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The peak of COVID-19 infections in China has just passed, and symptomatic manifestations in patients vary widely, with a minority experiencing severe morbidity and mortality. Early detection of adverse outcomes remains critical for clinical governance and prognosis in COVID-19. This review synthesized both national and international studies relevant to the prognostic evaluation of COVID-19 and summarized the prognostic implications of demographics (age and gender), specific laboratory parameters, adjunctive examination results, complications, and comorbidities in COVID-19 patients. Pertinent laboratory parameters chiefly included markers of inflammation, coagulation function, and electrolytic balance. Adjunctive examinations included thoracic CT and electrocardiographic evaluations. Major complications and comorbid conditions included thrombotic episodes, co-infections, secondary infections, chronic pulmonary disorders, cardiovascular diseases, acute and chronic renal diseases, diabetes mellitus, and cerebrovascular accidents. Moreover, this article discussed how these elements affected the prognosis of patients with COVID-19. By summarizing the information, it aimed to inform preventive and therapeutic strategies against COVID-19 infections in the forthcoming period.
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COVID-19 , Enfermedades Cardiovasculares , Coinfección , Humanos , Pronóstico , ChinaRESUMEN
Objective: To investigate and analyze the energy metabolism characteristics and the correlation between energy metabolism and the risk of secondary bacterial infection in patients with hepatitis B virus-related chronic liver disease (HBV-CLD). Methods: Data of 183 cases admitted to the Mengchao Hepatobiliary Hospital of Fujian Medical University from November 2017 to November 2020 were retrospectively analyzed. 79 cases of chronic hepatitis B, 51 cases of hepatitis B-related liver cirrhosis, and 53 cases of hepatitis B-related liver failure were collected. Among them patients with liver failure and decompensated liver cirrhosis were defined as severe liver disease group. The Quark RMR indirect calorimetry (COSMED Corporation, Italy) was used to exam the patients' energy metabolism condition, and the incidences of secondary bacterial infection of the patients during hospitalization were recorded. Shapiro-Wilk test and normal QQ plot were used to analyze the normal distribution of continuous variable data, which was consistent with the normal distribution and was described by mean ± standard deviation. In addition, if it did not conform to the normal distribution, the median and interquartile distance were used to describe it. Levene's test was used to test the homogeneity of variance of the data, which was consistent with the normal distribution. The t-test was used to compare the means of the two groups of samples. One-way analysis of variance was used to compare the mean values of the three groups of samples, and then the Tukey's test was used to compare the two groups. If the variance was uneven or did not conform to the normal distribution, the Wilcoxon rank sum test was used to compare the differences between the two groups. Kruskal-Wallis test (H test) was used to compare the differences between the three groups of samples, and then the Dunnett's test (Z test) was used for comparison between the two groups. Categorical variable data were analyzed using chi-square test. Logistic regression analysis was used to screen independent risk factors, and the criteria for variable inclusion (P < 0.05). Results: The respiratory entropy (RQ) and non-protein respiratory entropy (npRQ) of the three groups had statistically significant difference (P < 0.05). Among them, the RQ and npRQ of the chronic hepatitis B group were higher than hepatitis B-related liver cirrhosis group and hepatitis B-related liver failure group. There were statistically significant differences in fat oxidation rate (FAT%) and carbohydrate oxidation rate (CHO%) between the three groups (P < 0.05). Compared with hepatitis B-related liver cirrhosis group and hepatitis B-related liver failure group, chronic hepatitis B group (P < 0.05) had lower FAT% and higher CHO%. There were no statistically significant differences in the measured and predicted resting energy expenditure and protein oxidation rate (PRO%) between the three groups. The incidence of secondary bacterial infection in patients with severe liver disease was 48.39% (45/93). Compared with the non-infected group, the RQ and npRQ values ââof the infected group were significantly decreased (P < 0.05), while FAT% was significantly increased (P < 0.05). Logistic regression analysis showed that glutamyltransferase, cholesterol, and npRQ were independent risk factors for secondary bacterial infections in patients with severe liver disease. Glutamyltransferase elevation, and cholesterol and npRQ depletion had suggested an increased risk of secondary bacterial infection. Subgroup analysis of patients with hepatitis B-related liver failure also showed that compared with non-infected group, RQ value and npRQ value of secondary bacterial infection group were significantly decreased (P < 0.05), while FAT% was significantly increased (P < 0.05). Conclusion: Patients with hepatitis B virus-related chronic liver disease generally have abnormal energy metabolism. Low RQ, npRQ, CHO% and high FAT% are related to the severity of the disease; while npRQ reduction is related to the risk of secondary bacterial infection in patients with severe liver disease, and thus can be used as a clinical prognostic indicator.
