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2.
Cell Physiol Biochem ; 45(4): 1455-1471, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29466787

RESUMO

BACKGROUND/AIMS: Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years and has accumulated considerable knowledge concerning the in vivo efficacy of targeting complicated diseases. TCM formulae are a mixture of hundreds of chemical components with multiple potential targets, essentially acting as a combination therapy of multi-component drugs. However, the obscure substances and the unclear molecular mechanisms are obstacles to their further development and internationalization. Therefore, it is necessary to develop new modern drugs based on the combination of effective components in TCM with exact clinical efficacy. In present study, we aimed to detect optimal ratio of the combination of effective components based on Sheng-Mai-San for myocardial ischemia. METHODS: On the basis of preliminary studies and references of relevant literature about Sheng-Mai-San for myocardial ischemia, we chose three representative components (ginsenoside Rb1 (G), ruscogenin (R) and schisandrin (S)) for the optimization design studies. First, the proper proportion of the combination was explored in different myocardial ischemia mice induced by isoproterenol and pituitrin based on orthogonal design. Then, the different proportion combinations were further optimized through uniform design in a multi-model and multi-index mode. Finally, the protective effect of combination was verified in three models of myocardial ischemia injured by ischemia/reperfusion, chronic intermittent hypoxia and acute infarction. RESULTS: The optimized combination GRS (G: 6 mg/kg, R: 0.75 mg/kg, S: 6 mg/kg) obtained by experimental screening exhibited a significant protective effect on myocardial ischemia injury, as evidenced by decreased myocardium infarct size, ameliorated histological features, decreased myocardial myeloperoxidase (MPO) and malondiadehyde (MDA), calcium overload, and decreased serum lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), cardiac troponin I (cTn-I) activity. In addition, the interactions of three components in combination GRS were also investigated. The combination, compared to G, R and S, could significantly reduce the concentration of serum CK-MB and cTn-I, and decrease myocardial infarct size, which demonstrated the advantages of this combination for myocardial ischemia. CONCLUSION: Our results demonstrated that the optimized combination GRS could exert significant cardioprotection against myocardial ischemia injury with similar effect compared to Sheng Mai preparations, which might provide some pharmacological evidences for further development of new modern Chinese drug for cardiovascular diseases basing on traditional Chinese formula with affirmative therapeutic effect.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Isquemia Miocárdica/tratamento farmacológico , Animais , Creatina Quinase Forma MB/sangue , Ciclo-Octanos/uso terapêutico , Modelos Animais de Doenças , Combinação de Medicamentos , Ginsenosídeos/uso terapêutico , Coração/efeitos dos fármacos , Isoproterenol/toxicidade , L-Lactato Desidrogenase/sangue , Lignanas/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Infarto do Miocárdio/patologia , Isquemia Miocárdica/induzido quimicamente , Isquemia Miocárdica/mortalidade , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Hormônios Neuro-Hipofisários/toxicidade , Compostos Policíclicos/uso terapêutico , Espirostanos/uso terapêutico , Troponina I/sangue
3.
Gen Comp Endocrinol ; 260: 80-89, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29305879

RESUMO

In the present study, in vitro effects of synthetic vasotocin (VT), isotocin (4Ser, 8Ile- oxytocin; ITb) and the recently cloned IT gene paralog product (8Val-Isotocin, ITa) were studied on the expression of pituitary gonadotropin (GtH) subunit mRNA levels. In male pituitaries of early (preparatory phase) and late (prespawning phase) recrudescing catfish, Heteropneustes fossilis, VT (10 nM, 100 nM and 1000 nM) stimulated fshß expression dose-dependently. But in females, the dose-dependent effect was found only in the preparatory phase. In males, VT stimulated lhß expression only at higher doses. In females, VT produced a significant dose-dependent increase of the lhß expression only in the prespawning phase. VT stimulated the expression of gpα, dose-dependently in the preparatory phase in males and in the prespawning phase in females. The incubation of the pituitaries with ITb did not alter the fshß expression in either sex in both preparatory and prespawning phases. In males, ITb stimulated the expression of lhß and gpα only at the highest concentration (1000 nM) in both phases. In females, ITb stimulated both lhß and gpα expression only at 1000 nM in the preparatory phase and dose-dependently in the prespawning phase. The incubation of the pituitaries with ITa produced effects similar to ITb on the expression of fshß, lhß, and gpα. The results show that the basic peptide VT modulates both fshß and lhß expressions, which are influenced by the sex and reproductive stage. The neutral peptide ITA/ITb exerts an insignificant effect on the fshß expression regardless of sex or season. Both VT and ITa/ITb elicit a significant effect on the lhß expression in late recrudescent phase especially in females.


