 2018 were randomly divided into observation group and control group, with 58 patients in each group. Observation group was treated with Tongxie Yaofang orally. Control group was treated with pivalvonium orally. Both groups were treated for 4 weeks. Scores of traditional Chinese medicine pattern curative effect scoring system (TCM-PES), IBS quality of life questionnaire (IBS-QOL), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) of two groups were compared before and after treatment. Calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) were detected before and after treatment by enzyme-linked immunosorbent assay (ELISA). Real-time fluorescent quantitative polymerase chain reaction(Real-time PCR) was used to detect changes in Escherichia coli, Bifidobacteria, Lactobacillus acidophilus and Streptococcus faecalis and other intestinal flora before and after treatment. Result:TCM-PES and IBS-QOL scores of two groups were improved after treatment. TCM-PES and IBS-QOL scores of observation group were higher than those of control group (P<0.05). TCM syndromes of observation group were significantly higher than those of control group (P<0.05). SAS and SDS scores were significantly lower after treatment. SAS and SDS scores of observation group were lower than those of control group after treatment (P<0.05). Plasma CGRP and VIP decreased after treatment. Plasma CGRP and VIP in observation group were significantly lower than those in control group (P<0.05). There was no significant change in E. coli after treatment in two groups. After treatment, L. acidophilus, Bifidobacterium, and S. faecalis increased (P<0.05). In control group, intestinal L. acidophilus increased after treatment (P<0.05). The differences of intestinal L. acidophilus, Bifidobacterium, S. faecalis in two groups were statistically significant (P<0.05). Conclusion:TCM can alleviate clinical symptoms, such as abdominal pain and diarrhea in patients with IBS-D, improve patients' bad mood and improve their quality of life. This may be related to improvement of intestinal flora imbalance, regulation of brain intestinal peptide secretion and reduction of visceral hypersensitivity.