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Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease. It has been reported in the literature that COPD patients with chronic airway mucus hypersecretion have more frequent acute exacerbations, more severe lung function decline, and higher hospitalizations and mortality. Therefore, it is particularly critical to understand the pathogenesis of hypersecretion of mucus in chronic obstructive pulmonary disease and find out effective treatment. This article focuses on the structure, significance of airway mucus and the mechanism of hypersecretion of mucus in chronic obstructive pulmonary disease (COPD). In addition, we also summarized drug and non-drug therapy for chronic airway mucus hypersecretion in this article. Drug therapy includes traditional drug therapy, some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy, and non-drug therapy includes smoking cessation, physical therapy and bronchos-copy therapy. We hope that it will provide new ideas and directions for the treatment of mucus hypersecretion in COPD patients.
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Chronic obstructive pulmonary disease （COPD） is one of the most common chronic diseases of the respiratory system in the clinic. The disease has a long course and is difficult to cure， which seriously threatens human health. Airway mucus hypersecretion （AMH） is an independent risk factor for COPD and has a significant impact on the development and prognosis of the disease. The review finds that the abnormal proliferation of goblet cells and the excessive secretion of mucin are the direct causes of AMH. The pathogenesis of AMH may be closely related to the inhalation of heterogeneous particles， airway inflammation， the imbalance of mucin/water salt ratio， and the regulation of related signaling pathways. Traditional Chinese medicine （TCM） believes that AMH of COPD belongs to the category of lung distension with phlegm-fluid retention syndrome， and the disease is mainly treated from phlegm on the basis of lung distension. This article summarizes the relevant research in the field of TCM in recent years and finds that the single TCM that effectively intervened AMH of COPD is mainly phlegm-resolving TCM， and the main active ingredients of TCM are flavonoids， terpenoids， phenols， and alkaloids. The main TCM compounds are mainly designed to remove heat-phlegm， warmly resolve cold-phlegm， dry dampness to eliminate phlegm， invigorate Qi， promote blood circulation and dispel phlegm， and invigorate lung， spleen， and kidney. Its mechanism of action may be direct inhibition or indirect inhibition of airway epithelial goblet cell metaplasia and mucin expression by inhibiting airway inflammation， regulating aquaporins to correct the imbalance of mucin/water salt ratio， and regulating signaling pathways， so as to reduce mucus oversecretion in COPD. However， there are still some problems. For example， the research mainly focuses on TCM compounds instead of the single TCM or its effective components. The research on the mechanism of action is not thorough enough， and the research results are not interoperable. The clinical transformation rate of basic research is insufficient. This article systematically reviews the research status of AMH in the treatment of COPD with TCM and puts forward some thoughts on the existing problems， so as to provide a reference for clinical rational medication and in-depth research.
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The pathological position of hypersecretion of airway mucus is in airway mucosa. Modern TCM theory believes that the airway mucosa belongs to the triple energizer membranous system of TCM, and the airway mucus is a part of TCM water-liquid system. Based on the TCM physiological characteristics of children, this article explored the pathogenesis of airway mucus hypersecretion in children, and believed that the airway mucus hypersecretion was the result of the disorder of water-liquid metabolism in TCM, which was closely related to the function of qi transformation of triple energizer membranous system. Failure of qi transformation in triple energizer is the core pathogenesis of hypersecretion of airway mucus in children. The deficiency of yang qi in children leads to the disorganization of vaporization in triple energizer, which leads to the insufficiency of movement and transformation function, the failure of water and qi in water, the stop of water and water accumulation, the abnormity of water and grain. The disorder of water-liquid metabolism leads to the occurrence of high airway mucus secretion in children.
