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Sepsis is a condition of severe organ failure caused by the maladaptive response of the host to an infection. It is a severe complication affecting critically ill patients, which can progress to severe sepsis, septic shock, and ultimately death. As a vital part of the human innate immune system, neutrophils are essential in resisting pathogen invasion, infection, and immune surveillance. Neutrophil-produced reactive oxygen species (ROS) play a pivotal role in organ dysfunction related to sepsis. In recent years, ROS have received a lot of attention as a major cause of sepsis, which can progress to severe sepsis and septic shock. This paper reviews the existing knowledge on the production mechanism of neutrophil ROS in human organ function impairment because of sepsis.
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Humans , Critical Illness , Neutrophils , Reactive Oxygen Species , Sepsis/complications , Shock, SepticABSTRACT
Objective To investigate the clinicopathological characteristics of established genital and extragenital lichen sclerosus(LS)and compare the differences between them. Method The clinicopathological data of 55 patients with established genital and extragenital LS diagnosed by pathological examination in the Department of Dermatology of Beijing Hospital were retrospectively analyzed. Results The 55 patients included 11 males and 44 females.Among them,38,15,and 2 patients had genital lesions,extragenital lesions,and both genital and extragenital lesions,respectively.Extragenital LS mainly involved the back(14.55%)and extremities(7.27%).Among the patients,28.30% were asymptomatic,and 73.58% and 24.53% felt itchy and painful,respectively.The asymptomatic patients had a higher proportion in extragenital cases(
Subject(s)
Female , Humans , Male , Darier Disease , Extremities , Genitalia , Lichen Sclerosus et Atrophicus/epidemiology , Retrospective StudiesABSTRACT
An in vitro blood-brain barrier (BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous system. Though many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data for in vivo BBB drug transport. Induced-pluripotent stem cell (iPSC) technology provides reproducible cell resources for in vitro BBB modeling. Here, we generated a human in vitro BBB model by differentiating the human iPSC (hiPSC) line GM25256 into brain endothelial-type cells. The model displayed BBB characteristics including tight junction proteins (ZO-1, claudin-5, and occludin) and endothelial markers (von Willebrand factor and Ulex), as well as high trans-endothelial electrical resistance (TEER) (1560 Ω.cm ± 230 Ω.cm) and γ-GTPase activity. Co-culture with primary rat astrocytes significantly increased the TEER of the model (2970 Ω.cm to 4185 Ω.cm). RNAseq analysis confirmed the expression of key BBB-related genes in the hiPSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells, including P-glycoprotein (Pgp) and breast cancer resistant protein (BCRP). Drug transport assays for nine CNS compounds showed that the permeability of non-Pgp/BCRP and Pgp/BCRP substrates across the model was strongly correlated with rodent in situ brain perfusion data for these compounds (R = 0.982 and R = 0.9973, respectively), demonstrating the functionality of the drug transporters in the model. Thus, this model may be used to rapidly screen CNS compounds, to predict the in vivo BBB permeability of these compounds and to study the biology of the BBB.
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Objective To establish a rat model of spinal root avulsion and to validate the model by brain-derived neurotrophic factor(BDNF)treatment. Methods To evaluate the motor neuron loss,5 male SD rats were used to undergo spinal root avulsion surgery. One week later, the number of motor neurons in the ventral horn of the spinal cord was as-sessed by histopathology using immunohistochemical staining with a choline acetyl transferase(ChAT)antibody. After this pilot study,40 male SD rats at 7 weeks of age were randomly divided into 4 groups:two control groups,BDNF preventive and treatment groups. Results All rats recovered well post-surgery and no obvious abnormality was observed. Compared with the contralateral side,the number of motor neurons in the ipsilateral avulsed side was significantly decreased at one week after surgery(20.06%,P<0.05). Compared with the control group,there was a significant increase in ChAT posi-tive neurons in the BDNF preventive group(17.85% vs. 93.06%,P<0.0001)or BDNF treatment group(1week after surgery)(26.94% vs. 86.87%, P<0.0001), indicating that the motor neurons were effectively protected by BDNF. Conclusions A rat model of spinal root avulsion is successfully established,which can be valuable for studies of amyotro-phic lateral sclerosis and drug discovery efforts.
