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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(5): 457-463, 2019 May 25.
Article in Chinese | MEDLINE | ID: mdl-31104432

ABSTRACT

Objective: To evaluate the diagnostic value of three-dimensional endoanal ultrasound (3D-EAUS) for dyssynergic defecation (DD). Methods: A case-control study was performed to retrospectively collectclinical data of 46 DD patients, including 16 males and 30 females with median age of 51 (20 to 70) years, at Nanjing Hospital of Chinese Medicine from February 2012 to April 2015.All the patients met the diagnostic criteria of functional constipation of Rome III. The paradoxical contraction of puborectalis (PR) muscle was found by both rectal examination and anorectal manometry. In the same period,45 healthy volunteers, including 22 males and 23 females with median age of 48 (21 to 72) years, without pelvic operation history, and with normal defecation in recent 6 months, were enrolled as the control group. No significant differences were observed in age and gender between two groups (both P>0.05). Cleveland constipation score of DD group was higher than that of control group [15(8-24) vs. 5(1-9), t=15.720, P<0.001]. 3D-EAUS examination was performed in all the subjects. Thickness and length of internal anal sphincter (IAS) (anterior side and posterior side), thickness of PR muscle, length of external anal sphincter (EAS) plus PR muscle, and puborectalis angle were measured and compared by using student t test between two groups. Correlation between these ultrasound parameters and anorectal manometry was examined by Pearson correlation analysis. Results: Both male and female in the DD group had the greater thickness of IAS, as compared to those in the control group [male: (1.7±0.5) mm vs.(1.5±0.2) mm, t=2.516, P=0.016; female: (1.9±0.4) mm vs.(1.6±0.5) mm, t=2.034,P=0.047]. No significant differences between the two groups were observed with respect to the posterior length of IAS, length of EAS plus PR muscle, and thickness of PR muscle (all P>0.05). Compared to the control group, male in the DD group had smaller puborectalis angle during straining [(87.0±3.6)° vs. (90.5±1.8)°,t=3.502,P=0.002];female in the DD group had smaller puborectalis angle both in resting and straining [resting:(86.5±3.8)° vs. (90.1±2.1)°,t=4.047, P<0.001;straining: (84.1±4.5)° vs. (90.2±2.3)°, t=5.938, P<0.001]. Correlation analysis showed that anterior length of IAS was positively correlated with anal resting pressure (r=0.321, P=0.030); the length of EAS plus PR muscle was positively correlated with anal squeeze pressure (r=0.415, P=0.004). There were no correlations between the thickness and the posterior length of IAS and the anal resting pressure, or between the thickness of PR muscle and the anal squeeze pressure (all P>0.05). Conclusions: The 3D-EAUS can accurately assess the morphological features of anal canal in DD patients. There is a certain positive correlation between 3D-EAUS and anorectal manometry.


Subject(s)
Anal Canal/diagnostic imaging , Constipation/diagnostic imaging , Defecation/physiology , Endosonography , Rectal Diseases/diagnostic imaging , Adult , Aged , Anal Canal/physiopathology , Constipation/physiopathology , Female , Humans , Imaging, Three-Dimensional , Male , Manometry , Middle Aged , Rectal Diseases/physiopathology , Retrospective Studies , Young Adult
2.
Zhonghua Shao Shang Za Zhi ; 35(1): 12-17, 2019 Jan 20.
Article in Chinese | MEDLINE | ID: mdl-30678396