Assuntos
Peixes-Gato , Gonadotropinas Hipofisárias/genética , Hormônios Neuro-Hipofisários/farmacologia , Reprodução/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Animais , Peixes-Gato/genética , Peixes-Gato/crescimento & desenvolvimento , Peixes-Gato/metabolismo , Feminino , Subunidade beta do Hormônio Folículoestimulante/genética , Subunidade beta do Hormônio Folículoestimulante/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gonadotropinas Hipofisárias/metabolismo , Técnicas In Vitro , Hormônio Luteinizante Subunidade beta/genética , Hormônio Luteinizante Subunidade beta/metabolismo , Masculino , Ocitocina/análogos & derivados , Ocitocina/farmacologia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Reprodução/genética , Estações do Ano , Caracteres Sexuais , Maturidade Sexual/genética , Vasotocina/farmacologia
4.
Sci Rep ; 7(1): 9040, 2017 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-28831114

RESUMO

This research was conducted to verify the structural and functional characteristics of mast cells in the electroacupuncture (EA) effects on bradycardia. First, we examined the mast cell density at PC 6, adjacent acupoint LU 7, and a non-acupoint. We tested the effects of EA at PC 6 on heart rate (HR) and blood pressure (BP) in rabbits with pituitrin-induced bradycardia. We also injected sodium cromolyn (Cro), a mast cell membrane stabilizer, at PC 6 30 min before EA to investigate if it affected the EA effects. The results showed that in both PC 6 and LU 7, the mast cell densities were higher than in the non-acupoint (P < 0.05). EA could induce mast cell degranulation at PC 6, which could be suppressed by sodium cromolyn (P < 0.05). EA improved HR, though the change was relatively small in the initial stage with a significant change at 35 min after modelling (P < 0.05). BP significantly improved at 10 min after the onset of pituitrin-induced bradycardia (P < 0.05). The EA effects on both HR and BP were suppressed by sodium cromolyn (P < 0.05). Therefore, we concluded that mast cells in the acupoint are important for the EA effects against pituitrin-induced bradycardia in rabbits.


Assuntos
Pontos de Acupuntura , Bradicardia/etiologia , Bradicardia/fisiopatologia , Degranulação Celular/imunologia , Mastócitos/imunologia , Hormônios Neuro-Hipofisários/efeitos adversos , Animais , Pressão Sanguínea , Bradicardia/diagnóstico , Bradicardia/terapia , Contagem de Células , Modelos Animais de Doenças , Eletroacupuntura , Eletrocardiografia , Frequência Cardíaca , Masculino , Mastócitos/metabolismo , Mastócitos/patologia , Coelhos
5.
Mol Med Rep ; 16(3): 3125-3132, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28714023

RESUMO

Shexiang Tongxin Dropping Pill (STP) is an established traditional Chinese medicine that is widely used for the treatment of ischemic heart disease (IHD), although its mechanisms remain unclear. The present study investigated the protective effects of STP following pituitrin (PTT)­induced myocardial ischemia in rats. ST­segment elevation, blood rheology, and the serum levels of creatine kinase­MB (CK­MB) and lactate dehydrogenase (LDH) were measured. Following heart excision, histological analysis using hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling were performed. The mRNA expression levels of B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein (Bax) were determined using reverse transcription­quantitative polymerase chain reaction, and their protein expression was detected using immunohistochemistry. The results demonstrated that STP treatment protected against ST elevation, lowered whole blood viscosity, and reduced the serum levels of CK­MB and LDH following acute myocardial ischemia. In addition, STP treatment restored the histopathological change following PTT­induced myocardial ischemia, and resulted in downregulated expression of Bax and upregulated expression of Bcl­2 in myocardial tissue. The present study demonstrates the cardioprotective ability of STP in a rat model of myocardial ischemic injury, which may be attributed to its anti­apoptotic properties. The cardioprotective properties of STP require further investigation to determine whether it may be used for the clinical treatment of IHDs.


