RESUMEN
Objective:To confirm the protective effect of Xiangsha Yuyang decoction on acetic acid-induced gastric ulcer model rats and explore its mechanism, so as to provide experimental basis for clinical drug use. Method:The 60 SPF Wistar rats were randomly divided into 6 groups: group, model group, high, middle and low dose groups of Xiangsha Yuyang decoction and omeprazole control group. The rat model of gastric ulcer was induced by acetic acid. The rats in the high, middle and low dose groups of Xiangsha Yuyang decoction were intragastrically administered at the dose of 28,14,7 g·kg<sup>-1</sup>, and with omeprazole at the dose of 4.17 g·kg<sup>-1</sup>in normal saline, respectively. The rats in the blank group and model group were intragastrically infused with the same volume of normal saline once a day. After 14 days of continuous treatment, the rats were killed, the blood was collected, the area and inhibition rate of gastric ulcer were measured and calculated, the histopathological sections of gastric mucosa were made and the state of gastric mucosal injury was observed, and the changes of gastric mucosal repair factor, gastric tissue related protein, oxidative stress factor and inflammatory factor in serum were detected by enzyme-linked immunosorbent assay(ELISA). Detected the expression of p62 Kelch-like epichlorohydrin-related protein 1 (Keap1), nuclear transcription factor E2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) signal pathway-related proteins in gastric mucosa by Western blot. Result:Compared with control group, the gastric mucosa of the model group showed obvious pathological changes and a large number of leukocytes infiltrated. In model group, the ulcer area was significantly increased(<italic>P</italic><0.01), the contents of mucin mucoprotein 5AC (MUC5AC), epidermal growth factor (EGF), superoxide dismutase (SOD) and increased prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) were significantly decreased(<italic>P</italic><0.01), the gastrin (GAS), 8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA), tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>), cyclooxygenase-2 (COX-2) were significantly increased. The expression of HO-1 and Nrf2 protein decreased significantly(<italic>P</italic><0.01), the content of Keap1 increased significantly (<italic>P</italic><0.05), and the expression of p62 protein decreased. Compared with model group, the hierarchical structure of cells in Xiangsha Yuyang decoction high dose group and omeprazole group were clearer and regular, middle and low dose groups could also repair gastric mucosa to a certain extent. The high and middle dose groups of Xiangsha Yuyang decoction could significantly reduce the gastric ulcer area of acetic acid-induced gastric ulcer rat model (<italic>P</italic><0.01) and increase the ulcer inhibition rate. It can effectively promote the expression of MUC5AC and EGF in gastric mucosa, decrease the level of GAS(<italic>P</italic><0.05,<italic>P</italic><0.01), decrease the level of 8-OHdG and MDA, increase the activity of SOD(<italic>P</italic><0.01), decrease the expression level of TNF-<italic>α</italic> and COX-2, increase the content of PGE<sub>2</sub>, and significantly increase the amount of Nrf2 and HO-1 protein in gastric mucosa(<italic>P</italic><0.01). The high dose group of Xiangsha Yuyang decoction could decrease the protein expression of Keap1(<italic>P</italic><0.05) and increase the expression of p62 protein. Conclusion:Xiangsha Yuyang decoction is effective in the treatment of acetic acid-induced gastric ulcer model rats, which can effectively reduce the ulcer area, increase the ulcer inhibition rate and protect the ulcer tissue. Its mechanism may be related to activating p62/Keap1/Nrf2 signal pathway and regulating the expression of related genes so as to improve inflammatory response and regulate oxidative stress response.