ABSTRACT

Objective: To analyze the silver content, homogeneity, and cytotoxicity of silver-containing products. Methods: (1) Five kinds of silver-containing products A, B, C, D, and E were purchased from the market, and products A, B, C, and D are liquid or gel form while product E was dressing form. The silver content of each product and the homogeneity of product E were determined by flame method. The sample number was 3. (2) Human hepatocellular carcinoma cell line (HepG2) was selected as the evaluation model. Four silver-containing products A, B, C, and D were diluted with high-glucose dulbecco's modified eagle medium (DMEM) at multiple ratios of 1∶100, 1∶200, 1∶400, and 1∶800, and then they were used for cell culture. Cells cultured with high-glucose DMEM and high-glucose DMEM containing 20 µg/mL silver nitrate were used as blank control and positive control, respectively. The cell viability was determined by methyl thiazolyl tetrazolium assay, and each sample number was 5. (3) Four mass concentrations of 0.031 3, 0.062 5, 0.125 0, and 0.250 0 µg/mL were prepared from silver-containing product A, and then they were used to culture HepG2 cell. Cells cultured with high-glucose DMEM containing fetal calf serum and 294 µg/mL potassium dichromate were used as positive control, while those containing fetal calf serum were used as blank control. Hoechst 33258 staining method was used to detect apoptosis rate of cells. The tail moment, tail length, and the percentage of DNA in the tail of cells were observed by comet assay to evaluate DNA damage. The sample numbers were all 3. Data were processed with one-way analysis of variance and least significant difference-t test. Results: The silver content of products A, B, C, and D was (256.5±1.5) µg/mL, (271.5±1.3) µg/mL, (652.4±2.6) µg/g , (330.0±2.1) µg/g, which was in accordance with labelled amount. The silver content of product E was (0.158±0.013) mg/g, and the silver content of each piece of product E was (0.125±0.017) mg/g, showing good uniformity of product E. (2) Compared with the rate of blank control, the cell survival rates of product A at the dilution ratio of 1∶100, product B at the dilution ratio of 1∶100, and product C at the dilution ratio of 1∶100 and 1∶200 were significantly reduced (t=35.506, 8.914, 37.594, 30.693, P<0.01). Compared with the rate of positive control, the cell survival rates of product A at the dilution ratio of 1∶200, 1∶400, and 1∶800, product C at the dilution ratio of 1∶400 and 1∶800, products B and D at each dilution ratio were increased significantly (t=27.537, 18.262, 18.709, 26.333, 41.762, 15.776, 19.759, 20.443, 15.715, 26.792, 24.963, 31.803, 30.537, P<0.01). (3) The apoptosis rates of cells treated by 0.250 0 µg/mL product A and positive control were (6.1±0.4)% and (62.2±3.9)% respectively, which were significantly higher than the apoptosis rate of blank control [(3.3±0.7)%, t=13.327, 30.475, P<0.05]. The apoptosis rates of cells treated by 0.031 3, 0.062 5, 0.125 0 µg/mL product A were (2.9±0.4)%, (3.1±0.4)%, and (4.2±0.9)% respectively, which were close to the apoptosis rate of blank control (t=1.181, 0.133, 1.097, P>0.05). (4) The tail moment, tail length, and tail DNA percentage of cells cultured with 0.125 0 and 0.250 0 µg/mL product A were significantly higher than those cultured with blank control (t=29.026, 51.194, 21.851, 36.138, 24.721, 50.455, P<0.05 or P<0.01). However, the tail moment, tail length, and tail DNA percentage of cells cultured with 0.031 3 and 0.062 5 µg/mL product A were close to those cultured with blank control (t=5.878, 3.429, 2.779, 1.960, 1.328, 7.763, P>0.05). Conclusions: The silver content of silver-containing products meets the requirements of the labeling. The concentration of product C is higher than that of other products, leading to a greater possibility of decreasing the survival rate of HepG2 cells. It is suggested that the products A and B should be taken as reference in the concentration setting of silver ion products. The product solution with higher concentration may have higher risk of damage to cell DNA. Therefore, it is not recommended to upregulate silver content of relevant products blindly in order to achieve better antibacterial effect.


Subject(s)
Apoptosis/drug effects , Hep G2 Cells/drug effects , Silver/toxicity , Cell Line , Humans
3.
Zhonghua Shao Shang Za Zhi ; 34(3): 183-186, 2018 Mar 20.
Article in Chinese | MEDLINE | ID: mdl-29609281

ABSTRACT

Nowadays, antibacterial products containing silver ion are widely used in clinical wound treatment. The concentration of silver ion in products, pH value, and other factors may affect the release of silver ion and its antibacterial effects. In the treatment of clinical wound, silver ion product plays a good role in anti-infection, promoting healing and reducing medical expenses. In this paper, the related applications of silver ion products in wound surface are analyzed, and the antibacterial properties of silver ion and its therapeutic effects in wound treatment are summarized.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Bacterial Infections/drug therapy , Silver/chemistry , Surgical Wound Infection/drug therapy , Wound Healing/drug effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/administration & dosage , Bandages , Humans , Silver/therapeutic use , Treatment Outcome
4.
Zhonghua Shao Shang Za Zhi ; 32(10): 606-612, 2016 Oct 20.
Article in Chinese | MEDLINE | ID: mdl-27765092