Assuntos
Cardiotônicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Creatina Quinase Forma MB/sangue , Medicamentos de Ervas Chinesas/farmacologia , Hemorreologia/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , L-Lactato Desidrogenase/sangue , Masculino , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Hormônios Neuro-Hipofisários , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
6.
Int J Surg ; 35: 187-195, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27725243

RESUMO

OBJECTIVE: To determine the best haemostatic strategy for hysterectomy through a network meta-analysis. METHODS: We conducted a systematic literature search of the PubMed, Embase, and Cochrane Library databases and extracted data from randomized controlled trials comparing haemostatic strategies for hysterectomy. Direct comparisons and network meta-analyses were conducted in RevMan and ADDIS. Consistency models were established to identify the differences among different haemostatic strategies, and cumulative probability was used to rank the included strategies. Inconsistencies were also tested using node-splitting models. RESULTS: Twenty studies from 16 articles (2 articles contained 3 studies each) comprising 1392 patients were included. Direct meta-analysis showed that the LigaSure (SMD = -1.42 [-2.39, -0.44], P = 0.004), bipolar vessel sealing systems (BVSS) (SMD = -0.35 [-0.66, -0.03], P = 0.03), and pituitrin (SMD = -2.13 [-4.14, -0.13], P = 0.04) applications were effective haemostatic strategies. Based on the network meta-analysis and related subgroup analysis of different surgical procedures, the results showed that the application of pituitrin seemed to be the best haemostatic method for hysterectomy (Rank P = 0.64), especially for vaginal hysterectomy (Rank P = 0.72). The application of LigaSure was the best strategy for abdominal hysterectomy (Rank P = 0.54) but was not effective for laparoscopic hysterectomy (direct comparison with BVSS, MD = -31.39 [-146.61, 83.83], P = 0.59). The node-splitting models test revealed that no significant inconsistencies existed in this research. CONCLUSIONS: Pituitrin application seemed to be the most effective haemostatic strategy for hysterectomy and was especially suitable for vaginal hysterectomy. The best method for reducing blood loss in abdominal hysterectomy was the application of LigaSure.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Eletrocoagulação/métodos , Técnicas Hemostáticas , Hemostáticos/administração & dosagem , Histerectomia , Hormônios Neuro-Hipofisários/administração & dosagem , Feminino , Humanos , Histerectomia Vaginal , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Zhonghua Gan Zang Bing Za Zhi ; 24(8): 569-574, 2016 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-27788702

