RESUMO
Emerging research has suggested the anticancer potential of tanshinone IIA, the bioactive ingredient isolated from the traditional Chinese herb Salvia miltiorrhiza. However, the molecular mechanism of sodium tanshinone IIA sulfonate (STS) antilung cancer effect is not very clear. In this study, our purpose is to investigate the roles of STS and elongation factor-2 kinase (eEF-2K) in regulating the proliferation, migration, and invasion of A549 cells and explore the implicated pathways. We found that STS suppressed A549 cell survival and proliferation in a time- and xdose-dependent manner. Knockdown of eEF-2K and treatment with STS synergistically exerted antiproliferative, -migratory, and -invasive effects on A549 cells. These effects were caused by attenuation of the extracellular signal-regulated kinase (ERK) pathway via inhibition of tissue transglutaminase (TG2). In summary, the inhibition of eEF-2K synergizes with STS treatment, exerting anticancer effects on lung adenocarcinoma cells through the TG2/ERK signaling pathway, which provides a potential therapeutic target for treating lung adenocarcinoma.
Assuntos
Adenocarcinoma de Pulmão , MAP Quinases Reguladas por Sinal Extracelular , Células A549 , Proliferação de Células , Humanos , Sistema de Sinalização das MAP Quinases , Fatores de Alongamento de Peptídeos/farmacologiaRESUMO
PURPOSE: Postpartum depression (PPD) is the most common psychiatric condition after childbirth which not only effects the mother's health, but also might have impact on child's development and parenting behaviors. Because the etiology of PPD has not been fully cleared, the efforts towards identification of risk factors are crucial for both the children and mother's health. METHOD: PubMed, EMBASE and PsycINFO databases were searched since inception until July 2019 to collect data about the risk factors of PPD and only systematic review and meta-analysis can be included. RESULT: To identify the real risk factors, protective factors and controversial factors, nineteen parts of the interpretation were adopted. The risk factors are mainly concentrated in the following aspects: violence and abuse, immigration status, gestational diabetes, cesarean section, depressive history, vitamin D deficiency, obese and overweight, postpartum sleep disruption and poor postpartum sleep, lack of social support, traditional dietary pattern (Japanese, Indian, United Kingdom, and Brazilian dietary pattern), multiple births, preterm and low-birth-weight infants, postpartum anemia, negative birth experience. The controversial factors are serum level of cortisol, thyroid peroxidase autoantibodies status, acculturation, traditional confinement practices. Skin-to-skin care, higher concentrations of DHA in mothers' milk, greater seafood consumption, healthy dietary patterns, multivitamin supplementation, fish and PUFA intake, calcium, Vitamin D, zinc and possibly selenium are protective factors. CONCLUSION: Thirteen risk factors were identified, but five factors still controversial due to the insufficient of the evidence. What's more, skin-to-skin care and some nutrition related factors are protective factors against PPD.
Assuntos
Depressão Pós-Parto , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Brasil , Cesárea , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/etiologia , Metanálise como Assunto , Fatores de Risco , Revisões Sistemáticas como Assunto , Reino UnidoRESUMO
The study is aiming to evaluate the treatment safety and efficacy of greenlight laser photovaporization of the prostate (PVP) combined with transurethral electrovaporization resection (TUVP) for elderly (≥ 70 years) men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH/LUTS) with a large prostate volume (≥ 80 mL). One hundred twelve BPH/LUTS patients treated with PVP were divided into 2 groups according to prostate volume (PV), the outcomes of the 2 groups were assessed at 12 months after the operation. Patients in the PV ≥ 80 group (nâ=â51) had a higher level of maximum detrusor pressure (Pdet.max) than those in the PVâ<â80 group (nâ=â61) (97.14 â±â 36.68 vs 70.70â±â32.55, Pâ<â.001). Pdet.max level of the 2 groups was significantly decreased at the end of follow-up. International Prostate Symptom Score questionnaires (IPSS) score, maximum flow rate (Qmax), and residual urine volume (PVR) were significantly improved in comparison to the preoperative status (Pâ<â.001). PVP combined with TUVP can significantly improve outcomes (IPSS, Qmax, PVR) and is a safe and effective technique for elderly BPH/LUTS patients with a large prostate volume.
