Humans ; Metals ; Microwaves ; adverse effects ; Occupational Exposure ; adverse effects ; analysis ; Workplace

Objective To evaluate the influential factors of iron acquisition during Francisella tularensis LVS infection of mouse macrophages.Methods F.tularensis LVS expressing green fluorescent protein was used to infect murine macrophage J774A.1 cells.Transferrin receptor 1(Tfr1)was detected with mono-antibody and visualized with a goat-anti mouse IgG conjugated to Alexa 594.The expression profile of 5 iron metabolism related genes of J774A.1 murine macrophages uninfected or infected with F.tularensis LVS was determined with real-time PCR.Immunoblot analysis was used to compare the Tfr1 expression of live Francisella infected macrophage with dead bacteria.Tfr1 knock-off in J774A.1 cells was performed with siRNA.The transfected cells were infected with Francisella for immunoblotting and microscopy and infection assay.Results It was revealed that the live vaccine strain of F.tularensis induced the expression of Tfr1 in host macrophages.Gene expression analysis indicated that F.tularensis LVS drove an active iron acquisition program with induction of Tfr1 and iron regulatory proteins(Irp1 and Irp2).It was shown by Western-blotting that the siRNA-Tfrc-1 could knock off about 75% of Tfr1 in J774A.1 cells.It was determined by infection assay that,Tfr1 was knocked off,the bacteria number at 1h infection with Francisella was not different from that of control(F=1.06,P=0.326 5),while it was decreased significantly after 24h of infection(F=24.12,P=0.000 6).Conclusions It is demonstrated that upregulation of the Tfr1 may be mediated by post-transcriptional regulation during early infection,but sustained later through increased expression of Irp 1 and Irp 2.Increased expression of Tfr1 expands the intracellular iron pool through transferrin-mediated delivery and may thus be readily available for uptaking by Francisella.Knocking off the expression of Tfr1 does not affect bacterial invasion.Francisella,however,may fail to proliferate in macrophages in which the expression of transferrin receptor has been suppressed.

OBJECTIVE: To evaluate the sub-acute oral effect of titanium dioxide (TiO₂) nanoparticles on the oxidation/antioxidation biomarkers and inflammatory cytokines in blood, liver, intestine, and colon in rats. METHODS: Twenty four 4-week-old clean-grade Sprague Dawley (SD) rats were randomly devided into 4 groups by body weight (n=6, control, low, middle, and high), in which the rats were orally exposed to TiO₂ nanoparticles at doses of 0, 2, 10 and 50 mg/kg body weight/day for 28 consecutive days separately. Food intake, body weight and abnormal behaviors during the experiment were recorded. The rats were euthanized on the 29th day. The blood was collected via abdominal aortic method and centrifuged to collect the serum. Tissues from liver, intestine and colon were collected and homogenated. Then enzyme-linked immunosorbent assay (ELISA) and microwell plate methods were used to detect oxidation/antioxidation biomarkers including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total mercapto (T-SH), glutathione disulfide (GSSG), malomdialdehvde (MDA) and inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the serum, liver, intestine and colon in the rats. RESULTS: Compared with the control group, no significant differences in body weight, food intake and organ coefficients were observed in all the three groups after TiO₂ gavage. No significant changes in GSH, GSH-Px, T-SH, and IL-6 were observed. Compared with the control group, significant increase of SOD activity in serum in high dose group, signi-ficant increase of GSSG concentration in intestine in middle and high dose group and significant increase of MDA concentration in liver in low and high dose group were observed. Compared with the control group, a significant increase of TNF-α in liver in middle and high dose group was observed. CONCLUSION TiO₂ nanoparticle can increase antioxidant enzymes activities in blood, increase oxidative biomarkers in liver and intestine, increase inflammatory cytokines in liver in rats after a 28-day sub-acute orally administration. Among blood, liver, intestine, and colon, liver is most sensitive to the toxicity induced by TiO₂ nanoparticles, followed by intestine, blood, and colon in sequence.
Animals ; Antioxidants ; Biomarkers ; Cytokines ; Nanoparticles ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Titanium