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Objective To investigate the role of ATP￣binding cassette ( ABC ) family on the resistance of nasopharyngeal carcinoma (NPC) stem cells (CSCs) to cisplatin. Methods We compared the differences between the drug extravasation capability of CNE￣2 and CNE￣2S by using Rhodamine￣123 efflux assay. We determined the mRNA and protein expression levels of ABC transport family members, including ABCA3,ABCB1,ABCB5,ABCC1,ABCC2 and ABCG2,after 48 h being treated with 1 μmol.L-1 cisplatin by RT￣PC and Western blotting.Rhoamine￣123 efflux and apoptosis by cisplatin in two kinds of cells was examined by ABCA3 gene silencing with specific small￣interfering RNA. Results The IC50 of cisplatin on CNE￣2S was 4.1 fold to that on CNE￣2(P<0.05).For the relative drug effluent activity and Na+K+ ATPase activity,CNE￣2S was 4.8 fold to CNE￣2(P<0.05),suggested that CNE￣2S expressed more ABCA3,ABCB1,ABCC1 and ABCG2 in comparison to CNE￣2(P<0.05).After 48 h treatment with 1 μmol.L-1 cisplatin,ABCA3 specifically highly expressed in CNE￣2S (P<0.05), and knocking down of ABCA3 resulted in reduction of rhodamine￣123 efflux and increase of apoptosis. Conclusion The cisplatin resistance of NPC CSCs is associated with enhanced expression of ABCA3,ABCC1 and ABCG2, suppression of ABCA3 could reverse the resistance of NPC CSCs to cisplatin.
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As a vital component in an overall laboratory animal care and use program , development of a disaster plan plays a critical role for every research institution .Currently, most of domestic institutions would draw up an“emergency operation plan , EOP”, but ignoring a practicable “business continuity plan , BCP” in establishing a disaster plan.In this article, we will discusse about the definition of disaster , how to set up an EOP, and how to establish a thorough BCP , in order to show an integrated and professional disaster plan in laboratory animal care and use program .
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Objective To establish a satisfactory lung metastasis model of human choriocarcinoma using severe combined immunedeficient(SCID)mice and explore the appropriate cell concentration for the model.Methods Forty SCID mice aged between 5-6 weeks were randomly difided into four groups.1×107 cells/ml ×0.1 ml.5×106 cells/ml×0.2 ml and 1×106 cells/ml×0.1 ml of human choriocarcinoma cells JEG-3 were respectively injected in SCID mice of experimental groups by lateral tail vein,the remain group was assigned to the control group.The status and weisht of mice were observed every three days.When these mice were being dying.the size and the number of the lesions of lung metastasis in every mouse were inspected with Micro CT.After Micro CT inspection,the SCID mice were executed dissected to note whether there were tumors on all organ surfaces witll naked eyes.then made pathological sections from the metastaticfoci of fresh lung tissues,and cultured primarily cells and purified cells and passaged cells isolated from the same metastastic foci.The pathological sections were observed under the microscope.The special antigen human chorionic gonadotropin-beta subunit(β-hCG)of the choriocareinoma cells was immunohistochemically detected in the pathological sections and the cells out of cultured primarily cells.The chromosomes of the cells out of cultured primarily cells were analysed.Results Of the group inoeutated 1×107 cells/ml×0.1 ml.all mice died when inoculating.In the group of 5×106 cells/ml×0.2 ml,when inoculating, 3 mice died; the remain 7 mice were being dying on ( 18. 0 ±2. 0) days after injection. 5 of them, there were 1 - 3 lesions of lung metastasis after Micro CT inspection in each mice, and the diameter of the tumors lesions reached 1.5 - 3.5 ram, which was choriocarcinoma confirmed by pathological sections.The special antigen β-hCG was detected by immunohistoehemical method in the pathological sections of pulmonary tissue with tumor and in the cells, which were purified and passaged from being cultured primarily cells isolated from metastastic foci of fresh lung tissues from the SCID mice. The chromosome numbers of these cells out of cultured primarily ceils were variety from 19 to 128, and medal numbers were variety from 70 to 79. Conclusions We successfully established the lung metastatic model of human choriocarcinoma in SCID mice by injecting JEG-3 cells into lateral tail vein, of which 5 × 106 cells/ml × 0. 2 ml is the suitable concentration and volume for the model.
