RESUMO
Frailty syndrome denotes a decreased capacity of the body to maintain the homeostasis and stress of the internal environment, which simultaneously increases the risk of adverse health outcomes in older adults, including disability, hospitalization, falls, and death. To promote healthy aging, we should find strategies to cope with frailty. However, the pathogenesis of frailty syndrome is not yet clear. Recent studies have shown that the diversity, composition, and metabolites of gut microbiota significantly changed in older adults with frailty. In addition, several frailty symptoms were alleviated by adjusting gut microbiota with prebiotics, probiotics, and symbiosis. Therefore, we attempt to explore the pathogenesis of frailty syndrome in older people from gut microbiota and summarize the existing interventions for frailty syndrome targeting gut microbiota, with the aim of providing timely and necessary interventions and assistance for older adults with frailty.
Assuntos
Fragilidade , Microbioma Gastrointestinal , Probióticos , Humanos , Idoso , Fragilidade/terapia , Idoso Fragilizado , Probióticos/uso terapêutico , PrebióticosRESUMO
AIM: To explore the mechanism of the healing of tendon tissue and anti-adhesion, and to discuss the role of the transforming growth factor-ß3 (TGF-ß3)/cAMP response element binding protein-1 (CREB-1) signaling pathway in the healing process of tendons. METHOD: All mice were divided into four groups of 1, 2, 4, and 8 weeks respectively. Each time group was divided into four treatment groups: the amplification group, the inhibition group, the negative group, and the control group. When the tendon injury model was established, the CREB-1 virus was injected into the tendon injury parts. A series of methods such as gait behaviourism, anatomy, histological examination, immunohistochemical examination and collagen staining were employed to assess the tendon healing and the protein expression of TGF-ß3, CREB-1, Smad3/7 and type I/III collagen (COL-I/III). CREB-1 virus was sent to tendon stem cells to assess the protein expression of TGF-ß1, TGF-ß3, CREB-1, COL-I/III by methods such as immunohistochemistry and Western blot. RESULTS: The amplification group showed better gait behaviourism than the inhibition group in the healing process. The amplification group also had less adhesion than the negative group. Hematoxylin-eosin (HE) staining of tendon tissue sections showed that the number of fibroblasts in the amplification group was less than the inhibition group, and the immunohistochemical results indicated that the expression of TGF-ß3, CREB-1, and Smad7 at each time point was higher than the inhibition group. The expression of COL-I/III and Smad3 in the amplification group was lower than the inhibition group at all time points. The collagen staining indicated that the ratio of type I/III collagen in the amplification group was higher than the negative group at 2,4,8 week. The CREB-1 amplification virus could promote the protein expression of TGF-ß3, CREB-1 and inhibit the protein expression of TGF-ß1 and COL-I/III in the tendon stem cells. CONCLUSION: In the process of tendon injury healing, CREB-1 could promote the secretion of TGF-ß3, so as to promote the tendon healing and have the effect of anti-adhesion in tendons. It might provide new intervention targets for anti-adhesion treatment of tendon injuries.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Traumatismos dos Tendões , Fator de Crescimento Transformador beta3 , Cicatrização , Animais , Camundongos , Tendões , Traumatismos dos Tendões/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta3/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Células-Tronco , Análise da Marcha , Aderências Teciduais/prevenção & controleRESUMO
BACKGROUND: Fascial autografts, which are easily available grafts, have provided a promising option in patients with massive rotator cuff tears. However, no fascial autografts other than the fascia lata have been reported, and the exact healing process of the fascia-to-bone interface is not well understood. The objective of this study is to histologically and biomechanically evaluate the effect of the thoracolumbar fascia (TLF) on fascia-to-bone healing. METHODS: A total of 88 rats were used in this study. Eight rats were killed at the beginning to form an intact control group, and the other rats were divided randomly into 2 groups (40 rats per group): the TLF augmentation group (TLF group) and the repair group (R group). The right supraspinatus was detached, and a 3 × 5 mm defect of the supraspinatus was created. The TLF was used to augment the torn supraspinatus in the TLF group, whereas in the R group, the torn supraspinatus was repaired in only a transosseous manner. Histology and biomechanics were assessed at 1, 2, 4, 8, and 16 weeks postoperatively. RESULTS: The modified tendon maturation score of the TLF group was higher than that of the R group at 8 weeks (23.00 ± 0.71 vs. 24.40 ± 0.89, P = .025) and 16 weeks (24.60 ± 0.55 vs. 26.40 ± 0.55, P ≤ .001). The TLF group showed a rapid vascular reaction, and the peak value appeared at 1 week. Later, the capillary density decreased, and almost no angiogenesis was observed at 8 weeks postoperatively. Immunohistochemistry results demonstrated a significantly higher percentage of collagen I in the TLF group at 4, 8, and 16 weeks (24.78% ± 2.76% vs. 20.67% ± 2.11% at 4 weeks, P = .046; 25.46% ± 1.77% vs. 21.49% ± 2.33% at 8 weeks, P = .026; 34.77% ± 2.25% vs. 30.01% ± 3.17% at 16 weeks, P = .040) postoperatively. Biomechanical tests revealed that the ultimate failure force in the TLF group was significantly higher than that in the R group at the final evaluation (29.13 ± 2.49 N vs. 23.10 ± 3.47 N, P = .022). CONCLUSIONS: The TLF autograft can promote a faster biological healing process and a better fixation strength. It could be used as an alternative reinforcement or bridging patch when the fascia lata is not appropriate or available for superior capsule reconstruction (SCR).
Assuntos
Lesões do Manguito Rotador , Animais , Autoenxertos/patologia , Fenômenos Biomecânicos , Fascia Lata/transplante , Humanos , Ratos , Manguito Rotador/patologia , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/patologia , Lesões do Manguito Rotador/cirurgia , Transplante AutólogoRESUMO
PURPOSE: To observe the changes of gait behavior and the expression of wound healing factors of transforming growth factor-ß1 (TGF-ß1), TGF-ß3 and cAMP response element binding protein-1 (CREB-1) during the healing of Achilles tendon in a rat model, and to investigate whether gait analysis can be used to evaluate the tendon healing. METHODS: Achilles tendon of 40 healthy male Sprague-Dawley rats were transected and sutured to establish the Achilles tendon injury (ATI) model. They were randomly divided into 4 groups based on the observational time point at 1, 2, 4 and 6 weeks after injury (n = 10 for each group). Before modeling, 9 rats were randomly selected for CatWalk gait analysis, which contained step cycle, single stance time and average speed. Data were recorded as the normal controls. After then, ATI models were established in the left hind limbs of the all 40 rats (ATI group), while the right hind limbs were only cut and sutured without injury of the Achilles tendon (sham operation group). At 1, 2, 4 and 6 weeks after injury, the gait behavior of the corresponding group of rats (n = 9) as observed and recorded by CatWalk platform. After then, the rats were sacrificed and Achilles tendon of both limbs was harvested. The tendon healing was observed by gross anatomy and histological examination, and the protein and mRNA expression of TGF-ß1, TGF-ß3, CREB-1 were observed by immunohistochemistry and qPCR. The results of tendon gross grading were analyzed by Wilcoxon rank sum test, and other data were analyzed by one-way analysis of variance among multiple groups. RESULTS: Compared with normal controls, all gait indexes (step cycle, single stance time and average speed) were greatly affected following ATI, which however improved with time. The step cycle was significantly lower at 1, 2 and 4 weeks after ATI (compared with normal controls, all p < 0.05), but almost returned to the normal level at 6 weeks ((0.694 ± 0.102) vs. (0.503 ± 0.094) s, p > 0.05). The single stance time of the ATI group was significantly shorter at 1 and 2 weeks after operation ((0.078 ± 0.010) s at 1 week, (0.078 ± 0.020) s at 2 weeks, all p < 0.001) and revealed no significant difference at 4 weeks (p = 0.120). The average speed of ATI group at 1, 2, 4, 6 weeks was significantly lower than that in the normal control group (all p < 0.001). Gross observation showed that the grade of local scar adhesion in ATI group increased significantly at 2, 4 and 6 weeks, compared with the sham operation group (all p < 0.001). Extensive adhesion was formed at 6 weeks after ATI. The results of HE staining showed that the number of fibroblast increased