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Infecciones Bacterianas , Hepatitis B Crónica , Metabolismo Energético , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/metabolismo , Humanos , Hígado/metabolismo , Cirrosis Hepática/epidemiología , Cirrosis Hepática/metabolismo , Estudios RetrospectivosRESUMEN
Objective: To analyze the effect of chlorpyrifos on the expression of autophagy related proteins in rat hippocampal neurons, and to explore the role of autophagy in central nerve injury caused by acute chlorpyrifos poisoning. Methods: In October 2018, 35 male clean grade SD rats were randomly divided into 7 groups according to the observation time point, namely 0.5 d, 1 d, 2 d, 3 d, 5 d and 7 d groups and the control group, with 5 rats in each group. Each observation group was given 81.5 mg/kg chlorpyrifos by gavage, and the control group was given olive oil by gavage. The general conditions and poisoning symptoms of rats were observed continuously after exposure. The expressions of autophagy related proteins Beclin1, P62/SQSTM1 and LC3 in hippocampus were detected by Western blot. The cell morphology and LC3 expression in brain were observed by immunohistochemical staining. Results: Western blot results showed that compared with the control group, the expression of Beclin1 protein in hippocampal neurons of rats in the 1 d, 2 d, and 3 d groups increased, while the expression of P62/SQSTM1 protein in the 0.5 d, 1 d, and 2 d groups decreased, and the expression of LC3 protein was decreased in the 2 d group, and the differences were statistically significant (P<0.05) . The results of immunohistochemistry showed that the hippocampal neurons of rats in the 5 d group were arranged disorderly, and some nuclei contours disappeared, especially in the 7 d group. The LC3 protein was expressed in the cytoplasm, and the expression level gradually increased, reaching a peak on the second day. Conclusion: The early activation of autophagy in rats with acute chlorpyrifos poisoning may be involved in chlorpyrifos induced hippocampal neuronal injury.
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Cloropirifos , Animales , Proteínas Relacionadas con la Autofagia , Cloropirifos/toxicidad , Hipocampo , Masculino , Neuronas , Ratas , Ratas Sprague-DawleyRESUMEN
Objective: To investigate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in the lung tissue of rats with acute diquat (DQ) poisoning and the distribution of diquat in lungs. Methods: Fifty-four fasted male Wistar rats were randomized into control group (n=6) and exposure group (n=48) . According to the time point, the exposure group was divided into 2 h, 4 h, 12 h, 1 d, 3 d, 7 d, 11 d and 14 d groups with 6 rats in each group. Exposure groups were administered 11.55 mg/kg DQ (1 ml/100 g BW) by single-dose of intragastric administration, while the control group rats were given normal saline. The histopathological changes of lung tissue of rats in each group were observed. The expression of nrf2 in lung tissue was detected by immunohistochemistry, and the diquat concentration in lungs was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS) . Results: In the exposure group, DQ was detected in lungs on 2 hours after poisoning. The concentration of DQ in lung tissue decreased gradually over time, and there was no accumulation in lung tissue. The histopathological changes of lung tissue were not obvious in the early stage of poisoning. The injury was the most serious on the 3rd day, a large number of inflammatory cells could be seen in alveolar cavity and lung stroma, and the pathological injury of lung tissue began to be alleviated on the 7th day. The results of immunohistochemistry showed that Nrf2 was mainly expressed in the nucleus of pulmonery cells. The expression of Nrf2 in the exposure group was significantly higher than the control group. The expression of Nrf2 increased significantly at the 12th hour (P<0.05) , reached the peak on the 3rd day (P<0.05) . There was no difference between the control group and the 14th day (P>0.05) . Conclusion: There was no accumulation of DQ in the lung tissue for a long time, and there was a hysteresis in lung injury induced by redox reaction of DQ. Nrf2 was highly expressed in the lung tissue of rats with acute DQ poisoning, which was correlated with histopathology injury of lung tissue, suggesting that Nrf2 plays an important role in antagonizing acute lung injury induced by DQ.
