RESUMO
Based on the technology of platelet proteomics, the key regulatory proteins and pathogenesis of coronary heart disease with phlegm and blood stasis syndrome were explored and analyzed. Based on the previous laboratory research, the model of coronary heart disease in mini-swine with phlegm-stasis cementation syndrome was duplicated. The model was judged by the changes in blood lipid and myocardial tissue characteristics. Furthermore, the platelet proteins were studied by quantitative proteomics, and the differentially expressed proteins were screened. The critical regulatory proteins and biological pathways of coronary heart disease with phlegm-stasis cementation syndrome were analyzed by bioinformatics. After ten weeks of modeling, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL-C), triglyceride (TG), creatine kinase (CK) and creatine kinase-MB (CK-MB) in the model group were significantly increased, reflecting the pathological changes such as increased blood lipid, abnormal coagulation function and myocardial ischemia in the model group. In addition, compared with the sham group, there were 26 up-regulated proteins and 8 down-regulated proteins in the platelets of the model group. Combined with bioinformatics analysis, it was found that differential proteins mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction. Among them, lactate dehydrogenase B (LDHB), alcohol dehydrogenase 5 (ADH5), neuroblastoma ratsarcoma viral oncogene homolog (NRAS) and Kirsten ratsarcoma viral oncogene homolog (KRAS) play a central role when interacting with other proteins and simultaneously participate in multiple action pathways. The results showed that LDHB, ADH5, NRAS, and KRAS may be the marker proteins in CHD with phlegm-stasis cementation syndrome by regulating glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction and other biological processes.
RESUMO
Based on the ancient Chinese medical literature and modern clinical application literature, Mahuangtang was systematically analyzed, including its origin, composition, processing requirements and others, in order to provide support for the development of this famous classical formula. It was found that there were some doubts about Mahuangtang, such as the original variety, the processing of decoction pieces, and the dose conversion ratio. On the basis of fully considering the actual needs of the development of famous classical formula preparations and the usage habits of modern clinical practice, the development suggestions of the author were as follows:Ephedrae Herba should be selected Ephedra sinica without removing knots, Cinnamomi Ramulus should be selected from Cinnamomum cassia, Glycyrrhizae Radix et Rhizoma should select Glycyrrhiza uralensis and be roasted with honey, and Armeniacae Semen Amarum should be selected as Dan-processed products. The total dose of Mahuangtang was 24 g after conversion according to 1 Liang equal to 3 g as following the transition phenomenon and law. The preparation and usage method was as follows:took 1.8 L of water, first added Ephedrae Herba in water for decocting, evaporated 400 mL of water, removed the upper foam, then added the other three drugs, cooked over gentle heat to 500 mL, filtered the residue, took three times a day, about 160 mL warm decoction once. The major function recorded of Mahuangtang in ancient books was exterior sthenia syndrome of exogenous wind cold, it often used in the clinical treatment of cold, acute bronchitis, bronchial asthma and other diseases through the flexible application of the later doctors.
RESUMO
With continuous introduction of relevant national policies on famous classical formulas, the research of famous classical formulas is popular all over the country. Different from other new drugs, in the research and development process of famous classical formulas, substance benchmark is earlier than the product, suggesting that the research and development of substance benchmark is of great significance. Based on previous work of the authors, content of substance benchmark of famous classical formulas was analyzed, which was included in the document <italic>The Management Regulation of Simplified Registration and Approval over Chinese Herbal Medicine Compound Preparations of Ancient Famous Classical Formulas</italic> released by the National Medical Products Administration in May 2018. In this paper, the significance of substance benchmark development was described, a five-stage of research strategy was proposed, covering the prescription textual research and historical evolution, the collection and quality evaluation of medicinal materials, the processing method and quality evaluation of decoction pieces, the preparation and quality research of substance benchmark, the drafting and formulating of quality standard over substance benchmark. At the same time, some suggestions were put forward to the feasibility of compound preparations development over famous classical formulas, the implementation difficulty of resource evaluation over Chinese medicinal materials, and the irrationality on the quality correlation of Chinese medicinal materials. All of these are expected to provide reference and enlightenment for the development and policy officially landed over ancient famous classical formulas.