RESUMEN
BACKGROUND@#Primary pulmonary malignancies (PPMs) and non-pulmonary malignancies (PNPMs) may result in airway stenosis requiring stenting. This study aimed to compare and evaluate the clinical features and stent placement outcomes of airway stenosis caused by PPMs and PNPMs.@*METHODS@#A total of 141 patients with malignant airway stenosis who underwent Micro-Tech stent placements between January 2004 and October 2017 at Department of Respiratory Medicine, Beijing Tian Tan Hospital, Capital Medical University were divided into PPM (n = 100) and PNPM groups (n = 41). Patients' clinical features and stent placement outcomes were collected and analyzed. Chi-square test was used to compare the categorical variables, while independent- or paired-sample t test was used to compare the continuous variables.@*RESULTS@#There were no significant differences in age, sex, treatment history, respiratory symptoms, and incidence of obstructive pneumonia between groups. Multiple airway involvement (63.0% vs. 31.7%; χ = 11.459, P = 0.001) and atelectasis (17.0% vs. 2.4%; χ = 5.536, P = 0.019) were more common in the PPM group, while extraluminal obstruction (24.4% vs. 6.0%; χ = 8.033, P = 0.005) was more common in the PNPM group. Before stenting, the American Thoracic Society Dyspnea Index (ADI) and Karnofsky Performance Scale (KPS) scores showed no significant differences between groups (all P > 0.05). After stenting, a satisfactory rate of symptom improvement was achieved in both groups (98.0% and 100.0% in the PPM and PNPM groups, respectively; χ = 0.016, P = 0.898); ADI and KPS scores, which showed no significant differences between groups (all P > 0.05), were significantly improved in each group (all P < 0.001). Complications after stenting could be effectively managed using bronchoscopic procedures.@*CONCLUSIONS@#Among cases of malignant airway stenosis requiring stenting, those caused by PPM are more likely to involve multiple airways and are associated with atelectasis, while those caused by PNPM are more likely to cause extraluminal obstruction. Micro-Tech stent placement has the same immediate effect in terms of improvement in respiratory symptoms and performance status for both malignant airway stenosis caused by PPM and that caused by PNPM.
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pulmonares , Stents , Estenosis Traqueal , TerapéuticaRESUMEN
<p><b>BACKGROUND</b>Scarring airway stenosis is commonly seen in China as compared to other developed countries, due to the high prevalence of tuberculosis. Nowadays, interventional bronchoscopy treatment has been widely used to treat this disease in China. This study demonstrated the characteristics of scarring airway stenosis in Chinese adults and retrospectively evaluated the efficacy of interventional bronchoscopy treatment of this disease.</p><p><b>METHODS</b>Patients with scarring airway stenosis from 18 tertiary hospitals were enrolled between January 2013 and June 2016. The causes, site, and length of scarring airway stenosis were analyzed, and the efficacy of the interventional bronchoscopy treatment was evaluated.</p><p><b>RESULTS</b>The final study cohort consisted of 392 patients. Endotracheobronchial tuberculosis (EBTB) was the most common cause of scarring airway stenosis (305/392, 77.8%) in Chinese adults with a high rate of incidence in young women. The left main bronchus was most susceptible to EBTB, and most posttuberculosis airway scarring stenosis length was 1.1-2.0 cm. The average clinical success rate of interventional bronchoscopy treatment for scarring airway stenosis in Chinese patients is 60.5%. The stent was inserted in 8.7% scarring airway stenosis in China.</p><p><b>CONCLUSIONS</b>Scarring airway stenosis exhibits specific characteristics in Chinese patients. Interventional bronchoscopy is a useful and safe treatment method for the disease.</p>
RESUMEN
Tumor suppressor p53 protein can regulate the tran-scription of target genes, to control cell apoptosis, aging and other life activities,but mutant p53 is prone to losing antitumor function, thus promoting tumor development. At present, p53 protein has become one of the hot targets for the treatment of cancer. This article mainly introduces the structure and mechanism of small molecular compounds with restoring activity of mutant p53 as the target.
RESUMEN
Forest musk deer(Moschus berezovskii) is mainly distribute in Shaanxi and Sichuan provinces of China. The musk is a dry exudates in the mature male sachet with complex chemical composition, abundant modern identification methods, various pharmacological action, extensive clinical application. The population quantity and quality of wild and captive forest musk deer failed to improve because of lacking scientific management, excessive hunting and habitat destruction, etc. Carrying out the captive forest musk deer is an effective way to protect them, fast breeding of forest musk deer is the key to increase the yield of musk. Therefore, we should develop new technologies such as natural estrus and artificial insemination in order to speed up the breeding of musk deer and increase the yield of musk. This article reviews the research progress of new artificial propagation technique and musk, which teases some feasible research basis for optimization of forest musk deer species and the research of musk.