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Lesión Pulmonar Aguda , Diquat , Paraquat , Lesión Pulmonar Aguda/inducido químicamente , Animales , Diquat/toxicidad , Pulmón , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Paraquat/toxicidad , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Objective: To establish the Wistar rat model of acute diquat poisoning and observe the pathological damage of main target organs. Methods: Thirty-six Wistar rats were randomly divided into six groups (n=6) , including one normal saline control group and five treatment groups which were separately given single-dose of intragastric administration at the doses of 46.2 mg/kg, 77.0 mg/kg, 115.5 mg/kg, 231.0 mg/kg and 346.5 mg/kg. The pathological changes of lung, liver and kidney were observed by hematoxylin and eosin (HE) and Masson staining. The optimal dose was determined according to the general situation and pathological changes. Thirty-six Wistar rats were randomly divided into five treatment groups and one normal saline control group. Treatment groups were given single-dose of intragastric administration according to the optimal dose. The rats were sacrificed at 1st, 3rd, 7th, 11th and 14th day after exposed, respectively. The activity of serum glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminase (AST) were measured by chemical colorimetry. The pathological changes of lung, liver and kidney were observed by HE and Masson staining. Results: According to 14 d survival rate, the toxic symptoms and pathological changes, 115.50 mg/kg was determined the best dose. Given single-dose of intragastric administration at the doses of 115.50 mg/kg, it was found that the serum AST and ALT activity of rats on the first and third day of exposure was significant higher than those in control group. The results of pathological examination exhibited that in 115.50 mg/kg group, the pathological changes of lung, liver and kidney began to appear on the first day of exposure, the pathological changes were the most serious on the third day, and then gradually alleviated. On the 14th day, the alveolar septum was slightly widened, with inflammatory cell infiltration, local alveolar cavity became narrow, atrophy, peripheral alveolar compensation, bronchi and alveolar septum collagen fiber proliferation; The local renal tubular epithelial cells were enlarged and necrotic; the central vein surrounding hepatic cells showed vacuolar degeneration with punctate necrosis. Conclusion: The rat model of acute diquat poisoning can be successfully induced by single-dose of intragastric administration. The condition of wistar rats and the pathological damage of the main target organs could be observed during the whole course of 115.50 mg/kg administration.
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Diquat , Riñón , Hígado , Pulmón , Animales , Diquat/toxicidad , Modelos Animales de Enfermedad , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Pulmón/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas WistarRESUMEN
Objective: To investigate the coping styles and subjective well-being of nurses in the emergency treatment room of grade A tertiary hospitals in a province of China, and to explore the relationship between coping styles and subjective well-being. Methods: In January 2016, 189 nurses in the emergency treatment room were selected from 9 grade A tertiary hospitals in a province of China by random sampling. The general data, coping styles, and subjective well-being of these nurses were analyzed using the general questionnaire, coping style questionnaire, and Campbell index of well-being scale, respectively. Results: The total score of subjective well-being of nurses in the emergency treatment room was 7.54, and the subjective well-being was significantly different between the nurses with different professional titles and between those with different education levels (F=3.46 and 3.47, both P<0.05). The score of illusion coping style differed significantly across the nurses of different ages (F=5.17, P<0.05) , the scores of self-reproach, illusion, and withdrawal coping styles differed significantly across the nurses with different nursing years (F=3.99, 5.30, and 4.97, all P<0.05) , and the score of illusion coping style differed significantly across the nurses with different education levels (F=5.09, P<0.05). Most (71.9%) of the nurses in the emergency treatment room adopted the mature coping style. Subjective well-being was positively correlated with problem-solving, help-seeking, and rationalization (r=0.232, 0.018, and 0.167, all P<0.05) and negatively correlated with withdrawal (r=-0.146, P<0.05) . Conclusion: Most nurses in the emergency treatment room adopt the mature coping style. Their subjective well-being and coping style vary with different ages, nursing years, professional titles, and education levels, and the subjective well-being is relatively low.
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Adaptación Psicológica , Enfermedades Profesionales/psicología , Estrés Psicológico/etiología , China , Enfermería de Urgencia , Servicio de Urgencia en Hospital , Tratamiento de Urgencia , Femenino , Humanos , Masculino , Enfermedades Profesionales/epidemiología , Estrés Psicológico/epidemiología , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Centros de Atención Terciaria , Recursos Humanos , Carga de Trabajo/psicologíaRESUMEN
OBJECTIVE: To study the mechanism of paraquat (PQ) -induced renal injury in rats, the expression changes of ICAM-1 to assess the protective effect of Melatonin in PQ poisoning. METHODS: Ninety adult healthy Sprague-Dawley (SD) rats were divided into three groups at random. CONTROL GROUP: 30 rats; Poisoned group: 30 rats; Melatonin group: 30 rats. Control group and Poisoned group were treated intragastrically with 1 ml of PQ (50 mg/kg) diluted with normal saline. Control groupwere treated with the same dose of normal saline as Poisoned group and Melatonin group. Melatonin group were given 1 ml of Melatonin at a dose of 10 mg/kg diluted with normal saline (once daily, intraperitoneally) Control and Poisoned group were treated with the same dose of normal saline (once daily, intraperitoneally) as Melatonin group. Pathology of renal tissue were oberserved by HE staining, and electron microscope. The histopathological changes and the expression of ICAM-1 were observed with mmunohistochemistry (IHC). RESULTS: (1) There were no obvious pathological changes in Control group. Poisoned group Renal glomerulus had hyperemia and distension.Renal tubule epith elial cell had edema and vacuolar degeneration and renal tubule lumina was narrowing on day 1, There were serious edema exudation and necrosis on day 5,which gradually lessened furthermore; Compared with Poisoned group, the aforementioned pathological lesion was more palliative in Melatonin group. (2) No obvious abnomal changes in ultrastructure of renal tissues in Control group. There were swelling of mitochondrion and rupture of renal tubule epithelial cell and endoplasmic reticulum had extension, lysosome was mult and had much phagocytosis in Poisoned group. (3) There was a very weak expression of ICAM-1 in Control group. while in Poisoned group, there was already a significant higher expression of ICAM-1 of renal tubule on day 1 after PQ poisoning, Immunohistochemistry score (IHS) of Poisoned group on day 1, 3, 5, 7, 14 were (0.1561±0.0295ã0.2572±0.0259ã0.3028±0.0153ã0.2083±0.0227ã0.9309±0.0059) , compared with Control group (P<0.01) ; Melatonin group were (0.1259±0.0061ã0.2109±0.0280ã0.2679±0.0233ã0.1771±0.0186ã0.0791±0.0135) , compared with Control group (P<0.01) , compared with Poisoned group (P<0.05) ; CONCLUSION: ICAM-1 was involved in the procedures of renal injury; MT surely had a protective effect, which might be mediated by ICAM-1 in the paraquat-induced renal injury, but its regulation path still need a further exploration.