RESUMO
This study aimed to establish the HPLC characteristic chromatogram and content determination method for index components with the primary standard substances of the classical prescription Mahuang Decoction, and to provide data basis for the establishment of its quality standard and the development and utilization of compound preparations. First, HPLC was used to establish the material reference chromatograms of Mahuang Decoction, and 15 batches of standard samples of Mahuang Decoction were determined. Their similarity was calculated by the median method. Secondly, the content of the standard substances was determined and a simplecontent determination method was established by HPLC. Relevant methodology was investigated, and the extraction ratio, index component transfer rate and moisture content of 15 batches of primary standard samples were calculated. The results showed that the two sets of HPLC methods had their own characteristics. The six chromatographic peaks identified from the 10 common peaks in the former characteristic chromatogram covered all the herbal medicines in the standard substances, which can better indicate the quality characteristics of the standard substances of Mahuang Decoction. The latter method(content determination method) was simple and practical, so it was suitable for establishing the quality standard of its compound preparation. Two sets of methods were jointly used to evaluate the quality of 15 batches of Mahuang Decoction. The results were as follows: the similarity of 15 batches of samples was greater than 0.90; the average extraction ratio was 18.1%; the average moisture content was 9.7%; the average content and transfer rate of the standard ingredients ephedrine hydrochloride and total pseudoephedrine hydrochloride were 2.3% and 26.7% respectively, and the average content and transfer rate of amygdalin were 2.2% and 48.3% respectively. None of the data showed dispersion(beyond 70%-130% of the mean value), which met the application data requirements for the substance standards of ancient classical Chinese herbal compound preparations(draft for comments). Based on the above research, the primary substance quality standard of Mahuang Decoction was established in order to provide reference for the development and research of the compound preparation of Mahuang Decoction.
Assuntos
Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas , Ephedra sinica , Prescrições , Controle de Qualidade , Padrões de ReferênciaRESUMO
The grade classification of Chinese herbal medicines and their decoction pieces has always been a hot issue in the industry. In the trading history of Chinese herbal medicine,buyers and sellers often determine the price according to quality,so the naturally formed specifications and grades are changing with the change of technology and the increasing demand of the public for medical care.The planting,processing and circulation methods of Chinese medicinal materials have also changed greatly. Under the mode of pursuing yield and short-term benefit,the traditional rating evaluation method has been difficult to be used in the current quality status of prepared slices. Aurantii Fructus Immaturus is a genuine medicinal material of Jiangxi province,which is widely used,but has different quality levels on the market. In this paper,the quality levels were evaluated by the mass constant method. A set of grading method of Aurantii Fructus Immaturus slices was established,laying a foundation for " high quality and high price" Aurantii Fructus Immaturus slices. The grading method of Chinese herbal slices with quality constant was applied to 16 batches of Aurantii Fructus Immaturus slices collected form the market,and the final assessment results were as follows for different piece shapes( hemispherical type and thin type)respectively. The hemispherical Aurantii Fructus Immaturus pieces: quality constant ≥1. 11 for the first grade,< 1. 11 but ≥0. 69 for the second grade,and <0. 69 for the third grade. The thin type Aurantii Fructus Immaturus pieces: quality constant ≥0. 024 for the first grade,<0. 024 but ≥0. 015 for the second grade,and <0. 015 for the third grade. This work indicated that the quality constants grading method can be used to objectively classify the grades of traditional Chinese medicine,providing basis for standardizing market behavior and providing useful reference for grading of hemispherical or thin Aurantii Fructus Immaturus pieces.
Assuntos
Citrus , Química , Medicamentos de Ervas Chinesas , Padrões de Referência , Medicina Tradicional Chinesa , Controle de QualidadeRESUMO
A girl was diagnosed with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) due to pyrexia and hemoptysis for eight days. The girl was a school-age child with major clinical manifestations of pyrexia, skin rash, enlargement of bilateral cervical lymph nodes, conjunctival hyperaemia, red and cracked lips and strawberry-like tongue, followed by swelling of both hands and feet. Laboratory examination showed significant increases in white blood cell count, platelet count, C-reactive protein, erythrocyte sedimentation rate and liver enzymes, a significant reduction in albumin, and the presence of aseptic pyuria. After the first course of IVIG treatment, the girl still had recurrent pyrexia, with hemoptysis on day 2 after admission, and lung CT showed uneven luminance and patchy shadow. The symptoms were quickly alleviated after the second course of IVIG treatment combined with methylprednisolone and aspirin treatment. KD is a febrile disease characterized by multiple systemic vasculitis in childhood and can involve various organ systems such as the heart, lungs, kidneys and the nervous system. Therefore, it is necessary to carefully monitor and recognize the rare symptoms of KD, and early recognition of pulmonary complications of KD can avoid delay in diagnosis, prevent the development of more serious complications, and help with early treatment and disease recovery.