Assuntos
Terapia a Laser/métodos , Sintomas do Trato Urinário Inferior/cirurgia , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Idoso , Idoso de 80 Anos ou mais , Humanos , Terapia a Laser/efeitos adversos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Próstata/cirurgia , Hiperplasia Prostática/complicações , Estudos Retrospectivos , Ressecção Transuretral da Próstata/efeitos adversos , Resultado do Tratamento , Uretra/cirurgiaRESUMO
The purpose of this study is to assess the safety and efficacy of GreenLight laser photoselective vaporization of the prostate (PVP) for the treatment of benign prostate hyperplasia/lower urinary tract symptoms (BPH/LUTS) in patients with different post-void residual urine (PVR). BPH/LUTS patients treated with PVP from January 2014 to January 2016 were enrolled in the present study. All patients were divided into PVR > 50, 50 ≤ PVR < 400, and PVR ≥ 400 ml groups, and standard general and urological methods for BPH/LUTS were carried out. PVP surgery was performed, and the follow-up outcome was investigated 6 months after surgery. A total of 429 patients were included, and there were no significant differences in comorbid diseases or habits among the three groups. The maximum urinary flow rate (Qmax) differed significantly among the groups (P < 0.001), while patients in the PVR < 50 ml group had higher maximum detrusor pressure (Pdet.max) level than the other two groups (P < 0.001). Patients in 50 ≤ PVR < 400 (P < 0.001) and PVR ≥ 400 (P < 0.001) ml groups were more likely to develop detrusor underactivity than those in the PVR < 50 ml group. All patients were treated with PVP, and there were no severe complications requiring rehospitalization or reoperation except nine designed re-treatments. Follow-up data of 387 patients were available. Significant improvement in outcome parameters (International Prostate Symptom Score [IPSS], Qmax, and PVR) was observed in comparison with baseline measurements for the three groups. PVP significantly improved the IPSS, Qmax, and PVR in patients with different PVR; PVP is a safe and effective procedure for BPH/LUTS patients.
Assuntos
Terapia a Laser/métodos , Sintomas do Trato Urinário Inferior/cirurgia , Hiperplasia Prostática/cirurgia , Retenção Urinária/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Ressecção Transuretral da Próstata/métodos , Resultado do Tratamento , Retenção Urinária/etiologiaRESUMO
OBJECTIVE: To explore the value of multiparameter flow cytometry in diagnosis of non-Hodgkin's lymphoma (NHL). METHODS: Twenty patients with NHL admitted in Traditional Chinese Medicine Hospital of Zhengzhou from January 2009 to August 2014 years were enrolled into this study, among them 13 cases received lymnode puncture, 2 cases were given bone marrow aspiration, 2 cases received peripheral blood examination, 3 cases suffered lymphnode biopsy. RESULTS: After FCM immune typing and cytological smear, 6 cases was confirmed to be B-SLL, 1 case was B-NHL, 1 case was FL, 5 cases was DLBCL, 2 cases was T-NHL, 3 cases was T-LBL, 1 case was NK/T-NHL, 1 case was PTun. CONCLUSION: Multiparameter flow cytometry is valuable for diagnosis of non-Hodgkin's of lymphoma.