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Riñón , Animales , Inmunohistoquímica , Molécula 1 de Adhesión Intercelular , Melatonina , Mitocondrias , Paraquat , Ratas , Ratas Sprague-DawleyAsunto(s)
Adenina/análogos & derivados , Antivirales/uso terapéutico , Farmacorresistencia Viral/genética , Hepatitis B Crónica/tratamiento farmacológico , Organofosfonatos/uso terapéutico , Telbivudina/uso terapéutico , Carga Viral , Adenina/uso terapéutico , ADN Viral , Virus de la Hepatitis B , Humanos , MutaciónRESUMEN
Objective: To analyze the characteristics of trigeminal event-related potentials (tERPs) in different kinds of olfactory disorders (OD), and to evaluate the importance of tERPs for the patients with olfactory dysfunction. Methods: Clinical data of 314 patients with olfactory dysfunction from the Smell and Taste Clinics in Beijing Anzhen Hospital from 2015 to 2021 were retrospectively reviewed, including 158 males and 156 females, aging from 6 to 78 years. The control group consisted of healthy people from medical examination center, who were gender and age matched. The clinical characteristics of OD were analyzed using Sniffin' Sticks test, olfactory event-related potentials (oERPs), tERPs and acoustic rhinometry test. SPSS 17.0 software was used to compare the difference of tERPs between the two groups, and to analyze the related factors affecting trigeminal function. Results: The ratio of tERPs presence was different in OD caused by different reasons: head traumatic OD (54.9%), post-virus infection OD (63.6%), sinonasal inflammatory OD (68.4%) and OD due to other causes (56.9%). Compared with controls, tERPs signals in OD patients showed a significant lower amplitude in the N1 wave (all P<0.001), and lower amplitude in the P2 wave in most OD patients (head trauma t=-4.11, P<0.001; sinonasal inflammation t=-2.04, P=0.046; others t=-2.40, P=0.020) except in OD by post-virus infection (t=-1.98, P=0.052). tERPs signals in OD patients by sinonasal inflammation showed longer latency in the N1 wave (t=2.15, P=0.036), but this difference was not observed in other OD patients (all P>0.05). tERPs signals were significantly correlated with the Sniffin' Sticks score, deficiency of oERPs and nasal minimum cross-sectional area (all P<0.05). Conclusions: OD patients show neurophysiologic deficits in trigeminal function. The absence of tERPs or lower amplitude in N1 waves are the important characteristics of patients with OD.
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Trastornos del Olfato , Virosis , Potenciales Evocados/fisiología , Femenino , Humanos , Inflamación , Masculino , Trastornos del Olfato/etiología , Estudios Retrospectivos , Olfato/fisiología , Virosis/complicacionesRESUMEN
This study numerically investigates a two-dimensional physical model of methane/air mixture combustion in catalytic and non-catalytic porous media. The temperature distribution and flame stability of combustion in inert alumina (Al2O3) pellets and platinum (Pt) catalyst-supported alumina (Al2O3) pellets, were studied by changing the burner structure, operating parameters, and physical properties of alumina pellets. The simulation results indicated that the gas temperature in the inert porous medium is higher than that in a catalytic porous medium, while the solid temperature in an inert porous medium is lower than that in a catalytic porous medium. The flame moved toward the burner exit with the increasing diameter of the packed pellets at a lower equivalence ratio and moved toward upstream with the increased thermal conductivity of packed pellets. The flame location of the catalytic porous burner was more sensitive to the flame velocity and insensitive to thermal conductivity compared to the inert porous burner. The distance of the flame location to the burner inlet is almost constant with the increasing length of the porous media for both the catalytic and inert porous burner, while the relative position of the flame location moved toward the upstream.