ABSTRACT

Objective: To explore the acute toxic effect and the cumulative target organ of silver nitrate and nano-silver with two different particle diameters in rats. Methods: Thirty-six adult SD rats were divided into small particle size nano-silver group (SNS), large particle size nano-silver group (LNS), silver nitrate group (SN), and control group (C) according to the random number table, with 9 rats in each group. The rats of the four groups were respectively injected with 10 mg/mL nano-silver solution (particle diameter of 20 nm, prepared by saline) in silver dose of 30 mg/kg by tail vein for once, 10 mg/mL nano-silver solution (particle diameter of 100 nm, prepared by saline) in silver dose of 30 mg/kg, 1.67 mg/mL silver nitrate solution (prepared by glucose solution) in silver dose of 3 mg/kg, and 30 mg/mL polyvinylpyrrolidone solution (prepared by saline) in dose of 90 mg/kg. (1) Toxicity test. The general observation was performed within 14 days after injection, and the deviation between value of body mass before injection and each of that on post injection day (PID) 1, 7, and 14 were respectively recorded. On PID 1, 7, and 14, 3 rats of each group were harvested for determination of serum content of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, and albumin by fully automatic biochemical analyzer. Then the rats were sacrificed immediately, and heart tissue, liver tissue, spleen tissue, lung tissue, kidney tissue, and brain tissue were collected to calculate the organ coefficient. Organ samples with obvious changes in organ coefficient were collected for histopathological observation by HE staining, with 3 samples in each group at each time point. (2) Bio-distribution. The specimens of heart, liver, spleen, lung, and kidney of rats from groups SNS, LNS, and SN were collected for detection of silver content by inductively coupled plasma mass spectrometry, with 3 samples in each group at each time point. Data were processed with analysis of variance of factorial design, LSD test, and Dunnett's T3 test. Results: (1) The general condition of rats in groups C and SN after injection were normal. The state of rats of groups SNS and LNS was poor with black secretion in the eye and other phenomena on PID 1, which recovered from PID 3 on. (2) The deviations between values of body mass before injection and that on PID 14 in rats of groups LNS and SN were significantly decreased as compared with deviation of group C (with P values below 0.01), but deviation of group SNS was not significantly changed (P>0.05). The deviations between values of body mass before injection and each of that on PID 1 and 7 in rats in the other three groups were similar to those in group C (with P values above 0.05). (3) Compared with those in group C, the serum content of total protein of rats in group SN on PID 1 was significantly decreased, and liver coefficient was significantly increased (with P values below 0.05). On PID 1, the serum content of ALT of rats in group LNS was (61.0±8.7) U/L, which was significantly higher than that in group C [(40.0±4.6) U/L, P<0.01]. Compared with those in group C [(126.0±3.5) U/L and 4.05±0.23], the serum content of AST of rats in groups SNS and LNS on PID 1[(249.7±107.2) and (237.0±38.3) U/L] was significantly increased, and liver coefficients (3.50±0.38 and 3.31±0.07) were significantly decreased, with P values below 0.05. Compared with those in group C [(69.2±4.8) U/L and 4.32±0.39], the serum content of AST of rats in groups SNS and LNS on PID 7 [(181.0±51.5) and (167.7±16.5) U/L] was also significantly increased, and liver coefficients (3.55±0.18 and 3.62±0.21) were also significantly decreased, P<0.05 or P<0.01. On PID 14, the four liver biochemical indexes in serum and all organ coefficients of rats in the other three groups were similar to those in group C (with P values above 0.05). (4) The liver of rats in group SN had slight degeneration on PID 1, the liver cells around the central vein of liver of rats in group SNS had slight degeneration on PID 7, and the liver cells got severely eosinophilic degeneration in liver of rats in group LNS on PID 7. There was no significant pathological change in the liver of rats in each group at the rest time points. (5) The silver content of lung and kidney in rats of group SNS on PID 1, that of spleen and kidney in rats of group LNS on PID 1, and that of heart and kidney in rats of groups LNS and SNS on PID 7 was significantly less than that of group SN (with P values below 0.05). The silver content of liver and spleen in rats of group SNS on PID 14 was significantly more than that of group SN (with P values below 0.05). Compared with that of group SN, the silver content of lung on PID 1 and liver on PID 7 in rats of group LNS was significantly increased (with P values below 0.05). On PID 14, there was no significant change in the silver content of all organs of rats between group SN and group LNS (with P values above 0.05). The silver content of heart, lung, and kidney on PID 1 and heart on PID 7 in rats of group LNS was significantly more than that of group SNS (with P values below 0.05). On PID 14, the silver content of each organ of rats in group SNS was close to that in group LNS (with P values above 0.05). Conclusions: Silver nitrate and nano-silver with two different particle diameters have a short acute toxic effect on the liver of rats, and the liver has certain ability of self-healing. Nano-silver is mainly accumulated in the liver. The distribution of nano-silver with large particle diameter in organs is more widely than that of nano-silver with small particle diameter.


Subject(s)
Nanoparticles/toxicity , Silver Nitrate/toxicity , Alanine Transaminase , Animals , Burns , Hepatocytes , Kidney , Liver , Lung , Rats , Rats, Sprague-Dawley , Silver , Spleen
5.
Zhonghua Shao Shang Za Zhi ; 32(10): 631-634, 2016 Oct 20.
Article in Chinese | MEDLINE | ID: mdl-27765095

ABSTRACT

With the rapid development of modern science and technology, the application of nanomaterial is ubiquitous in our daily life and medical field, in which the application related to nano-silver is more extensive. On one hand, it can make positive effects, such as anti-bacteria, anti-virus, anti-fungi, anti-parasitic infection and anti-tumor. In particular, its anti-bacterial activity in some acute or chronic treatment of infected wounds is more prominent. The application in diseases of gynecology, orthopedics, cardiovascular system, oral cavity, and ophthalmology is increasing. On the other hand, it can induce negative impacts and potential toxicity. It can be harmful to skin, gastrointestinal tract, respiratory tract, cardiovascular system, and so on. This article summarizes the antimicrobial application of nano-silver on treatment of diseases, its potential toxic effects on some organs or systems, and the possible toxic mechanism, as well as makes prospects of the research trends of nano-silver in future.


Subject(s)
Metal Nanoparticles/toxicity , Silver/toxicity , Anti-Infective Agents , Humans , Metal Nanoparticles/therapeutic use , Silver/therapeutic use
6.
J Int Med Res ; 40(4): 1467-75, 2012.
Article in English | MEDLINE | ID: mdl-22971498

ABSTRACT

OBJECTIVES: To investigate the effects of atypical antipsychotics on prepulse inhibition, startle response and habituation in acutely psychotic patients with schizophrenia, and investigate whether prepulse inhibition deficit improvements are a result of the direct impact of atypical antipsychotics or improvements in antipsychotic-related symptoms. METHODS: Prepulse inhibition, habituation and acoustic startle response were evaluated in healthy control subjects and patients with schizophrenia (either unmedicated with antipsychotics at the time of hospitalization or medicated with atypical antipsychotics for ≥1 month before hospitalization). RESULTS: Data were analysed for 26 patients in the unmedicated group, 20 patients in the medicated group and 31 control subjects. Compared with controls, both medicated and unmedicated patients showed prepulse inhibition deficits; however, there were no significant differences between the two patient groups. Lower prepulse inhibition levels were correlated with higher levels of positive, negative, general and total scores on the Positive and Negative Syndrome Scale. CONCLUSIONS: These results suggest that effects of atypical antipsychotics on prepulse inhibition may not be evident when patients with schizophrenia are acutely symptomatic, and do not directly influence prepulse inhibition.