Asunto(s)
Animales , Femenino , Masculino , Cruzamiento , Métodos , China , Ciervos , Ácidos Grasos Monoinsaturados , Química , Inseminación ArtificialRESUMEN
<p><b>BACKGROUND</b>Tracheobronchial mucoepidermoid carcinoma (MEC) is a rare airway tumor in adults for which surgery is considered a first-line treatment. However, some patients already lost the best opportunity of a surgical intervention when diagnoses are confirmed, and surgery causes considerable trauma resulting in partial loss of pulmonary function. Moreover, the tumor is resistant to radiotherapy and chemotherapy. These factors make the treatment of tracheobronchial MEC challenging. This study aimed to evaluate the safety and efficacy of interventional bronchoscopic therapy in adult patients with tracheobronchial MEC.</p><p><b>METHODS</b>We retrospectively analyzed the clinical manifestations, bronchoscopic interventions, complications, and outcomes of 11 adult patients with tracheobronchial MEC. Paired t-test was used to analyze the parameters of the American Thoracic Society Dyspnea Index and the Karnofsky Score before and after the first interventional bronchoscopic therapy.</p><p><b>RESULTS</b>All tumors occurred in the main bronchus and were easily visualized by bronchoscopy. After interventional bronchoscopic therapy, the symptoms of all patients showed significant improvement. The American Thoracic Society Dyspnea Index decreased from 1.91 ± 1.22 to 0.27 ± 0.47 (t = 6.708, P < 0.001) and the Karnofsky Score increased from 78.18 ± 16.62 to 95.46 ± 8.20 (t = -5.190, P < 0.001). Bronchoscopic intervention did not result in serious complications or mortality. During the follow-up period between 3 and 96 months after the first therapy, the following results were noted: (1) among the eight patients with low-grade tracheobronchial MEC, only one patient had a relapse and agreed to surgical treatment; (2) among the three patients with high-grade tracheobronchial MEC, one patient required repeated bronchoscopic interventions, one patient died of pulmonary infection, and one patient died of systemic failure owing to tumor metastasis.</p><p><b>CONCLUSIONS</b>Interventional bronchoscopic therapy, as an alternative treatment, shows promise in some adult patients with low-grade tracheobronchial MEC confined to the bronchus. However, for adult patients with high-grade tracheobronchial MEC, early diagnosis and surgical treatment are still strongly recommended.</p>
RESUMEN
Complement activation-related pseudo-allergic reactions (CARPA) may represent 77% of all immune-mediated immediate hypersensitivity reactions. Because of the universality of the CARPA response and correlation between it and drug properties, complement activity tests are recommended as one of the tests for immunotoxicity and bioequivalence of drugs. However, in-vivo tests of complement activation are complicated, and the immunological differences between different individuals and between human and animal, making it very necessary to establish a standard and sample evaluation model for testing the effects of drugs on complement activity. In this study, the standard reaction serum was prepared by pooling sera collected from 40 healthy blood donors; a standard positive control was prepared by incubation with a heat-agglutinated IgG and zymosan A; SC5b-9, C5a, C4d and Bb were chosen as the test targets and evaluation criteria of the results was defined, all of these constituted the in-vitro model. By using this in-vitro model, the immunological toxicity of the different prescription of antifungal drug amphotericin B, and voriconazole for injection, and the bioequivalence of amphotericin B liposome formulations were studied.