Assuntos
Citometria de Fluxo , Linfoma não Hodgkin/diagnóstico , Biópsia , Medula Óssea , Hospitalização , Humanos , Linfoma de Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma de Células T/diagnósticoRESUMO
PURPOSE: In traditional Chinese medicine, Tanshinone IIA is used to treat chronic kidney disease (CKD). However, its biological activity and mechanism of action in renal fibrosis and inflammation are not fully identified. The current study was conducted to determine the effects of Tanshinone IIA treatment on CKD by assessing potential modulation of the TGF-ß/Smad and NF-κB signaling pathway. METHODS: CKD was produced in rats by 5/6 nephrectomy. They were then divided into the following groups: control (sham operation); CKD (5/6 nephrectomy); 5/6 nephrectomy+Tanshinone IIA (10mg/kg in average, once a day for 16 weeks). Serum and urine samples were obtained from animals in each group, and serum creatinine (Scr), blood urea nitrogen (BUN) levels and 24h urinary protein excretion were measured. Tissue samples from the kidney were used for morphometric studies (Masson's trichrome). The expression of fibronectin protein and collagen types I, III, IV, and TGF-ß, TNF-α, CXCL-1, MCP-1, RANTES mRNA were evaluated using immunohistochemistry and RT-PCR analysis; the TGF-ß/Smad and NF-κB signaling pathway was detected by immunohistochemistry and Western blot analysis. RESULTS: The following effects were observed in CKD rats treated with Tanshinone IIA: (1) marked improvements in Scr, and 24h urine protein excretion; (2) significant reductions in protein and mRNA levels of fibronectin, collagen III, and collagen IV and TNF-α, MCP-1, and CXCL-1; (3) significantly inhibited the TGF-ß/Smad and NF-κB signaling activation. CONCLUSIONS: These results suggest that Tanshinone IIA suppresses renal fibrosis and inflammation via altering expression of TGF-ß/Smad and NF-κB pathway in the remnant kidney, thus supporting the potential of Tanshinone IIA as a new therapeutic agent for slowing the progression of CKD.
Assuntos
Abietanos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Rim/patologia , NF-kappa B/biossíntese , Insuficiência Renal Crônica/tratamento farmacológico , Proteínas Smad/biossíntese , Fator de Crescimento Transformador beta/biossíntese , Abietanos/administração & dosagem , Abietanos/efeitos adversos , Animais , Western Blotting , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Fibrose , Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica , Rim/efeitos dos fármacos , Rim/imunologia , Testes de Função Renal , Masculino , Medicina Tradicional Chinesa , NF-kappa B/genética , Nefrectomia , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/patologia , Transdução de Sinais , Proteínas Smad/genética , Fator de Crescimento Transformador beta/genéticaRESUMO
The ample expression of chemokines and their receptors by neurons in the brain suggests that they play a functional role beyond the coordination of inflammatory and immune responses. Growing evidence implicates brain chemokines in the regulation of neuronal activity and neurohormonal release. This study examined the potential role of brain chemokines in regulating hemodynamic, sympathetic, and neuroendocrine mechanisms in rats with ischemia-induced heart failure (HF). Immunohistochemical analysis revealed that the chemokine stromal cell-derived factor 1 (SDF-1)/CXCL12 was highly expressed in the hypothalamic paraventricular nucleus and subfornical organ and that SDF-1 expression was significantly increased in HF rats compared with sham-operated (SHAM) control rats. ICV injection of SDF-1 induced substantial and long-lasting increases in blood pressure, heart rate, and renal sympathetic nerve activity in both SHAM and HF rats, but responses were exaggerated in HF rats. Bilateral microinjection of SDF-1 into the paraventricular nucleus also elicited exaggerated increases in blood pressure, heart rate, and renal sympathetic nerve activity in the HF rats. A 4-hour ICV infusion of SDF-1 increased plasma levels of arginine vasopressin, adrenocorticotropic hormone, and norepinephrine in normal rats, responses that were prevented by pretreatment with ICV SDF-1 short-hairpin RNA (shRNA). ICV administration of SDF-1 shRNA also reduced plasma arginine vasopressin, adrenocorticotropic hormone, and norepinephrine levels in HF rats. These data suggest that the chemokine SDF-1, acting within the brain, plays an important role in regulating sympathetic drive, neuroendocrine release, and hemodynamic function in normal and pathophysiological conditions and so may contribute to the neural and humoral activation in HF.