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Tenascin-C (TN-C) is a key component of extracellular matrix (ECM) and its expression process is poorly understood during rheumatic heart valvular disease (RHVD). In this study, we found that interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and TN-C concentrations in patients with RHVD were significantly higher than in normal controls. More IFN-gamma receptors and TNF receptors were found being expressed on rheumatic aortic valves interstitial cells than on non-rheumatic ones and their expression was patients' sera dependent. Antibodies neutralizing IFN-gamma or TNF-alpha could attenuate patients' sera-induced TN-C transcription by isolated rheumatic aortic valves interstitial cells. By application with different protein kinase inhibitors, we found that combined with cyclic strain, TNF-alpha and IFN-gamma induced TN-C transcription through the RhoA/ROCK signalling pathway. At the same time, p38 mitogen-activated protein kinase was involved in TNF-alpha and IFN-gamma induced TN-C transcription. TNF-alpha also increased TN-C mRNA level by additional PKC and ERK 1/2 activation. Our finding revealed a new insight into ECM remodelling during RHVD pathogenesis and new mechanisms involved in the clinical anti-IFN-gamma and anti-TNF-alpha therapy.
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Válvula Aórtica/metabolismo , Citocinas/fisiología , Cardiopatía Reumática/metabolismo , Tenascina/biosíntesis , Adulto , Válvula Aórtica/anomalías , Válvula Aórtica/patología , Células Cultivadas , Femenino , Corazón Auxiliar , Humanos , Interferón gamma/sangre , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Receptores de Interferón/metabolismo , Receptores del Factor de Necrosis Tumoral/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Cardiopatía Reumática/sangre , Cardiopatía Reumática/patología , Estrés Mecánico , Tenascina/sangre , Tenascina/genética , Activación Transcripcional/inmunología , Factor de Necrosis Tumoral alfa/sangre , Adulto Joven , Receptor de Interferón gammaRESUMEN
OBJECTIVE: To investigate the biological function of microRNA-1179 (miRNA-1179) in regulating the proliferative and migratory abilities of the hepatocellular carcinoma (HCC) by targeting zinc-finger E-box-binding homeobox 2 (ZEB2). PATIENTS AND METHODS: The miRNA-1179 level in 40 HCC tissues and matched normal tissues was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The association between the miRNA-1179 level and the clinical parameters of HCC patients was analyzed. The regulatory effects of miRNA-1179 on influencing proliferative and migratory abilities of HepG2 and Bel-7402 cells were assessed. The dual-luciferase reporter gene assay was conducted to verify the binding relationship between miRNA-1179 and ZEB2. Subsequently, the expression pattern and the biological function of ZEB2 in HCC were explored. The rescue experiments were finally carried out to uncover the role of the miRNA-1179/ZEB2 axis in regulating the progression of HCC. RESULTS: MiRNA-1179 was downregulated in HCC tissues and cell lines. HCC patients with low expression of miRNA-1179 had higher metastatic rates (lymphatic metastasis and distant metastasis) and worse prognosis relative to those with low expression. The overexpression of miRNA-1179 attenuated the proliferative and migratory abilities of HCC cells. ZEB2 was confirmed to be the direct target of miRNA-1179 and its level was negatively regulated by miRNA-1179. ZEB2 was upregulated in HCC tissues and cell lines. The high expression of ZEB2 predicted a worse prognosis of HCC. The overexpression of ZEB2 reversed the inhibitory effects of miRNA-1179 on the proliferative and migratory abilities in HCC cells. CONCLUSIONS: MiRNA-1179 is closely related to lymphatic metastasis, distant metastasis, and overall survival of HCC. It alleviates the malignant progression of HCC by downregulating ZEB2.