RESUMEN
Benign cicatricial airway stenosis (BCAS) is a potentially life-threatening disease. Recurrence occurs frequently after endoscopic treatment. Paclitaxel is known to prevent restenosis, but its clinical efficacy and safety is undetermined. Therefore, in this study, we investigated the efficacy and associated complications of paclitaxel as adjuvant treatment for BCAS of different etiologies. The study cohort included 28 patients with BCAS resulting from tuberculosis, intubation, tracheotomy, and other etiologies. All patients were treated at the Department of Respiratory Diseases, Beijing Tian Tan Hospital, Capital Medical University, China, between January 2010 and August 2014. After primary treatment by balloon dilation, cryotherapy, and/or high-frequency needle-knife treatment, paclitaxel was applied to the airway mucosa at the site of stenosis using a newly developed local instillation catheter. The primary outcome measures were the therapeutic efficacy of paclitaxel as adjuvant treatment, and the incidence of complications was observed as well. According to our criteria for evaluating the clinical effects on BCAS, 24 of the 28 cases achieved durable remission, three cases had remission, and one case showed no remission. Thus, the durable remission rate was 85.7%, and the combined effective rate was 96.4%. No differences in outcomes were observed among the different BCAS etiologies (P=0.144), and few complications were observed. Our results indicated that paclitaxel as an adjuvant treatment has greater efficacy than previously reported BCAS treatment methods.
Asunto(s)
Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Bronquios , Patología , Quimioterapia Adyuvante , Cicatriz , Quimioterapia , Cirugía General , Paclitaxel , Usos Terapéuticos , Complicaciones Posoperatorias , Insuficiencia Respiratoria , Quimioterapia , Cirugía General , Estenosis Traqueal , Quimioterapia , Cirugía General , TraqueotomíaRESUMEN
<p><b>BACKGROUND</b>Currently available silicone and metallic stents for tracheal stenosis are associated with many problems. Granulation proliferation is one of the main complications. The present study aimed to evaluate the efficacy of paclitaxel drug-eluting tracheal stent in reducing granulation tissue formation in a canine model, as well as the pharmacokinetic features and safety profiles of the coated drug.</p><p><b>METHODS</b>Eight beagles were randomly divided into a control group (bare-metal stent group, n = 4) and an experimental group (paclitaxel-eluting stent group, n = 4). The observation period was 5 months. One beagle in both groups was sacrificed at the end of the 1st and 3rd months, respectively. The last two beagles in both groups were sacrificed at the end of 5th month. The proliferation of granulation tissue and changes in tracheal mucosa were compared between the two groups. Blood routine and liver and kidney function were monitored to evaluate the safety of the paclitaxel-eluting stent. The elution method and high-performance liquid chromatography were used to characterize the rate of in vivo release of paclitaxel from the stent.</p><p><b>RESULTS</b>Compared with the control group, the proliferation of granulation tissue in the experimental group was significantly reduced. The drug release of paclitaxel-eluting stent was the fastest in the 1st month after implantation (up to 70.9%). Then, the release slowed down gradually. By the 5th month, the release reached up to 98.5%. During the observation period, a high concentration of the drug in the trachea (in the stented and adjacent unstented areas) and lung tissue was not noted, and the blood test showed no side effect.</p><p><b>CONCLUSIONS</b>The paclitaxel-eluting stent could safely reduce the granulation tissue formation after stent implantation in vivo, suggesting that the paclitaxel-eluting tracheal stent might be considered for potential use in humans in the future.</p>
Asunto(s)
Animales , Perros , Broncoscopía , Modelos Animales de Enfermedad , Stents Liberadores de Fármacos , Tejido de Granulación , Microscopía Electrónica de Rastreo , Paclitaxel , Usos Terapéuticos , Tráquea , Patología , Estenosis Traqueal , Quimioterapia , Cirugía GeneralRESUMEN
<p><b>OBJECTIVE</b>To investigate the histopathological features, complications, diagnosis, and differential diagnosis of coal workers' pneumoconiosis (CWP).</p><p><b>METHODS</b>The lung tissue sections from 14 autopsy cases of CWP were subjected to HE staining and observed under a light microscope, and a retrospective analysis was performed considering the occupational history and clinical features.</p><p><b>RESULTS</b>The 14 cases were 46-71 years of age (mean, 57.7 years). Two cases were diagnosed as dust reaction, 1 case as simple CWP (stage I anthracosilicosis), and 11 cases as complicated CWP (9 cases of stage II anthracosilicosis, 1 case of stage III anthracosilicosis, and 1 case of stage III silicosis). Twelve cases were complicated by chronic bronchitis and emphysema, 8 cases by pulmonary heart disease, 4 cases by pulmonary tuberculosis, 3 cases by liver cirrhosis and liver cancer with pulmonary metastases, and 2 cases by cerebral hemorrhage.</p><p><b>CONCLUSION</b>Among patients with CWP, the pathological changes of lung tissue become more complex with increasing years of dust exposure. Coal macule is the common pathological feature of CWP, and dust nodules and massive fibrosis are the necessary indices of pathological diagnosis.</p>
Asunto(s)
Anciano , Humanos , Masculino , Persona de Mediana Edad , Antracosis , Patología , Minas de Carbón , Fibrosis , Pulmón , Patología , Estudios RetrospectivosRESUMEN
Glucokinase (GK) is a new target for the treatment of type II diabetes mellitus (T2DM). In order to find a structure-simplified small molecule GK activator, 19 salicylic acid derivatives were designed and synthesized based on new lead compound (1). Experimental results showed that the potency of compound 8h is superior to control RO-28-0450 in GK activation.