Assuntos
Quimiocina CXCL12/metabolismo , Insuficiência Cardíaca/metabolismo , Hipotálamo/metabolismo , Neurotransmissores/metabolismo , Receptores CXCR4/metabolismo , Análise de Variância , Animais , Pressão Sanguínea , Western Blotting , Modelos Animais de Doenças , Ecocardiografia Doppler , Insuficiência Cardíaca/diagnóstico por imagem , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Valores de Referência , Sistema Nervoso Simpático/fisiologiaRESUMO
OBJECTIVE: The mechanisms by which inflammation activates sympathetic drive in heart failure and hypertension remain ill-defined. In this study, an intracerebroventricular injection of lipopolysaccharide (LPS) was used to induce the expression of cytokines and other inflammatory mediators in the brain, in the absence of other excitatory mediators, and the downstream signaling pathways leading to sympathetic activation were examined using intracerebroventricular injections of blocking or inhibiting agents. METHODS AND RESULTS: In anesthetized rats, intracerebroventricular injection of LPS (5 microg) increased (P < 0.05) renal sympathetic nerve activity, blood pressure and heart rate. LPS increased (P < 0.05) hypothalamic mRNA for NAD(P)H oxidase subunits p47 and gp91, NAD(P)H oxidase-dependent superoxide generation, hypothalamic mRNA for tumor necrosis factor-alpha, cyclooxygenase-2 and cerebrospinal fluid levels of tumor necrosis factor-alpha and prostaglandin E2. In the paraventricular nucleus of hypothalamus, dihydroethidium staining for superoxide expression and c-Fos activity (indicating neuronal excitation) increased. The superoxide scavenger tempol significantly (P < 0.05) diminished the expression of inflammatory mediators, as well as superoxide expression and neuronal excitation in paraventricular nucleus. SB203580 (p38 mitogen-activated protein kinase inhibitor) also reduced the expression of inflammatory mediators in hypothalamus and cerebrospinal fluid. Tempol, apocynin [NAD(P)H oxidase inhibitor], SB203580 and NS398 (cyclooxygenase-2 inhibitor) all reduced cerebrospinal fluid prostaglandin E2 and the sympathoexcitatory response to LPS. LPS also increased angiotensin II type 1 receptor mRNA, a response blocked by apocynin and tempol but not by SB203580. CONCLUSION: These findings suggest that central inflammation in pathophysiological conditions activates the sympathetic nervous system via NAD(P)H oxidase and p38 mitogen-activated protein kinase-dependent synthesis of prostaglandin E2.
Assuntos
Lipopolissacarídeos/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NADPH Oxidases/metabolismo , Sistema Nervoso Simpático/fisiologia , Acetofenonas/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Óxidos N-Cíclicos/farmacologia , Ciclo-Oxigenase 2/líquido cefalorraquidiano , Ciclo-Oxigenase 2/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipotálamo/metabolismo , Hipotálamo/fisiopatologia , Mediadores da Inflamação/metabolismo , Injeções Intraventriculares , Lipopolissacarídeos/metabolismo , Masculino , NADPH Oxidases/genética , NADPH Oxidases/fisiologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Núcleo Hipotalâmico Paraventricular/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/metabolismo , Transdução de Sinais , Marcadores de Spin , Superóxidos/metabolismo , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: Systemic administration of the superoxide scavenger tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) reduces blood pressure (BP), heart rate (HR) and sympathetic nerve activity in normotensive and hypertensive animals. The global nature of the depressor response to tempol suggests an inhibitory influence on cardiovascular presympathetic regions of the brain. This study examined several possible mechanisms for such an effect. METHODS AND RESULTS: In urethane anesthetized rats, as expected, intravenous tempol (120 microg mol/kg) reduced mean arterial pressure, HR and renal sympathetic nerve activity (RSNA). Concomitant central neuronal recordings revealed reduced spontaneous discharge (spikes/s) of neurons in the paraventricular nucleus of hypothalamus (from 2.9 +/- 0.4 to 0.8+/- 0.2) and the rostral ventrolateral medulla (RVLM; from 9.8 +/- 0.5 to 7.2 +/-0.4), two cardiovascular and autonomic regions of the brain. Baroreceptor-denervated rats had exaggerated sympathetic and cardiovascular responses. Pretreatment with the hydroxyl radical scavenger dimethyl sulfoxide (intravenous) attenuated the tempol-induced decreases in BP, HR and RSNA, but the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (intravenous or intracerebroventricular) had no effect. CONCLUSION: These findings suggest that systemically administered tempol acts upon neurons in paraventricular nucleus and RVLM to reduce BP, HR and RSNA, perhaps by reducing the influence of reactive oxygen species in those regions. The arterial baroreflex modulates the depressor responses to tempol. These central mechanisms must be considered in interpreting data from studies using systemically administered tempol to assess the role of reactive oxygen species in cardiovascular regulation.
