ABSTRACT
Parkinson’s disease (PD) is characterized by the presence of α-synuclein (α-syn) inclusions in the brain and the degeneration of dopamine-producing neurons. There is evidence to suggest that the progression of PD may be due to the prion-like spread of α-syn aggregates, so understanding and limiting α-syn propagation is a key area of research for developing PD treatments. Several cellular and animal model systems have been established to monitor α-syn aggregation and propagation. In this study, we developed an in vitro model using A53T α-syn-EGFP overexpressing SH-SY5Y cells and validated its usefulness for high-throughput screening of potential therapeutic targets. Treatment with preformed recombinant α-syn fibrils induced the formation of aggregation puncta of A53T α-syn-EGFP in these cells, which were analyzed using four indices: number of dots per cell, size of dots, intensity of dots, and percentage of cells containing aggregation puncta. Four indices are reliable indicators of the effectiveness of interventions against α-syn propagation in a one-day treatment model to minimize the screening time. This simple and efficient in vitro model system can be used for high-throughput screening to discover new targets for inhibiting α-syn propagation.
ABSTRACT
Astrocytes are activated in response to brain damage. Here, we found that expression of Kir4.1, a major potassium channel in astrocytes, is increased in activated astrocytes in the injured brain together with upregulation of the neural stem cell markers, Sox2 and Nestin. Expression of Kir4.1 was also increased together with that of Nestin and Sox2 in neurospheres formed from dissociated P7 mouse brains. Using the Kir4.1 blocker BaCl2 to determine whether Kir4.1 is involved in acquisition of stemness, we found that inhibition of Kir4.1 activity caused a concentration-dependent increase in sphere size and Sox2 levels, but had little effect on Nestin levels. Moreover, induction of differentiation of cultured neural stem cells by withdrawing epidermal growth factor and fibroblast growth factor from the culture medium caused a sharp initial increase in Kir4.1 expression followed by a decrease, whereas Sox2 and Nestin levels continuously decreased. Inhibition of Kir4.1 had no effect on expression levels of Sox2 or Nestin, or the astrocyte and neuron markers glial fibrillary acidic protein and β-tubulin III, respectively. Taken together, these results indicate that Kir4.1 may control gain of stemness but not differentiation of stem cells.
ABSTRACT
Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the aging population after Alzheimer’s disease (AD). Defects in the lysosomal systems and mitochondria have been suspected to cause the pathogenesis of PD. Nevertheless, the pathogenesis of PD remains obscure. Abnormal cholesterol metabolism is linked to numerous disorders, including atherosclerosis. The brain contains the highest level of cholesterol in the body and abnormal cholesterol metabolism links also many neurodegenerative disorders such as AD, PD, Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). The blood brain barrier effectively prevents uptake of lipoprotein-bound cholesterol from blood circulation. Accordingly, cholesterol level in the brain is independent from that in peripheral tissues. Because cholesterol metabolism in both peripheral tissue and the brain are quite different, cholesterol metabolism associated with neurodegeneration should be examined separately from that in peripheral tissues. Here, we review and compare cholesterol metabolism in the brain and peripheral tissues. Furthermore, the relationship between alterations in cholesterol metabolism and PD pathogenesis is reviewed.
Subject(s)
Aging , Amyotrophic Lateral Sclerosis , Atherosclerosis , Blood Circulation , Blood-Brain Barrier , Brain , Cholesterol , Metabolism , Mitochondria , Neurodegenerative Diseases , Parkinson DiseaseABSTRACT
Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is highly expressed in neurons, and gathering evidence indicates that UCH-L1 may play pathogenic roles in many neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease (PD). Additionally, lipid rafts have attracted interest in neurodegeneration as playing a common role in many neurodegenerative diseases. In the present study, we demonstrated that UCH-L1 associates with lipid rafts as with other PD-associated gene products. In addition, UCH-L1 regulates lipid raft-dependent endocytosis and it is not dependent on the expression and degradation of caveolin-1 or flotillin-1. Finally, UCH-L1 regulates cell-to-cell transmission of α-synuclein. This study provides evidence that many PD-associated gene products share common signaling pathways to explain the pathogenesis of PD.
