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<p><b>OBJECTIVE</b>To investigate the nephrotoxic effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs.</p><p><b>METHOD</b>Beagle dogs were randomly divided into negative control group(blank tablet), methyl cantharidimide tablets group (6.11,12.21, 24.42 mg x kg(-1)), continuously 30 days of oral adminiStration, once a day. The drug and control group were collected and determined fresh urine in 1, 2, 3 and 4 weeks of the administration; Serum urea nitrogen (BUN), creatinine (Crea), total protein (TP) and albumin (ALB) as well as sodium, potassium, chloride electrolyte were determined on 15 and 30 days of the administration; Urine albumin (mAlb), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin( NGAL), N-acetyl-beta-D-glucosaminidase (NAG), clusterin, beta2-microglobulin (beta2-MG), alpha1-microglobulin (alpha1-MG), alanine aminopeptidase( AAP) and im- munoglobulins IgG were tested on 15 and 30 days of the administration.</p><p><b>RESULT</b>Compared with the control group, urine protein and white blood cells was significantly increased in each dose group. On 15 days of the administration, mAlb were higher in each dose group, KIM-1, NGAL, clusterin, NAG and AAP were significantly higher in high-dose group, while the middle and low dose group had no significant difference, as well as blood SCr and BUN no obvious abnormalities. On 30 days, mAlb, KIM-1, clusterin, NAG, AAP were increased in each dose group, appearing dose-effect relationship, beta2-MG and NGAL levels were significantly increased in high-dose group. Contents above indicators were increased with significant dose and time relationship, and serum BUN, Scr were correlated, suggesting that urine mAlb, KIM-1, clusterin, NAG and AAP indicators that can sensitively respond the changes of proteins and enzymes in urine.</p><p><b>CONCLUSION</b>Methyl cantharidimide tablets has a renal toxicity, urine mAlb, KIM-1, clusterin, NAG and AAP can be used as the early nephrotoxic biomarkers of methyl cantharidimide tablets.</p>
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Animais , Cães , Feminino , Masculino , Biomarcadores , Urina , Rim , Nefropatias , Proteínas , Metabolismo , Comprimidos , Urina , QuímicaRESUMO
<p><b>OBJECTIVE</b>To explore the cellular and molecular mechanism of the inhibitory effect of asiaticoside on capsular contracture following breast augmentation.</p><p><b>METHODS</b>Contracture capsule derived fibroblasts were cultured in medium with different concentration of asiaticoside. The cell proliferation, collage synthesis and alpha-SMA expression were detected by means of 3H-thymidine incorporation, 3H-proline incorporation, and Western-blot. The results were analyzed by SPSS 11.0 with t test.</p><p><b>RESULTS</b>DNA and collagen synthesis of fibroblasts were dramatically inhibited when the asiaticoside reached the concentration of 50 mg/L. The inhibitory rate was 34.7% and 30.1% respectively, showing a significant difference from that in control group (P < 0.05). The inhibitory effect increased with the rise of the asiaticoside concentration in a dose-dependent manner. When the concentration of asiaticoside reached 25 mg/L, the expression of alpha-SMA was down-regulated with an activation index of 1.673, showing a significant difference when compared with that in control group (P < 0.05).</p><p><b>CONCLUSIONS</b>asiaticoside can effectively inhibit the DNA and collagen synthesis of capsule-derived fibroblasts. The trans-differentiation of fibroblast to myo-fibroblasts is also prevented by it.</p>
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Adulto , Feminino , Humanos , Mama , Cirurgia Geral , Transdiferenciação Celular , Células Cultivadas , Colágeno , Contratura , DNA , Fibroblastos , Biologia Celular , Mamoplastia , Complicações Pós-Operatórias , Triterpenos , Usos TerapêuticosRESUMO