RESUMO

Objective: To investigate the effects of desmopressin acetate and pituitrin on the proliferation, contraction, and secretion of hepatic stellate cells (HSCs). Methods: The human HSC cell line LX-2 was selected as the research model. And three groups were designed: blank control group, desmopressin acetate group (three subgroups: 1×10-10mol/L, 1×10-9mol/L, and 1×10-8mol/L desmopressin acetate), and pituitrin group (three subgroups: 0.1 U/L, 1.0 U/L, and 10.0 U/L pituitrin). Water-soluble tetrazolium salt (WST)-1 assay was used to evaluate cell proliferation; collagen gel contraction assay was used to assess cell contraction; enzyme-linked immunosorbent assay (ELISA) was used to identify cell secretion. The data was subjected to one-way analysis of variance. Results: (1) The results of WST-1 assay showed that the values of A450in three desmopressin acetate subgroups (1×10-10mol/L, 1×10-9mol/L, and 1×10-8mol/L) were 0.459±0.017, 0.467±0.024, and 0.436±0.015, respectively. And the values of A450 in three pituitrin subgroups (0.1 U/L, 1.0 U/L, and 10.0 U/L) were 0.495±0.011, 0.507±0.015, and 0.501±0.009, respectively. Compared with the control group, the desmopressin acetate at high concentration significantly inhibited the cell proliferation (P< 0.05), but the pituitrin at three different concentrations significantly promoted the cell proliferation (P< 0.05). (2) The collagen gel area ratios in three desmopressin acetate subgroups (1×10-10mol/L, 1×10-9mol/L, and 1×10-8mol/L) were 77.07±4.42, 75.85±3.70, and 72.74±3.92, respectively. And the collagen gel area ratios in three pituitrin subgroups (0.1 U/L, 1.0 U/L, and 10.0 U/L) were 57.83±3.96, 50.28±6.69, and 43.56±7.68, respectively. Compared with the control group, the pituitrin at three different concentrations significantly reduced the collagen gel area (P< 0.01). (3) The matrix metalloproteinase(MMP)-2 concentrations in three desmopressin acetate subgroups (1×10-10mol/L, 1×10-9mol/L, and 1×10-8mol/L) were 13.321±0.098, 12.230±0.153, and 12.061±0.126, respectively. And the MMP-2 concentrations in three pituitrin subgroups (0.1 U/L, 1.0 U/L, and 10.0 U/L) were 12.899±0.150, 13.662±0.152, and 13.698±0.119, respectively. Compared with the control group, the desmopressin acetate at low concentration significantly increased the secretion of MMP-2 (P< 0.01); the desmopressin acetate at high concentration significantly decreased the MMP-2 concentration (P< 0.05); the pituitrin at three different concentrations significantly increased the MMP-2 concentration (P< 0.01). The transforming growth factor-beta 1 (TGF-ß1) concentrations in three desmopressin acetate subgroups (1×10-10mol/L, 1×10-9mol/L, and 1×10-8mol/L) were 5.233±0.102, 17.749±0.188, and 36.060±0.227, respectively. And the TGF-ß1 concentrations in three pituitrin subgroups (0.1 U/L, 1.0 U/L, and 10.0 U/L) were 15.615±0.099, 38.460±0.209, and 49.053±0.115, respectively. Compared with the control group, desmopressin acetate and pituitrin significantly promoted the secretion of TGF-ß1 in a concentration-dependent manner (P< 0.01) and pituitrin had a stronger effect than desmopressin acetate (P< 0.01). Desmopressin acetate and pituitrin had no effect on the secretion of the collagenase type I and III (P> 0.05). Conclusion: Desmopressin acetate and pituitrin can induce the changes in the function and morphology of HSCs and may increase vascular resistance in the hepatic sinus. However, desmopressin acetate has less influence on HSCs than pituitrin.


Assuntos
Proliferação de Células/efeitos dos fármacos , Desamino Arginina Vasopressina/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Hormônios Neuro-Hipofisários/farmacologia , Animais , Western Blotting , Células Cultivadas , Colágeno , Ensaio de Imunoadsorção Enzimática , Humanos , Fígado , Fator de Crescimento Transformador beta1/biossíntese
9.
J Neurosurg ; 124(5): 1538-42, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26517776

RESUMO

In 1955, Vincent du Vigneaud (1901-1978), the chairman of the Department of Biochemistry at Cornell University Medical College, was awarded the Nobel Prize for Chemistry for his research on insulin and for the first synthesis of the posterior pituitary hormones-oxytocin and vasopressin. His tremendous contribution to organic chemistry, which began as an interest in sulfur-containing compounds, paved the way for a better understanding of the pituitary gland and for the development of diagnostic and therapeutic tools for diseases of the pituitary. His seminal research continues to impact neurologists, endocrinologists, and neurosurgeons, and enables them to treat patients who had no alternatives prior to du Vigneaud's breakthroughs in peptide structure and synthesis. The ability of neurosurgeons to aggressively operate on parasellar pathology was directly impacted and related to the ability to replace these hormones after surgery. The authors review the life and career of Vincent du Vigneaud, his groundbreaking discoveries, and his legacy of the understanding and treatment of the pituitary gland in health and disease.