Subject(s)
Antipsychotic Agents/pharmacology , Reflex, Startle/drug effects , Schizophrenia/drug therapy , Schizophrenic Psychology , Sensory Gating/drug effects , Adult , Analysis of Variance , Antipsychotic Agents/therapeutic use , Case-Control Studies , Female , Habituation, Psychophysiologic/drug effects , Humans , Male , Schizophrenia/physiopathology , Statistics, Nonparametric , Young Adult
7.
Eur Respir J ; 34(3): 676-86, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19386686

ABSTRACT

We and other investigators have hypothesised that the CXC chemokine receptor (CXCR)3/CXCR3 ligand biological axis is involved in the formation of sarcoid lung granulomas; however, significant discrepancies in the current literature remain. In an effort to clarify previous conflicting findings, we performed the largest observational study to date of interferon-inducible ELR(-) (lacking the sequence glutamic acid-leucine-arginine) CXC chemokines in sarcoid bronchoalveolar fluid (BALF). BALF chemokine levels from sarcoid patients (n = 72) and healthy controls (n = 8) were measured with the ELISA method. Immunohistochemical staining was performed for CXCR3 and its ligands. BALF CXC chemokine ligand (CXCL)10 levels from sarcoid patients were not significantly increased compared with controls. BALF CXCL11 levels from sarcoid patients demonstrated a trend towards elevation; subgroup analysis by stage showed significant BALF CXCL11 elevation in stage I sarcoid patients compared with controls. BALF CXCL9 levels were elevated from sarcoid patients compared with controls. CXC11, CXCL9 and CXCR3 were expressed from epithelioid histiocytes, multinucleated giant cells and other inflammatory cells forming sarcoid lung granulomas. Our data suggest that CXCL9 and CXCL11 are important mediators in recruiting CXCR3-expressing cells. Importantly, we have made the novel observation that both lymphocytes and cells of monocyte linage express CXCR3 and are involved in the formation of sarcoid lung granulomas.


Subject(s)
Chemokines, CXC/metabolism , Receptors, CXCR3/metabolism , Sarcoidosis, Pulmonary/metabolism , Sarcoidosis, Pulmonary/pathology , Adult , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Case-Control Studies , Female , Humans , Interferons/physiology , Ligands , Male , Middle Aged , Sarcoidosis, Pulmonary/etiology , Severity of Illness Index
8.
Am J Transplant ; 8(7): 1512-22, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18513272

ABSTRACT

Pulmonary CMV infection (CMVI) and disease (CMVD) is associated with reduced long-term survival post-lung transplantation, however, the specific biologic mechanisms remain unclear. We have demonstrated a role of CC chemokines during lung allograft dysfunction. Based on these findings, we hypothesized that pulmonary CMV upregulates the expression of multiple CC chemokines that leads to allograft dysfunction and decreased long-term survival. We performed a nested case control study in lung transplant recipients to investigate alterations in CC chemokine biology during pulmonary CMV. Levels of CC chemokines were measured in bronchoalveolar lavage fluid (BALF) from recipients with CMVI (n = 33), CMVD (n = 6), and in healthy lung transplant controls (n = 33). We found a trend toward increased levels of MIP-1alpha/CCL3 during pulmonary CMVI. Levels of MCP-1/CCL2 and RANTES/CCL5 were significantly elevated during pulmonary CMV. Interestingly, elevated levels of CCL3 in BALF were protective with regards to survival. Importantly, elevated levels of CCL2 in BALF predicted the development of BOS, while elevated levels of CCL5 in BALF predicted an increase in mortality post-lung transplant. Altered levels of specific CC chemokines during pulmonary CMV are associated with future clinical outcomes. These results suggest a possible utility of BALF CC chemokines as biomarkers for guiding risk assessment during pulmonary CMV post-lung transplantation.


Subject(s)
Bronchiolitis Obliterans/blood , Bronchiolitis Obliterans/mortality , Chemokines, CC/blood , Cytomegalovirus Infections/blood , Lung Transplantation/mortality , Bronchiolitis Obliterans/virology , Bronchoalveolar Lavage Fluid/virology , Case-Control Studies , Chemokine CCL2/blood , Chemokine CCL3/blood , Cytomegalovirus Infections/mortality , Female , Graft Survival , Humans , Male , Middle Aged , Receptors, Chemokine/blood , Risk Assessment , Up-Regulation
9.
J Clin Invest ; 108(4): 547-56, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11518728