gradually and arranged more orderly in ATI group at 1, 2 and 4 weeks (all p < 0.001), and decreased at 6 weeks, but it was still significantly higher than that of the sham operation group (p < 0.001). Immunohistochemistry showed that the positive expression of TGF-ß1, TGF-ß3, CREB-1 in ATI group was higher than that in the sham operation group at 4 time points (all p < 0.05), which reached the peak at 2 weeks after operation and decreased at 4 weeks (p = 0.002, p < 0.001, p = 0.041, respectively). The results of qPCR suggested that the mRNA expression of TGF-ß1, TGF-ß3, CREB-1 in ATI group was higher than that in the sham operation group at all-time points (all p < 0.05), which reached the peak at 2 weeks after operation, decreased at 4 weeks, and significantly decreased at 6 weeks (all p < 0.001). CONCLUSION: Gait behavior indexes are associated with Achilles tendon healing. The study gives an insight of TGF-ß1, TGF-ß3, CREB-1 changes in the coursing of Achilles tendon healing and these cytokines may be able to be used to regulate the Achilles tendon healing.
Assuntos
Tendão do Calcâneo , Animais , Proteína de Ligação a CREB , Análise da Marcha , Masculino , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta3 , CicatrizaçãoRESUMO
BACKGROUND: Chronic muscle injury is characteristics of fatty infiltration and fibrosis. Recently, fibro/adipogenic progenitors (FAPs) were found to be indispensable for muscular regeneration while were also responsible for fibrosis and fatty infiltration in muscle injury. Many myokines have been proven to regulate the adipose or cell proliferation. Because the fate of FAPs is largely dependent on microenvironment and the regulation of myokines on FAPs is still unclear. We screened the potential myokines and found Interleukin-15 (IL-15) may regulate the fatty infiltration in muscle injury. In this study, we investigated how IL-15 regulated FAPs in muscle injury and the effect on muscle regeneration. METHODS: Cell proliferation assay, western blots, qRT-PCR, immunohistochemistry, flow cytometric analysis were performed to investigate the effect of IL-15 on proliferation and adipogensis of FAPs. Acute muscle injury was induced by injection of glycerol or cardiotoxin to analyze how IL-15 effected on FAPs in vivo and its function on fatty infiltration or muscle regeneration. RESULTS: We identified that the expression of IL-15 in injured muscle was negatively associated with fatty infiltration. IL-15 can stimulate the proliferation of FAPs and prevent the adipogenesis of FAPs in vitro and in vivo. The growth of FAPs caused by IL-15 was mediated through JAK-STAT pathway. In addition, desert hedgehog pathway may participate in IL-15 inhibiting adipogenesis of FAPs. Our study showed IL-15 can cause the fibrosis after muscle damage and promote the myofiber regeneration. Finally, the expression of IL-15 was positively associated with severity of fibrosis and number of FAPs in patients with chronic rotator cuff tear. CONCLUSIONS: These findings supported the potential role of IL-15 as a modulator on fate of FAPs in injured muscle and as a novel therapy for chronic muscle injury.
Assuntos
Adipogenia , Interleucina-15/metabolismo , Células-Tronco Mesenquimais/citologia , Músculos/fisiologia , Regeneração , Adipócitos/citologia , Animais , Diferenciação Celular , Regulação para Baixo , Humanos , Janus Quinases/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição STAT/metabolismoRESUMO
Hypertension is the most prevalent chronic disease and a risk factor for various diseases. Although its mechanisms and therapies are constantly being updated and developed, they are still not fully clarified. In recent years, novel gut microbiota and its metabolites have attracted widespread attention. It is strongly linked with physiological and pathological systems, especially TMA and TMAO. TMA is formed by intestinal microbial metabolism of choline and L-carnitine and converted into TMAO by FMO3. This paper collected and collated the latest researches and mainly discussed the following four parts. It introduced gut microbiota; provided a focus on TMA, TMA-producing bacteria, and TMAO; summarized the alternations in hypertensive patients and animals; discussed the mechanisms of TMAO with two respects; and summarized the regulatory factors may be as new interventions and therapies of hypertension. And, more relevant studies are still prospected to be accomplished between hypertension and TMA/TMAO for further clinical services.