Subject(s)
alpha-Synuclein , Alzheimer Disease , Caveolin 1 , Endocytosis , Neurodegenerative Diseases , Neurons , Parkinson Disease , Prion Diseases , Ubiquitin Thiolesterase , UbiquitinABSTRACT
Mutation of leucine-rich repeat kinase 2 (LRRK2) causes an autosomal dominant and late-onset familial Parkinson's disease (PD). Recently, we reported that LRRK2 directly binds to and phosphorylates the threonine 474 (T474)-containing Thr-X-Arg(Lys) (TXR) motif of focal adhesion kinase (FAK), thereby inhibiting the phosphorylation of FAK at tyrosine (Y) 397 residue (pY397-FAK), which is a marker of its activation. Mechanistically, however, it remained unclear how T474-FAK phosphorylation suppressed FAK activation. Here, we report that T474-FAK phosphorylation could inhibit FAK activation via at least two different mechanisms. First, T474 phosphorylation appears to induce a conformational change of FAK, enabling its N-terminal FERM domain to autoinhibit Y397 phosphorylation. This is supported by the observation that the levels of pY397-FAK were increased by deletion of the FERM domain and/or mutation of the FERM domain to prevent its interaction with the kinase domain of FAK. Second, pT474-FAK appears to recruit SHP-2, which is a phosphatase responsible for dephosphorylating pY397-FAK. We found that mutation of T474 into glutamate (T474E-FAK) to mimic phosphorylation induced more strong interaction with SHP-2 than WT-FAK, and that pharmacological inhibition of SHP-2 with NSC-87877 rescued the level of pY397 in HEK293T cells. These results collectively show that LRRK2 suppresses FAK activation through diverse mechanisms that include the promotion of autoinhibition and/or the recruitment of phosphatases, such as SHP-2.
Subject(s)
Focal Adhesion Protein-Tyrosine Kinases , Glutamic Acid , Parkinson Disease , Phosphoric Monoester Hydrolases , Phosphorylation , Phosphotransferases , Protein Tyrosine Phosphatase, Non-Receptor Type 11 , Threonine , TyrosineABSTRACT
The development of a serological marker for early diagnosis of isocyanate-induced occupational asthma (isocyanate-OA) may improve clinical outcome. Our previous proteomic study found that expression of vitamin D-binding protein (VDBP) was upregulated in the patients with isocyanate-OA. In the present study, we evaluated the clinical relevance of VDBP as a serological marker in screening for isocyanate-OA among exposed workers and its role in the pathogenesis of isocyanate-OA. Three study groups including 61 patients with isocyanate-OA (group I), 180 asymptomatic exposed controls (AECs, group II), 58 unexposed healthy controls (NCs, group III) were enrolled in this study. The baseline serum VDBP level was significantly higher in group I compared with groups II and III. The sensitivity and specificity for predicting the phenotype of isocyanate-OA with VDBP were 69% and 81%, respectively. The group I subjects with high VDBP (> or = 311 microg/ml) had significantly lower PC20 methacholine levels than did subjects with low VDBP. The in vitro studies showed that TDI suppressed the uptake of VDBP into RLE-6TN cells, which was mediated by the downregulation of megalin, an endocytic receptor of the 25-hydroxycholecalciferol-VDBP complex. Furthermore, toluene diisocyanate (TDI) increased VEGF production and secretion from this epithelial cells by suppression of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] production. The findings of this study suggest that the serum VDBP level may be used as a serological marker for the detection of isocyanate-OA among workers exposed to isocyanate. The TDI-induced VEGF production/secretion was reversed by 1,25(OH)2D3 treatment, which may provide a potential therapeutic strategy for patients with isocyanate-OA.