Assuntos
Criança , Feminino , Humanos , Sedimentação Sanguínea , Febre , Hemoptise , Imunoglobulinas Intravenosas , Síndrome de Linfonodos MucocutâneosRESUMO
A girl, aged 8 years, developed jaundice and liver dysfunction in the neonatal period, with congenital glaucoma diagnosed on day 5 after birth, hypertension and unusual facies (broad forehead, hypertelorism and deep-set eyes). Cholestasis was the main type of liver dysfunction. Cardiac macrovascular CTA showed stenosis at the abdominal aorta and the beginning of the bilateral renal arteries. Whole exon sequencing revealed a heterozygous frameshift mutation, c.1485delC (absence of cytosine), in exon 12 of the JAG1gene. The girl was diagnosed with Alagille syndrome and was given transaminase-lowering, cholagogic and antihypertensive treatment with multiple drugs. There were significant reductions in serum levels of alanine aminotransferase, aspartate aminotransferase and total bile acid, but blood pressure fluctuated between 102-140 mm Hg/53-89 mm Hg. After renal artery angiography and balloon dilatation angioplasty, the girl was given oral administration of antihypertensive drugs, and blood pressure was controlled at a level of 110-120 mm Hg/60-80 mm Hg. The rare disease Alagille syndrome should be considered when a child has refractory hypertension with the involvement of multiple systems, especially liver dysfunction with cholestasis as the main manifestation. Genetic causes should be analyzed for a early diagnosis.
Assuntos
Criança , Feminino , Humanos , Síndrome de Alagille , Pressão Sanguínea , Hipertensão , Hepatopatias , Artéria RenalRESUMO
The quality constant evaluation method was applied to the grading evaluation of Albiziae Cortex decoction pieces. The morphological and component indexes of 12 batches of the decoction pieces were measured, their quality constants were calculated and graded. The results showed that the quality constant ranged from 0.041 to 0.167. If the percentage quality constant ≥ 80%was the first-grade decoction pieces, <80%and ≥ 50%was the second-grade decoction pieces, <50%was the third-grade decoction pieces; the quality constant of the first-grade decoction pieces was ≥ 0.133 6, the second-grade decoction pieces was ≥ 0.083 5 and <0.133 6, and the third-grade decoction pieces was <0.083 5. In this paper, the authors further applied the quality constant evaluation method of skin piece in the grading evaluation of Albiziae Cortex decoction pieces, which proved that the method was reasonable and scientific, and it can provide a reference for the quality grading of this decoction pieces.
RESUMO
To prepare the standard decoction of Moutan Cortex, and research its quality standard. According to the preparation principle of standard decoction of Chinese herbal medicines, the extraction conditions were optimized, and the 14 batches of standard decoction of Moutan Cortex were prepared. The content of paeonol was determined by HPLC; the transfer rate was calculated; and the extraction rate, pH value and the fingerprint of the decoction were determined. The results showed that the transfer rate of paeonol in the standard decoction of 14 batches of samples was at the range of 43.9%-67.3%; the range of extraction rate was 22.0%-38.7%, and the pH value range was 3.98-4.77. At the same time, the fingerprints of 14 batches of Moutan Cortex standard decoction were established; 9 common peaks were determined, and the similarities were more than 0.9. The preparation method in this study was standardized with good reproducibility, and can be used for the preparation and quality standard of standard decoction of Moutan Cortex, providing reference for the quality evaluation of Moutan Cortex dispensing granules.
RESUMO
To build the quality standard of processed Cinnamomi Cortex standard decoction and provide quality reference for Cinnamomi Cortex formula granules. Fourteen batches of Cinnamomi Cortex standard decoction pieces were prepared according to the preparation requirements for standard decoction of Chinese herbal medicine containing volatile oil. With cinnamaldehyde as the quantitative index, the transfer rate and extraction rate were calculated; pH value was determined and HPLC fingerprint analysis method was established. By the measurement of 14 batches of standard decoction, the transfer rate ranged from 25.0% to 68.4%; the extraction rate was at a range of 3.7% to 10.1% and pH was 3.72 to 5.48. Then the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (2012A) was used to analyze and compare the fingerprints. Four common peaks were determined and three were identified including coumarin (peak 1), cinnamic acid (peak 2) and cinnamaldehyde (peak 3). Moreover, the similarity was 1.0. This study established an HPLC fingerprint analysis method of processed Cinnamomi Cortex standard decoction. The method showed good precision, stability and repeatability in fingerprint analysis, with significance in identification.