Asunto(s)
Diseño de Fármacos , Activación Enzimática , Activadores de Enzimas , Química , Farmacología , Glucoquinasa , Metabolismo , Hipoglucemiantes , Química , Farmacología , Estructura Molecular , Salicilatos , Química , Farmacología , Tiazoles , FarmacologíaRESUMEN
<p><b>OBJECTIVE</b>To study the 3, 4- dinitro-furazan-based oxidation furazan (DNTF) of sub-acute toxicity and chronic toxicity, to determine the acute toxicity classification DNTF, the nature of toxic effects and major target organ for the development provide the basis for occupational exposure limits.</p><p><b>METHODS</b>( 1) Acute toxicity: The oral gavage method once infected, symptoms of poisoning of animals observed to calculate the LD50DNTF and 95% confidence limits. ( 2) sub-chronic experiment: selection of 96 healthy SD rats were randomly divided into four groups, doses of 25, 56.2, 125 mg/kg and the negative control group, Exposure for ninety days,five days a week, once a day, The rats were killed at end of Exposure, heart, liver, spleen, lung, kidney, brain,testis, uterus were taken to observe the pathological changes.</p><p><b>RESULTS</b>( 1) Acute oral toxicity test results indicate that DNTF rat oral LD50 greater than 5000 mg/kg, DNTF mice treated by oral LD50 4589 mg/kg, 95%confidence limit for the 4026-5230 mg/kg, Acute toxicity grade level is low toxicity compounds. (2) Sub-chronic toxicity experiment, the high-dose male rats, high, medium and low-dose group female rats weight gain than the negative control group, compared with the control group, the difference was statistically significant (P<0.05).125 mg/kg of serum alanine aminotransferase, aspartate aminotransferase was significantly higher. 125 mg/kg dose groups, liver, kidney, lung, testicular factor was significantly higher. Liver, kidney, lung histological examination showed obvious morphological changes.</p><p><b>CONCLUSION</b>Acute toxicity grade DNTF low toxicity level compounds, target organ toxicity of liver, kidney and lung.</p>
Asunto(s)
Animales , Femenino , Masculino , Ratones , Ratas , Dosificación Letal Mediana , Nitrofurazona , Toxicidad , Oxadiazoles , Toxicidad , Ratas Sprague-Dawley , Pruebas de ToxicidadRESUMEN
<p><b>OBJECTIVE</b>To study the teratogenicity of new high-energy compounds, 3, 4 two furazan-based oxidation furazan (DNTF) and the impact on human health, occupational exposure limits were provided for the following research.</p><p><b>METHODS</b>Pregnant SD rats were randomly divided into five groups by Standard teratogenicity test, including three dose groups (5.0, 15.8, 50.0 mg/kg), the negative control (vegetable oil), and the positive control group (CP 10.0 mg/kg). Each 10 to 15 rats were in one group. Gavage was consecutive for rats during pregnancy 7 ∼ 12 d and then sacrifice after 20 d.</p><p><b>RESULTS</b>There were no significantly difference between the three dose groups and negative controls in the pregnancy rate, the weight of pregnant rats, fetal weight, fetal growth, fetal malformation rate and internal organs,</p><p><b>CONCLUSION</b>There were no maternal toxicity, embryo toxicity and teratogenicity for rats when DNTF in the range 5.0 ∼ 50.0 mg/kg.</p>
Asunto(s)
Animales , Femenino , Embarazo , Ratas , Nitrofurazona , Toxicidad , Ratas Sprague-Dawley , TeratógenosRESUMEN
<p><b>OBJECTIVE</b>Through a detection of dust in the coal mines workplace, to understand the status of occupational hazards, and the evaluation of occupational hazards, provide subject to control occupational hazards.</p><p><b>METHOD</b>According to production process and "hazardous substances in workplace air monitoring, sampling norms" and other standards to determine the sampling points and sampling of coal dust.</p><p><b>RESULT</b>Underground mining operations in 21 subjects with time-weighted average concentration of dust types pass rate of 28.6%, of which five types of dust hazard grade II, six types of dust hazard rating of 0, and the remaining types of grade I dust hazard levels. Coal dust test six types of time-weighted average concentration of 83.3% pass rate, only one types of dust hazard grade I, all the rest is 0. Calculated by the detection of dust overrun 18 times operating sites, the pass rate of 72.2% results.</p><p><b>CONCLUSION</b>Purified water spray and air flow curtain of dust control has played a certain role, but the work of underground working conditions and environmental constraints, most of the dust concentration in workplace occupational exposure limits do not meet the requirements, recommended the strengthening of dust or Dust the daily management and maintenance of equipment, strengthen the ventilation, personal protection officers to strengthen operations.</p>