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OBJECTIVE@#To explore the mechanism of Yifei Jianpi recipe for improving cigarette smoke- induced inflammatory injury and mucus hypersecretion in cultured human bronchial epithelial cells.@*METHODS@#Serum samples were collected from 40 SD rats treated with Yifei Jianpi recipe (n=20) or normal saline (n=20) by gavage. Cultured human bronchial epithelial 16HBE cells were stimulated with an aqueous cigarette smoke extract (CSE), followed by treatment with the collected serum at different dilutions. The optimal concentration and treatment time of CSE and the medicated serum for cell treatment were determined with CCK-8 assay. The expressions of TLR4, NF-κB, MUC5AC, MUC7, and muc8 at both the mRNA and protein levels in the treated cells were examined with RT- qPCR and Western blotting, and the effects of TLR4 gene silencing and overexpression on their expressions were assessed. The expressions of TNF-α, IL-1 β, IL-6 and IL-8 in the cells were detected using ELISA.@*RESULTS@#At the optimal concentration of 20%, treatment with the medicated serum for 24 h significantly lowered the mRNA and protein expressions of TLR4, NF- κB, MUC5AC, MUC7, and MUC8 in CSE- exposed 16HBE cells, and these effects were further enhanced by TLR4 silencing in the cells. In 16HBE cells with TLR4 overexpression, the expressions of TLR4, NF-κB, MUC5AC, MUC7, and MUC8 were significantly increased after CSE exposure and were lowered following treatment with the medicated serum (P < 0.05). The medicated serum also significantly lowered the levels of TNF-α, IL-1β, IL-6 and IL-8 in CSE-exposed 16HBE cells (P < 0.05).@*CONCLUSIONS@#In the 16HBE cell model of chronic obstructive pulmonary disease (COPD), treatment with Yifei Jianpi recipe-medicated serum improves inflammation and mucus hypersecretion possibly by reducing MUC secretion and inhibiting the TLR4/NF-κB signaling pathway.
Subject(s)
Humans , Rats , Animals , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolism , Interleukin-8/metabolism , Tumor Necrosis Factor-alpha/metabolism , Cigarette Smoking/adverse effects , Interleukin-6/metabolism , Rats, Sprague-Dawley , Pulmonary Disease, Chronic Obstructive/drug therapy , Signal Transduction , Epithelial Cells/metabolism , Mucus/metabolism , RNA, Messenger/metabolismABSTRACT
RESUMEN El síndrome de Cushing endógeno deriva de un aumento crónico, inapropiado y sostenido de glucocorticoides principalmente como respuesta al exceso en las concentraciones séricas elevadas de la hormona adrenocorticotropa (ACTH) desde un tumor adenohipofisiario, enfermedad de Cushing; o producida de forma ectópica por tumores neuroendocrinos. El Cushing suprarrenal se origina por tumores de la corteza adrenal que producen de forma autónoma cortisol y es independiente de ACTH. El curso clínico, tratamiento, pronóstico y posibles complicaciones dependen de identificar de forma correcta la lesión desencadenante; situación que en múltiples ocasiones resulta en una experiencia retadora para los clínicos. Se presenta el caso de una mujer de 62 años, ingresada por síntomas constitucionales con hipocaliemia severa de difícil corrección e hipercortisolismo severo.
ABSTRACT Endogenous Cushing syndrome derives from a chronic, inappropriate, and sustained increase in glucocorticoids, mainly in response to remarkably high serum concentrations of adrenocorticotropic hormone (ACTH) secreted from an adenohypophyseal tumor, Cushing's disease, or due to ectopic production by neuroendocrine tumors. Adrenal Cushing's disease is caused by tumors of the adrenal cortex that autonomously produce cortisol and this is independent from ACTH action. Clinical course, treatment, prognosis, and possible complications depend on correctly identifying the triggering lesion; this situation frequently becomes a challenging experience for clinicians. We present the case of a 62-year-old woman, admitted for constitutional symptoms with severe hypokalemia that was difficult to correct and severe hypercortisolism.