RESUMO
To prepare standard decoction of Phellodendri Chinensis Cortex pieces, establish quality standards, and provide reference for evaluating the quality of formula granule of Phellodendri Chinensis Cortex. 15 batches Phellodendri Chinensis Cortex pieces in different levels of quality were collected from market. The standard extraction process was used to prepare the standard decoction, and then the transfer rate of the index components berberine and phellodendrine was calculated to measure dry extraction ratio and pH value. So the method for Phellodendri Chinensis Cortex's fingerprint and content determination of index components was established. The result revealed that the extraction ratio was from 12.81% to 19.41%, with an average value of 16.54%. The transfer rate of berberine was at the range of 36.4%-56.6%, with an average value of 48.9%. The transfer rate of Phellodendri Chinensis Cortex piece was at the range of 47.5%-83.3%, with an average value of 63.1%. The pH value was between 5.2 and 5.9. The Similarity Evaluation System for Chromatographic Fingerprint of traditional Chinese medicine TCM (2012A) was used to analyze and compare the fingerprint and the similarity between the fingerprint of formula granule of Phellodendri Chinensis Cortex and the reference fingerprint was over 0.9. The preparation method in this paper showed good precision, stability and repeatability in fingerprint analysis, suitable for quality evaluation of Phellodendri Chinensis Cortex pieces standard decoction.
RESUMO
To build an evaluation standard for quality of Leonuri Herba standard decoction. 13 batches of Leonuri Herba standard decoction with different quality were prepared. The contents of leonurine hydrochloride and stachydrine hydrochloride were determined; then the transfer rate and the extract rate were calculated and pH value was measured; and HPLC fingerprint method was established for analysis. The results of 13 batches of samples revealed that the transfer rate of leonurine hydrochloride and stachydrine hydrochloride was 30.0%-53.4% and 67.0%-82.6%, respectively; the extract rate was 12.1%-18.3% and the pH value was 5.87-6.22. Moreover, 12 common chromatographic peaks were determined based on fingerprint by using Similarity Evaluation System for Chromatographic fingerprint of Traditional Chinese Medicine (2012A). The similarity of 13 batches of samples was analyzed and compared, and the results showed that the similarity was higher than 0.9. In this study, the preparation method for Leonuri Herba decoction was standard, with high similarity in fingerprint, showing high precision, stability and repeatability in fingerprint analysis. Thus, this study can provide a reference for the quality control of Leonuri Herba dispensing granules.
RESUMO
To prepare Cinnamomi Ramulus pieces standard decoction and establish its quality standard, provide quality reference for formula granules and other clinic non-traditional forms of medicines, and lay a foundation for standard decoction research for the pieces containing essential oil. 14 batches of Cinnamomi Ramulus pieces with different quality were collected from market and their extraction process was further improved based on the preparation principle of standard decoction to prepare the standard decoction of Cinnamomi Ramulus pieces. Then its transfer rate of Cinnamaldehyde, dry extract rate and pH value were calculated to evaluate its process stability; and a method for chromatographic fingerprint and content determination was also established. Results revealed that the dry extract rate for standard decoction of Cinnamomi Ramulus pieces was from 6.06%-8.95%, with an average value of 7.18%; the transfer rate of cinnamaldehyde was at the range of 29.6%-54.3%, with an average of 43.2%; and the pH value was at the range of 4.33-4.82. The fingerprint similarities between 14 batches of standard decoction of Cinnmomi Rammulus pieces and reference fingerprint were all>0.9. The established method for standard decoction was stable and its quality standard was perfect, suitable for evaluating the quality of standard decoction of Cinnanomi Ramulus pieces.
