RESUMO
BACKGROUND: At present, liver transplantation (LT) is one of the best treatments for hepatocellular carcinoma (HCC). Accurately predicting the survival status after LT can significantly improve the survival rate after LT, and ensure the best way to make rational use of liver organs. AIM: To develop a model for predicting prognosis after LT in patients with HCC. METHODS: Clinical data and follow-up information of 160 patients with HCC who underwent LT were collected and evaluated. The expression levels of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, Golgi protein 73, cytokeratin-18 epitopes M30 and M65 were measured using a fully automated chemiluminescence analyzer. The best cutoff value of biomarkers was determined using the Youden index. Cox regression analysis was used to identify the independent risk factors. A forest model was constructed using the random forest method. We evaluated the accuracy of the nomogram using the area under the curve, using the calibration curve to assess consistency. A decision curve analysis (DCA) was used to evaluate the clinical utility of the nomograms. RESULTS: The total tumor diameter (TTD), vascular invasion (VI), AFP, and cytokeratin-18 epitopes M30 (CK18-M30) were identified as important risk factors for outcome after LT. The nomogram had a higher predictive accuracy than the Milan, University of California, San Francisco, and Hangzhou criteria. The calibration curve analyses indicated a good fit. The survival and recurrence-free survival (RFS) of high-risk groups were significantly lower than those of low- and middle-risk groups (P < 0.001). The DCA shows that the model has better clinical practicability. CONCLUSION: The study developed a predictive nomogram based on TTD, VI, AFP, and CK18-M30 that could accurately predict overall survival and RFS after LT. It can screen for patients with better postoperative prognosis, and improve long-term survival for LT patients.
Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Nomogramas , alfa-Fetoproteínas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/sangue , Masculino , Transplante de Fígado/efeitos adversos , Pessoa de Meia-Idade , Feminino , Fatores de Risco , alfa-Fetoproteínas/análise , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/análise , Prognóstico , Adulto , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Queratina-18/sangue , Queratina-18/análise , Técnicas de Apoio para a DecisãoRESUMO
The question of whether rare 10,11-seco-lathyranes are natural products or artifacts is thoughtfully considered after a Brønsted acid-mediated chemical conversion of naturally abundant 5/11/3 lathyrane type diterpenes into 10,11-seco-lathyranes was developed. Benefiting from this concise route, a series of 10,11-seco-lathyrane products (1-14) were smoothly synthesized. The conversion may involve an acid promoted cyclopropane ring opening accompanied by a double bond shift with final trapping of carbocation. The ease of this chemical conversion under mildly acidic conditions may imply that the 10,11-seco-lathyranes isolated to date are artifacts. This work not only develops a new modular synthetic strategy for efficient constructing rare 10,11-seco-lathyranes, but also provides a promising bioactive diterpene with excellent effect against the NO production on LPS-induced BV-2 cells.
Assuntos
Artefatos , Diterpenos , Diterpenos/farmacologia , Diterpenos/química , Estrutura MolecularRESUMO
A series of novel myrsinane-type Euphorbia diterpene derivatives (1-37) were synthesized from the abundant natural lathyrane-type Euphorbia factor L3, using a multi-step chemical process guided by a bioinspired skeleton conversion strategy, with the aim of discovering potential anti-Alzheimer's disease (AD) bioactive lead compounds. The synthesis process involved a concise reductive olefin coupling reaction through an intramolecular Michael addition with a free radical, followed by a visible-light-triggered regioselective cyclopropane ring-opening. The cholinesterase inhibitory and neuroprotective activities of the synthesized myrsinane derivatives were evaluated. Most of the compounds showed moderate to strong potency, highlighting the importance of ester groups in Euphorbia diterpene. In particular, derivative 37 displayed the most potent acetylcholinesterase (AChE) inhibition, with an IC50 value of 8.3 µM, surpassing that of the positive control, tacrine. Additionally, 37 also showed excellent neuroprotective effect against H2O2-induced injury in SH-SY5Y cells, with a cell viability rate of 124.2% at 50 µM, which was significantly higher than that of the model group (viability rate 52.1%). Molecular docking, reactive oxygen species (ROS) analysis, immunofluorescence, and immunoblotting were performed to investigate the mechanism of action of myrsinane derivative 37. The results indicated that derivative 37 may be a promising myrsinane-type multi-functional lead compound for the treatment of Alzheimer's disease. Furthermore, a preliminary SAR analysis was performed to study the acetylcholinesterase inhibitory and neuroprotective activities of these diterpenes.