ABSTRACT

Bronchiolitis obliterans syndrome (BOS) is the major limitation to survival after lung transplantation. Acute rejection, its main risk factor, is characterized by perivascular/bronchiolar leukocyte infiltration. BOS is characterized by persistent peribronchiolar leukocyte recruitment leading to airway fibrosis and obliteration. The specific mechanism(s) by which these leukocytes are recruited are unknown. Because MCP-1, acting through its receptor CCR2, is a potent mononuclear cell chemoattractant, we hypothesized that expression of this chemokine during an allogeneic-response promotes persistent recruitment of leukocytes and, ultimately, rejection. We found that elevated levels of biologically active MCP-1 in human bronchial lavage fluid (BALF) were associated with the continuum from acute to chronic allograft rejection. Translational studies in a murine model of BOS demonstrated increased MCP-1 expression paralleling mononuclear cell recruitment and CCR2 expression. Loss of MCP-1/CCR2 signaling, as seen in CCR2(-/-) mice or in WT mice treated with neutralizing antibodies to MCP-1, significantly reduced recruitment of mononuclear phagocytes following tracheal transplantation and led to attenuation of BOS. Lymphocyte infiltration was not reduced under these conditions. We suggest that MCP-1/CCR2 signaling plays an important role in recruitment of mononuclear phagocytes, a pivotal event in the pathogenesis of BOS.


Subject(s)
Bronchiolitis Obliterans/etiology , Chemokine CCL2/physiology , Chemotaxis, Leukocyte/physiology , Graft Rejection/etiology , Heart-Lung Transplantation , Lung Transplantation , Postoperative Complications/etiology , Animals , Bronchiolitis Obliterans/metabolism , Bronchoalveolar Lavage Fluid/chemistry , Chemokine CCL2/analysis , Chemokine CCL2/genetics , Chemokine CXCL2 , Chemokines/analysis , Chemokines/physiology , Cohort Studies , Female , Graft Rejection/metabolism , Humans , Immunophenotyping , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Middle Aged , Models, Animal , Phagocytosis , Postoperative Complications/metabolism , RNA, Messenger/biosynthesis , Receptors, CCR2 , Receptors, Chemokine/biosynthesis , Receptors, Chemokine/deficiency , Receptors, Chemokine/genetics , Receptors, Chemokine/physiology , Signal Transduction
10.
J Immunol ; 165(9): 5269-77, 2000 Nov 01.
Article in English | MEDLINE | ID: mdl-11046061

ABSTRACT

We have previously shown that members of the ELR(+) CXC chemokine family, including IL-8; growth-related oncogenes alpha, beta, and gamma; granulocyte chemotactic protein 2; and epithelial neutrophil-activating protein-78, can mediate angiogenesis in the absence of preceding inflammation. To date, the receptor on endothelial cells responsible for chemotaxis and neovascularization mediated by these ELR(+) CXC chemokines has not been determined. Because all ELR(+) CXC chemokines bind to CXC chemokine receptor 2 (CXCR2), we hypothesized that CXCR2 is the putative receptor for ELR(+) CXC chemokine-mediated angiogenesis. To test this postulate, we first determined whether cultured human microvascular endothelial cells expressed CXCR2. CXCR2 was detected in human microvascular endothelial cells at the protein level by both Western blot analysis and immunohistochemistry using polyclonal Abs specific for human CXCR2. To determine whether CXCR2 played a functional role in angiogenesis, we determined whether this receptor was involved in endothelial cell chemotaxis. We found that microvascular endothelial cell chemotaxis in response to ELR(+) CXC chemokines was inhibited by anti-CXCR2 Abs. In addition, endothelial cell chemotaxis in response to ELR(+) CXC chemokines was sensitive to pertussis toxin, suggesting a role for G protein-linked receptor mechanisms in this biological response. The importance of CXCR2 in mediating ELR(+) CXC chemokine-induced angiogenesis in vivo was also demonstrated by the lack of angiogenic activity induced by ELR(+) CXC chemokines in the presence of neutralizing Abs to CXCR2 in the rat corneal micropocket assay, or in the corneas of CXCR2(-/-) mice. We thus conclude that CXCR2 is the receptor responsible for ELR(+) CXC chemokine-mediated angiogenesis.


Subject(s)
Chemokines, CXC/physiology , Endothelium, Vascular/metabolism , Neovascularization, Physiologic/immunology , Receptors, Interleukin-8B/metabolism , Administration, Topical , Amino Acid Motifs , Amino Acid Sequence , Angiogenesis Inhibitors/physiology , Animals , Antibodies, Blocking/physiology , Cell Migration Inhibition , Cells, Cultured , Chemokines, CXC/administration & dosage , Chemokines, CXC/chemistry , Cornea/blood supply , Endothelium, Vascular/cytology , Endothelium, Vascular/immunology , Endothelium, Vascular/physiology , Humans , Immune Sera/pharmacology , Mice , Mice, Inbred C57BL , Mice, Knockout , Microcirculation/cytology , Microcirculation/immunology , Microcirculation/metabolism , Molecular Sequence Data , Neovascularization, Physiologic/genetics , Pertussis Toxin , Rats , Receptors, Interleukin-8B/biosynthesis , Receptors, Interleukin-8B/genetics , Receptors, Interleukin-8B/immunology , Virulence Factors, Bordetella/pharmacology
11.
J Immunol ; 165(1): 461-72, 2000 Jul 01.
Article in English | MEDLINE | ID: mdl-10861085