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Objective To establish the high-performance liquid chromatography(HPLC)method for measuring concentrations of methotrexate(MTX)in rat lung and some other tissues through internal iliac artery infusion.Methods Fifly female Sprague-Dawley rats were included in this study.The rats were randomly assigned to two groups.Methotrexate was injected to group one through internal iliac artery,and was injected to group two through femoral vein.Blood and tissues were collected in each group at 15,30,60.90 and 120 minutes for detection of the drug concentrations with HPLC.Results The area under the concentration time curve(AUC)in rat lung,ovary and uterus in the artery group were separately(3.77±0.28),(4.40±0.40),(9.97±0.89)μg·h-1·g-1,which were significantly different from those of the vein group[(2.31±0.25),(3.91±0.19),(7.65±1.54)μg·h-1·g-1;P<0.05].The AUC in the rat plasma,heart,kidney,liver and spleen in the artery group were separately(6.13±0.53),(1.90 ±0.11),(5.32±0.89),(14.16±1.96),(0.76±0.20)μg·h-1·g-1.There were no significant differences from the vein group[(5.79±0.71),(1.64±0.29),(5.15±1.69),(14.29 ±3.47),(0.76±0.13)μg·h-1·g-1;P>0.05].Conclusions Through internal iliac artery infusion,there are higher drug concentrations in lung.uterus and ovarian compared to venous injection.The internal-arterial chemotherapy may be used to treat pulmonary metastasis of gynecological tumor.
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ObjectiveTo investigate the relationship between sepsis induced high mobility group 1 (HMG 1) gene expression and endotoxemia in rats. MethodsSepsis was induced by cecal ligation puncture (CLP). One hundred Wistar model rats were randomly divided into four groups: normal control group ( n =10), sham operation (SO) group ( n =10), CLP group (further subdivided into 2?h, 6?h, 12?h, 24?h, 48?h and 72?h post CLP, n =10 in each subgroup), and bactericidal/permeability increasing protein(rBPI 21 ) treatment group (further subdivided into 12?h, 24?h post CLP, n =10 in each subgroup). Tissue samples from the liver, lungs and kidneys were harvested for the measurement of endotoxin concentrations and HMG 1 mRNA expression by RT PCR. Results Compared to normal control and SO groups the HMG 1 mRNA levels significantly increased in tissues during 6～72?h post CLP ( P
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Objective To investigate the fluctuated pattern of endogenous bactericidal/permeability-increasing protein(BPI)levels,and to elucidate its significance in endotoxin response after major abdominal surgery.Methods Eleven patients undergoing major abdominal surgery were involved in present study.The levels of plasma BPI,lipopolysaccharide-binding protein(LBP)and interleukin-6(IL-6)were measured preoperatively and on postoperative days 1,3,5,7,and 14 by ELISA.Plasma endotoxin concentration was determined with the chromogenic limulus amebocyte lysate(LAL),which was modified by perchloric acid(PCA)pretreatment of samples.The polymorphonuclear neutrophil count was also done at each time point.Results In comparison with normal controls,plasma BPI/LBP ratios [(1.058?0.074)?10-3,P=0.004] were significantly increased on postoperative day 1,maintained at same level on day 3,and declined on day 5.No plasma IL-6 was detected from the blood of all the 11 patients prior to operation,but plasma IL-6 level rose rapidly on day 1 after operation(27.440?12.144pg/ml,P=0.04),maintaining a high level(11.530?5.312pg/ml)on postoperative day 3,and disappeared on day 5.Conclusions Plasma BPI/LBP ratios were markedly elevated during 3 days after a major abdominal surgery,and endogenous elevated BPI may play an important role in prevention from the development of endotoxemia in surgical patients.
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Forty patients who underwent sub-total gastrectomy were divided into four groups, one of them for comparison, the other three groups received 10%, 30% and 100% branched-chain amino acid (BCAA) respectively. The results showed that in BCAA-10 and BCAA-3H group, negative balance was partially corrected, but in BCAA-10 group nitrogen remained an obvious negative balance on the 3rd postoperative day. There were more than ten of plasma AA lower than preoperative day in these two groups. In BCAA-30 group, after surgery, negative nitrogen balance was significantly corrected, and changes of plasma AA had no statistic significance compared with that before operation.Creatinine of urine had no significant difference between each group.In BCAA-30 group, transferrin (Tf) was increased compared with that before operation. It is suggested that the protein synthesis is corrected but the catabolism is not restrained.BCAA may play a regulatory role in muscle protein metabolism, BCAA can serve as fuel substrate to promote synthesis and reduce breakdown of muscle protein to correct negative nitrogen balance.Application of large quantities of BCAA should be based on isotonic AA solution.