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Objective:To explore the mechanism of Bufei Yishen formula (BYF) on attenuating cigarette smoke extract (CSE)-induced airway mucus hypersecretion by regulating Notch signaling pathway.Methods:The human airway epithelial cell 16HBE was cultured in vitro, and the cells in logarithmic growth phase were used for the experiments. ① Intervention condition screening experiment: the 16HBE cells were grouped, methylthiazolyldiphenyl-tetrazolium (MTT) method and enzyme-linked immunosorbent assay (ELISA) were used to detect the effects of different concentrations of CSE (2.5%, 5%, 10%, 20%, 40%), different concentrations of BYF drug-containing serum (5%, 10%, 20%, 40%), and different concentrations of Notch signal pathway blocker DAPT (5, 10, 20, 40 μmol/L) on cell activity and secretion of mucin 5AC (MUC5AC) levels. In addition, a blank control group was set up to screen out the best conditions for preparing CSE-induced cell mucus hypersecretion model and BYF and DAPT intervention. ② Intervention experiment: the 16HBE cells were divided into four groups. The blank control group was not given any treatment; the 16HBE cells were induced by 10% CSE for 24 hours to prepare mucus hypersecretion model in the CSE model group; the cells in the CSE+BYF group and CSE+DAPT group were given 10% BYF or 20 μmol/L DAPT, respectively, for intervention at the same time for 24 hours. Real-time fluorescent quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expressions of MUC5AC, Notch3 and hairy and enhancer of split 1 (HES1) in the cells. Western blotting was used to detect the protein expressions of Notch3 and HES1 in the cells. Results:① Results of the screening experiment of intervention conditions: compared with the blank control group, 10% CSE induction for 24 hours was the best condition for establishing cell mucus hypersecretion model that neither affected cell viability nor increased the secretion of MUC5AC; while 10% BYF and 20 μmol/L DAPT was the optimal intervention condition. ② Intervention experiment results: compared with the blank control group, the mRNA expressions of MUC5AC, Notch3, and HES1 and the protein expressions of Notch3 and HES1 in the CSE model group were significantly increased, indicating that CSE activated Notch3 and HES1 signal activation and induced 16HBE cells to secrete mucus protein. Compared with the CSE model group, BYF and DAPT could significantly down-regulate the mRNA and protein expressions of MUC5AC, Notch3, and HES1 in cells [MUC5AC mRNA (2 -ΔΔCT): 1.03±0.13, 0.96±0.05 vs. 1.35±0.07, Notch3 mRNA (2 -ΔΔCT): 1.10±0.14, 1.10±0.02 vs. 1.31±0.15, HES1 mRNA (2 -ΔΔCT): 1.26±0.10, 1.14±0.15 vs. 1.45±0.08, Notch3 protein (Notch3/GAPDH): 0.10±0.03, 0.16±0.03 vs. 0.31±0.09, HES1 protein (HES1/GAPDH): 0.37±0.06, 0.34±0.08 vs. 0.50±0.05, all P < 0.05]. Conclusion:The mechanism of BYF attenuating mucus hypersecretion of 16HBE cells induced by CSE was associated with the inhibition of Notch signaling pathway activation.
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The incidence rate of chronic airway inflammatory diseases caused by airway mucus hypersecretion caused by mycoplasma pneumoniae(MP) infection is increasing year by year.In this paper, the damage of MP on airway mucosa through its adhesion, migration, community acquired respiratory distress syndrome toxin(CARDS Tx)and other virulence factors is described, which directly damages the structure and function of airway epithelium and affects the metabolism of ciated cells.It can also cause the increase of airway pro-inflammatory cytokines and the up regulation of toll-like receptor, resulting in the increase of airway mucus secretion.In addition, when MP infects airway epithelial cells, it will increase mucin(MUC)production through signal transduction pathway, which will increase the secretion of MUC5AC and lead to airway mucus hypersecretion.Controling airway mucus hypersecretion caused by MP infection can reduce the occurrence of chronic airway inflammation and helpful to the treatment of refractory MP infection.
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ObjectiveTo observe the effects of Bufei Yishen prescription on airway mucus hypersecretion and Notch signaling pathway related protein Notch3 and enhancer of split homologue 1 （HES1） in rats with chronic obstructive pulmonary disease （COPD） and to explore its action mechanism. MethodForty-eight SD rats were randomly divided into the control group， model group， Bufei Yishen prescription group， and aminophylline （APL） group，with 12 rats in each group. The stable COPD rat model was established via cigarette smoking exposure combined with Klebsiella bacterial infection for 12 weeks， and the corresponding drugs （3.7 g·kg-1·d-1 Bufei Yishen prescription and 54 mg·kg-1·d-1 APL） were administered by gavage during the next eight weeks. After the last administration at week 20， the lung tissue was sampled for observing the pathological changes and the rat lung function was detected. The tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and mucoprotein 5AC （MUC5AC） in bronchial alveolar lavage fluid and the mRNA and protein expression levels of Notch3， HES1， and MUC5AC in lung tissues were assayed. ResultCompared with the control group， the model group exhibited significantly weakened pulmonary function （P<0.05，P<0.01）， reduced average number of alveoli （P<0.01）， elevated mean linear intercept （P<0.01）， and up-regulated TNF-α， IL-6， and MUC5AC in bronchial alveolar lavage fluid and Notch3， HES1， and MUC5AC mRNA and protein expression in lung tissue （P<0.05，P<0.01）. Compared with the model group， Bufei Yishen prescription and APL remarkably enhanced pulmonary function， alleviated its pathological injury （P<0.05，P<0.01）， and down-regulated TNF-α， IL-6， and MUC5AC in bronchial alveolar lavage fluid and the mRNA and protein expression levels of Notch3， HES1， and MUC5AC in lung tissues （P<0.05，P<0.01）. ConclusionThe mechanism of Bufei Yishen prescription in inhibiting airway mucus hypersecretion of COPD rats was related to its regulation of Notch3 and HES1.