Subject(s)
Adult , Animals , Female , Humans , Male , Middle Aged , Rats , Asthma/blood , Cell Line , Epithelial Cells , Gene Expression/drug effects , Isocyanates/toxicity , Occupational Diseases/blood , Toluene 2,4-Diisocyanate/toxicity , Vitamin D-Binding Protein/bloodABSTRACT
BACKGROUND: Cytotoxic function of killer cells is inhibited by specific recognition of class I MHC molecules on target cells by inhibitory killer Ig-like receptors (KIR) expressed on NK cells and some cytotoxic T cells. The inhibitory effect of KIR is accomplished by recruitment of SH2-containing protein tyrosine phosphatase (SHP) to the phosphotyrosine residues in the cytoplasmic tail. METHODS: By in vitro coprecipitation experiments and transfection analysis, we investigated the association of KIR with an adaptor protein Shc in Jurkat T cells. RESULTS: The cytoplasmic tail of KIR appeared to associate with an adaptor protein Shc in Jurkat T cell lysates. Similar in vitro experiments showed that phosphorylated KIR cytoplasmic tail bound SHP-1 and Shc in Jurkat T cell lysates. The association of KIR with Shc was further confirmed by transfection analysis in 293T cells. Interestingly, however, Shc appeared to be replaced by SHP-2 upon engagement of KIR in 293T cells. CONCLUSION: Our data indicate that KIR associate with an adaptor protein Shc in Jurkat T cells, and suggest that KIR might have an additional role which is mediated by this adaptor protein.
Subject(s)
Cell Proliferation , Cytoplasm , Killer Cells, Natural , Phosphotyrosine , Protein Tyrosine Phosphatases , T-Lymphocytes , TransfectionABSTRACT
BACKGROUND: It is difficult to differentiate between tuberculous pneumonia and Community Acquired Pneumonia, so the diagnosis and treatment of tuberculous pneumonia can be delayed frequently. In this study, we attempted to retrospectively evaluate the clinical and radiologic characteristics of tuberculous pneumonia. METHODS: We conducted a retrospective analysis of clinical characteristics of 58 patients diagnosed with tuberculous pneumonia from Nov. 1997 to May 2001 at Korea university kuro hospital. RESULT: The male to female ratio was 1:1 and the mean age at diagnosis was 54.5+/-18.6 years. Fifty five patients were confirmed microbiologically and three patients pathologically. There were 20 patients(34.5%) who had diabetes mellitus(8cases), chronic obstructive pulmonary disease(3cases), malignancy(3cases), bronchiectasis(2cases), chronic renal failure(1cases) or long term history of corticosteroid treatment(3cases). Many patients had multilobar infiltration in chest X-ray, dominantly in the lower lobe. thirty two patients(55.2%) had infiltration in more than 2 lobes and 5 patients in more than 4 lobes. The significant correlation between the diabetes mellitus and the infiltrated Rt lower lobe(RLL) was found on the borders of confidence limit.(P=0.07<0.1). There was significant correlation between woman and infiltrated lobe(RML, RLL, LLL) excluding the both upper lobe(P=0.029). CONCLUSION: We must consider tuberculous pneumonia when lobar pneumonia with consolidation resistant to antibiotics, especially in the patients who have diabetes mellitus, chronic obstructive pulmonary disease, malignancy, bronchiectsis, chronic renal failure or long term history of corticosteroid treatment.
Subject(s)
Female , Humans , Male , Anti-Bacterial Agents , Diabetes Mellitus , Diagnosis , Kidney Failure, Chronic , Korea , Pneumonia , Pulmonary Disease, Chronic Obstructive , Retrospective Studies , ThoraxABSTRACT
A 68-year-old woman was admitted after suffering facial edema with neck vein engorgement ofr approximately 2 months. A chest X-ray showed a mild widening of the superior mediastinum and a luminal obliteration of the super ior vena cava (SVC) was noted on a computed tomograph. Venography showed that both subclavian veins were obstructed at the level of the poxima clavicle with a nonvisualization of the SVC. The SVC, both the innominate and the left inthrnal jugular veins were completely obstructed with extensive cord-like fibrotix changes despite the obsence of mediastinal involvement. The microscopic features showed a chronic granulomatous inflammation with a fibrosis minimally invading the mediastinal fat, which is cosistent with fibrosing mediastinitis.