Assuntos
Microbioma Gastrointestinal/fisiologia , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Metilaminas/metabolismo , Animais , Carnitina/metabolismo , Colina/metabolismo , Microbioma Gastrointestinal/imunologia , Glucose/metabolismo , Humanos , Inflamação/metabolismo , Metabolismo dos LipídeosRESUMO
OBJECTIVE: To study the correlation between the Narcotrend index, cerebral state index and predicted effect site concentration during different state of consciousness in the absence of surgery in elderly patients with target controlled infusion of propofol. METHODS: Twenty patients aged from 65-75 years categorized as ASA class I - II who were scheduled to undergo general surgery under general anesthesia with target controlled infusion of propofol were recruited. During the target controlled infusion of propofol, the propofol infusion was set at an initial effect site concentration of 0.5 mg/L and increased by 0.5 mg /L every 5 min until the modified observer's assessment of alertness / sedation scale (OAA/S) values of zero. The predicted effect site concentration of propofol, the values of CSI and NCT were recorded and the sedation level was examined by the modified OAA/S every 20 s. The predicted effect site concentrations of propofol in target controlled infusion (TCI) system were recorded when they increased by more than 0.1 mg/L. The predicted effect site concentrations of propofol and the values of NCT and CSI at LVC and LOC of the patients were recorded. RESULTS: There was a good linear correlation between NCT and the predicted effect site concentration of propofol (R2 = 0. 867, P < 0.01), as well as that between CSI and the predicted effect site concentration of propofol (R2 = 0.893, P < 0.01). The predicted effect site concentrations of propofol at LVC was (1.56 +/- 0.13) mg/L while the values of NCT was 74.00 +/- 4.69 and CSI 69.82 +/- 5.47. The predicted effect site concentrations of propofol at LOC was (2.15 +/- 0.27) mg/L while the values of NCT and CSI were 63.30 +/- 7.50 and 58.78 +/- 6.90 respectively. All of the values of NCT, CSI and the predicted effect site concentrations had a good linear correlation with OAA/S. There was a negative correlation between OAA/S and the predicted effect site concentration. At the same time, there was a positive correlation between OAA/S and NCT as well as that between OAA/S and CSI. And the correlation coefficients were - 0.968, 0.938, 0.940 respectively (P < 0.01). The values of NCT were higher significantly than that of CSI in different degree of LOC (P < 0.01). CONCLUSION: During elder people's target controlled infusion of propofol, LVC and LOC occur within a definite range of predicted effect site concentrations. There is a good linear correlation between NCT, CSI and the predicted effect site concentrations of propofol. For the elders, both NCT and CSI reflect the sedation level of propofol. Although there is a significant correlation between NCT and CSI, a deviation does exist in a certain range. Therefore a simple 1:1 transfer from NCT to CSI is inadequate.
Assuntos
Anestesia/métodos , Sedação Consciente/métodos , Sedação Profunda , Propofol/administração & dosagem , Idoso , Anestésicos Intravenosos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Monitorização IntraoperatóriaRESUMO
BACKGROUND: Study shows that signal transducer and activator of transcription 3 (STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2 (PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats. AIM: To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats. METHODS: A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with N-methyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen (PCNA), STAT3, and PKM2 were examined by Western blot and immunofluorescence. RESULTS: We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liver precancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression, PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells. Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2. CONCLUSION: The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.