Objective To explore the effect of L-carnosine on neuronal cell apoptosis in young rats with experimental febrile seizures(FS).Methods Forty 15-day SD rats were randomly divided into intervention group(n=30)and FS group(n=10).Warm water was used to induce 10 times FS.The intervention group was divided into E,G and H group,10 rats in each group.Intraperitoneal injection of L-carnosine(250 mg/kg)was separately given to the rats in E group,G group and H group respectively after 30,60 and 120 min of seizure.FS group were induced FS,but they were not given intervention.The rats were sacrificed at 12 hours after the last seizure.Neuronal cell apoptosis was determined by terminal eoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)in situ cell death kit.TUNEL positive cells were stained and counted as apoptosis in hippocampus and cortex.Ultrastructural changes of apoptosis neurons were observed under the electron microscope.Results The neuronal cells apoptosis count was 25.37?1.95 in FS group,12.36?1.13 in E group,17.85?2.04 in G group,and 22.69?2.69 in H group.Neuronal apoptosis of FS group was apparently higher than that of interventional groups(F=10.75 P0.05).Under the electron microscope,neuronal damage on hippocampal CA1 area and dentate gyrus of FS group and H group was obviously higher than that of E group.Conclusions Early injection of L-carnosine would not only relieve neuronal apoptosis of repeated FS,but also play a role in the protection of neuronal cells.

0.05).Conclusions Early injection of L-carnosine would not only improve cerebral oxidative phosphorylation,relieve neuronal injury of repeated FS,but play a role in the protection of neuronal cells.

OBJECTIVETo study the therapeutic effects and its mechanism of combination of hemofiltration (HF) and peritoneal dialysis (PD) in the treatment of severe acute pancreatitis (SAP).

METHODSForty patients with SAP were divided at random into the HF + PD group (therapeutic group, 25 patients) and the non-HF + PD group (contrast group, 15 patients). Both groups were treated by the conventional mode of therapy. The release time of abdominal pain and distention, CT scores, APACHE II scores, the time of hospital stay, cost of treatment in hospital, operative rate and rate of complications and recovered rate of the two groups were compared. Simultaneously, the concentration of serum and fluid filtrated pro-inflammatory cytokines TNF, IL-6 and IL-8 were also determined pro and post the therapy.

RESULTSThe time needed for the disappearance of abdominal pain and the amelioration of abdominal distension, CT scores, APACHE II scores, the average hospital stay and hospital cost of the therapeutic group were significantly decreased compared with those of the contrast group. The cytokines detected at the end of 1d, 2d after HF + PD were decreased significantly compared with those observed in pro HF + PD and the contrast group.

CONCLUSIONSThe above results show that the cytokines overproduced during the development of SAP can be removed effectively from the circulation and the fluid filtrated by means of HF + PD. The continual deterioration of the local focus and systemtic presentation could be prevented effectively too, and the earlier the treatment of HF + PD, the better the prognosis.

Acute Disease ; Combined Modality Therapy ; Female ; Hemofiltration ; Humans ; Interleukin-6 ; blood ; Interleukin-8 ; blood ; Length of Stay ; Male ; Pancreatitis ; blood ; therapy ; Peritoneal Dialysis ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; analysis

OBJECTIVETo assess the binding ability of microbubbles targeted to alphavbeta3-integrin (MBp) for thrombus-targeted contrast-enhanced ultrasound.

METHODSTargeted microbubbles were prepared by conjugating the monoclonal antibody against alphavbeta3-integrin to lipid shell of the microbubble via the avidin-biotin bridges. Equivalent isotype control microbubbles (MB) or targeted ultrasound microbubbles (MBp) were randomly added into the flow chamber. After a 30-min incubation with the thrombus fixed in an agarose flow chamber model, the thrombus was washed with a continuous flow of PBS solution (15 cm/s) for 2, 4, 6, 8 and 10 min, followed by thrombus imaging using contrast-enhanced ultrasound and measurement of the video intensity (VI) values of the images.

RESULTSThe VI of the thrombus in MBp group was reduced by 28%-66%, while that in control MB group was decreased by 87%-94%, and the VI values of the thrombus group were significantly greater in former group at each of the time points (P<0.05).

CONCLUSIONMBP has good targeting ability to the thrombus with resistance to the shear stress after adhesion to the thrombus. In vitro evaluation of the thrombus-binding capability of the targeted microbubble (MBp) by simulating the shear stress in vivo can be helpful for predicting the in vivo effects of ultrasonic molecular imaging using MBp.

Antibodies, Monoclonal ; chemistry ; immunology ; Contrast Media ; chemistry ; Humans ; Integrin alphaVbeta3 ; immunology ; metabolism ; Microbubbles ; Sepharose ; Thrombosis ; diagnostic imaging ; Ultrasonography

OBJECTIVETo assess the feasibility of usage of microbubbles conjugated with RGD peptides and contrast enhanced ultrasound (CEU) in detection of tumor angiogenesis.