ABSTRACT

Lung transplantation is a therapeutic option for patients with end-stage lung disease. Acute allograft rejection is a major complication of lung transplantation and is characterized by the infiltration of activated mononuclear cells. The specific mechanisms that recruit these leukocytes have not been fully elucidated. The CC chemokine, RANTES, is a potent mononuclear cell chemoattractant. In this study we investigated RANTES involvement during acute lung allograft rejection in humans and in a rat model system. Patients with allograft rejection had a 2.3-fold increase in RANTES in their bronchoalveolar lavages compared with healthy allograft recipients. Rat lung allografts demonstrated a marked time-dependent increase in levels of RANTES compared with syngeneic control lungs. RANTES levels correlated with the temporal recruitment of mononuclear cells and the expression of RANTES receptors CCR1 and CCR5. To determine RANTES involvement in lung allograft rejection, lung allograft recipients were passively immunized with either anti-RANTES or control Abs. In vivo neutralization of RANTES attenuated acute lung allograft rejection and reduced allospecific responsiveness by markedly decreasing mononuclear cell recruitment. These experiments support the idea that RANTES, and the expression of its receptors have an important role in the pathogenesis of acute lung allograft rejection.


Subject(s)
Chemokine CCL5/physiology , Graft Rejection/immunology , Lung Transplantation/immunology , Acute Disease , Animals , Cell Movement/immunology , Chemokine CCL5/biosynthesis , Chemokine CCL5/genetics , Chemokine CCL5/immunology , Graft Rejection/metabolism , Graft Rejection/pathology , Humans , Immune Sera/administration & dosage , Injections, Subcutaneous , Lung/immunology , Lung/metabolism , Lung Transplantation/pathology , RNA, Messenger/biosynthesis , RNA, Messenger/metabolism , Rats , Rats, Inbred BN , Rats, Inbred Lew , Receptors, CCR1 , Receptors, CCR5/biosynthesis , Receptors, Chemokine/biosynthesis , Time Factors , Transplantation, Homologous
12.
Hum Gene Ther ; 11(2): 247-61, 2000 Jan 20.
Article in English | MEDLINE | ID: mdl-10680839

ABSTRACT

Angiogenesis is an absolute requirement for tumor growth beyond 2 mm3 in size. The balance in expression between opposing angiogenic and angiostatic factors controls the angiogenic process. The CXC chemokines are a group of chemotactic cytokines that possess disparate activity in the regulation of angiogenesis. Non-small cell lung carcinoma (NSCLC) has an imbalance in expression of ELR+ (angiogenic) compared with ELR- (angiostatic) CXC chemokines that favors angiogenesis and progressive tumor growth. We found that the level of the ELR- CXC chemokine MIG (monokine induced by interferon gamma) in human specimens of NSCLC was not significantly different from that found in normal lung tissue. These results suggested that the increased expression of ELR+ CXC chemokines found in these tumor samples is not counterregulated by a concomitant increase in the expression of the angiostatic ELR-CXC chemokine MIG. This would result in an even more profound imbalance in the expression of regulatory factors of angiogenesis that would favor neovascularization. We hypothesized that MIG might be an endogenous inhibitor of NSCLC tumor growth in vivo and that reconstituion of MIG in the tumor microenvironment would result in the inhibition of tumor growth and metastasis. In support of this hypothesis, we demonstrate here that overexpression of the ELR-CXC chemokine MIG, by three different strategies including gene transfer, results in the inhibition of NSCLC tumor growth and metastasis via a decrease in tumor-derived vessel density. These findings support the importance of the ELR- CXC chemokine MIG in inhibiting NSCLC tumor growth by attenuation of tumor-derived angiogenesis. Furthermore, these findings demonstrate the potential of gene therapy as an alternative means to deliver and overexpress a potent angiostatic CXC chemokine.


Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Chemokines, CXC/genetics , Intercellular Signaling Peptides and Proteins , Interferon-gamma/genetics , Lung Neoplasms/therapy , Adenoviridae/genetics , Animals , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Division/drug effects , Cell Division/genetics , Chemokine CXCL10 , Chemokine CXCL9 , Genetic Vectors , Humans , Lung/metabolism , Lung Neoplasms/metabolism , Mice , Mice, SCID , Mice, Transgenic , Neoplasm Transplantation , Neovascularization, Pathologic/genetics , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Receptors, Interleukin-2/metabolism , Recombination, Genetic , Time Factors , Transfection , Tumor Cells, Cultured
13.
Space Med Med Eng (Beijing) ; 13(2): 104-8, 2000 Apr.
Article in Chinese | MEDLINE | ID: mdl-11543048

ABSTRACT

OBJECTIVE: To observe the features of the cardiovascular reactions to gravitational forces along different axes of the body. METHOD: Dogs were exposed to gravitational forces along axes of body on an animal centrifuge. RESULT: It was found that when the direction of G force changed from +Gz to +Gx, the predominating effect on the cardiovascular system changed from the drop of eye level blood pressure to the increase of central venous pressure, and the reactions of the organism changed from a presson reflex of the arterial system to the inhibition of cardiac activities at higher G levels. The turning point was found to be at the back angle of 75 degrees with respect to the direction of the gravitational force. CONCLUSION: These findings provide an important reference for choosing the optimal seat back angle in a manned space vehicle.