Assuntos
Transformação Celular Neoplásica/patologia , Neoplasias Hepáticas/patologia , Lesões Pré-Cancerosas/patologia , Piruvato Quinase/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Linhagem Celular , Transformação Celular Neoplásica/efeitos dos fármacos , Óxidos S-Cíclicos/farmacologia , Modelos Animais de Doenças , Glicólise/efeitos dos fármacos , Hepatócitos , Humanos , Peróxido de Hidrogênio/toxicidade , Fígado/citologia , Fígado/patologia , Masculino , Metilnitronitrosoguanidina/toxicidade , Fosforilação/efeitos dos fármacos , Lesões Pré-Cancerosas/induzido quimicamente , Ratos , Ratos Wistar , Fator de Transcrição STAT3/antagonistas & inibidores , Células-Tronco , Regulação para CimaRESUMO
BACKGROUND: Arthroscopic ankle arthrodesis (AAA) is recognized as the standard treatment for the end-stage ankle arthritis. Two-screw configuration fixation is a typical technique for AAA; however, no consensus has been reached on how to select most suitable inserted position and direction. For better joint reduction, we developed a new configuration (2 home run-screw configuration: 2 screws are inserted from the lateral-posterior and medial-posterior malleolus into the talar neck) and investigated whether it turned out to be better than the other commonly used 2-screw configurations. METHODS: In this study, we investigated three kinds of 2-screw configurations: 2 "home run"-screw configuration (group A), crossed transverse configuration (the screw is inserted from the medial malleolus into the anterior talus and the other from the lateral tibia maintains posterior talus, group B), and 2 parallel screw configuration (2 parallel screws are inserted from the posteromedial side of the tibia into talus, group C). The effects of the above three insertions on the loading stress of the tibio-talar joint were comparatively analyzed with a three-dimensional finite element model. RESULTS: Group A was better than groups B and C in respect of stress distribution uniformity and superior to both groups B and C in anti-flexion strength and anti-internal rotation strength. Group A was slightly worse than group C but better than group B in anti-dorsiflexion and anti-valgus and varus strength. CONCLUSIONS: Two "home run"-screw configuration facilitates the reduction of anterior talus dislocation of end-stage ankle arthritis. Our finite element analysis demonstrates the configuration is superior to crossed transverse and parallel configuration for arthroscopic ankle arthrodesis in terms of stress distribution and initial stability.
Assuntos
Articulação do Tornozelo/cirurgia , Artrite/cirurgia , Artrodese/métodos , Parafusos Ósseos , Adulto , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/fisiopatologia , Artrite/diagnóstico por imagem , Artrodese/instrumentação , Análise de Elementos Finitos , Humanos , Imageamento Tridimensional/métodos , Instabilidade Articular/prevenção & controle , Masculino , Estresse Mecânico , Tíbia/cirurgia , Tomografia Computadorizada por Raios X/métodos , Suporte de CargaRESUMO
OBJECTIVE: To study the effects of selective head mild hypothermia on endogenous neuroprotection in brain following global cerebral ischemia/reperfusion. METHODS: Fifteen dogs were randomly divided into three groups: nonischemic control group (Group A, n = 4), undergoing thoracotomy without cerebral ischemia and general care for 8 hours thereafter; cerebral ischemia/reperfusion group (Group B, n = 5) undergoing thoracotomy, clipping of the ascending aorta for 18 min, cardiac resuscitation, maintenance of respiration and circulation for 8 h; and mild hypothermia group (Group C, n = 6), received selective head mild hypothermia, i.e. lowering