Subject(s)
Aged , Female , Humans , Clavicle , Edema , Fibrosis , Inflammation , Jugular Veins , Mediastinitis , Mediastinum , Neck , Phenobarbital , Phlebography , Subclavian Vein , Thorax , VeinsABSTRACT
Protein-tyrosine phosphatases (PTPs) constitute a family of receptor-like, and cytoplasmic enzymes, which catalyze the dephosphorylation of phosphotyrosine residues in a variety of receptors and signaling molecules. Together with protein tyrosine kinases (PTKs), PTPs are critically involved in regulating many cellular signaling processes. In this study, diverse compounds were screened for PTP inhibition and selectively screened for inhibitors with the end product inhibition properties. Among phosphate analogues and their derivatives for PTP inhibition, Keggin compounds phosphomolybdate (PM) and phosphotungstate (PT) strongly inhibited both PTP-1B and SHP-1, with K(i) values of 0.06-1.2 micromM in the presence of EDTA. Unlike the vanadium compounds, inhibition potencies of PM and PT were not significantly affected by EDTA. PM and PT were potent, competitive inhibitors for PTPs, but relatively poor inhibitors of Ser/Thr phosphatase. Interestingly, PM and PT did not inhibit alkaline phosphatase at all. The crystal structure of PTP-1B in complex with PM, at 2.0 A resolution, reveals that MoO(3), derived from PM by hydrolysis, binds at the active site. The molybdenium atom of the inhibitor is coordinated with six ligands: three oxo-ligands, two apical water molecules and a S atom of the catalytic cysteine residue. In support of the crystallographic finding, we observed that molybdenium oxides (MoO(3), MoO(2), and MoO(2)Cl(2)) inhibited PTP-1B with IC(50) in the range 5-15 micromM.
Subject(s)
Humans , Binding, Competitive , Catalytic Domain , Crystallography, X-Ray , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Edetic Acid/pharmacology , Enzyme Inhibitors/pharmacology , Inhibitory Concentration 50 , Kinetics , Models, Molecular , Molybdenum/pharmacology , Phosphoric Acids/pharmacology , Protein Structure, Tertiary , Protein Tyrosine Phosphatases/antagonists & inhibitors , Substrate Specificity , Tungsten Compounds/pharmacologyABSTRACT
BACKGROUND AND OBJECT: Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the TH1-type immune response and down-regulate the TH2-type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperrestponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma. MATERIALS AND METHODS: 10 normal controls(NC) and 26 asthmatic rats, which were generated by ovallbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl)on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-(TH1-type cytokine) and IL-4(TH2-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue. RESULTS: In the BALF of the CpG group, the IFN-γ concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5Ac gene expression was observed between the CpG group and the Ac group. CONCLUSION: ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the TH1-type immune response with the down-regulation of the TH2-type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.
Subject(s)
Animals , Rats , Asthma , Bronchoalveolar Lavage , Down-Regulation , Eosinophils , Gene Expression , Goblet Cells , Inflammation , Interleukin-4 , Lung , Mucus , Up-RegulationABSTRACT
Fat embolism syndrome is a rare but serious complication occurring most of the time in patients with long bone fractures. And it occasionally occurs when patient had underlying disease. For example, pancreatitis, diabetes mellitus, alcoholic liver disease and connective tissue disease can be risk factors. The 44-year old woman visited to the Korea university hospital because of sudden dry cough, blood tinged sputum, and exertional dyspnea. We found petechiae on her anterior chest wall. Chest X-ray and CT showed patchy opacities and multifocal ground-glass opacities in both lung fields. Open lung biopsy demonstrated diffuse pulmonary hemorrhage and intravascular macrovesicular fat bubbles. After conservative management, her symptoms and radiologic findings were significantly improved. We report a case of fat embolism syndrome without any known risk factors.