Assuntos
Prêmio Nobel , Hormônios Neuro-Hipofisários/história , Compostos de Enxofre/história , História do Século XX , Faculdades de Medicina/história , Estados Unidos
10.
Int J Clin Pharmacol Ther ; 53(5): 408-11, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25740269

RESUMO

Osmotic demyelination syndrome (ODS) may be precipitated by aggressive correction of a hypoosmolar state. We report the case of a 24-year-old woman who developed ODS during rapid correction of asymptomatic hyponatremia caused by pituitrin prescribed for hemoptysis. After hyponatremia correction by NaCl supplementation, the patient developed limb weakness, blurred vision, hand and perioral numbness, and lisp. Magnetic resonance imaging (MRI) revealed bilateral signal hyperintensity of the globus pallidus and caudate nucleus, compatible with extra-pontine ODS. These symptoms improved gradually with treatment, and brain MRI ~ 3 months later indicated substantial resolution of ODS. This case serves as a warning to physicians that hypoosmotic correction must be achieved at a controlled rate.


Assuntos
Doenças Desmielinizantes/induzido quimicamente , Hemoptise/tratamento farmacológico , Hiponatremia/tratamento farmacológico , Osmose , Hormônios Neuro-Hipofisários/efeitos adversos , Cloreto de Sódio/efeitos adversos , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/fisiopatologia , Doenças Desmielinizantes/terapia , Feminino , Humanos , Hiponatremia/induzido quimicamente , Hiponatremia/diagnóstico , Imagem por Ressonância Magnética , Modalidades de Fisioterapia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
BMC Neurol ; 14: 189, 2014 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-25294308

RESUMO

BACKGROUND: Hyponatremia is the most common electrolyte abnormality encountered in hospitalized patients, resulting from a varied spectrum of conditions. Both the primary disturbance and its correction can result in life-threatening neurological consequences. Extrapontine myelinolysis is one such complication that is associated with the rapid correction of hyponatremia. Here we describe a patient who developed extrapontine myelinolysis unexpectedly after the correction of hyponatremia, which involved the drug pituitrin. CASE PRESENTATION: A 24-year-old Chinese woman was transferred to our neurology department with the symptoms of dysarthria and quadriparesis developing one day after the correction of hyponatremia (from 118 mmol/L to 140 mmol/L), which followed with a continuous intravenous drip of pituitrin used to control hemoptysis in the emergency room. During the course, she developed involuntary movement. Magnetic resonance imaging changes were consistent with extrapontine myelinolysis. CONCLUSION: This present case describes the mechanism of profound hyponatremia involving pituitrin, and the subsequent development of extrapontine myelinolysis. Physicians may approach effective clinical management of patients through awareness of the adverse effect of pituitrin on serum sodium levels, and avoid rapid correction of hyponatremia in clinical practice.


Assuntos
Hiponatremia/terapia , Mielinólise Central da Ponte/induzido quimicamente , Hormônios Neuro-Hipofisários/efeitos adversos , Feminino , Humanos , Hiponatremia/etiologia , Imagem por Ressonância Magnética , Hormônios Neuro-Hipofisários/administração & dosagem , Adulto Jovem
12.
Curr Pharm Des ; 20(42): 6702-13, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25190061

RESUMO

The regulation of neurohypophyseal peptides secretion reflects the convergence of a large number of afferent neural pathways on vasopressinergic and oxytocinergic neurons of supraoptic (SON) and paraventricular nuclei (PVN). In addition to afferent input, vasopressin and oxytocin can also exert an autocrine regulation of neuronal activity. In fact, magnocellular neurons (MCNs) of SON and PVN are able to secrete these hormones not only at the endings of their terminal axons, but also from their dendrites and this local release, by activating a range of ion gated, ion channel and G protein coupled receptors, participate in pre- and post-synaptic modulation of neural activity of MCNs. In this review we analyzed the molecular mechanisms involved in the control of neurohypophyseal hormones secretion and related possible pharmacological targets.