the tympanic temperature to (34 +/- 0.5) degrees C for 8 hours after cerebral ischemia. The neurological function was assessed by Glasgow coma scale and Pittsburgh brain stem score. At the end of experiment, the dog brains were taken out to obtain the right parietal cerebral cortex. Immunohistochemistry was used to detect the parvalbumin (PV) and HSP(70). Xanthine oxidase method was used to detect the superoxide dismutase (SOD) activities: total SOD (T-SOD), manganese SOD (Mn-SOD), and copper-zinc SOD (Cu-ZnSOD). Spectrophotometry was used to detect the activities of glutathione (GSH) and glutathione peroxidase (GSH-Px). RESULTS: The comprehensive neurological score of Group C was 23.4 +/- 1.5, significantly higher than that of Group B (18.6 +/- 1.0, P < 0.05). The cerebral cortex of Group A showed a lot of PV positive neurons, the density of PV-positive neurons decreased significantly in Group B (P < 0.05), and the density of PV-positive neurons win Group C was significantly higher then that of Group B, however, still significantly lower than that of Group A (both P < 0.05). The density of HSP70-LI neurons of Group A was very low (5.5 +/- 2.1), those of Groups B and C were significantly higher than that of Group A (15.6 +/- 3.7 and 27.1 +/- 4.9 respectively, P < 0.05 or P < 0.01), that of Group C being significantly higher than that of Group B (P < 0.05). The contents of GSH, T-SOD, MnSOD, Cu-ZnSOD, and GSH-Px of Group B were all significantly lower than those of Group A (P < 0.05 or P < 0.01). The contents of GSH, T-SOD, and Cu-ZnSOD of Group C were significantly higher than those of Group B (P < 0.05 or P < 0.01), CONCLUSION: Mild hypothermia may up-regulate the endogenous neuroprotection in brain tissue following cerebral ischemia/reperfusion and may be beneficial to cerebral ischemia.
Assuntos
Isquemia Encefálica/complicações , Encéfalo/patologia , Hipotermia Induzida/métodos , Traumatismo por Reperfusão/terapia , Animais , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Contagem de Células , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Modelos Animais de Doenças , Cães , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico HSP70/análise , Imuno-Histoquímica , Neurônios/metabolismo , Neurônios/patologia , Parvalbuminas/análise , Traumatismo por Reperfusão/etiologia , Espectrofotometria/métodosRESUMO
OBJECTIVE: To investigate the effects of intravenous anesthetics on LPS-induced inflammatory responses of primary cultures of rat glial cells in vitro. METHODS: The primary cultures of rat glial cells were stimulated with lipopolysaccharide( LPS) to produce inflammatory responses. Glial cells were divided into 8 groups (n=4): blank control (Group C), LPS(Group L), 100micromol/L ketamine with LPS(Group K1), 1000micromol/L ketamine with LPS (Group K2), 30micromol/L propofol with LPS (Group P1), 300micromol/L propofol with LPS (Group P2), 3micromol/L midazolane with LPS (Group M1), and 30micromol/L midazolane with LPS (Group M2). TNF-alpha released into the culture media was measured by radioimmunity assay. RESULTS: Compared with the blank control Group C, LPS-induced TNF-alpha productions in Group L, K1, K2, P1, P2, M1 and M2 increased significantly. The levels of TNF-alpha in Group K1 and K2 were significantly lower than those in Group L (P<0.05), but TNF-alpha productions in Group P1, P2, M1 and M2 were not significantly different as compared with that in Group L. CONCLUSION: Ketamine can reduce LPS-induced TNF-alpha production of glial cells, thereby inhabiting some of the inflammatory responses. Propofol and midazolam have no effect on the production of TNF-alpha from LPS-stimulated glial cells.