Subject(s)
Acceleration , Cardiovascular Physiological Phenomena , Gravitation , Posture/physiology , Aerospace Medicine , Animals , Blood Pressure/physiology , Cardiac Output/physiology , Central Venous Pressure/physiology , Centrifugation , Dogs , Heart Rate/physiology , Hypergravity , Stroke Volume/physiology
14.
J Immunol ; 163(10): 5686-92, 1999 Nov 15.
Article in English | MEDLINE | ID: mdl-10553099

ABSTRACT

Few studies have addressed the importance of vascular remodeling in the lung during the development of bleomycin-induced pulmonary fibrosis (BPF). For fibroplasia and deposition of extracellular matrix to occur, there must be a geometric increase in neovascularization. We hypothesized that net angiogenesis during the pathogenesis of fibroplasia and deposition of extracellular matrix during BPF are dependent in part on a relative deficiency of the angiostatic CXC chemokine, IFN-gamma-inducible protein-10 (IP-10). To test this hypothesis, we measured IP-10 by specific ELISA in whole lung homogenates in either bleomycin-treated or control mice and correlated these levels with lung hydroxyproline. We found that lung tissue from mice treated with bleomycin, compared with that from saline-treated controls, demonstrated a decrease in the presence of IP-10 that was correlated to a greater angiogenic response and total lung hydroxyproline content. Systemic administration of IP-10 significantly reduced BPF without any alteration in lung lymphocyte or NK cell populations. This was also paralleled by a reduction in angiogenesis. Furthermore, IP-10 had no direct effect on isolated pulmonary fibroblasts. These results demonstrate that the angiostatic CXC chemokine, IP-10, inhibits fibroplasia and deposition of extracellular matrix by regulating angiogenesis.


Subject(s)
Adjuvants, Immunologic/physiology , Bleomycin/toxicity , Chemokines, CXC/physiology , Interferon-gamma/physiology , Neovascularization, Pathologic/prevention & control , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/physiopathology , Animals , Biological Assay , Cell Division/immunology , Cells, Cultured , Chemokine CXCL10 , Chemokines, CXC/administration & dosage , Chemokines, CXC/antagonists & inhibitors , Chemokines, CXC/biosynthesis , Corneal Neovascularization/immunology , Corneal Neovascularization/prevention & control , Female , Fibroblasts/cytology , Fibroblasts/immunology , Lung/blood supply , Lung/drug effects , Lung/metabolism , Lymphocyte Subsets/immunology , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Neovascularization, Pathologic/immunology , Pulmonary Fibrosis/immunology , Pulmonary Fibrosis/pathology , Rats , Rats, Long-Evans
15.
Am J Pathol ; 154(5): 1503-12, 1999 May.
Article in English | MEDLINE | ID: mdl-10329603

ABSTRACT

Prostate cancer is the second leading cause of malignancy-related mortality in males in the United States. As a solid tumor, clinically significant tumor growth and metastasis are dependent on nutrients and oxygen supplied by tumor-associated neovasculature. As such, there is a selective tumorigenic advantage for those neoplasms that can produce angiogenic mediators. We show here that human prostate cancer cell lines can constitutively produce angiogenic CXC chemokines. Tumorigenesis of PC-3 prostate cancer cells was shown to be attributable, in part, to the production of the angiogenic CXC chemokine, interleukin (IL)-8. Neutralizing antisera to IL-8 inhibits PC-3 tumor growth in a human prostate cancer/SCID mouse model. Furthermore, angiogenic activity in PC-3 tumor homogenates was attributable to IL-8. In contrast, the Du145 prostate cancer cell line uses a different angiogenic CXC chemokine, GRO-alpha, to mediate tumorigenicity. Neutralizing antisera to GRO-alpha but not IL-8 reduced tumor growth in vivo and reduced the angiogenic activity in tumor homogenates. Thus, prostate cancer cell lines can use distinct CXC chemokines to mediate their tumorigenicity.


Subject(s)
Chemokines, CXC/physiology , Prostatic Neoplasms/physiopathology , Animals , Humans , Male , Mice , Mice, SCID , Neovascularization, Pathologic , Paracrine Communication/physiology , Prostatic Neoplasms/pathology , Severe Combined Immunodeficiency/pathology , Severe Combined Immunodeficiency/physiopathology , Tumor Cells, Cultured
16.
Space Med Med Eng (Beijing) ; 12(5): 328-32, 1999 Oct.
Article in Chinese | MEDLINE | ID: mdl-12022175

ABSTRACT

OBJECTIVE: To define whether QT interval could be used to predict the response of pilots to +Gz stress. METHOD: 37 pilots underwent +4 Gz acceleration on a human centrifuge. According to their responses to +Gz stress, subjects were divided into group A (good reaction group, n=18), group B (hyperfunction reaction group, n=14) and group C (inhibition reaction group, n=1). QT and RR interval were measured pre-, during and post-G. The data of 33 subjects (89.2%) whose QT interval could be measured were analyzed statistically. RESULT: During +Gz, QT and RR interval were shortened and sensitivity of QT interval to RR interval was augmented significantly (vs. pre-G, P<0.001); group B had higher sensitivity of QT interval to RR interval during +Gz (P<0.001, as compared with group A); discrimination functions established by QT and RR interval during +Gz were efficient and their accurate judgement rate was 81.8%. CONCLUSION: The changes in QT interval of ECG were related to autonomic nervous imbalance under +Gz; QT interval and RR interval could be used to predict the response of pilots to +Gz stress. These suggested that the parameters and method in this study might be used in G-LOC warning system.