RESUMO
Hennekam syndrome (HS) is a rare autosomal recessive syndrome characterized by defective lymphatic development. A 34-month-old boy with HS and who had unexplained developmental retardation and hypoalbuminemia as main clinical manifestations is reported here. He had a history of generalized edema and poor feeding. He was not thriving well. He manifested as facial anomalies (hypertelorism, flat nasal bridge and flat face), fracture of teeth, and superficial lymph nodes enlargement. He had low serum total protein, low serum albumin, and low serum immunoglobulin levels. Duodenal bulb biopsy revealed lymphangiectasia. Color Doppler ultrasound, magnetic resonance imaging and CT scan showed multi-site lymphangioma, and HS was thus confirmed. Mutations in CCBE1 and FAT4 have been found responsible for the syndrome in a part of patients. Diagnosis of the disease depends on the familial history, clinical signs, pathological findings and genetic tests.
Assuntos
Pré-Escolar , Humanos , Masculino , Anormalidades Craniofaciais , Diagnóstico , Terapêutica , Doenças dos Genitais Masculinos , Diagnóstico , Terapêutica , Linfangiectasia Intestinal , Diagnóstico , Terapêutica , Linfedema , Diagnóstico , Terapêutica , SíndromeRESUMO
<p><b>OBJECTIVE</b>To investigate the clinical and electrophysiological characteristics and prognosis of acute motor axonal neuropathy (AMAN) in children in South China.</p><p><b>METHODS</b>The clinical and electrophysiological data of 6 children with AMAN was analyzed, and they were followed up.</p><p><b>RESULTS</b>The mean age of onset was 4.4 years. Most patients came from rural areas and 5 cases had a history of prodromal infection. There were no seasonal differences in clinical onset among the patients. The most common first symptom was muscle weakness, and the mean time from onset to the most severe disease status was 4.2 days. Nerve conduction test results revealed that all patients showed significantly lower amplitude of motor nerve action potential, only 22.3%-73.4% of the lower limit of normal. Injury to the nerves of distal extremities was more serious than injury to the nerves of proximal extremities (P<0.05), while there was no significant difference in the injury to the nerves of upper and lower extremities (P>0.05). Motor nerve conduction velocity and sensory nerve conduction velocity were normal. All patients received intravenous immunoglobulin (IVIG). Of the 6 AMAN patients, 4 could walk independently after a follow-up of 3 months to 1 year.</p><p><b>CONCLUSIONS</b>AMAN in children occurs mostly in rural areas. There is no seasonal difference in the clinical onset of the disease. Muscle weakness is the most common first symptom and the worst status of AMAN appears in the early stage of the disease. Electrophysiological examination provides important information for the diagnosis of AMAN. Some children with AMAN regain the ability to walk independently 1 year after onset. Early application of IVIG treatment may help recovery of neural function.</p>
Assuntos
Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Síndrome de Guillain-Barré , Tratamento Farmacológico , Alergia e Imunologia , Imunoglobulinas Intravenosas , Usos Terapêuticos , Condução Nervosa , Fisiologia , PrognósticoRESUMO
<p><b>OBJECTIVE</b>To analyze the characteristic of T cell response to specific antigen proteins in patients with hepatitis B virus infection.</p><p><b>METHODS</b>76 cases were recruited, including four groups, acute hepatitis B (AHB), active phase of chronic hepatitis B (CHB), inactive HBV carriers (AsC) and past HBV infection. T cell responses stimulated by 3 antigen specific proteins of HBV were detected using enzyme linked immunospot (ELISPOT) assay.</p><p><b>RESULTS</b>(1) There were no significant difference in frequencies to HBsAg, HBcAg and HBeAg in AHB and CHB. The frequencies to HBsAg and HBcAg in AsC were lower than that to HBeAg, and the frequencies to HBsAg in group of past HBV infection were significantly lower than that to HBcAg and HBeAg. (2) The frequencies to HBsAg in AHB and CHB both were higher than in group of past HBV infection. The frequencies to HBcAg of AHB, CHB and AsC were higher than that of group of past HBV infection. (3) There were no significant difference in magnitude to HBsAg, HBcAg and HBeAg in AHB and AsC. In CHB, the magnitude to HBsAg was lower than that to HBcAg. The magnitude of in group of past HBV infection were HBcAg > HBeAg > HBsAg. (4) In four groups, the sequence of the magnitude to HBsAg from high to low was AHB, CHB, group of past HBV infection and AsC. The magnitude to HBcAg in of AsC was lower than other three groups. As to the magnitude to HBeAg, the difference was no significant between any two groups except between AHB and CHB.</p><p><b>CONCLUSIONS</b>The T cell responses in group of AsC to HBeAg were the highest, while the T cell responses to HBcAg were the highest in group of other groups.</p>