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Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , MicroARNs/genética , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/genética , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Masculino , Metástasis de la Neoplasia , PronósticoRESUMEN
In vitro studies have shown that corticosterone (B) directly inhibits testosterone (T) production by purified Leydig cells but does so only at high concentrations. 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) in Leydig cells oxidatively inactivates B, lowering its effective concentration, thus protecting against the suppressive effect of glucocorticoid on T production. The aim of the present study was to assess the significance of B at physiological levels in modulating T production and 11 beta-HSd activity in Leydig cells. To determine the effects of endogenous B on Leydig cell steroidogenesis, male rats (200-250 g body wt) were adrenalectomized (ADX), while control rats were subjected to sham surgery (SHAM). Seven days after surgery: T and LH were measured in serum; T production was measured in aliquots of spent culture media from 3-h incubations of purified Leydig cells; 11 beta-HSD activity and messenger RNA was measured in purified Leydig cells. ADX rats had elevated serum T (P < 0.05) in contrast to SHAM control or ADX rats that received B replacement (1 mg/100 g body wt per day, i.p., on the final 3 days). Serum LH levels were uninfluenced by ADX, with or without B replacement (SHAM), 0.45 +/- 0.16 ng/ml; ADX, 0.35 +/- 0.13 ng/ml; ADX + B, 0.61 +/- 0.09 ng/ml, NS, P > 0.05). This indicated that the alteration of T production was induced by a mechanism that is independent of LH. ADX nearly doubled LH-stimulated T production by purified Leydig cells, from 106.3 +/- 9.3 (SHAM) to 183.2 +/- 16.7 (ADX) ng/10(6) cells.3 h (mean +/- SEM for three replications of the experiment, P < or = 0.02). T production by Leydig cells from the ADX + B treatment group was suppressed to 53% of SHAM values, indicating that B inhibits T production after ADX. The oxidative activity of 11 beta-HSD in Leydig cells exceeded its reductive activity, and both activities declined after ADX. The decline in 11 beta-HSD activities after ADX was prevented by B replacement. Similarly, the steady state levels of 11 beta-HSD messenger RNA declined in Leydig cells after ADX, and this decline was prevented by B replacement. We conclude that physiological levels of B exert a tonic, negative control directly on Leydig cell steroidogenesis and also induce intracellular 11 beta-HSD activity, thereby protecting against B-mediated inhibition of T production. By modulating the level of active glucocorticoid in Leydig cells, 11 beta-HSD is thus a significant determinant of their steroidogenic capacity.
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Corticosterona/sangre , Células Intersticiales del Testículo/metabolismo , Testosterona/biosíntesis , 11-beta-Hidroxiesteroide Deshidrogenasas , Adrenalectomía , Animales , Secuencia de Bases , Corticosterona/farmacología , Hidroxiesteroide Deshidrogenasas/genética , Hidroxiesteroide Deshidrogenasas/metabolismo , Células Intersticiales del Testículo/efectos de los fármacos , Hormona Luteinizante/sangre , Masculino , Datos de Secuencia Molecular , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Testosterona/sangreRESUMEN
We have proposed that the 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) of Leydig cells protects against glucocorticoid-induced inhibition of testosterone (T) production. However, Leydig cells express type I 11 beta-HSD, which has been shown to be reductive in liver parenchymal cells. Because reduction would have the opposite effect of activating glucocorticoid, the present study was designed to determine: 1) whether Leydig cell 11 beta-HSD is primarily oxidative or reductive; and 2) whether oxidative and reductive activities are separately modified by known regulators of Leydig cell steroidogenic function. Leydig cells and liver parenchymal cells were purified from mature male Sprague-Dawley rats (250 g BW), and 11 beta-HSD oxidative and reductive activities were measured using radiolabeled substrates and TLC of triplicate media samples from 1-h incubations immediately after cell isolation. Enzyme activities also were examined in purified Leydig cells at the end of 3 days of culture in vitro in the presence of LH (10 ng/ml), dexamethasone (DEX, 100 nM), T (50 nM), or epidermal growth factor (EGF, 50 ng/ml). In confirmation of previous reports, the reductive activity of 11 beta-HSD was predominant over oxidation in liver parenchymal cells. In contrast, 11 beta-HSD oxidative activity prevailed over reduction in Leydig cells by a ratio of 2:1. The activities of 11 beta-HSD also were analyzed in Leydig cells that were purified 7 days after endogenous glucocorticoid levels were suppressed by adrenalectomy (ADX). Oxidative activity declined in Leydig cells after ADX (22.53 +/- 1.12 pmol/h.10(6) cells, mean +/- SEM vs. 31.47 +/- 1.48 pmol/.10(6) cells in sham-operated controls, P < 0.05), whereas there was no change in reductive activity. This indicated that physiologically active corticosterone is involved in maintaining the predominance of 11 beta-HSD oxidation. When enzyme activities were analyzed in Leydig cells after 3 days of hormonal treatment in vitro, oxidation and reduction were observed to change in opposing directions. Culture of Leydig cells from sham-operated control rats with either LH, T, or EGF resulted in declines in oxidative activity from 33.35 +/- 0.77 to 28.24 +/- 1.93, 27.30 +/- 0.96, and 24.13 +/- 1.02 pmol/ h.10(6) cells (x +/- SE), respectively. However, EGF stimulated 11 beta-HSD reductive activity in cultured Leydig cells from both control (from 18.97 +/- 1.10 to 27.16 +/- 0.71 pmol/h.10(6) cells and ADX rats (from 16.51 +/- 0.75 to 23.56 +/- 0.84 pmol/h.10(6) cells). Among the hormonal treatments, only DEX increased oxidative activity and simultaneously decreased reductive activity in Leydig cells from ADX rats. This increase accentuated the predominance of oxidative activity in Leydig cells, with a ratio of oxidative to reductive activity of 4:1 after DEX treatment, compared with 2:1 in controls that were untreated. We conclude that 11 beta-HSD activity in Leydig cells is primarily oxidative. Moreover, oxidation and reduction are regulated separately by hormones.