Assuntos
Óxidos N-Cíclicos/farmacologia , Hipotálamo/efeitos dos fármacos , Bulbo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Animais , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Óxidos N-Cíclicos/administração & dosagem , Dimetil Sulfóxido/administração & dosagem , Dimetil Sulfóxido/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Infusões Intravenosas , Injeções Intravenosas , Injeções Intraventriculares , Rim/inervação , Masculino , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Óxido Nítrico Sintase/metabolismo , Ratos , Ratos Sprague-Dawley , Marcadores de Spin , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/cirurgiaRESUMO
In heart failure (HF), angiotensin II type 1 receptor (AT(1)-R) expression is upregulated in brain regions regulating sympathetic drive, blood pressure, and body fluid homeostasis. However, the mechanism by which brain AT(1)-R are upregulated in HF remains unknown. The present study examined the hypothesis that the angiotensin II (Ang II)-triggered mitogen-activated protein kinases (MAPKs) p44/42, p38, and c-Jun N-terminal kinase contribute to upregulation of the AT(1)-R in the hypothalamus of rats with HF. AT(1)-R protein, AT(1)-R mRNA, and AT(1)-R immunoreactivity increased in the paraventricular nucleus of hypothalamus and the subfornical organ of rats with ischemia-induced HF compared with sham-operated controls. Phosphorylated p44/42 MAPK, c-Jun N-terminal kinase, and p38 MAPK also increased in paraventricular nucleus and subfornical organ. A 4-week ICV infusion of the AT(1)-R antagonist losartan decreased AT(1)-R protein and phosphorylation of p44/42 MAPK, c-Jun N-terminal kinase, and p38 MAPK in the HF rats. A 4-week ICV infusion of the p44/42 MAPK inhibitor PD98059 or the c-Jun N-terminal kinase inhibitor SP600125 significantly decreased AT(1)-R protein and AT(1)-R immunoreactivity in the paraventricular nucleus and subfornical organ, but the p38 MAPK inhibitor SB203580 did not. Treatment with ICV losartan, PD98059, and SP600125 had no effect on AT(1)-R expression by Western blot in sham-operated rats. In untreated HF rats 4 weeks after coronary ligation, a 3-hour ICV infusion of PD98059, SP600125, or losartan reduced AT(1)-R mRNA in paraventricular nucleus and subfornical organ. These data indicate that MAPK plays an important role in the upregulation of AT(1)-R in the rat forebrain in HF and suggest that Ang II upregulates its own receptor by this mechanism.