Assuntos
Humanos , Hepatite B , Alergia e Imunologia , Virologia , Anticorpos Anti-Hepatite B , Alergia e Imunologia , Antígenos do Núcleo do Vírus da Hepatite B , Alergia e Imunologia , Antígenos de Superfície da Hepatite B , Alergia e Imunologia , Antígenos E da Hepatite B , Alergia e Imunologia , Vírus da Hepatite B , Alergia e Imunologia , Linfócitos T , Alergia e ImunologiaRESUMO
Evidence suggests that the deterioration of communication between the sympathetic nervous system and cardiovascular system always accompanies the aging of human and animals. Cardiac sympathetic norepinephrine (NE) transporter (NET) on presynaptic membrane is a predominant component to eliminate released NE in the synaptic cleft and maintains the sensitivity of the beta-adrenergic receptor (beta-AR). In the present study, we investigated NET and beta1-AR mRNA levels and sympathetic nerve density in cardiac sympathetic ganglion and left ventricular myocardium in 2- and 16-month-old rats with Northern blot analysis and immunohistochemistry. The expression levels of NET mRNA, NET protein and beta1-AR mRNA in the ganglia or myocardia of 16-month-old rats were markedly reduced by 67%, 26%, and 43%, respectively, in comparison with those in 2-month-old rats. Our results also show that aging induces a strong decrease of the catecholaminergic nerve fiber density.
Assuntos
Animais , Masculino , Ratos , Envelhecimento , Fisiologia , Regulação da Expressão Gênica , Genética , Miocárdio , Metabolismo , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Genética , Metabolismo , RNA Mensageiro , Genética , Ratos Sprague-Dawley , Receptores Adrenérgicos beta 1 , MetabolismoRESUMO
<p><b>OBJECTIVE</b>Cytokine mediated cell immunity is the main mode of anti-tumor immunity in organism, and the disequilibrium of cytokine network is the main cause of tumor cells escaping immunologic surveillance. High mobility group box 1 (HMGB1), a nuclear protein, has recently been identified as an important mediator of local and systemic inflammatory diseases when released into the extracellular milieu. In the present study, the investigators explored the clinical significance of alteration in the serum levels of HMGB1 in childhood acute lymphocytic leukemia (ALL) and the mechanism of HMGB1-induced tumor necrosis factor (TNF)-alpha secretion in leukemic cells.</p><p><b>METHODS</b>The serum levels of HMGB1 in healthy children and childhood ALL were assayed by Western blotting. K562 leukemic cells were stimulated with recombinant HMGB1 protein in vitro, and the secretion of TNF-alpha was determined by using ELISA. The effects of HMGB1 on activation of p38, c-Jun amino-terminal kinase (JNK), and extracellular-signal regulated protein kinase (ERK) and mitogen-activated protein kinase (MAPK) in K562 cells were assayed by using Western blotting. The effects of inhibitors specific for the MAPK on HMGB1-induced TNF-alpha secretion were assayed by using ELISA.</p><p><b>RESULTS</b>The serum levels of HMGB1 were significantly higher in ALL initial treatment group (n = 15, 43.78 +/- 4.62 microg/ml) than those in healthy control group (n = 15, 0.60 +/- 0.48 microg/ml, P < 0.01) and ALL complete remission group (n = 15, 0.89 +/- 0.62 microg/ml, P < 0.01). No significant difference was found between the healthy control group and ALL complete remission group in HMGB1 levels (P > 0.05). TNF-alpha started to become detectable at 2 h and was still increasing at 16 h after HMGB1 (1 microg/ml) treatment in K562 cell culture. TNF-alpha was also secreted from K562 cells in a dose-dependent manner after HMGB1 (1 ng/ml-1 microg/ml) exposure. HMGB1 induced the phosphorylation of p38, JNK and ERK in k562 cells. Inhibitors specific for the JNK (SP600125), MEK (PD98059), and p38 MAPK (SB203580), abrogated HMGB1-induced TNF-alpha secretion.</p><p><b>CONCLUSIONS</b>The measurement of serum HMGB1 is helpful to evaluate the prognosis of the childhood ALL. HMGB1 stimulates leukemic cells to secrete TNF-alpha through a MAPK-dependent mechanism.</p>
Assuntos