Assuntos
Hormônios Neuro-Hipofisários/metabolismo , Animais , Humanos , Neurônios/metabolismo , Ocitocina/metabolismo , Vasopressinas/metabolismo
13.
Pharmacol Rep ; 66(5): 908-14, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25150000

RESUMO

BACKGROUND: The pharmacokinetic (PK) studies of phosphocreatine (PCr) and its active metabolite creatine (Cr) are considerably lacking. This study is to comparatively investigate the PK profiles of PCr and Cr in mice plasma and myocardium as well as the ATP level. METHODS: After iv administration of equimolar PCr and preformed Cr to healthy and Pit-induced myocardial ischemic mice, plasma and myocardium samples were analyzed for exogenous PCr, Cr and related ATP concentrations using a specific ion-pair reversed-phase HPLC-UV assay. RESULTS: The plasma C-T data of iv PCr and Cr were well fitted to two-compartment model. Following iv PCr, Cr appeared in plasma as early as 1.0 min postdose with a longer t1/2 than PCr and had a fm of 72%. The mice dosed iv PCr preceded 5 min by ip Pit 30 U/kg showed longer t1/2ß PCr and t1/2 Cr in plasma and elevated Cmax, Cr and Cmax, ATP in myocardium compared with mice dosed iv PCr alone, and it was estimated that about 40% ATP produced by iv PCr was from Cr. CONCLUSION: The PCr in plasma is converted to Cr rapidly and mostly, and shows an elimination rate limited (ERL) metabolite disposition. Iv PCr caused a significantly elevated and long-lasing myocardial ATP and Cr levels. The Pit-induced myocardial ischemia brings slower elimination of PCr and Cr and higher peak concentrations of Cr and ATP in myocardium. The metabolite Cr at least partially mediates PCr-caused rise in myocardial ATP level and also possibly the cardio-protective effects of PCr.


Assuntos
Creatina/metabolismo , Isquemia Miocárdica/fisiopatologia , Miocárdio/metabolismo , Fosfocreatina/farmacocinética , Trifosfato de Adenosina/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Meia-Vida , Masculino , Camundongos , Hormônios Neuro-Hipofisários/administração & dosagem , Espectrofotometria Ultravioleta
14.
Zhonghua Yi Xue Za Zhi ; 94(4): 306-9, 2014 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-24731501

RESUMO

OBJECTIVE: To explore the protective effect of pituitrin on the development of paraquat-induced lung injury in rats. METHODS: Sixty healthy Sprague Dawley female rats were randomized into 3 groups of control, paraquat and treatment (80 mg/kg, intragastric) groups (n = 20 each) Each group was divided into 4, 6, 12 and 24 h subgroups (n = 5 each). The treatment group received pituitrin, injection via internal jugular vein 30 minutes after paraquat dosing. As controls, control and paraquat groups were injected with an equal volume of saline. The paraquat content in serum and lung tissue was measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS). And the levels of tumor necrosis factor-alpha (TNF-α) in sera and nuclear factor-kappa B (NF-κB) in lung tissue and the content of protein in bronchoalveolar lavage (BAL) fluid were detected at various timepoints. Lung wet-to-dry weight ratio (W/D) was recorded after pituitrin dosing. In addition, pathological changes were also observed. RESULTS: The highest drug concentration of paraquat in lung tissue was far lower in the treatment group than that in the paraquat group ((7.67 ± 0.91) vs (13.27 ± 0.95) µg/g, P = 0.002). There were the same result in sera ((1 695 ± 274) vs (5 377 ± 576) ng/ml, P = 0.003). The area under the concentration-time curve in the treatment group was significantly lower than that in the paraquat group (10 482 vs 43 441, P = 0.000). The levels of NF-κB in lung tissue and TNF-α in sera in the treatment group were lower than those in the paraquat group (TNF-α: 24 h: (1.85 ± 0.22) vs (2.59 ± 0.13) ng/ml, P = 0.020; NF-κB: 24 h: (88.0 ± 2.7) vs (101.8 ± 2.8) ng/g, P = 0.003). And there was a decrease in the content of protein in BAL fluid in the treatment group versus the paraquat group (BALF protein: 24 h: (125.9 ± 4.2) vs (192.7 ± 6.5)µg/ml, P = 0.003), lung W/D significantly decreased in the treatment group versus the paraquat group (12 h: 3.50 ± 0.14 vs 3.73 ± 0.15, P = 0.043; 24 h: 3.41 ± 0.06 vs 3.61 ± 0.09, P = 0.047). In addition, when compared with the paraquat group, the pituitrin-treated rats showed a mitigation of inflammatory response in lungs and reduced pulmonary edema. CONCLUSION: Pituitrin treatment decreases the content of paraquat in sera and lung homogenate in intoxicated rats and alleviates lung injury so that it may become a useful adjuvant in the treatment of acute lung injury.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Paraquat/envenenamento , Hormônios Neuro-Hipofisários/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Feminino , Hormônios Neuro-Hipofisários/farmacologia , Ratos , Ratos Sprague-Dawley
15.
J Pept Sci ; 20(6): 406-14, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24644276

