RESUMO
Objective: To explore the mechanism of nerve growth factor (NGF) in the skeletal muscle fiber remodeling in ischemic limbs during therapeutic angiogenesis. Methods: Eighteen female mice with SPF grade, 6 weeks old and 25-30 g weighed were randomly allocated to sham-operated group (n=6), blank control group (n=6) and NGF gene transfection group (n=6). The left hindlimb ischemia models were established by ligating the femoral artery in blank control group and NGF gene transfection group. Seven days after the operation, mice in the three groups were separately injected with normal saline, empty plasmids, and NGF plasmids. Gastrocnemius of left hindlimbs was harvested after the blood perfusion assessment of the ischemic limb on the 21st postoperative day. The gastrocnemius muscle specimens were stained with HE, CD31 and proliferating cell nuclear antigen (PCNA) immunohistochemistry staining, the mRNA expressions of myosin heavy chain-â (MHC-â ), MHC-â ¡a and MHC-â ¡b were measured by real-time PCR, and the protein level of NGF and peroxisome proliferator-activated receptors-ß/δ (PPAR ß/δ) were detected by Western blot. The expression of cytochrome C oxidase (COX), isocitrate dehydrogenase (IDH) and adenosine triphosphate (ATP) were examined by enzyme-linked immunosorbent assay (ELISA). Results: On the 21st day after operation, the blood perfusion of the ischemic limb in NGF gene transfection group was (195.70±9.99)PU, which was lower than that in sham-operated group (312.15±17.32)PU (P=0.001), while it was higher than that in blank control group (82.11±8.55)PU (P=0.001). The degree of muscle atrophy in the NGF gene transfection group was lower than that in the blank control group. The capillary density of NGF gene transfection group (0.34±0.05) was higher than that of sham-operated group (0.11±0.03) and blank control group (0.27±0.04) (P<0.05). The endothelial cell proliferation index in NGF gene transfection group (0.39±0.19) was significantly higher than that in sham-operated group (0.18±0.01) and blank control group (0.25±0.14) (P<0.05). The expression of NGF, PPAR ß/δ, COX, IDH, ATP, and MHC-â mRNA in NGF gene transfection group were significantly higher than those in sham-operated group and blank control group (P<0.05). Conclusions: NGF gene transfection can promote angiogenesis in the ischemic limbs of mice, increase the blood perfusion, and thus induce the remodeling of skeletal muscle fibers to type â . This process may be related to NGF-induced PPAR ß/δ expression and promote the cellular aerobic metabolism in skeletal muscle.
Assuntos
Fator de Crescimento Neural , PPAR beta , Feminino , Camundongos , Animais , PPAR beta/metabolismo , PPAR beta/uso terapêutico , Membro Posterior/irrigação sanguínea , Membro Posterior/metabolismo , Isquemia/tratamento farmacológico , Fibras Musculares Esqueléticas/metabolismo , Extremidade Inferior , Modelos Animais de Doenças , RNA Mensageiro , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/uso terapêuticoRESUMO
Objective: To evaluate the early and long-term outcomes of carotid endarterectomy for carotid artery stenosis and analyse the risk factors for the outcomes. Methods: A retrospective review of 369 patients underwent carotid endarterectomy(CEA) in Peking Union Medical College Hospital from Oct 2006 to Nov 2012 was conducted. Clinical data including general conditions, perioperative and follow-up outcomes were collected. Results: Three hundred sixty-nine patients underwent 407 CEAs. The long-term follow-up rate (≥30 d) was 89.9% and follow-up period was 11.8-48.3 months. Among 407 CEAs, patients with symptomatic carotid artery stenosis, carotid stenosis over 70% and contralateral severe carotid stenosis occupied 78.0%(317/407), 98.4%(400/407) and 12.04%(49/407) respectively. Total early complications (<30 d) of stroke, cardiac events and death was 3.93% (16/407). Univariate analysis showed no risk factor had significant effect on early complications (P>0.05). Total long-term complications of stroke, cardiac events and death was 8.7% (32/366). Univariate analysis showed that total long-term complication rate of smoking group was higher than non-smoking group (12.1% vs 5.1%, P<0.05), contralateral carotid artery stenosis group was higher than opposite one (28.6% vs 8.0%, P<0.05). Multivariate Logistic regression showed the HR of long-term complications rate in patients aged over 65 years, smoking history, myocardial infarction and contralateral carotid stenosis were 2.59, 2.66, 2.48 and 6.06, respectively. Conclusions: CEA is safe method for the treatment of carotid stenosis. To CEA, age over 65 years, smoking history, myocardial infarction and contralateral carotid stenosis are risk factors for long-term adverse outcomes.