Subject(s)
Acceleration , Electrocardiography , Heart Rate/physiology , Hypergravity , Adult , Aerospace Medicine , Autonomic Nervous System/physiology , Centrifugation , Humans , Male , Predictive Value of Tests , Unconsciousness/prevention & control
17.
Med Biol Eng Comput ; 36(3): 355-8, 1998 May.
Article in English | MEDLINE | ID: mdl-9747577

ABSTRACT

An experimental animal hypoxia model has been developed. It consists of two sensors (an in vitro and in vivo model), an experimental device and a computer signal processing system. This method can easily be applied to determine and analyse blood oxygen saturation at various hypoxia levels. It can also be used to evaluate the accuracy of pulse oximetry over a wide range of oxyhemoglobin desaturation levels. The DC and AC components of recorded red and infra-red signals, the dual-wavelength ratio R12 and the reading of a pulse oximeter (SpO2) can be automatically calculated and displayed on a computer screen. Preliminary results of the animal hypoxia test indicate that the measurements made by the instrument correlate well with the oxygen saturation readings of the automatic blood gas analyser AVL945. The computer analysis system is suitable for repeated estimations in the animal model.


Subject(s)
Electronic Data Processing , Hypoxia/blood , Oximetry , Animals , Disease Models, Animal , Rabbits , Sensitivity and Specificity
18.
J Clin Invest ; 102(3): 465-72, 1998 Aug 01.
Article in English | MEDLINE | ID: mdl-9691082

ABSTRACT

We report here the role of the CXC chemokine, epithelial neutrophil activating peptide (ENA-78), as an angiogenic factor in human non-small cell lung cancer (NSCLC). In freshly isolated human specimens of NSCLC, elevated levels of ENA-78 were found that strongly correlated with the vascularity of the tumors. In a SCID mouse model of human NSCLC tumorigenesis, expression of ENA-78 in developing tumors correlated with tumor growth in two different NSCLC cell lines. Furthermore, passive immunization of NSCLC tumor-bearing mice with neutralizing anti-ENA-78 antibodies reduced tumor growth, tumor vascularity, and spontaneous metastases, while having no effect on the proliferation of NSCLC cells either in vitro or in vivo. These findings suggest that ENA-78 is an important angiogenic factor in human NSCLC.


Subject(s)
Adenocarcinoma/blood supply , Carcinoma, Non-Small-Cell Lung/blood supply , Chemokines, CXC , Interleukin-8/analogs & derivatives , Lung Neoplasms/blood supply , Neoplasm Proteins/physiology , Neovascularization, Pathologic/physiopathology , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Animals , Apoptosis , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/pathology , Cell Division , Chemokine CXCL5 , Female , Humans , Immunization, Passive , Interleukin-8/metabolism , Interleukin-8/physiology , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Mice , Mice, SCID , Neoplasm Transplantation , Rats , Tumor Cells, Cultured
19.
J Gravit Physiol ; 2(1): P23-4, 1995.
Article in English | MEDLINE | ID: mdl-11538918

ABSTRACT

The direct consequence of cardiovascular adaptation to weightlessness (WL) is the decrease of G tolerance. In studying the mechanism of G intolerance after WL, respiration, heart rate, electrocardiogram, temporal arterial flow, loss of vision were usually used as the indices for evaluation of G tolerance. However the changes of microcirculation and blood rheological indices were seldom observed. Considering that the changes of status of blood circulation after WL may be one of the important factors causing decrease of G tolerance, the purpose of this paper is to observe the changes of microcirculation, blood rheological and the structure and circulatory status of four organs in rabbits during -4Gx after exposure to simulated weightlessness (SWL), in order to understand the cause of G intolerance after WL.


Subject(s)
Cardiovascular Deconditioning/physiology , Head-Down Tilt/adverse effects , Heart Rate/physiology , Hemorheology , Hypergravity , Animals , Brain/pathology , Ear/blood supply , Kidney/pathology , Lung/pathology , Male , Microcirculation , Myocardium/pathology , Rabbits , Weightlessness Simulation
20.
Yao Xue Xue Bao ; 27(1): 74-80, 1992.
Article in Chinese | MEDLINE | ID: mdl-1529719

ABSTRACT

This paper uses several preparation methods, such as thin-film, reverse-phase evaporation and freeze-thawing methods, and also compares encapsulation percentage of Ara-A in liposome (EN%) of these methods. The best operational conditions of preparing liposome-encapsulated Ara-A are explored. A higher EN%, about 50%, which is ten times that reported in foreign literature, is obtained by using improved freeze-thawing method, and this method is easy to operate and repeatable. At the same time, the physical and chemical stabilities of the liposome-encapsulated Ara-A were observed. The result shows that there are no distinct changes in shape, size distribution of liposome, and EN% as well as Ara-A contained in liposome by means of sterilization at 100 degrees C for 30 minutes. Accelerating test at a constant temperature indicates that liposome-entrapped Ara-A has certain chemical stability.


Subject(s)
Vidarabine/administration & dosage , Drug Stability , Liposomes , Particle Size
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