<p><b>OBJECTIVE</b>To investigate the role of connective tissue growth factor (CTGF) induced TGF-beta 1 in the transdifferentiation of human hypertrophic scar fibroblast (HSFb).</p><p><b>METHODS</b>Human hypertrophic scar fibroblasts were cultured in vitro, 5 cell samples were stimulated with TGF-beta 1 (0, 2.5, 5.0, 7.5, 10.0 ng/mL, respectively) for 48 hours; other cell samples were divided into: normal control (NC) group, CTGF group (with addition of 10 ng/mL rhCTGF into culture medium), TGF-beta 1 group (with addition of 10 ng/mL TGF-beta 1 into culture medium), CTGF ASODN group (with addition of 10% FBS-DMEM after transfection of CTGF ASODN), CTGF ASODN + TGF-beta 1group (with addition of 10 ng/mL TGF-beta 1 after transfection of CTGF ASODN). Expression of CTGF was determined by Western blotting with stimulation of different concentration of TGF-beta 1. Expression of alpha-smooth muscle actin (alpha-SMA) was measured by Western blotting. Positive cell rate of alpha-SMA was examined by flow cytometry.</p><p><b>RESULTS</b>With stimulation of 10.0 ng/mL TGF-beta 1, the expression of CTGF was obviously higher than that of non-stimulation (P < 0.05). Expression of alpha-SMA in the CTGF group and the TGF-beta 1 group was obviously higher than that in NC group (P < 0.01), while there was no obvious difference among NC, CTGF ASODN, CTGF ASODN + TGF-beta 1 groups (P > 0.05). The positive cell rate of alpha-SMA in NC, CTGF, TGF-beta 1, CTGF ASODN, CTGF ASODN + TGF-beta 1 groups was (10.8 +/- 2.8)%, (29.1 +/- 4.0)%, (28.7 +/- 4.8)%, (10.7 +/- 2.3)%, (14.3 +/- 2.9)%, respectively, which was similar to expression of alpha-SMA on statistic analysis.</p><p><b>CONCLUSIONS</b>CTGF is one of the most important downstream efforts for TGF-beta 1 in inducing the transdifferentiation of HSFb.</p>
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Humanos , Diferenciação Celular , Células Cultivadas , Cicatriz Hipertrófica , Metabolismo , Fator de Crescimento do Tecido Conjuntivo , Farmacologia , Fibroblastos , Biologia Celular , Metabolismo , Fator de Crescimento Transformador beta1 , FarmacologiaRESUMO
<p><b>OBJECTIVE</b>To observe the effects of Panax notoginseng on the transdifferentiation of the cultured human fibroblasts from hypertrophic scar in vitro, and explore its anti-fibrosis mechanism.</p><p><b>METHODS</b>The fibroblasts from human hypertrophic scar were cultured in vitro. Different amount of Panax notoginseng was added into the medium, respectively (400 microg/ml and 800 microg/ml). A culture without addition of the drug served as control. The fibroblast-populated collagen lattice method was used to detect the gel contraction, and contraction ratio was calculated. The immunocytochemistry staining method was used to detect the expression of alpha-smooth muscle actin. The flow cytometry method was used to detect the positive rate of alpha-smooth muscle actin.</p><p><b>RESULTS</b>The contraction degree of the fibroblasts after PNS administration was ameliorated at each time-point, with contraction index lower than that of controls (P < 0.05 or P < 0.01). Scattered distribution of alpha-SMA positive granules were observed in the cytoplasma, and the positive rate of alpha-SMA expression in 400 microg/ml (31.52%) and 800 microg/ml (24.28%) PNS groups were obviously lower than that in control group (45.74%, P < 0.05). The staining intensity of positive cells in 400 microg/ml and 800 microg/ml PNS groups was also obviously lower than that in control group (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Panax notoginseng can inhibit the transdifferentiation of the cultured human fibroblasts from hypertrophic scar, and it exhibits an anti-fibrosis effect on hypertrophic scar in vitro.</p>
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Humanos , Divisão Celular , Transdiferenciação Celular , Células Cultivadas , Cicatriz Hipertrófica , Patologia , Fibroblastos , Biologia Celular , Ginsenosídeos , Farmacologia , Panax notoginseng , Química , CicatrizaçãoRESUMO