Assuntos
Estenose das Carótidas , Endarterectomia das Carótidas , Acidente Vascular Cerebral , Idoso , Humanos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To analyze the efficacy and safety of surgery and endovascular management in treating Takayasu arteritis. METHODS: The data of 116 patients (24 males and 92 females; mean age (32±12) years) with Takayasu arteritis and underwent surgery or endovascular therapy was retrospective analyzed. According to the two different surgical procedures, the patients were divided into two groups: open repair group and endovascular repair group. One hundred and fifty-four surgical procedures were done including 69 cases of open repair and 85 cases of endovascular repair. A total of 211 arterial lesions were revascularized (open repair 114; endovascular repair 97). RESULTS: Among the 154 surgical procedures, 11(7.1%) presented a complication during perioperative period including 6(8.7%) of open repair and 5(5.9%) of endovascular repair. After a median follow-up of 38.5(0.5-142.0) months, three(4.3%) cases of stroke and death were observed in open repair group, two(2.3%) cases of stroke and 4(4.7%) cases of death were observed in endovascular repair group. At 1, 3, 5 and 10 years of follow-up, primary patency rate of open repair and endovascular repair were 95.0% and 89.3%, 84.3% and 69.8%, 73.3% and 56.3%, 53.4% and 48.1%, respectively; Primary assisted patency rate were 100% and 97.5%, 90.4% and 78.2%, 79.1% and 72.8%, 60.7% and 54.0%, respectively; Secondary patency rate were 100% and 98.8%, 95.6% and 92.7%, 85.8% and 78.1%, 74.8% and 58.0%, respectively. Cumulative survival rate were 97.0% and 100%, 97.0% and 97.6%, 97.0% and 90.6%, 91.3% and 84.5%, respectively (χ(2)=0.182, P=0.669). CONCLUSIONS: Both of the surgical revascularization and endovascular management are safe and effective in the treatment of Takayasu arteritis. Although long-term patency of endovascular therapy is low, it can be performed repeatedly and can be used as a preferred approach in treating a short stenosis. Surgical repair shows excellent long-term durability, it seems to be more suitable for complex lesions and failure cases of endovascular management.
Assuntos
Implante de Prótese Vascular , Procedimentos Endovasculares/métodos , Arterite de Takayasu/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Constrição Patológica , Feminino , Humanos , Masculino , Período Perioperatório , Reoperação , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
AIMS: To estimate the efficacy of specific egg yolk immunoglobulin (IgY) for the treatment of lipopolysaccharide (LPS)-induced endotoxemia using a mouse model. METHODS AND RESULTS: Specific IgY was obtained from the yolk of hens immunized with formaldehyde-killed Escherichia coli O111 and showed a high binding activity to LPS when subjected to an ELISA. Endotoxemia was induced in mice by intraperitoneal injection of LPS at a dose of 20 mg kg(-1) for measuring survival rate and 10 mg kg(-1) for cytokine measurement. The survival rate of mice treated with 200 mg kg(-1) specific IgY or 5 mg kg(-1) dexamethasone was 70% while none of the mice in the normal saline-treated group survived more than 7 days. Specific IgY significantly (P < 0.05) decreased tumour necrosis factor-α (TNF-α) level and increased interleukin-10 (IL-10) level in the serum of endotoxemia mice. Specific IgY had less of an effect on TNF-α than dexamethasone, while its effect on increasing IL-10 was stronger than dexamethasone. Haematoxylin and eosin-stained sections indicated that IgY attenuated the damage to the lung and liver observed in mice with endotoxemia. CONCLUSIONS: The specific IgY increased the survival rate of mice with endotoxemia induced by LPS, down-regulated TNF-α and up-regulated IL-10 in serum and attenuated the extent of damage to the lung and liver. SIGNIFICANCE AND IMPACT OF THE STUDY: The specific IgY has potential for the treatment of LPS-induced endotoxemia.
Assuntos
Endotoxemia/tratamento farmacológico , Imunoglobulinas/uso terapêutico , Lipopolissacarídeos/efeitos adversos , Animais , Galinhas , Dexametasona/uso terapêutico , Gema de Ovo/imunologia , Endotoxemia/sangue , Endotoxemia/patologia , Feminino , Interleucina-10/sangue , Fígado/patologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Taxa de Sobrevida , Fator de Necrose Tumoral alfa/sangueRESUMO
Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca(2+) dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic ß receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic ß receptors, and a nitric oxide associated relaxing mechanism.
Assuntos
Jejuno/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Miosinas/metabolismo , Taurina/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Atropina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Cimetidina/farmacologia , Difenidramina/farmacologia , Sistema Nervoso Entérico/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Jejuno/fisiologia , Masculino , Antagonistas Muscarínicos/farmacologia , Quinase de Cadeia Leve de Miosina/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Fentolamina/farmacologia , Fosforilação , Propranolol/farmacologia , Ratos Sprague-Dawley , Taurina/antagonistas & inibidores , Tetrodotoxina/farmacologia , Verapamil/farmacologiaRESUMO
Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.
Assuntos
Animais , Masculino , Jejuno/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Miosinas/metabolismo , Taurina/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Atropina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Cimetidina/farmacologia , Difenidramina/farmacologia , Sistema Nervoso Entérico/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , /farmacologia , Jejuno/fisiologia , Antagonistas Muscarínicos/farmacologia , Quinase de Cadeia Leve de Miosina/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico/metabolismo , Fosforilação , Fentolamina/farmacologia , Propranolol/farmacologia , Ratos Sprague-Dawley , Taurina/antagonistas & inibidores , Tetrodotoxina/farmacologia , Verapamil/farmacologiaRESUMO
Surface geometry affects strongly superhydrophobic behavior. To characterize the effect, roughness as a comprehensive geometrical parameter is used, but this parameter in its general mathematic expression cannot reflect exactly such a geometrical effect, in particular, for the regularly textured or ordered patterned superhydrophobic surfaces. In this study, we propose a new parameter to mathematically describe roughness for such superhydrophobic surfaces. On the basis of this parameter, an ideal surface texture with the maximum roughness for achieving the superhydrophobicity is suggested, which is consistent with the previous experimental observations and theoretical considerations.