Asunto(s)
Humanos , Contaminantes Ocupacionales del Aire , Minas de Carbón , Polvo , Monitoreo del Ambiente , Exposición Profesional , Lugar de TrabajoRESUMEN
<p><b>OBJECTIVE</b>To study the mutagenicity and teratogenicity induced by ammonium dinitramide(ADN).</p><p><b>METHODS</b>According to technical specifications for toxicity determination of chemicals, Salmonella typhimurium reverse mutation assay (Ames assay), in vivo mammalian erythrocyte micronucleus test, sperm malformation test and teratogenesis test were used to detect the mutagenicity and teratogenicity induced by AND.</p><p><b>RESULTS</b>When the exposure doses of AND were 8-5000 pg/plate, the result of Ames assay was negative. As compared with control group, the micronucleus rate of mice exposed to 113.8 mg/kg AND significantly increased(P<0.05), the sperm malformation rates of mice exposed to 54.4-272.0 mg/kg AND did not increased significantly. The survival rate of fetuses decreased, the rate of assimilated fetuses increased, the rate of fetus sternum agenesis enhanced in mice exposed to 319 mg/kg AND, as compared with controls. The rates of in the 4th-6th fetus sternum agenesis in groups exposed to 21.3, 79.7 and 319 mg/kg AND were higher than that in control group. The malformation rate of fetus bowels in groups exposed to 319 mg/kg AND was higher than that in control group. The teratogenic index of ADN was 30.</p><p><b>CONCLUSION</b>AND may be a mutagen and induce the teratogenic effect.</p>
Asunto(s)
Animales , Femenino , Masculino , Ratones , Embarazo , Embrión de Mamíferos , Patología , Ratones Endogámicos , Pruebas de Micronúcleos , Pruebas de Mutagenicidad , Nitritos , Toxicidad , Compuestos de Amonio Cuaternario , Toxicidad , Espermatozoides , Patología , Esternón , PatologíaRESUMEN
<p><b>OBJECTIVE</b>To study the acute, subacute and subchronic toxicity induced by ammonium dinitramide (ADN), and to ascertain the gradation and target organs of acute toxicity induced by AND.</p><p><b>METHODS</b>According to technical specifications for toxicity determination of chemicals, the oral tests for acute, subacute and subchronic toxicity induced by AND were performed for 90 days.</p><p><b>RESULTS</b>The oral LDx for mouse and rat was 568.9 mg/kg and 616.6 mg/kg ADN respectively. The gradation of acute toxicity induced by AND was low level. The results of oral subacute and subchronic toxicity tests (for 28 and 90 days) showed that a gain in weight in group exposed to 123 mg/kg AND was significantly lower than that in control group (P<0.05), the TBIL and ALT in group exposed to 61.6 and 123 mg/kg AND significantly increased and the ratio of liver weight to body weight obviously decreased, as compared with control group, the number of animals with hepatic pathological changes in group exposed to 61.6 and 123 mg/kg AND was significantly higher than that in control group (P<0.05).</p><p><b>CONCLUSION</b>The gradation of acute toxicity induced by ADN was low level. When the exposure dose of AND was 30.8 mg/kg, the adverse effect was not observed, and the target organ was liver.</p>
Asunto(s)
Animales , Femenino , Masculino , Ratones , Ratas , Peso Corporal , Hígado , Patología , Ratones Endogámicos , Nitritos , Toxicidad , Compuestos de Amonio Cuaternario , Toxicidad , Ratas Sprague-Dawley , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad SubcrónicaRESUMEN
<p><b>BACKGROUND</b>Therapeutic approaches for tracheal stenosis caused by the formation of exuberant granulation tissues usually include electrocautery, mechanical dilation, laser therapy, argon plasma coagulation (APC), cryotherapy and stent placement. However, restenosis after stent insertion remains a significant limitation. We examined the efficacy of three different approaches, including induction of mechanical lesions, APC performed with different powers or durations and cryotherapy, to identify the method that limited the formation of granulation tissue.</p><p><b>METHODS</b>Twelve specially bred research mongrel dogs were divided into three groups. In group 1 (four dogs) mild (procedure 1; two dogs) or moderate (procedure 2; two dogs) damage was induced mechanically. Group 2 (six dogs) received APC at different powers or durations (procedure 3: 30 W, 1 cm/s; procedure 4: 30 W, 2 cm/s; procedure 5: 25 W, 3 cm/s). Group 3 (two dogs) received cryotherapy (procedure 6: two freeze-thaw cycles of 30 seconds). Uncovered self-expandable metallic stents were inserted in all dogs to maintain a continuous stimulus to the trachea mucosa. Dogs were monitored for 4 weeks and the relationship between granulation tissue proliferation and method used was analyzed.</p><p><b>RESULTS</b>In group 1, granulation tissue growth increased with more severe mechanical damage. The growth of granulation tissue in group 2 was more pronounced than in group 1, and both dogs in procedure 3 died because of severe stenosis. In this group, the formation of granulation tissue decreased with decreasing power and duration. In group 3, no obvious granulation tissue was found at week 4.</p><p><b>CONCLUSIONS</b>Lesions and stimuli from a foreign body (the stent) are two important factors that lead to overgrowth of granulation tissue. Thermal lesions, such as APC, seem to induce greater granulation tissue growth and cartilage damage compared with mechanical and cryotherapy lesions. Cryotherapy in combination with mechanical dilation may be a safe and effective treatment method for managing tracheal stenosis caused by the formation of granulation tissue.</p>
Asunto(s)
Animales , Perros , Broncoscopía , Métodos , Crioterapia , Tejido de Granulación , Patología , Coagulación con Láser , Métodos , Stents , Estenosis Traqueal , TerapéuticaRESUMEN
Objective To assess the therapeutic effect and safety ofpramipexole combined with Madopar and Madopar alone in the treatment of Parkinson's disease (PD). Methods This randomized, controlled open-label trial involved 70 PD patients who were randomly assigned to receive pramipexole combined with Madopar (n=35) or Madopar alone (n=35) for 12 consecutive weeks. The therapeutic effect was assessed primarily by the Unified Parkinson's Disease Rating Scale (UPDRS). The main effect was motor symptoms of UPDRS Ⅲ and activities of daily living of UPDRS Ⅱ. The secondary effect was the changes relative to the baseline levels in the consciousness, behavior, and emotion of UPDRS Ⅰ, the complications of UPDRS Ⅳ and daily Madopar dosage. The safety of the drugs was evaluated according to the adverse reactions. Results Compared to the baseline levels, 12 weeks of treatment with pramipexole combined with Madopar resulted in significantly greater reduction in the total scores ofUPDRS Ⅲ than Madopar alone (11.40 vs 9.26, P<0.05), but the reduction in the total DOI: 10.3760/cma.j .issn. 1671.8925.2009.07.010scores of UPDRS Ⅱ and UPDRS Ⅰ was comparable between the two treatments (4.57 vs 4.50 and 0.66 vs 1.14, respectively, P>0.05). The combined treatment reduced the total score of UPDRS Ⅳ by 0.22 whereas Madopar alone increased the score by 0.06, showing significant difference between the two treatments (P<0.05). The daily Madopar dosage in the combined treatment group was decrease by 163.57 rag, but that in Medopar group increased by 8.57 rag (P<0.05). The frequencies of wearing-off, symptom fluctuation and movement disorder were significantly lower in combined treatment group than in Madopar group. Obvious wearing-off, symptom fluctuation and movement disorder occurred in Madopar group, which were not noted in the combined treatment group but two patients developed sudden sleep, one reported drowsiness, and another exhibited orthostatic hypotension. Conclusion Pramipexole combined with Madopar results in better improvement of the motor symptoms than Madopar alone in PD patients, but they show similar effect on the activities of daily living and consciousness, behavioral and emotional changes. Pramipexole can significantly decrease the daily dose of Madopar and help reduce the complications, suggesting its safety and effectiveness in the treatment of PD, but its adverse effects should be given due attention in clinical application.