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Objective:To evaluate the compatibility laws of effective-component compatibility of Bufei Yishen formula Ⅲ (ECC-BYFⅢ) in regulating mucus hypersecretion of chronic obstructive pulmonary disease (COPD).Methods:According to the efficacy of the original Chinese medicine, the components of ECC-BYFⅢ were divided into four categories: Buqi (Ginsenoside Rh1+Astragaloside), Bushen (Icariin), Huatan (Nobiletin), and Huoxue (Paeonol). The four categories were divided into 14 groups based on the method of mathematical permutation. ① The rats were divided into control group, model group, ECC-BYFⅢ, and different components compatibility groups according to the random number table, totaling 17 groups. COPD rat model in stable phase was established by cigarette smoke exposure combined with repeated bacterial infections. The corresponding drugs were given by gavage at the 9th week of modeling, and the samples were collected at the end of the 16th week. The levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase 1 (TIMP-1) in serum and bronchoalveolar lavage fluid (BALF), and the levels of mucin (MUC) 5AC in lung tissue and BALF were detected by enzyme linked immunosorbent assay (ELISA). ② Human lung epithelial cells BEAS-2B were divided into blank group, model group, and different components compatibility groups. Hypoxia-induced mucus hypersecretion model of human lung epithelial cells BEAS-2B was established 4 hours after corresponding drug pretreatment. The mRNA expressions of MUC5AC, MUC5B, and MUC1 were detected by quantitative polymerase chain reaction (PCR). The mucus secretion indexes of rats and BEAS-2B cells were evaluated by Region (R) value comprehensive evaluation method.Results:① Compared with the control group, MMP-9 in serum and BALF from the model group were significantly increased, the level of TIMP-1 was significantly decreased, and MUC5AC in lung tissue and BALF were significantly increased. The results of R value comprehensive evaluation showed that except for the Buqi and Bushen groups, ECC-BYFⅢ and other components compatibility groups significantly corrected mucus hypersecretion in COPD rats, ECC-BYFⅢ, Bushen Quxie, Fuzheng Huatan, and Quxie groups were much better (R values were 2.15±0.42, 2.11±0.23, 2.16±0.23 and 2.16±0.55, respectively), compared with the model group (R value: 3.00±0.00), the differences were statistically significant (all P < 0.05). ② Compared with the blank group, the mRNA expressions of MUC5AC, MUC5B, and MUC1 increased in the model group. But different components compatibility groups had no significant effects on the mucus secretion of BEAS-2B cells. ③ The comprehensive evaluation results of R value about each in vivo and in vitro index showed that ECC-BYFⅢ, Huoxue, Quxie, Bushen Huoxue, Fuzheng Huatan, Buqi Quxie groups significantly corrected the mucus hypersecretion (R values were 2.30±0.43, 2.33±0.44, 2.12±0.68, 2.27±0.64, 2.24±0.27 and 2.29±0.47, respectively), compared with the model group (R value: 3.00±0.00), the difference was statistically significant (all P < 0.01). The order was: Quxie > Fuzheng Huatan > Bushen Huoxue > Buqi Quxie > ECC-BYFⅢ > Huoxue. Conclusions:Different components compatibility of ECC-BYFⅢ had different effects on COPD mucus secretion. The components containing Huatan (Nobiletin) or Huoxue (Paeonol) showed a better inhibitory effect on mucus secretion.