Assuntos
Insuficiência Cardíaca/genética , Hipotálamo/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , RNA Mensageiro/genética , Receptor Tipo 1 de Angiotensina/genética , Regulação para Cima , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Animais , Western Blotting , Modelos Animais de Doenças , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Imuno-Histoquímica , Infusões Intravenosas , Losartan/administração & dosagem , Masculino , Proteínas Quinases Ativadas por Mitógeno/biossíntese , Reação em Cadeia da Polimerase , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/biossínteseRESUMO
The expression of proinflammatory cytokines increases in the hypothalamus of rats with heart failure (HF). The pathophysiological significance of this observation is unknown. We hypothesized that hypothalamic proinflammatory cytokines upregulate the activity of central neural systems that contribute to increased sympathetic nerve activity in HF, specifically, the brain renin-angiotensin system (RAS) and the hypothalamic-pituitary-adrenal (HPA) axis. Rats with HF induced by coronary ligation and sham-operated controls (SHAM) were treated for 4 wk with a continuous intracerebroventricular infusion of the cytokine synthesis inhibitor pentoxifylline (PTX, 10 microg/h) or artificial cerebrospinal fluid (VEH). In VEH-treated HF rats, compared with VEH-treated SHAM rats, the hypothalamic expression of proinflammatory cytokines was increased, along with key components of the brain RAS (renin, angiotensin-converting enzyme, angiotensin type 1 receptor) and corticotropin-releasing hormone, the central indicator of HPA axis activation, in the paraventricular nucleus (PVN) of the hypothalamus. The expression of other inflammatory/excitatory mediators (superoxide, prostaglandin E(2)) was also increased, along with evidence of chronic neuronal excitation in PVN. VEH-treated HF rats had higher plasma levels of norepinephrine, ANG II, interleukin (IL)-1beta, and adrenocorticotropic hormone, increased left ventricular end-diastolic pressure, and increased wet lung-to-body weight ratio. With the exception of plasma IL-1beta, an indicator of peripheral proinflammatory cytokine activity, all measures of neurohumoral excitation were significantly lower in HF rats treated with intracerebroventricular PTX. These findings suggest that the increase in brain proinflammatory cytokines observed in rats with ischemia-induced HF is functionally significant, contributing to neurohumoral excitation by activating brain RAS and the HPA axis.
Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Insuficiência Cardíaca/metabolismo , Hipotálamo/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Isquemia Miocárdica/complicações , Pentoxifilina/farmacologia , Potenciais de Ação , Hormônio Adrenocorticotrópico/metabolismo , Angiotensina II/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Ciclo-Oxigenase 2/metabolismo , Citocinas/sangue , Dinoprostona/metabolismo , Modelos Animais de Doenças , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotálamo/metabolismo , Hipotálamo/fisiopatologia , Infusões Parenterais , Interleucina-1beta/metabolismo , Masculino , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Norepinefrina/metabolismo , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Pentoxifilina/administração & dosagem , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Sistema Renina-Angiotensina/efeitos dos fármacos , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , UltrassonografiaRESUMO
The brain renin-angiotensin system (RAS) contributes to increased sympathetic drive in heart failure (HF). The factors upregulating the brain RAS in HF remain unknown. We hypothesized that aldosterone (ALDO), a downstream product of the systemic RAS that crosses the blood-brain barrier, signals the brain to increase RAS activity in HF. We examined the relationship between circulating and brain ALDO in normal intact rats, in adrenalectomized rats receiving subcutaneous infusions of ALDO, and in rats with ischemia-induced HF and sham-operated controls. Brain ALDO levels were proportional to plasma ALDO levels across the spectrum of rats studied. Compared with sham-operated controls rats, HF rats had higher plasma and hypothalamic tissue levels of ALDO. HF rats also had higher expression of mRNA and protein for angiotensin-converting enzyme and angiotensin type 1 receptors in the hypothalamus, increased reduced nicotinamide-adenine dinucleotide phosphate oxidase activity and superoxide generation in the paraventricular nucleus of the hypothalamus, increased excitation of paraventricular nucleus neurons, and increased plasma norepinephrine. HF rats treated for 4 weeks with intracerebroventricular RU28318 (1 microg/h), a selective mineralocorticoid receptor antagonist, had less hypothalamic angiotensin-converting enzyme and angiotensin type 1 receptor mRNA and protein, less reduced nicotinamide-adenine dinucleotide phosphate-induced superoxide in the paraventricular nucleus, fewer excited paraventricular nucleus neurons, and lower plasma norepinephrine. RU28318 had no effect on plasma ALDO or on angiotensin-converting enzyme or angiotensin type 1 receptor expression in brain cortex. The data demonstrate that ALDO of adrenal origin enters the hypothalamus in direct proportion to plasma levels and suggest that ALDO contributes to the upregulation of hypothalamic RAS activity and sympathetic drive in heart failure.