Criança , Humanos , Linhagem Celular Tumoral , Citocinas , Metabolismo , Proteína HMGB1 , Metabolismo , Imidazóis , Farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno , Metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno , Metabolismo , Proteínas Quinases Ativadas por Mitógeno , Metabolismo , Fosforilação , Leucemia-Linfoma Linfoblástico de Células Precursoras , Metabolismo , Inibidores de Proteínas Quinases , Farmacologia , Piridinas , Farmacologia , Transdução de Sinais , Fator de Necrose Tumoral alfa , MetabolismoRESUMO
Objective: To investigate the changes of myo cardial contractile function during myocardial stunning in calcium overload rats and the protective effects of tetrandrine. Methods: Forty-six rats were randomized into control, myocardial ischemia, myocardial stunning, low and high dose of tetrandrine groups. Another 10 rats were used to identify the calcium overload. vitamin D3 (0.3 million Unit/kg) and nicotinic acid were adm inistered. After 16 d when calcium overload occured, left anterior descending ar tery was ligated. Twenty minutes of myocardial ischemia followed by 60 min of re perfusion was induced. The contractile function parameters were determined dynam ically. At the end of experiment, myocardial cytosolic [Ca2+]i was deter mined in various groups. In tetrandrine groups, tetrandrine (62.2 or 93.6 μmol/ kg ) was administered by gastrogavage daily.After 16 d, the rats undergone the e xperiments mentioned above. Results: Sixteen days after vitamin D3 , nicotinic acid were given, [Ca2+]i increased by 2.6 folds (146.8±10.8 ) vs (368.5±22.6) nmol/L, (P<0.01). Whereas, [Ca2+]i in tetrand rine groups were (210.8±16.4) and (198.6±15.3) nmol/L, which were significantl y lower than that of calcium overload group. Twenty minutes of myocardial ische mia resulted in the decrease of dp/dtmax and Vmax in all groups with the most si gnificant in stunning and calcium overload groups. The contractile function rest ored gradually after reperfusion. At all time points, dp/dtmax and Vmax in both tetrandrine groups were higher than those in both stunning and calcium overload groups. And effect with higher dose of tetrandrine were more significant than in low dose of tetrandrine. After 60 min of reperfusion, dp/dtmax in stunning, cal cium overload, low and high dose of tetrandrine groups were 49.7%, 51.5%, 71.0% and 83.4% of that in control, respectively, and Vmax were 55.0%, 49.8%, 73.9% and 77.5% of that in control, respectively. Conclusion: T he myocardial contractile function in vitamin D3-induced calcium overload gro up is impaired. On basis of myocardiocyte calcium overload, transient ischemia l eads to myocardial stunning. At the stage of ischemia, the impaired degree of my ocardial contractile function is similar to that in stunning group, suggesting a t this stage the effect of ischemia on myocardial function is greater than that of calcium overload. Tetrandrine chronically improves the myocardial function in Vitamin D3-induced calcium overload rats.
RESUMO
Objective: To assess the effect of balloon angiopl asty on circulating endothelin (ET) and TNF-α levels and tissue endothelin in experimental atherosclerosis in rabbits. Methods: After 20 New Z ealand rabbits had a high cholesterol diet for at least 8 weeks, successful ball oon angioplasty was performed in rihgt iliac arteries in 18 rabbits. Circulatin g levels of ET and TNF-α were measured before as well as immediately and 24 h after balloon angioplasty. Tissue endothelin immunoreactivity in atherosclerotic iliac artery wall after balloon angioplasty was assessed by immunohistochemica l technique. Results: Plasma levels of ET and TNF-α were signi ficantly increased immediately after ballon angioplasty (76.40±13.58)pg/ml vs (92.67±11.38) pg/ml and (31.35±6.23) U/ml vs (56.26±7.37) U/ml, resp ectively (P<0.05) .There was no change in plasma ET and TNF-α levels 24 h after balloon angioplasty (77.13±12.87) pg/ml vs (76.40±13.58) pg/ml and (33.41±6.79) U/ml vs (31.35±6.23) U/ml, respectively (P>0.05). T issue endothelin immunoreactiuvity was markedly increased in right iliac artery wall after balloon angioplasty than that in opposite iliac artery wall. Conclusion: The increase of plasma ET, TNF-α levels and tissue ET-IR in iliac artery wall after balloon angioplasty may be associated with the injury of l ocal vascular intima, suggesting that ET and TNF-α may take part in the corona ry constriction and the development of coronary restenosis after percutaneous tr ansluminal coronary angioplasty.