Assuntos
Anestésicos Intravenosos/farmacologia , Ketamina/farmacologia , Lipopolissacarídeos/farmacologia , Neuroglia/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese , Animais , Células Cultivadas , Feminino , Proteína Glial Fibrilar Ácida/biossíntese , Imuno-Histoquímica , Neuroglia/citologia , Neuroglia/metabolismo , Propofol/farmacologia , Ratos , Ratos WistarRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Mistletoe (Viscum coloratum (Kom.) Nakai) has long been categorized as a traditional herbal medicine in Asia. In addition to its application in cancer therapy, mistletoe has also been used in the treatment of chronic hepatic disorders in China. In the present study, we investigated the antifibrotic effect and mechanisms of action of mistletoe extracts in a rat model of carbon tetrachloride (CCl4)-induced hepatotoxicity. MATERIALS AND METHODS: An experimental model of hepatic fibrosis was established by intraperitoneal injection of rats with CCl4 for 8 weeks. Rats were subsequently treated with a mistletoe alkaloid fraction preparation via oral administration (120mg/kg daily for 8 weeks) or with distilled water as a control. Histopathological changes were observed by hematoxylin and eosin staining and Masson׳s trichrome staining. The expression of markers relevant to hepatic stellate cell (HSC) activation in the liver was assessed by real-time reverse transcription-polymerase chain reaction, immunohistochemistry and western blotting. The anti-fibrosis activity and mechanisms of action of mistletoe alkaloid fractions were further investigated in the HSC-T6 HSC line, following treatment with mistletoe alkaloid fractions (12mg/ml) for 48h. RESULTS: Hepatic fibrosis decreased markedly in CCl4-treated animals following treatment with mistletoe alkaloid fractions, compared to controls. The mRNA levels of transforming growth factor-ß1 (TGF-ß1), procollagen I and tissue inhibitors of metalloproteinases (TIMPs) were significantly downregulated, by about 40%, 40% and 45%, respectively, in liver tissues from rats treated with mistletoe alkaloid fractions. Furthermore, significant downregulation of TGF-ß1, TGF-ß1 receptor, phosphorylated Smad 2 and alpha smooth muscle actin (α-SMA) proteins, by about 45%, 30% and 40%, respectively, was also observed in liver tissues from mistletoe alkaloid fractions-treated rats. In contrast, Smad 7 levels were significantly increased by about 30% in mistletoe alkaloid fractions-treated rats. Treatment of HSC-T6 cells with mistletoe alkaloid fractions significantly induced Smad 7 expression and inhibited the expression of α-SMA, TGFß1, TGF-ß1 receptor, Smad 2 and TIMP-1, in vitro. CONCLUSION: We demonstrate that mistletoe alkaloid fractions decrease extracellular matrix accumulation by inhibiting HSC activation. Mechanistically, this may occur via inhibition of TGF-ß1/Smad 2 and Smad 7 signal transduction, thereby blocking the synthesis of procollagen I and TIMP-1. These findings suggest that mistletoe alkaloid fractions may be a potential therapeutic agent for the treatment of hepatic fibrosis.
Assuntos
Alcaloides/farmacologia , Intoxicação por Tetracloreto de Carbono/prevenção & controle , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/prevenção & controle , Erva-de-Passarinho/química , Extratos Vegetais/farmacologia , Animais , Sequência de Bases , Intoxicação por Tetracloreto de Carbono/metabolismo , Linhagem Celular , Primers do DNA , Células Estreladas do Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Proteínas Smad/antagonistas & inibidores , Fator de Crescimento Transformador beta/antagonistas & inibidoresRESUMO
OBJECTIVE: To study the feasibility of using Narcotrend (NCT) in monitoring the anesthetic depth during endotracheal intubation in sevoflurane anesthesia. METHODS: Thirty ASA I-II patients (aged 20-49 years) undergoing gynecologic surgery under general anesthesia with tracheal intubation were randomized into sevoflurane group (n=15) and sevoflurane plus rocuronium group (n=15). In the former group, anesthesia was induced with sevoflurane at the primary concentration of 8% till the final end expiratory concentration reaching 2 MAC(minimum alveolar concentration) for 3 min, followed then by tracheal intubation and further observation of the indicators for another 3 min. The patients in sevoflurane plus rocuronium group received identical anesthesia procedures except for the administration of intravenous injection of rocuronium (0.6 mg/kg) after the loss of eyelash reflex. The NCT, BIS and hemodynamics were recorded during the process. RESULTS: No significant differences were noted in NCT, bispectral index (BIS), MAP and heart rate before tracheal intubation between the two groups (P>0.05). The NCT and BIS increased significantly after tracheal intubation in sevoflurane group (P<0.05), but remained below 60. No significant changes in NCT and BIS occurred during intubation in sevoflurane plus rocuronium group (P>0.05). The mean arterial pressure (MAP) and heart rate were significantly increased in both groups after tracheal intubation in comparison with those before tracheal intubation (P<0.05), but the increment in sevoflurane group was significantly greater (P<0.05). CONCLUSION: NCT may reflect the changes of the anesthetic depth resulting from the nociceptive stimulus of tracheal intubation in sevoflurane- induced anesthesia. NCT and BIS can not serve such a purpose in combined anesthesia with sevoflurane and rocuronium.