Objective To analyze the clinical characteristics and the outcome of severe trauma of various ages in emergency department,to improve the therapeutic effect of emergency rescuing.Methods Two thousand and sixty nine patients of severe trauma were treated during a seven-year period from October 1997 to October 2004.The studied patients were divided into 5 groups:(1)adolescent group(Group A,<13 years old,n=106);(2)juvenile group(Group B, 13-18 years old,n=128);(3)youth group(Group C,18-40 years old,n=1518);(4)middle age group(Group D, 40-60 years old,n=215);and(5)elderly group(Group E,>60 years old,n=102).All the patients were evaluated with Injury Severity Score(ISS),and the result was≥16 in all of the studied patients.Results The incidence of severe trauma in male in all 5 groups was higher than that in female,and it was significantly higher in Group C,Group D and Group E when compared with that in the other groups(P<0.01).Traffic accident was the leading cause of injury,and its incidence in Group A,Group B and Group D was higher than that in other groups(P<0.01).However,injury caused by falling from high places was the second cause of injury,being significantly increased in Group A,while armed fighting and injury during work being significantly increased in Group B,Group C and Group D,slip fall injury being significantly increased in Group E(P<0.01).Head injury was mainly found in Group A and Group E,extremities injury and/or spinal injury were increased markedly in Group B,Group C and Group D(P<0.05),abdominal injury was significantly decreased in Group E(P<0.001).The total mortality was 11.9%(246/2069).The mortality within 24 hours (20.6%,21/102)was significantly higher than that beyond 24 hours(7.8%,8/102)in Group E(P<0.01).The time of staying in the emergency department differed significantly between the survived patients and those died in all 5 groups (P<0.01).Conclusion The gender,the incidence and the characteristics of the injury causes and injury sites differed between severely injured patients of various ages.Mortality in the elderly is significantly increased following severe trauma. The idea of“golden one hour”and“platinum ten minutes”,measures of shortening the time of staying in the emergency clinic,early definite operation and damage control operation should be emphasized.
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Objective To study senile severe trauma patients admitted to Emergency Surgical Department of the second affiliated hospital of Guangzhou Medical college from October 1997 to October 2004,to investigate constructive suggestions of emergency treatment for urban senile trauma.Method Retrospective analysis on 102 senile severe trauma patients screened out from trauma patients admitted to the Emergency Surgical Department was carried out.Results There were 76 male and 26 female patients,the ratio of male to female was 2.9:1,mean age was 69.2 years old(range 60~83 years),the mean trauma score(TS)was(14.5?2.6),the mean Glasgo Coma Score(GCS)was(11.8?3.1),the mean Injury Severity Score(ISS)was(24.5?10.7),there were 61 patients of multiple injuries,transportation accident 45 patients(43.3 %),tumbling injury 23 case(22.5 %), falling injury 19 patients(18.6%),shock 65 patients.Definitive rescue surgery was carried out in 68 patients. The time from emergency treatment to operation departments was(58?19)minutes for the survival patients and (111?34)minutes for those died,there was significant difference between the two groups(P
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<p><b>OBJECTIVE</b>To explore the effects of connective tissue growth factor (CTGF) on the pathogenesis of human keloid.</p><p><b>METHODS</b>CTGF antisense oligonucleotides (ASODN) conjugated with isothiocyanate fluorescence was encapsulated by liposome, and then added into the human keloid fibroblast (HKF) culturing media. The intracellular distribution of CTGF ASODN was observed with fluorescence microscopy in the fixed HKF. The proliferation of HKF was measured by MIT test. The apoptosis of HKF was measured with a flow cytometer. The collagen synthesis of HKF was measured by using H3-proline incorporation method.</p><p><b>RESULTS</b>The CTGF ASODN inhibited the proliferation and collagen synthesis of the HKF, compared with the control, but it increased the apoptosis after the transfection (P < 0.01).</p><p><b>CONCLUSION</b>CTGF ASODN may has anti-fibrotic effects on human keloid in vitro, and the CTGF may play an important role in promoting the fibrosis of human keloid.</p>
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Humanos , Apoptose , Diferenciação Celular , Células Cultivadas , Fator de Crescimento do Tecido Conjuntivo , Genética , Fibroblastos , Biologia Celular , Queloide , Metabolismo , Patologia , Oligonucleotídeos Antissenso , Genética , TransfecçãoRESUMO