Asunto(s)
Hidroxiesteroide Deshidrogenasas/metabolismo , Células Intersticiales del Testículo/enzimología , 11-beta-Hidroxiesteroide Deshidrogenasas , Adrenalectomía , Animales , Células Cultivadas , Factor de Crecimiento Epidérmico/farmacología , Glucocorticoides/farmacología , Hidroxiesteroide Deshidrogenasas/genética , Hígado/enzimología , Hormona Luteinizante/farmacología , Masculino , Oxidación-Reducción , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Testosterona/farmacologíaRESUMEN
Leydig cells are susceptible to direct glucocorticoid-mediated inhibition of testosterone biosynthesis but can counteract the inhibition through 11beta-hydroxysteroid dehydrogenase (11beta-HSD), which oxidatively inactivates glucocorticoids. Of the two isoforms of 11beta-HSD that have been identified, type I is an NADP(H)-dependent oxidoreductase that is relatively insensitive to inhibition by end product and carbenoxolone (CBX). The type I form has been shown to be predominantly reductive in liver parenchymal cells and other tissues. In contrast, type II, which is postulated to confer specificity in mineralocorticoid receptor (MR)-mediated responses, acts as an NAD-dependent oxidase that is potently inhibited by both end product and CBX. The identity of the 11beta-HSD isoform in Leydig cells is uncertain, because the protein in this cell is recognized by an anti-type I 11beta-HSD antibody, but the activity is primarily oxidative, more closely resembling type II. The goal of the present study was to determine whether the kinetic properties of 11beta-HSD in Leydig cells are consistent with type I, type II, or neither. Leydig cells were purified from male Sprague-Dawley rats (250 g), and 11beta-HSD was evaluated in Leydig cells by measuring rates of oxidation and reduction, cofactor preference, and inhibition by end product and CBX. Leydig cells were assayed for type I and II 11beta-HSD and MR messenger RNAs (mRNAs), and for type I 11beta-HSD protein. Leydig cell 11beta-HSD had bidirectional catalytic activity that was NADP(H)-dependent. This is consistent with the hypothesis that type I 11beta-HSD is present in rat Leydig cells. However, unlike the type I 11beta-HSD in liver parenchymal cells, the Leydig cell 11beta-HSD was predominantly oxidative. Moreover, analysis of kinetics revealed two components, the first being low a Michaelis-Menten constant (Km) NADP-dependent oxidative activity with a Km of 41.5 +/- 9.3 nM and maximum velocity (Vmax) of 7.1 +/- 1.2 pmol x min x 10(6) cells. The second component consisted of high Km activities that were consistent with type I:NADP-dependent oxidative activity with Km of 5.87 +/- 0.46 microM and Vmax of 419 +/- 17 pmol x min x 10(6) cells, and NADPH-dependent reductive activity with Km of 0.892 +/- 0.051 microM and Vmax of 117 +/- 6 pmol x min x 10(6) cells. The results for end product and CBX inhibition were also inconsistent with a single kinetic activity in Leydig cells. Type I 11beta-HSD mRNA and protein were both present in Leydig cells, whereas type II mRNA was undetectable. We conclude that the low Km NADP-dependent oxidative activity of 11beta-HSD in Leydig cells does not confirm to the established characteristics of type I and may reside in a new form of this protein. We also demonstrated the presence of the mRNA for MR in Leydig cells, and the low Km component could allow for specificity in MR-mediated responses.
Asunto(s)
Hidroxiesteroide Deshidrogenasas/metabolismo , Isoenzimas/metabolismo , Células Intersticiales del Testículo/enzimología , Microsomas/enzimología , 11-beta-Hidroxiesteroide Deshidrogenasas , Animales , Carbenoxolona/farmacología , Cortisona/metabolismo , Hidroxiesteroide Deshidrogenasas/biosíntesis , Isoenzimas/biosíntesis , Cinética , Hígado/enzimología , Masculino , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , RatasRESUMEN
The concentration of Salvia miltiorrhizae (SM) was detected at different time after renal intracapsular injection in S.D rats. It showed that SM concentration was higher in kidney than in plasma (P < 0.05). SM concentration in kidney increased gradually, it reached the peak at 24 hour and still remained in higher level at 48 hour. The SM injected in renal capsule could be passively transported to renal tissue and maintained at a high level. This result demonstrated that renal intracapsular injection could be applied as an important therapeutical method for different renal disease.