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Objective:To observe the effect of Yunpi-Xiefei-Huatan Decoction on airway mucus hypersecretion of asthmatic rats and its regulation on epidermal growth factor receptor (EGFR) / mucin 5AC (MUC5AC) signal pathway. Methods:Seventy SD rats were randomly divided into normal group, model group, high dose group, medium dose group, low dose group, western medicine group and combined group, with 10 rats in each group. Except the normal group, the other groups were sensitized with 1 ml ovalbumin and aluminum hydroxide mixture to establish the asthma rat model. On the 16th day of the experiment, the high, medium and low dose groups were given Yunpi-Xiefei-Huatan Decoction of 40, 20, 10 g/kg, respectively, the western medicine group was given carboxymethylstein tablets of 150 mg/kg, and the combined group was given Yunpi-Xiefei-Huatan Decoction of 20 g/kg and carboxymethylstein tablets of 150 mg/kg, once a day, for 4 weeks. The levels of tumor necrosis factor (TNF-α) and interleukin-13 (IL-13) in serum of rats were detected by Enzyme-linked Immunosorbent Assay (ELISA), the total number and classification of leukocytes in BALF were observed by Wright Giemsa staining, the pathological changes of lung tissue were observed by glycogen staining (PAS). The protein expression of epidermal growth factor receptor (EGFR) and MUC5AC (MUC5AC) were detected by Western blotting, and the mRNA expression of EGFR and MUC5AC was detected by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Results:Compared with the model group, the level of IL-13 and TNF-α in the high, medium and low dose groups of traditional Chinese medicine, western medicine group and combined group was significantly decreased ( P<0.05). The levels of WBC, eosinophils and neutrophils in rat alveolar lavage fluid were significantly decreased ( P<0.05). The expression of EGFR (0.466 ± 0.023, 0.354 ± 0.047, 0.667 ± 0.066, 0.553 ± 0.065, 0.290 ± 0.033 vs. 0.782 ± 0.047) and MUC5AC (0.424 ± 0.022, 0.313 ± 0.033, 0.603 ± 0.051, 0.495 ± 0.041, 0.243 ± 0.024 vs. 0.806 ± 0.090) significantly decreased ( P<0.05), the m RNA expression of EGFR (2.302 ± 0.321, 2.549 ± 0.623, 3.084 ± 0.453, 2.585 ± 0.314, 1.810 ± 0.379 vs. 4.101 ± 0.567), MUC5AC (3.243 ± 0.742, 3.283 ± 1.064, 4.419 ± 0.572, 3.817 ± 0.637, 2.469 ± 0.424 vs. 5.840 ± 0.661) in the high, medium and low dose groups, western medicine group and combined group was significantly decreased ( P<0.05). Conclusion:Yunpi-Xiefei-Huatan Decoction ccould inhibit asthma, and its mechanism mightbe related to the EGFR/MUC5AC signaling pathway.
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Abstract Objectives: to analyze, evaluate and describe the usefulness of petrosal sinus sampling for diagnosing central Cushing's syndrome. Materials and methods: the technical aspects and results of bilateral venous sampling of the petrosal sinuses at the Hospital Universitario San Vicente de Paul in Medellín, Colombia, from January 1, 2012 to December 31, 2018, were analyzed. Results: the average age was 43.3 years, with a range from 19 to 69 years. Laterality could be shown in 68.2% of cases, with a tendency to be located on the left in 53.3%. The central source of ACTH production could be shown in 95.4% of cases, with a basal average central/peripheral ratio of 21.7, and 70.8 after stimulation. All samples at 3, 5 and 10 minutes were confirmatory following stimulation. Conclusion: in our retrospective study, petrosal sinus catheterization provided laboratory confirmation of the central source of ACTH production in a high percentage of patients, with no immediate complications.