Assuntos
Doença de Alzheimer , Diterpenos , Euphorbia , Neuroblastoma , Fármacos Neuroprotetores , Humanos , Euphorbia/química , Acetilcolinesterase/metabolismo , Simulação de Acoplamento Molecular , Peróxido de Hidrogênio , Doença de Alzheimer/tratamento farmacológico , Diterpenos/química , Esqueleto/metabolismo , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Estrutura Molecular , Relação Estrutura-Atividade , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
Molecular hybridization is a widely employed approach in pharmaceutical chemistry for modifying drugs with the aim of improving pharmacological efficacy and reducing adverse effects. A prime example of this is the case of benorylate, which was created by combining aspirin and acetaminophen, two non-steroidal anti-inflammatory drugs (NSAIDs). Diterpenoid alkaloids, which exhibit potent anti-inflammatory activity, have limitations in their application due to their toxicity and side effects. Thus, we aimed to design new anti-inflammatory lead compounds through the molecular hybridization of the anti-inflammatory active skeletons (lappaconitine, aconorine, and bulleyaconitine A) of diterpenoid alkaloids with classical NSAIDs. In this study, we synthesized 25 diterpenoid alkaloid derivatives with NSAIDs, organized into four series. Among these derivatives, lappaconitine derivative 1e demonstrated the strongest inhibition of lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells with minimal cytotoxicity. Additionally, 1e effectively suppressed the inflammatory response induced by carrageenan in vivo, with a swelling rate of only 1%. This anti-inflammatory potency was found to be significantly superior to that of naproxen. The molecular docking analysis revealed that the binding affinity of 1e was scored as -10.3 kcal/mol, suggesting that it forms a stable complex with cyclooxygenase-2 (COX-2). Therefore, compound 1e holds potential as a lead anti-inflammatory compound that could be further developed.
Assuntos
Alcaloides , Anti-Inflamatórios não Esteroides , Simulação de Acoplamento Molecular , Estrutura Molecular , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios/farmacologia , Aconitina , Alcaloides/farmacologia , Ciclo-Oxigenase 2/metabolismo , Desenho de FármacosRESUMO
A series of new N-aryl galantamine analogues (5a-5x) were designed and synthesized by modification of galantamine, using Pd-catalyzed Buchwald-Hartwig cross-coupling reaction in good to excellent yields. The cholinesterase inhibitory and neuroprotective activities of N-aryl derivatives of galantamine were evaluated. Among the synthesized compounds, the 4-methoxylpyridine-galantamine derivative (5q) (IC50 = 0.19 µM) exhibited excellent acetylcholinesterase inhibition activity, as well as significant neuroprotective effect against H2O2-induced injury in SH-SY5Y cells. Molecular docking, staining, and Western blotting analyses were performed to demonstrate the mechanism of action of 5q. Derivative 5q would be a promising multifunctional lead compound for the treatment of Alzheimer's disease.
Assuntos
Doença de Alzheimer , Neuroblastoma , Fármacos Neuroprotetores , Humanos , Galantamina/farmacologia , Galantamina/uso terapêutico , Acetilcolinesterase/metabolismo , Paládio , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Simulação de Acoplamento Molecular , Peróxido de Hidrogênio , Doença de Alzheimer/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Catálise , Relação Estrutura-Atividade , Estrutura MolecularRESUMO
A series of lathyrane-type Euphorbia diterpene derivatives featured 3R configuration (H-3ß) were synthesized from natural rich Euphorbia factor L3via modified Mitsunobu reaction based on configuration inversion strategy. The antiproliferation activity and MDR reversal ability of the lathyrane derivatives were evaluated, and the most synthesized compounds showed moderate or strong potencies. Among them, diterpenes 21 (IC50 values of 2.6, 5.2 and 13.1 µM, respectively) and 25 (IC50 values of 5.5, 8.6 and 1.3 µM, respectively) presented the strong cytotoxicity against MCF-7, 4 T1 and HepG2 cells. Meanwhile, derivative 25 exhibited excellent MDR reversal ability with the reversal fold of 16.1 higher than that of verapamil. The cellular thermal shift assay and molecular docking proved direct engagement of diterpene 25 to ABCB1, suggesting 25 could be a promising MDR modulator. Furthermore, the preliminary SARs of these diterpenes were also discussed.