METHODSLipid microbubbles (MB) were prepared, and the RGD peptides were covalently conjugated to the lipid shell of MB (MB(RGD)). Six nude mice with tumor created by dorsal inoculation of HepG2 tumor cells were used as the test group. Six nude mice without tumor were served as the control group. 10 minutes after bolus injection of MB and MB(RGD) randomly (30 min interval) via a tail vein catheter, CEU was performed on the tumors of the test group and the thigh skeletal muscles of control group. The video intensity (VI) of tumors and the skeletal muscles were measured. The tumors and the skeletal muscles were harvested for immunohistochemical examination.

RESULTSOnly a slight contrast enhancement of the tumor was seen with MB, and the VI was 5.33 ± 1.71. While a remarkable enhancement of the tumor was observed after injection of MB(RGD). The VI was up to 17.03 ± 3.58, 3.18 folds higher as compared with that obtained by injection of MB (P < 0.05). As expected, there were no obvious contrast enhancement of the skeletal muscles with both MB(RGD) and MB. There was a high expression of αvβ3-integrin in tumor neovascular endothelium, however, no apparent expression of αvβ3-integrin was observed in the skeletal muscle vascular endothelium.

CONCLUSIONCEU with MB(RGD) can be used to effectively evaluate the angiogenesis of tumors, and it may greatly contribute to the early judgement of the nature of tumor.

Animals ; Cell Line, Tumor ; Contrast Media ; Endothelium, Vascular ; diagnostic imaging ; metabolism ; Female ; Humans ; Integrin alphaVbeta3 ; metabolism ; Liver Neoplasms ; blood supply ; diagnostic imaging ; metabolism ; pathology ; Male ; Mice ; Mice, Nude ; Microbubbles ; Muscle, Skeletal ; blood supply ; Neoplasm Transplantation ; Neovascularization, Pathologic ; diagnostic imaging ; metabolism ; pathology ; Oligopeptides ; Ultrasonics ; methods ; Ultrasonography

ObjectiveTo compare the clinical results between minimally invasive transforaminal lumbar(mini-TLIF) and posterior open surgery in treatment of lumbar spondylolisthesis.MethodsFrom March 2008 to August 2010,a total of 49 cases with lumbar spondylolisthesis underwent surgical intervention were retrospectively analyzed,including 23 cases with mini-TLIF and 26 with open surgery.Operation time,intra-operative bleeding,and radiation exposure times were recorded.Pre- and postoperative back pain was assessed by visual analogue scale(VAS),and lumbar function was evaluated by Oswestry disability index (ODI).The clinical results were assessed by Macnab criterion,and the pre and postoperative radiologic parameters were compared.ResultsThe mean follow-up time was 11 months(ranged,9-22).Both groups got good clinical results and satisfactory radiologic parameters.The group of mini-TLIF was superior to the group of open surgery in intra-operative bleeding,VAS of the second day postoperatively and the willingness of reoperation(P＜0.05).The ODI in the patients with open surgery were decreased from 31.2％±8.2％ to 16.1％±6.8％ corresponding to the pre-oporation and the final follow-up.The ODI in the patients with mini-TLIF were decreased from 34.4％±11.7％ to 15.3％±4.3％ corresponding to the pre-operation and the final follow-up.There is no significant difference of the change of ODI between two groups (t=0.673,P=0.412).The group of mini-TLIF need more operation time and were exposed to more X-ray when compared to the open surgery group(P＜0.05).ConclusionMini-TLIF and open surgery can both get satisfactory clinical outcomes in treatment of lumbar spondylolisthesis.Mini-TLIF was superior to open surgery in intra-operative bleeding and VAS of the second day postoperatively,but it needs more operation time and radiation exposure.

The relationship of HLA-A, -Cw alleles on HIV infection and AIDS disease progression in the Chinese Yi ethnic group of Sichuan province were investigated. The genetic polymorphisms of HLA-A, -Cw alleles of 102 unrelated healthy Chinese Yi ethnic individuals, 68 HIV-1 infected and 21 HIV positive long-time survivors were typed by PCR-SSP assay. Statistic signifiance was determined by the χ2 test with the SPSS software. No significant differences were observed between the HLA-A, -Cw alleles of the 68 HIV-1 infected and 102 non-infected Chinese Yi control individuals. Whereas the prevalence of A*3601,Cw*14(01-03)and Cw*0304 was significantly higher in 21 long time survivors compared with 102 healthy controls with P values of 0.016, 0.016 and 0.000 by χ2 or the Fisher exact test respectively. The result implies that A*3601,Cw*14(01-03) and Cw*0304 may be associated with slow AIDS disease progression in the Chinese Yi ethnic group, further studies on this association may yield insight on the pathogenesis of HIV-1 infection.