Resumen Objetivos: analizar, evaluar y describir la utilidad del muestreo de senos petrosos para diagnóstico del síndrome de Cushing de origen central. Material y métodos: se analizaron los aspectos técnicos y resultados del muestreo bilateral venoso de senos petrosos, desde el 1° de enero de 2012 a 31 de diciembre de 2018 en el Hospital Universitario San Vicente de Paúl en Medellín, Colombia. Resultados: el promedio de edad fue 43.3 años con un rango de edad desde los 19 hasta los 69 años. La lateralidad pudo ser demostrada en 68.2% de los casos con una tendencia a la localización en el lado izquierdo en 53.3%. El origen central de producción de ACTH logró ser demostrado en 95.4% de los casos, con una relación central/periferia basal promedio de 21.7 y postestimulación de 70.8. Todas las muestras a los 3, 5 y 10 minutos fueron confirmatorias tras la estimulación. Conclusión: en nuestro estudio retrospectivo el cateterismo de senos petrosos confirmó la fuente central de producción de ACTH por laboratorio en un alto porcentaje de pacientes sin ninguna complicación inmediata.
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Humans , Male , Female , Adult , Aged , Cushing Syndrome , Pituitary Diseases , Phlebography , Petrosal Sinus Sampling , Pituitary ACTH Hypersecretion , ACTH-Secreting Pituitary AdenomaABSTRACT
Pituitary diseases such as acromegaly and Cushing's disease require surgical or medical therapy. In some functioning pituitary tumors, a spontaneous remission of hormonal hypersecretion is observed, mainly associated to apoplexy or pituitary infarction. We report the evolution of two female patients older than 70 years at the time of diagnosis, with multiple comorbidities. In case 1, acromegaly was diagnosed at 74 years of age. Sellar CT scan showed a 10-mm adenoma. During her follow-up, IGF1 levels remained normal. Nine years later, a magnetic resonance (MR) showed a 7-mm adenoma. In case 2, clinical and biochemical diagnosis of Cushing's disease was done being 71 years old. Sellar MR showed a 6-mm adenoma. Three years later, urinary cortisol normalized with no changes in adenoma at MR. Seven years later, she remains without clinical or biochemical signs of hypercortisolism. In both cases, no signs of hemorrhage were observed at MR.
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Humans , Male , Female , Aged, 80 and over , Pituitary Neoplasms/diagnostic imaging , Acromegaly/diagnostic imaging , Adenoma/diagnostic imaging , Pituitary ACTH Hypersecretion/diagnostic imaging , Pituitary Neoplasms , Remission, Spontaneous , Acromegaly/physiopathology , Pituitary Apoplexy , Magnetic Resonance Imaging , Adenoma/physiopathology , Pituitary ACTH Hypersecretion/physiopathologyABSTRACT
Objective To investigate the inhibitory effect of limonin on airway inflammation and mucus hypersecre-tion. Methods The experiment was divided into three groups(n=10),namely blank control group,PM2.5 group (the rat models of chronic airway inflammation were established by aerosolized PM2.5 suspension) and PM2.5+limonin group(intervening with the extract from tangerine peel). mRNA,protein of inflammatory cytokines,mucin (MUC) and TAS2Rs were measured by ELISA,RT-PCR and Western blot respectively. Results The mRNA and protein expression of IL-1β, CINC-1 and MUC5AC and MUC5B in PM2.5 group were significantly higher than those in control group(P<0.05),and the expression of MUC5AC protein in broncho alveolar lavage fluid(BALF) was increased. Compared with PM2.5 stimulated group,mRNA and protein of TAS2R14 in PM2.5+limonin inter-vented group were significantly higher (P<0.05). Moreover, the expression of IL-1β, CINC-1 and MUC5AC, MUC5B was lower than PM2.5 group (P<0.05).While the expression of MUC5B was mainly increased in BALF.Conclusions The production of mucin can be inhibited by aerosolized limonin, meanwhile the secretion of mucin also can be promoted.This effect is achieved by activating the expression of TAS2Rs in the lungs, which enhances the anti-inflammatory effect of airway inflammation.
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Abstract The symptoms of chikungunya virus (CHIKV) infection include fever, headache, muscle aches, skin rash, and polyarthralgia, characterized by intense pain, edema, and temporary functional impairment. This is the first report of encephalitis caused by CHIKV infection associated with an atypical presentation of syndrome of inappropriate antidiuretic hormone secretion, evolving to cognitive impairment and apraxia of speech.