RESUMO

Two glycosylated peptides have been studied using NMR spectroscopy supported by molecular modeling. Peptide I is an oxytocin (OT) analogue in which glutamine 4 was replaced by serine with attached α-d-mannose through the oxygen ß atom, whereas peptide II is a lysine-vasopressin (LVP) analogue with lysine 8 side chain modified by the attachment of glucuronic acid through an amide bond. Both peptides exhibit very weak uterotonic effect and are less susceptible to proteolytic degradation than the mother hormones. Additionally, peptide II reveals very weak pressor and antidiuretic activities. Our results have shown that the conformational preferences of glycosylated analogues are highly similar to those of their respective mother hormones. OT glycosylated analogue (I) exhibits a 3,4 ß-turn characteristic of OT-like peptides, and vasopressin-glycosylated analogue (II) exhibits ß-turns typical of vasopressin-like peptides. Therefore, the lack of binding of the glycosylated analogues to the receptors can be attributed to a steric interference between the carbohydrate moieties and the receptors. We also consider this to be the reason of the very low activity of the analyzed glycopeptides. We expect that results from these studies will be helpful in designing new OT-like and vasopressin-like drugs.


Assuntos
Glicoconjugados/química , Hormônios Neuro-Hipofisários/química , Modelos Moleculares , Conformação Molecular , Ressonância Magnética Nuclear Biomolecular , Hormônios Neuro-Hipofisários/síntese química , Hormônios Neuro-Hipofisários/isolamento & purificação , Conformação Proteica
17.
Ukr Biokhim Zh (1999) ; 85(3): 85-9, 2013.
Artigo em Ucraniano | MEDLINE | ID: mdl-23937052

RESUMO

It was established in experiments on the rats in the acute period of modeling pituitrin-isadrin myocardial infarction the formation of nitrogen monoxide decreases along with its accelerated transformation into peroxynitrite. It was evidenced by more than double inhibition of NO synthase activity in the myocardium and by decreasing the amount of nitrates on the background of the increasing level of peroxynitrites' marker--nitrotyrosine by 246.6% at an average. Experimental therapy of rats by ademol which is a derivate of adamantan (1-adamantiloxy-3-morpholino-2 propanol hydrochloride) better than by corvitin normalizes the processes of synthesis of nitric oxide. At the same time ademol probably exceeded the reference drug in ability to increase NO synthase activity and amount of nitrate, and promoted a decrease of the level of nitrotyrosine in the myocardium on the average by 36.3; 50.6 and 12.7%, respectively. Corrective influence of ademol on indicators of metabolism in NO system under the conditions of acute cardiac ischemia indicates to promicing development of domestic cardioprotector on its base.