Assuntos
Aldosterona/fisiologia , Encéfalo/fisiologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Angiotensina II/fisiologia , Animais , Pressão Sanguínea/fisiologia , Modelos Animais de Doenças , Hemostasia/fisiologia , Hipotálamo/metabolismo , Masculino , Núcleo Hipotalâmico Paraventricular/metabolismo , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Receptores de Mineralocorticoides/metabolismo , Sistema Renina-Angiotensina/genética , Superóxidos/metabolismo , Regulação para Cima/fisiologiaRESUMO
Aldosterone acts upon mineralocorticoid receptors in the brain to increase blood pressure and sympathetic nerve activity, but the mechanisms are still poorly understood. We hypothesized that aldosterone increases sympathetic nerve activity by upregulating the renin-angiotensin system (RAS) and oxidative stress in the brain, as it does in peripheral tissues. In Sprague-Dawley rats, aldosterone (Aldo) or vehicle (Veh) was infused for 1 wk via an intracerebroventricular (ICV) cannula, while RU-28318 (selective mineralocorticoid receptor antagonist), Tempol (superoxide dismutase mimetic), losartan [angiotensin II type 1 receptor (AT(1)R) antagonist], or Veh was infused simultaneously via a second ICV cannula. After 1 wk of ICV Aldo, plasma norepinephrine was increased and mean arterial pressure was slightly elevated, but heart rate was unchanged. These effects were ameliorated by ICV infusion of RU-28318, Tempol or losartan. Aldo increased expression of AT(1)R and angiotensin-converting enzyme (ACE) mRNA in hypothalamic tissue. RU-28318 minimized and Tempol prevented the increase in AT(1)R mRNA; RU-28318 prevented the increase in ACE mRNA. Losartan had no effect on AT(1)R or ACE mRNA. Immunohistochemistry revealed Aldo-induced increases in dihydroethidium staining (indicating oxidative stress) and Fra-like activity (indicating neuronal excitation) in neurons of the hypothalamic paraventricular nucleus (PVN). RU-28318 prevented the increases in superoxide and Fra-like activity in PVN; Tempol and losartan minimized these effects. Acute ICV infusions of sarthran (AT(1)R antagonist) or Tempol produced greater sympathoinhibition in Aldo-treated than in Veh-treated rats. Thus aldosterone upregulates key elements of brain RAS and induces oxidative stress in the hypothalamus. Aldosterone may increase sympathetic nerve activity by these mechanisms.
Assuntos
Aldosterona/farmacologia , Química Encefálica/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Eletrofisiologia , Imunofluorescência , Frequência Cardíaca/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiologia , Imuno-Histoquímica , Injeções Intraventriculares , Masculino , Antagonistas de Receptores de Mineralocorticoides , Peptidil Dipeptidase A/biossíntese , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Superóxidos/metabolismoRESUMO
OBJECTIVE: To study the different manufacturers Vitmin C (Vc) Yinqiao tablets, and the quality of the analysis of the problem, to provide a theoretical basis for the correct evaluation of the quality of medicines and improving the standard drugs. METHOD: 11 manufacturers of 18 batches of samples for determination of the weight of the core tablets, powder samples were observed with microscope, determination of Vc, and the establishment of the Vc Yinqiao tablets HPLC method for determination of chlorogenic acid and arctigenin, chlorogenic acid and arctigenin in the samples were measured and compared. RESULT: There is a big difference of microscope and various measured results in different manufacturers products. CONCLUSION: Because different manufacturers to produce the same, there are big differences in the quality of the products.