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Humans , Female , Encephalitis, Viral/virology , Encephalitis, Viral/diagnostic imaging , Chikungunya Fever/complications , Inappropriate ADH Syndrome/virology , Magnetic Resonance Imaging , Inappropriate ADH Syndrome/diagnostic imaging , Middle AgedABSTRACT
Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. However, medical/pharmacological therapy plays an important role in controlling hormone-producing pituitary adenomas, especially for patients with acromegaly and Cushing disease (CD). In the case of non-functioning pituitary adenomas (NFAs), pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies. For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available. Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Improvements in biochemical and “tumor mass” disease control can positively affect patient quality of life, comorbidities and overall survival. In this review, the medical armamentarium for treating CD, acromegaly, prolactinomas, NFA, and carcinomas/aggressive atypical adenomas will be presented. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided. Medical therapies currently under clinical investigation are also briefly discussed.
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Humans , Acromegaly , Adenoma , Comorbidity , Drug Therapy , Patient Selection , Pituitary ACTH Hypersecretion , Pituitary Neoplasms , Prolactinoma , Quality of LifeABSTRACT
Objective To explore the mechanism ofJiedu Qingfei Mixture for airway mucus hypersecretion of rat models with chronic obstructive pulmonary disease (COPD).Methods Airway instilling lipopolysaccharide combining fuming method was used to establish COPD models. Forty clean level Wistar strain rats were randomly divided into blank control group, model group,Jiedu Qingfei group, and clarithromycin group. Model group, Jiedu Qingfei group, and clarithromycin group were given normal saline,Jiedu Qingfei Mixture, and clarithromycin by gavage respectively, while the blank control group was raised normally for 30 d. All rats were killed on the 31st day for taking lung tissue (6 rats from each group were chosen randomly). Pathological changes of lung tissue and mucous glands hyperplasia were observed by HE staining method. NE and MUC5AC mRNA expression on lung tissue were detected by RT-PCR method. Protein expressions of NE and MUC5AC on pulmonary tissue and airway epithelium were detected by immunohistochemical method.Results Compared with blank control group, mucous glands hyperplasia on airway epithelium, mRNA expression of NE and MUC5AC in lung tissue, and protein expressions of NE and MUCA5C on airway epithelium in the model group significantly increased (P<0.05,P<0.01). Compared with model group, mucous glands hyperplasia on airway epithelium inJiedu Qingfei group significantly decreased (P<0.01), as same as clarithromycin group;Jiedu Qingfei group showed better effects on down-regulating NE and MUC5AC mRNA expression in lung tissue compared with clarithromycin group. MUC5AC protein expression on airway epithelium inJiedu Qingfei group significantly decreased (P<0.05), as same as clarithromycin group.Jiedu Qingfei group and clarithromycin group had no difference on NE protein expression in airway epithelium compared with model group.Conclusion Jiedu Qingfei group Mixture can reduce airway mucus hypersecretion of COPD by down-regulating MUC5AC expression through neutrophil elastase.
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Objective To observe the effects of Qingjin Huatan Decoction on EGFR/MAPK signaling pathway of airway mucus hypersecretion rats with chronic obstructive pulmonary disease (COPD). Methods Intratracheal instillation of LPS combined with smudging method was used to establish COPD airway mucus hypersecretion rat models. Experimental rats were randomly divided into blank group, model group, Qingjin Huatan Decoction group and clarithromycin group. The blank group was normally fed, while the other three groups were given NS, Qingjin Huatan Decoction, and clarithromycin respectively for gavage, once a day for 30 days. All rats were killed on the 31st day, and pathological changes of lung tissue and mucous glands hyperplasia were observed by HE staining method. The gene expressions of EGFR and MUC5AC in lung tissue were detected by RT-PCR method. The protein expressions of P-EGFR, P-ERK, P-JNK, P-p38 and MUC5AC in pulmonary tissue and airway epithelium were detected by immunohistochemical method. Results Compared with the blank group, mucous glands hyperplasia on airway epithelium, protein expressions of P-EGFR, P-ERK, P-JNK, P-p38 and MUC5AC on airway epithelium significantly increased in the model group (P<0.01); gene expression of MUC5AC of lung tissue increased (P<0.05). Compared with the model group, mucous glands hyperplasia on airway epithelium, P-p38, P-ERK and MUC5AC protein expression on airway epithelium in Qingjin Huatan Decoction group significantly decreased (P<0.05, P<0.01); the protein expression of P-JNK increased significantly (P<0.01). EGFR and MUC5AC mRNA in lung tissue in Qingjin Huatan Decoction group decreased significantly (P<0.01). Conclusion Qingjin Huatan Decoction can reduce airway mucus hepersecrection of COPD by inhibiting ERK and p38 signal pathway on EGFR downstream.