Assuntos
Antineoplásicos , Diterpenos , Euphorbia , Humanos , Linhagem Celular Tumoral , Diterpenos/síntese química , Diterpenos/farmacologia , Euphorbia/química , Células Hep G2 , Simulação de Acoplamento Molecular , Estrutura Molecular , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologiaRESUMO
Objective: To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha ( PPP2R3A) and hexokinase 1 ( HK1) in glycolysis of hepatocellular carcinoma (HCC). Methods: In HepG2 and Huh7 cells, PPP2R3A expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The PPP2R3A-related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of PPP2R3A and HK1. Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by PPP2R3A. Results: RNA sequencing data revealed that PPP2R3A siRNA significantly downregulated the expression of HK1. PPP2R3A gene overexpression promotes, while gene silencing suppresses, the level of HK1 and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. HK1 inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by PPP2R3A overexpression in liver cancer cells. Conclusion: Our findings showed the correlation of PPP2R3A and HK1 in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of PPP2R3A in cancer.
Assuntos
Carcinoma Hepatocelular , Hexoquinase/metabolismo , Neoplasias Hepáticas , Proteína Fosfatase 2/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glicólise , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteína Fosfatase 2/genética , RNA Interferente Pequeno/metabolismoRESUMO
Myricetin is a flavonoids compound extracted from edible myrica rubra. We aimed to evaluate the efficacy of Myricetin on colonic chronic inflammation and inflammation-driven tumorigenesis in mice. Myricetin was administrated by gavage for 4 consecutive weeks. Mice were sacrificed and the number of colonic polyps was counted. Myricetin significantly inhibited AOM/DSS-induced colitis and colorectal tumorigenesis. Myricetin prevented the incidence of colorectal tumorigenesis and reduced the size of colorectal polyps. Histopathologic analysis showed that Myricetin could attenuate the degree of colonic inflammation and colorectal tumorigenesis. Further analysis showed that Myricetin strongly reduced the levels of inflammatory factors TNF-α, IL-1ß, IL-6, NF-κB, p-NF-κB, cyclooxygenase-2 (COX-2), PCNA and Cyclin D1 in the colonic tissues as analyzed by the assays of immunohistochemical staining, Western blotting and Q-RT-PCR. Our results demonstrated that Myricetin possesses the biological activities of chemoprevention colonic chronic inflammation and inflammation-driven tumorigenesis. We suggest that Myricetin could be developed as a promising chemopreventive drug for reducing the risk of colorectal cancer.
Assuntos
Colite/tratamento farmacológico , Neoplasias Colorretais/prevenção & controle , Flavonoides/farmacologia , Inflamação/tratamento farmacológico , Animais , Anticarcinógenos/farmacologia , Western Blotting , Doença Crônica , Colite/complicações , Pólipos do Colo/prevenção & controle , Modelos Animais de Doenças , Inflamação/complicações , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
AIM: To investigate the role of Δ133p53 isoform in nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC)-mediated growth inhibition of MKN45 gastric cancer cells. METHODS: The growth rate of MKN45 cells after treatment with different concentrations of only PDTC or PTDC in combination with cisplatin was detected by the CCK-8 assay. mRNA expression levels of Δ133p53, p53ß, and the NF-κB p65 subunit and p65 protein levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence, respectively. Growth of MKN45 cells was significantly inhibited by PDTC alone in a dose-dependent manner (P < 0.01). Moreover, the inhibitory effect of cisplatin was remarkably enhanced in a dose-dependent manner by co-treatment with PDTC (P < 0.01). RESULTS: RT-PCR analysis revealed that mRNA expression of p65 was curbed significantly in a dose-dependent manner by treatment with only PDTC (P < 0.01), and this suppressive effect was further enhanced when co-treated with cisplatin (P < 0.01). With respect to the other p53 isoforms, mRNA level of Δ133p53 was significantly reduced in a dose-dependent manner by treatment with only PDTC or PTDC in combination with cisplatin (P < 0.01), whereas p53ß mRNA expression was not altered by PDTC treatment (P > 0.05). A similar tendency of change in p65 protein expression, as observed for the corresponding mRNA, was detected by immunofluorescence analysis (P < 0.01). Pearson correlation analysis demonstrated that Δ133p53 and p65 mRNA expression levels were positively related, while no significant relationship was observed between those of p65 and p53ß (r = 0.076, P > 0.01). CONCLUSION: Δ133p53 isoform (not p53ß) is required in PDTC-induced inhibition of MKN45 gastric cancer cells, indicating that disturbance in the cross-talk between p53 and NF-κB pathways is a promising target in pharmaceutical research for the development of treatment strategies for gastric cancer.