<p><b>OBJECTIVE</b>To explore the effect of connective tissue growth factor on the pathogenesis of human hypertrophic scar.</p><p><b>METHODS</b>Normal skin and hypertrophic scar fibroblasts were cultured in vitro. The collagen synthesis of fibroblasts were measured by H3-proline incorporation method. The expression of connective tissue growth factor protein and mRNA of fibroblasts were detected with immunocytochemistry staining and reverse transcription polymerase chain reaction methods.</p><p><b>RESULTS</b>Compared with normal skin fibroblast, the collagen synthesis and the expression of connective tissue growth factor protein and mRNA in the hypertrophic scar fibroblast was higher (P < 0.01).</p><p><b>CONCLUSION</b>Connective tissue growth factor may play an important role in promoting the fibrotic process of hypertrophic scar.</p>
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Humanos , Células Cultivadas , Cicatriz Hipertrófica , Genética , Metabolismo , Patologia , Colágeno , Fator de Crescimento do Tecido Conjuntivo , Fibroblastos , Metabolismo , Patologia , Expressão Gênica , Proteínas Imediatamente Precoces , Genética , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular , Genética , RNA Mensageiro , Genética , Metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
<p><b>OBJECTIVE</b>To establish an ideal model of human hyperplastic scar (HS) in nude mice, so as to provide us a new model to carry out further studies on the mechanism of HS development.</p><p><b>METHODS</b>Full skin defect sized 2.0 cm x 1.5 cm was created on the back of 100 nude mice. The defect was thereafter covered with full thickness human skin. After the grafted skin survived, the nude mice were subjected to deep partial thickness burn of the grafted skin with heated copper rod. The development of the hyperplasia of the scar after wound healing was observed histologically and grossly.</p><p><b>RESULTS</b>Grafted full-thickness human skin took and survived well in 86 out of 100 nude mice. There was obvious and continuous hyperplasia of scar in 67 mice (78%). The external appearance and histological features of the HS appeared similar to those in human HS. The average thickness of the scar was 0.34 cm, with the thickest part measuring 0.6 cm. In addition, the time of hyperplastic change lasted for 63 - 217 days in average of 128 days.</p><p><b>CONCLUSION</b>Obvious and continuous scar hyperplasia could be found in this model, and the whole process beginning from wound healing to the formation of HS could be easily observed. The model was therefore suitable and ideal for the study of HS.</p>
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Animais , Feminino , Masculino , Camundongos , Cicatriz Hipertrófica , Patologia , Modelos Animais de Doenças , Camundongos NusRESUMO
<p><b>OBJECTIVE</b>To study the role of connective tissue growth factor (CTGF) in the pathogenesis of human keloid.</p><p><b>METHODS</b>Human keloid fibroblasts (HKF) were isolated from human keloid and cultured in vitro. The cells were then divided into 3 groups according to different processing, i.e. ASODN treatment (AT), in which phosphorothioate CTGF antisense oligonucleotides (ASODN) labeled by fluorescent isothiocyananate were transfected into the HKFs by liposome; liposome control (LC, with liposome only); control groups (without liposome or ASODN). The distribution of CTGF ASODN in all groups of cells was observed under fluorescent microscope. The CTGF mRNA index (RI) of HKF was assessed by reverse transcription polymerase chain reaction method (RT-PCR). The collagen synthesis of HKF was assessed by (3)H-proline incorporation method.</p><p><b>RESULTS</b>A large amount of fluorescence could be observed in the cytoplasm of HKFs in AT 12 hours after transfection, but not in LC and C groups. The CTGF mRNA index of HKF in AT group 48 hours after transfection was significantly lower than that in LC and C groups (0.12 +/- 0.62 vs 0.51 +/- 0.18 vs 0.54 +/- 0.35, P < 0.01). The (3)H-proline incorporation rate in AT group (108.96 +/- 79.05) was lower than that in LC and C groups (P < 0.01).</p><p><b>CONCLUSION</b>The expression of CTGF gene and collagen synthesis of the cultured HKF could be inhibited by CTGF ASODN, implying that CTGF played a role in the development of excessive fibrosis of human keloid.</p>