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Objective To investigate the action mechanism of Qingjin Huatan Decoction on regulating COPD rats with mucus hypersecretion in airway. Methods Fifty 6-8 week old Wistar male rats were randomly divided into healthy group, model group, Qingjin Huatan Decoction group, clarithromycin group, 10 rats in each group. Except for healthy group, all the other groups were used the combination method of injecting LPS and smudging to establish COPD models. The last three groups were fed with normal saline, Qingjin Huatan Decoction, clarithromycin respectively for 30 days. On the 31st day of the experiment, the rats were put to death to take lung tissue. 6 rats from each group were chosen randomly, and the protein expressions of NE, EGFR and MUC5AC mRNA in lung tissue were detected by real-time fluorescent quantitative PCR. Results The expressions of NE, MUC5AC mRNA in lung tissue of COPD rats were higher than the healthy group. Compared with model group, the expressions of NE mRNA and MUC5AC mRNA in Qingjin Huatan Decoction group and clarithromycin group were markedly lower, while the expressions of NE, MUC5AC mRNA in Qingjin Huatan Decoction group were significantly lower than those in clarithromycin group. The expression of EGFR mRNA in Qingjin Huatan Decoction group was lower than that in model group. Conclusion Qingjin Huatan Decoction can inhibit mucus hypersecretion in airway through NE/EGFR/MUC5AC signal transduction pathway.
ABSTRACT
Cushing's disease (CD) is a rare disorder characterized by the overproduction of adrenocorticotropic hormone due to a pituitary adenoma that ultimately stimulates excessive cortisol secretion from the adrenal glands. Prior to the detection of pituitary adenomas, various clinical signs of CD such as central obesity, moon face, hirsutism, and facial plethora are usually already present. Uncontrolled hypercortisolism is associated with metabolic, cardiovascular, and psychological disorders that result in increased mortality. Hence, the early detection and treatment of CD are not only important but mandatory. Because its clinical manifestations vary from patient to patient and are common in other obesity-related conditions, the precise diagnosis of CD can be problematic. Thus, the present set of guidelines was compiled by Korean experts in this field to assist clinicians with the screening, diagnoses, and treatment of patients with CD using currently available tests and treatment modalities.
Subject(s)
Humans , Adrenal Glands , Adrenocorticotropic Hormone , Corticotropin-Releasing Hormone , Cushing Syndrome , Diagnosis , Hirsutism , Hydrocortisone , Korea , Mass Screening , Mortality , Obesity, Abdominal , Petrosal Sinus Sampling , Pituitary ACTH Hypersecretion , Pituitary NeoplasmsABSTRACT
Cushing disease is caused by excessive adrenocorticotropic hormone (ACTH) production by the pituitary adenoma. Transsphenoidal surgery is its first-line treatment. The incidence of Cushing disease in children and adolescents is so rare that long-term prognoses have yet to be made in most cases. We followed-up on a 16-year-old male Cushing disease patient who presented with rapid weight gain and growth retardation. The laboratory findings showed increased 24-hour urine free cortisol and lack of overnight cortisol suppression by low-dose dexamethasone test. The serum cortisol and 24-hour urine free cortisol, by high-dose dexamethasone test, also showed a lack of suppression, and a bilateral inferior petrosal sinus sampling suggested lateralization of ACTH secretion from the right-side pituitary gland. However, after a right hemihypophysectomy by the transsphenoidal approach, the 24-hour urine free cortisol levels were persistently high. Thus the patient underwent a total hypophysectomy, since which time he has been treated with hydrocortisone, levothyroxine, recombinant human growth hormone, and testosterone enanthate. Intravenous bisphosphonate for osteoporosis had been administered for three years. At his current age of 26 years, his final height had attained the target level range; his bone mineral density was normal, and his pubic hair was Tanner stage 4. This report describes the long-term treatment course of a Cushing disease patient according to growth profile, pubertal status, and responses to hormone replacement therapy. The clinical results serve to emphasize the importance of growth optimization, puberty, and bone health in the treatment management of Cushing disease patients who have undergone transsphenoidal surgery.