Assuntos
NF-kappa B/antagonistas & inibidores , Proteína Oncogênica p65(gag-jun)/metabolismo , Pirrolidinas/farmacologia , Neoplasias Gástricas/metabolismo , Tiocarbamatos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Humanos , NF-kappa B/metabolismo , Isoformas de Proteínas/metabolismo , Pirrolidinas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tiocarbamatos/uso terapêuticoRESUMO
AIM: To investigate the mechanism for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion. METHODS: Muscle-stripped guinea pig ileal preparations were mounted in Ussing flux chambers for the recording of short-circuit current (Isc). Basal Isc and Isc stimulated by BK when preincubated with the BK receptors antagonist and other chemicals were recorded using the Ussing chamber system. Prostaglandin E2 (PGE2) production in the intestine was determined by enzyme immunologic assay (EIA). RESULTS: Application of BK or B2 receptor (B2R) agonist significantly increased the baseline Isc compared to the control. B2R antagonist, tetrodotoxin and scopolamine (blockade of muscarinic receptors) significantly suppressed the increase in Isc evoked by BK. The BK-evoked Isc was suppressed by cyclooxygenase (COX)-1 or COX-2 specific inhibitor as well as nonselective COX inhibitors. Preincubation of submucosa/mucosa preparations with BK for 10 min significantly increased PGE2 production and this was abolished by the COX-1 and COX-2 inhibitors. The BK-evoked Isc was suppressed by nonselective EP receptors and EP4 receptor antagonists, but selective EP1 receptor antagonist did not have a significant effect on the BK-evoked Isc. Inhibitors of PLC, PKC, calmodulin or CaMKII failed to suppress BK-induced PGE2 production. CONCLUSION: The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, CaMK, IP3 and MAPK.
RESUMO
OBJECTIVE: To investigate the significance of increasing circulating immune complex (CIC) in patients during the progression from chronic hepatitis B to hepatocellular carcinoma (HCC). METHODS: Serum levels of CIC from 20 hospitalized patients diagnosed by pathology with primary HCC, and 13 with hepatic hemangioma, and from 45 subjects with chronic HBV infection who finally developed into HCC (45 cases), and age- and gender-matched 45 subjects who kept the chronic HBV infection after consecutively followed up for 10 - 13 years by June of 2009 were quantified by ELISA. The serum levels of anti liver-kidney microsomal (anti LKM-1) antibodies were also measured by ELISA, and that of HBV-DNA were quantified by Taqman probe-based real time PCR in the followed up chronic HBV infection subjects. In the 45 chronic HBV subjects who finally developed into HCC and the 45 controls, serum samples were collected and determined at 3 time points: the baseline when the subjects were recruited, the middle point during the follow-up, and the end of follow-up. RESULTS: The serum level of CIC was significantly higher in the 20 HCC patients than that in the 13 hemangioma cases (P < 0.001). When HCC was diagnosed, the CIC concentration was significantly higher than that in the baselines (P < 0.001) in the 45 chronic HBV subjects who finally developed into HCC after the consecutively follow-up for 5 - 13 years. Of them, 36 patients (80.0%) showed progressively increased CIC during the follow-up (P < 0.001). In the controls, the CIC levels were kept relatively stable during the follow-up. Among them, 17 patients (37.8%) showed CIC slightly increased (P = 0.046). Kaplan-Meier survival analysis indicated that elevated serum CIC during the follow-up increased cumulative HCC incidence (HR = 2.77, 95%CI 1.47 - 5.22). In addition, the serum levels of anti-LKM-1 and HBV-DNA were also significantly higher in the patients who finally progressed into HCC than that in the controls and maintained at a high level during the follow-up tested at all the 3 time points. Further analysis indicated that the serum level of CIC was correlated with that of serum HBV-DNA only when HCC was diagnosed (r = 0.344, P = 0.026). CONCLUSION: Progressive increase of serum CIC level may be one of risk factors reflecting HCC development from chronic HBV infection.