Assuntos
Ácido Ascórbico/química , Ácido Clorogênico/análise , Medicamentos de Ervas Chinesas/química , Furanos/análise , Lignanas/análise , Arctium/química , Cromatografia Líquida de Alta Pressão , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/normas , Lonicera/química , Plantas Medicinais/química , Controle de Qualidade , ComprimidosRESUMO
Blocking brain mineralocorticoid receptors (MRs) reduces the high circulating levels of tumor necrosis factor (TNF)-alpha in heart failure (HF) rats. TNF-alpha and other proinflammatory cytokines activate neurons in the paraventricular nucleus (PVN) of hypothalamus, including corticotropin-releasing hormone (CRH) neurons, by inducing cyclooxygenase (COX)-2 activity and synthesis of prostaglandin E2 by perivascular cells of the cerebral vasculature. We tested the hypothesis that systemic treatment with a MR antagonist would reduce hypothalamic COX-2 expression and PVN neuronal activation in HF rats. Rats underwent coronary ligation to induce HF, confirmed by echocardiography, or sham surgery, followed by 6 weeks treatment with eplerenone (30 mg/kg per day, orally) or vehicle (drinking water). Eplerenone-treated HF rats had lower plasma TNF-alpha, interleukin (IL)-1beta and IL-6, less COX-2 staining of small blood vessels penetrating PVN, fewer PVN neurons expressing Fra-like activity (indicating chronic neuronal activation), and fewer PVN neurons staining for TNF-alpha, IL-1beta, and CRH than vehicle-treated HF rats. COX-2 and CRH protein expression in hypothalamus were 1.7- and 1.9-fold higher, respectively, in HF+vehicle versus sham+vehicle rats; these increases were attenuated (26% and 25%, respectively) in HF+eplerenone rats. Eplerenone-treated HF rats had less prostaglandin E2 in cerebrospinal fluid, lower plasma norepinephrine levels, lower left ventricular end-diastolic pressure, and lower right ventricle/body weight and lung/body weight ratios, but no improvement in left ventricular function. Treatment of HF rats with anticytokine agents, etanercept or pentoxifylline, produced very similar results. This study reveals a previously unrecognized effect of MR antagonism to minimize cytokine-induced central neural excitation in rats with HF.
Assuntos
Citocinas/biossíntese , Insuficiência Cardíaca/fisiopatologia , Hipotálamo/fisiopatologia , Mediadores da Inflamação/metabolismo , Antagonistas de Receptores de Mineralocorticoides , Isquemia Miocárdica/complicações , Animais , Citocinas/antagonistas & inibidores , Sinergismo Farmacológico , Ecocardiografia , Eplerenona , Etanercepte , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etiologia , Imunoglobulina G/farmacologia , Masculino , Toxina Pertussis/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores do Fator de Necrose Tumoral , Espironolactona/análogos & derivados , Espironolactona/farmacologiaRESUMO
<p><b>OBJECTIVE</b>To compare the short-term curative effect of clozapine (CZ) and its combination with electroacupuncture (EA) in treating schizophrenia.</p><p><b>METHODS</b>Ninety schizophrenia patients were randomly divided into two groups equally: the EA group treated with combination of CZ (200 - 300 mg/d in mean) and EA, and the CZ group treated with CZ alone. The effects of treatment were evaluated with PANSS, CGI and TESS before and at the 2th, 4th, 6th and 8th weekend of the treatment.</p><p><b>RESULTS</b>The initiation of effect in the two groups was the same, the total effective rate was 75% in the EA group and 73% in the CZ group. However, somatic complaint was lower and compliance was higher in the EA group than that in the CZ group respectively.</p><p><b>CONCLUSION</b>With the effect equal to CZ, combination of CZ and EA shows higher compliance in treating schizophrenia, which would be beneficial in the later stage treatment for consolidation.</p>
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia por Acupuntura , Clozapina , Usos Terapêuticos , Terapia Combinada , Eletroacupuntura , Esquizofrenia , TerapêuticaRESUMO
Despite recent therapeutic advances, the prognosis for patients with heart failure remains dismal. Unchecked neurohumoral excitation is a critical element in the progressive clinical deterioration associated with the heart failure syndrome, and its peripheral manifestations have become the principal targets for intervention. The link between peripheral systems activated in heart failure and the central nervous system as a source of neurohumoral drive has therefore come under close scrutiny. In this context, the forebrain and particularly the paraventricular nucleus of the hypothalamus have emerged as sites that sense humoral signals generated peripherally in response to the stresses of heart failure and contribute to the altered volume regulation and augmented sympathetic drive that characterize the heart failure syndrome. This brief review summarizes recent studies from our laboratory supporting the concept that the forebrain plays a critical role in the pathogenesis of ischemia-induced heart failure and suggesting that the forebrain contribution must be considered in designing therapeutic strategies. Forebrain signaling by neuroactive products of the renin-angiotensin system and the immune system are emphasized.