Assuntos
Benzotiadiazinas/farmacologia , Cardiotônicos/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Adamantano/farmacologia , Animais , Flavonoides/farmacologia , Injeções Intramusculares , Injeções Intraperitoneais , Isoproterenol , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/patologia , Ácido Peroxinitroso/metabolismo , Hormônios Neuro-Hipofisários , Ratos , Tirosina/análogos & derivados , Tirosina/análise , Tirosina/metabolismo , Regulação para Cima/efeitos dos fármacos
18.
Int J Clin Pharmacol Ther ; 51(8): 615-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23782580

RESUMO

OBJECTIVE: This study aimed to test the effects of hypophysin on hemodynamics and coronary artery caliber of patients with hypotension and decreased systemic vascular resistance (SVR) following cardiopulmonary bypass (CPB). METHODS: Twenty-four patients with mean arterial pressure (MAP) < 60 mmHg, mean aorta pressure < 70 mmHg, SVR < 800 dynes.sec.cm-5, cardiac index (CI) > 2.5 l.min-1.m-2, central venous pressure > 8 mmHg and refractory to dopamine, norepinephrine, and fluid resuscitation were treated with hypophysin at an initial dose of 0.6 IU and a continuous infusion rate of 1 - 4 IU/h till the end of operation. The hemodynamics and the diameter of proximal left main coronary artery were evaluated before incision, before hypophysin administration, 5 min after hypophysin administration, and at the end of operation. RESULTS: MAP, SVR, and the diameter of proximal left main coronary artery increased whereas heart rate, CI, stroke volume index, and mean pulmonary artery pressure had no significant changes after hypophysin administration compared with before hypophysin administration. All hypophysin-treated patients successfully recovered. CONCLUSION: Hypophysin may improve the hemodynamics and dilate the proximal left main coronary artery in hypotensive patients with low SVR following CPB.


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Hipotensão/tratamento farmacológico , Hormônios Neuro-Hipofisários/uso terapêutico , Resistência Vascular/efeitos dos fármacos , Adulto , Idoso , Pressão Arterial/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
J Neuroendocrinol ; 25(2): 97-106, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22913624

RESUMO

The renin-angiotensin-aldosterone system makes a critical contribution to body fluid homeostasis, and abnormalities in this endocrine system have been implicated in certain forms of hypertension. The peptide hormone angiotensin II (AngII) regulates hydromineral homeostasis and blood pressure by acting on both peripheral and brain targets. In the brain, AngII binds to the angiotensin type 1 receptor (AT1R) to stimulate thirst, sodium appetite and both arginine vasopressin (AVP) and oxytocin (OT) secretion. The present study used an experimental model of endogenous AngII to examine the role of p44/42 mitogen-activated protein kinase (MAPK) as a signalling mechanism to mediate these responses. Animals were given a combined treatment of furosemide and a low dose of captopril (furo/cap), comprising a diuretic and an angiotensin-converting enzyme inhibitor, respectively, to elevate endogenous AngII levels in the brain. Furo/cap induced p44/42 MAPK activation in key brain areas that express AT1R, and this effect was reduced with either a centrally administered AT1R antagonist (irbesartan) or a p44/42 MAPK inhibitor (U0126). Additionally, furo/cap treatment elicited water and sodium intake, and irbesartan markedly reduced both of these behaviours. Central injection of U0126 markedly attenuated furo/cap-induced sodium intake but not water intake. Furthermore, p44/42 MAPK signalling was not necessary for either furo/cap- or exogenous AngII-induced AVP or OT release. Taken together, these results indicate that p44/42 MAPK is required for AngII-induced sodium appetite but not thirst or neurohypophysial secretion. This result may allow for the discovery of more specific downstream targets of p44/42 MAPK to curb sodium appetite, known to exacerbate hypertension, at the same time as leaving thirst and neurohypophysial hormone secretion undisturbed.


Assuntos
Angiotensina II/metabolismo , Apetite/fisiologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Hormônios Neuro-Hipofisários/metabolismo , Sódio na Dieta/administração & dosagem , Sede/fisiologia , Antagonistas de Receptores de Angiotensina/farmacologia , Animais , Apetite/efeitos dos fármacos , Diuréticos/farmacologia , Furosemida/farmacologia , Masculino , Modelos Biológicos , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Sede/efeitos dos fármacos
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