Assuntos
Complexo Antígeno-Anticorpo/sangue , Autoanticorpos/sangue , Carcinoma Hepatocelular/virologia , Hepatite B Crônica/complicações , Neoplasias Hepáticas/virologia , Carcinoma Hepatocelular/imunologia , DNA Viral/sangue , Progressão da Doença , Feminino , Seguimentos , Hemangioma/imunologia , Vírus da Hepatite B/genética , Hepatite B Crônica/imunologia , Humanos , Neoplasias Hepáticas/imunologia , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
AIM: To explore the anti-inflammatory mechanism of Diammonium Glycyrrhizinate in a rat model of ulcerative colitis induced by acetic acid. METHODS: Spragur-Dawley female rats were divided into four groups: Diammonium Glycyrrhizinate group, dexamethasone group, acetic acid control and normal control group. Colonic inflammation was evaluated by disease activity index, gross morphologic damage, histological injury and colonic myeloperoxidase activity. Immunohistochemistry was used to detect the expression of NF-kappaB, TNF-alpha and ICAM-1 in colonic mucosa. RESULTS: Compared to the acetic acid control, both Diammonium Glycyrrhizinate and dexamethasone showed a significant anti-inflammatory effect (P < 0.01). The expression of NF-kappaB, TNF-alpha and ICAM-1 in colonic mucosa was significantly lower in the Diammonium Glycyrrhizinate group and dexamethasone group than in the acetic acid group. CONCLUSION: Diammonium Glycyrrhizinate could reduce inflammatory injury in a rat model of ulcerative colitis. This may occur via suppression of NF-kappaB, TNF-alpha and ICAM-1 in colonic mucosa.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Ácido Glicirrízico/uso terapêutico , Ácido Acético , Animais , Anti-Inflamatórios/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glicirrízico/farmacologia , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Peroxidase/genética , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIM: To testify the immunogenicity of a conservative B-cell linear epitope of Helicobacter pylori (H pylori) flagellin A. METHODS: Different programs were used to analyze the secondary structure, molecular hydropathy, and surface accessibility of H pylori flagellin A. Linear B-cell epitopes were estimated based on the structural and physiochemical information. Analysis of residue divergence was proposed to screen a conservative linear epitope. The 29-peptide (Pep29mer) synthesized by chemical method, including the predicted conservative B-cell epitope and a known K2d compatible T-cell epitope, was used to immunize mice, and then H pylori-specific antibodies were detected by ELISA. RESULTS: Based on the analyses of divergent amino acid residues, structural and physiochemical characteristics, it was strongly suggested that the short fragment NDSDGR was the core of a conservative linear epitope in flagellin A. Animals immunized by Pep29mer acquired efficient immune response. In detail, serum H pylori-specific IgA and IgG1 increased significantly in immunized group, while IgG2a only had an insignificant change. H pylori-specific IgA in gastrointestinal flushing fluid also increased significantly. CONCLUSION: The conservative short fragment NDSDGR is the core of a linear B-cell epitope of flagellin A.