Assuntos
Anestesia , Anestésicos Intravenosos/administração & dosagem , Intubação Intratraqueal/métodos , Éteres Metílicos/administração & dosagem , Monitorização Intraoperatória/métodos , Adulto , Androstanóis/administração & dosagem , Hemodinâmica , Humanos , Pessoa de Meia-Idade , Rocurônio , Sevoflurano , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Recent studies have suggested that nuclear factor κB (NF-κB) may play a role in mediating nerve injury-induced neuropathic pain. Here, we examined the effects of intrathecal pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor, on the development of neuropathic pain, spinal microglial activation, and CX3CR1 expression induced by sciatic chronic constriction injury (CCI) model in rats. METHODS: Under chloral hydrate anesthesia, male Sprague-Dawley rats (300-350 g) fitted with intrathecal catheters underwent either sciatic CCI or sham surgery. Intrathecal saline or PDTC (100 or 1000 pmol/d) was infused 1 day before or 3 days after CCI (n = 8). The rat hind-paw withdrawal threshold to mechanical stimuli and withdrawal latency to radiant heat were determined before surgery and from days 1 to 7 after CCI. Spinal microglial activation was evaluated with OX-42 immunoreactivity, and spinal CX3CR1 expression was assessed by Western blotting. RESULTS: Chronic constriction injury induced mechanical allodynia and thermal hyperalgesia and microglial activation as demonstrated by OX-42 expression. Whereas it had no apparent effect on spinal cord histology, intrathecal administration of PDTC prevented the development of the mechanical and thermal hyperalgesia and inhibited nerve injury-induced microglial activation and spinal CX3CR1 expression. CONCLUSIONS: In this study, we have shown the protective effect of intrathecal PDTC on the development of nociceptive behaviors induced by CCI in rats. The activation of NF-κB pathway may contribute to spinal microglial activation and CX3CR1 up-regulation.
Assuntos
Neuralgia/tratamento farmacológico , Pirrolidinas/uso terapêutico , Neuropatia Ciática/tratamento farmacológico , Tiocarbamatos/uso terapêutico , Animais , Western Blotting , Receptor 1 de Quimiocina CX3C , Cateterismo , Constrição Patológica , Temperatura Alta , Hiperalgesia/tratamento farmacológico , Imuno-Histoquímica , Injeções Espinhais , Locomoção/fisiologia , Masculino , Microglia/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Limiar da Dor/efeitos dos fármacos , Estimulação Física , Pirrolidinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptores de Quimiocinas/efeitos dos fármacos , Tiocarbamatos/administração & dosagemRESUMO
OBJECTIVE: To observe the prophylactic effect of granisetron on postoperative nausea and vomiting (PONV) after supratentorial craniotomy. METHODS: Seventy ASA I-II patients undergoing elective supratentorial craniotomy were randomly and double-bindly divided into two groups: control group (Group C, n = 35) and granisetron group (Group G, n = 35). All the patients received either 0.9% NS (Group C) or granisetron 3 mg (Group G) via intravenous injection. The incidences of postoperative nausea and vomiting were recorded at 24 h, 48 h, 72 h after supratentorial craniotomy. RESULTS: The incidence of PONV in Group G was lower than that in Group C (25.7% vs 57.1%, P < 0.01). The incidence of server nausea with vomiting or vomiting in Group G was lower than that in Group C (17.2% vs 48.6%, P < 0.01). CONCLUSION: Granisetron can be used effectively and safely to prevent PONV in supratentorial craniotomy.