RESUMEN
Pin1 is a phosphorylation-dependent peptidyl-prolyl cis/trans isomerase, which specifically catalyzes the amide bond isomerization of phosphoserine-proline or phosphothreonine-proline in mitotic phosphoproteins. Pin1 induces the conformational changes to control the function of phosphoproteins. Depletion of Pinl on various human cancer cell lines cause mitotic arrest and apoptosis. Pin1 is an attracting therapeutic target for anticancer and its inhibitors might be potential anticancer drug. In this review, Pin1 inhibitors and the catalytic mechanism, the biological function of Pin1 and its role in oncogenesis are summarized.
Asunto(s)
Humanos , Apoptosis , Inhibidores Enzimáticos , Farmacología , Mitosis , Peptidilprolil Isomerasa de Interacción con NIMA , Neoplasias , Isomerasa de Peptidilprolil , Metabolismo , Fosfoproteínas , Química , Metabolismo , Fosforilación , Transducción de SeñalRESUMEN
<p><b>OBJECTIVE</b>To study the diagnostic value of CT/HRCT for the coal workers' pneumoconiosis (CWP) with large opacities.</p><p><b>METHODS</b>Sixty-two patients with CWP were examined with both chest radiograph and CT/HRCT scan. Comparison was done.</p><p><b>RESULTS</b>Large opacities were found in 19 patients in the chest radiograph of 62 patients with CWP. The detection rate was 30.6%. Thirty large opacities were found using chest radiograph. Forty-three patients with large opacities were found using the CT/HRCT. The detection rate was 69.4%. One hundred and twenty-three large opacities were found using CT/HRCT. Ninety-three more large opacities were found by CT/HRCT than by chest radiograph. The total detection rate of large opacities by CT was 4.1 times than by chest radiograph. Both differences were statistically significant (chi2 = 18.58, P < 0.01). CT/HRCT found all patients with large opacities detected in the chest radiograph. Seventeen patients with Stage III large opacities (>or= 1.0 cm x 2.0 cm) were found by the chest radiograph. The detection rate was 27.4% (17/62). Twenty-seven large opacities were found using chest radiograph. Thirty-four patients with Stage III large opacities were found using the CT/HRCT. The detection rate was 54.8%. The found Stage III large opacities added up to 67. The found Stage III large opacities by CT/HRCT were 40 more than using chest radiograph. Both differences were statistically significant (chi2 = 9.63, P < 0.01). CT/HRCT was reliable to show the morphology, the inside structure, the tiny lesion and the special location of the large opacities of CWP. It could provide more important information for differential diagnosis.</p><p><b>CONCLUSION</b>CT/HRCT is significantly better than the chest radiograph in the diagnosis of complicated CWP. It can find the large opacities that the chest radiograph can not. It has a great diagnostic and practical value as an assistant examination method. CT/HRCT could be considered as the reference and evidence for staging progression in diagnosis of pneumoconiosis.</p>