Asunto(s)
Medicamentos Herbarios Chinos/farmacocinética , Riñón/metabolismo , Agregación Plaquetaria/efectos de los fármacos , Animales , Medicamentos Herbarios Chinos/administración & dosificación , Masculino , Extractos Vegetales , Ratas , Ratas Sprague-Dawley , Salvia miltiorrhizaRESUMEN
In the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise mechanism of IL-6 induction by the stress-related hormone norepinephrine (NE) is not clear, and, furthermore, there are no reports about the effect of NE on IL-6 expression in gastric epithelial cells. In this study, we examined the effect of NE on IL-6 expression in immortalized human gastric epithelial cells (GES-1 cells). Using real-time PCR and enzyme-linked immunoassay, we demonstrated that NE can induce IL-6 mRNA and protein expression in GES-1 cells. The induction is through the ß-adrenergic receptor-cAMP-protein kinase A pathway and mainly at the transcriptional level. Progressive 5'-deletions and site-directed mutagenesis of the parental construct show that, although activating-protein-1 (AP-1), cAMP-responsive element binding protein (CREB), CCAAT-enhancer binding protein-ß (C/EBP-ß), and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding sites are all required in the basal transcription of IL-6, only AP-1 and CREB binding sites in the IL-6 promoter are required in NE-induced IL-6 expression. The results suggest that chronic stress may increase IL-6 secretion of human gastric epithelial cells, at least in part, by the stress-associated hormone norepinephrine, and provides basic data on stress and gastric cancer progression.
Asunto(s)
Células Epiteliales/efectos de los fármacos , Interleucina-6/metabolismo , Norepinefrina/farmacología , Transducción de Señal/fisiología , Línea Celular , Ensayo de Inmunoadsorción Enzimática , Células Epiteliales/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Regulación de la Expresión Génica/fisiología , Humanos , Interleucina-6/genética , FN-kappa B/metabolismo , Norepinefrina/metabolismo , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Adrenérgicos beta/metabolismo , Factores de Transcripción/fisiología , Regulación hacia ArribaRESUMEN
In the current literature, there is evidence that psychological factors can affect the incidence and progression of some cancers. Interleukin 6 (IL-6) is known to be elevated in individuals experiencing chronic stress and is also involved in oncogenesis and cancer progression. However, the precise mechanism of IL-6 induction by the stress-related hormone norepinephrine (NE) is not clear, and, furthermore, there are no reports about the effect of NE on IL-6 expression in gastric epithelial cells. In this study, we examined the effect of NE on IL-6 expression in immortalized human gastric epithelial cells (GES-1 cells). Using real-time PCR and enzyme-linked immunoassay, we demonstrated that NE can induce IL-6 mRNA and protein expression in GES-1 cells. The induction is through the β-adrenergic receptor-cAMP-protein kinase A pathway and mainly at the transcriptional level. Progressive 5′-deletions and site-directed mutagenesis of the parental construct show that, although activating-protein-1 (AP-1), cAMP-responsive element binding protein (CREB), CCAAT-enhancer binding protein-β (C/EBP-β), and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding sites are all required in the basal transcription of IL-6, only AP-1 and CREB binding sites in the IL-6 promoter are required in NE-induced IL-6 expression. The results suggest that chronic stress may increase IL-6 secretion of human gastric epithelial cells, at least in part, by the stress-associated hormone norepinephrine, and provides basic data on stress and gastric cancer progression.
Asunto(s)
Humanos , Células Epiteliales/efectos de los fármacos , /metabolismo , Norepinefrina/farmacología , Transducción de Señal/fisiología , Línea Celular , Ensayo de Inmunoadsorción Enzimática , Células Epiteliales/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Regulación de la Expresión Génica/fisiología , /genética , FN-kappa B/metabolismo , Norepinefrina/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , ARN Mensajero/metabolismo , Receptores Adrenérgicos beta/metabolismo , Factores de Transcripción/fisiología , Regulación hacia ArribaRESUMEN
Aloperine, an alkaloid isolated from Sophora alopecuroides L, showed a marked suppressive effect on the swelling of the rat's hind paw induced by injecting carrageenin, macostatin, PGE2, histamine, 5-HT, on the rat's scald oedema induced by scalding its hind paw, and on the increased permeability of capillaries caused by histamine and the leukocytic migratory response. The swelling induced by injecting carrageenin into the hind paw of adrenolectomized rats was still significantly inhibited. Noticeably, aloperine reduced the content of PGE and histamine in the exudate formed after injecting carrageenin and dextran into the rat's hind paw, and increased the stability of red cell membranes, the activity of catalase (CAT) in hepatic tissue of mice, and reduced the content of malondialdehyde (MDA) in hepatic tissue of intoxicated mice. It had no apparent effect either on the activity of superoxide dismutase (SOD) in mice serum or on the phagocytosis of the monocyte-macrophage system, or on Forssman cutaneous vasculitis and the content of immune complex in serum of rats with Arthus reaction. But it had certain inhibitory effect on the PCA reaction and significant inhibitory effect upon such allergic reaction as Arthus reaction, reversible passive Arthus reaction, the delayed hypersensitivity reaction induced by tuberculin in rats, and adjuvant arthritis.