Assuntos
Flagelina/imunologia , Helicobacter pylori/imunologia , Sequência de Aminoácidos , Animais , Antígenos de Bactérias/imunologia , Ensaio de Imunoadsorção Enzimática , Epitopos/imunologia , Suco Gástrico/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Camundongos , Dados de Sequência MolecularRESUMO
AIM: To demonstrate the effect of Hewei-Decoction (Decoction for regulating the stomach) on chronic atrophic gastritis (CAG) and eradication of Helicobacter pylori. METHODS: Ninety patients with CAG entering the investigation were divided into six differentiation syndromes, based on their major symptoms and signs. Hewei-Decoction was taken by all the patients orally for 4 or 8 wk. The efficacy was assessed by both the composite accumulation of reduced scores of major symptoms and the eradication of H pylori. chi(2) test was used to compare the efficacy between H pylori-positive and negative cases, and to disclose the relationship between efficacy and eradication of H pylori. RESULTS: In patients with six different syndrome types, the efficacy of Hewei-Decoction was 91.67% (11/12), 92.86% (13/14), 97.22% (35/36), 87.50% (14/16), 75.00% (6/8), 75.00% (3/4) respectively. The rate of highly efficacious was 58.33% (7/12), 50.00% (7/14), 77.78% (28/36), 62.50% (10/16), 12.50% (1/8) and 25.00% (1/4), respectively. The total efficacy was 91.11% (82/90), and the rate of highly efficacious was 60.00% (54/90). The eradication rate of H pylori was 67.86% (38/56). The therapeutic effect of Hewei-Decoction was better in H pylori positive cases than that in H pylori-negative cases with the total effect of 96.43% vs 82.35% (P<0.05). In 56 H pylori positive cases, the therapeutic effect was better in H pylori eradicated cases than that in H pylori- existent cases with the total effect of 97.37% vs 72.22% (P<0.01). CONCLUSION: Hewei-Decoction is effective in most cases of all the syndrome types. The results indicate that eradication of H pylori is one of the important mechanisms for alleviation of symptoms and signs. Also, the decoction is efficacious in H pylori-negative cases.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Gastrite/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Administração Oral , Adulto , Idoso , Atrofia , Doença Crônica , Feminino , Mucosa Gástrica/patologia , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Atrophic body gastritis (ABG) is common in China. Although histology via endoscopy is an efficient and reliable means of diagnosing ABG, it is an invasive procedure. Therefore, in the present study serum pepsinogen (PG) was used as a biomarker to develop a novel noninvasive test as the first option for screening of ABG in certain groups of Chinese. METHODS: The study population consisted of 81 selected dyspeptic patients (mean age, 64.8 +/- 0.7 years; M:F, 43:38) who underwent diagnostic gastroscopy. At least four biopsy specimens were taken from the antrum and corpus of the stomach (two specimens from each site) for histological diagnosis. Blood samples for ELISA assays of serum pepsinogen I (PGI), pepsinogen II (PGII) and IgG antibodies against Helicobacter pylori (Hp IgG) were drawn after endoscopy. Cut-off points were calculated using receiver operating curves (ROC). RESULTS: There was no correlation between serum PG and atrophy in the antral mucosa. The mean serum concentration of PGI was lower (P < 0.05) in patients with ABG (89.9 microg/L) than in those with normal mucosa (NM) and non-ABG (123.7 microg/L and 139.1 microg/L). The mean ratio of PGI:PGII was also lower (P < 0.01) in patients with ABG (6.2) than in those with NM and non-ABG (11.6 and 11.7). There was no difference in serum PGI or the PGI:PGII ratio between patients with and without H. pylori infection. For diagnosing ABG, the area under the ROC of PGI and the PGI:PGII ratio was 0.741 (95% CI: 0.627-0.856) and 0.874 (95% CI: 0.788-0.961), respectively. The maximum of the Youden's index (YI) of PGI and the PGI:PGII ratio was 0.426 and 0.722, respectively. The best cut-off point for PGI was 97.1 microg/L with sensitivity of 67% and specificity of 76%, and for PGI:PGII ratio was 8.1 microg/L, with sensitivity of 89% and specificity of 83%. CONCLUSIONS: The serum PGI:PGII ratio appears to be a sensitive and specific assay for corpus atrophy, thus providing a noninvasive and indicative test for diagnosis of atrophic gastritis.