Subject(s)
Adult , Female , Humans , Biopsy , Connective Tissue Diseases , Cough , Diabetes Mellitus , Dyspnea , Embolism , Embolism, Fat , Fractures, Bone , Hemorrhage , Korea , Liver Diseases, Alcoholic , Lung , Pancreatitis , Purpura , Risk Factors , Sputum , Thoracic Wall , Thorax , TolnaftateABSTRACT
BACKGROUND: The phagolysosomal function of alveolar macrophage against M. tuberculosis infection is influenced by Nramp1, which is encoded by the NRAMP1 gene. There are several genetic polymorphisms in NRAMP1, and these polymorphisms affect the innate host resistance through the defect in production and function of Nramp1. To investigate this relationship, we determined the NRAMP1 genetic polymorphism in patients with primary tuberculous pleurisy was determined. METHODS : 56 Fifty-six primary tuberculous pleurisy patient (,) who were diagnosed by pleural biopsy(,) were designated to the pleurisy group and 45 healthy adults were designated to the healthy control group. 3 Three genetic polymorphisms of NRAMP1 (,) such as a single point mutation in intron 4(469+14G/C, INT4), a nonconservative single-base substitution at codon 543 that changes aspartic acid to asparagine(D543N) and a TGTG deletion in the 3' untranslated region(1729+55del4, 3'UTR)(,) were determined. Polymerase chain reaction(PCR) and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) were used. RESULTS: The frequencies of mutanat mutant genotypes of INT4 and 3'UTR were significantly high in pleurisy group(p=0.001, p=0.023). But the frequencies of D543N were not significantly different between the both two groups(p=0.079). Odds The odds ratios(,) which are a comparison with wild genotype for determining mutant genotypes(,) were 8.022(95% confidence interval=2.422 ~26.572) for INT4 and 5.733(95% confidence interval=1.137 ~28.916) for 3'UTR which were ;these were statistically significant. But the odds ratio for D543N was not significant. In the combined analysis of the INT4 and 3'UTR polymorphisms, as compared with GG/++ homozygotes, (delete) the odds ratios were 6.000(95% confidence interval=1.461 ~ 24.640) for GC/++ genotype and 14.000(95% confidence interval=1.610 ~121.754) for GC/+del when compared with GG/++ homozygotes which ;these were statisticallysignificant. CONCLUSION: Among the NRAMP1 genetic polymorphisms, a single point mutation in intron 4(469+14G/C, INT4) and a TGTG deletion in the 3' untranslated region(1729+55del4, 3'UTR) were closely related to the primary tuberculous pleurisy.
Subject(s)
Adult , Humans , 3' Untranslated Regions , Aspartic Acid , Codon , Genotype , Homozygote , Introns , Macrophages, Alveolar , Odds Ratio , Pleurisy , Point Mutation , Polymorphism, Genetic , Tuberculosis , Tuberculosis, PleuralABSTRACT
The prevalence of nonspecific interstitial pneumonitis(NSIP) in HIV-positive patients with pulmonary disease has varied from 11 to 38%. But NSIP in HIV-positive patients is indistinguishable from Pneu mocystis carinii pneumonia(PCP) clinically and radiologically. The number of HIV-positive patients is less in Korea than in western developed countries, so little attention has been paid to the differential diagnosis between NSIP and PCP. We report a case of NSIP in HIV-positive, 61-year-old man which mimicked PCP. He presented with cough, sputum and mild exertional dyspnea. Lung sound was clear. But, chest X-ray and HRCT demonstrated diffuse patch and bilateral ground-glass opacities in central and perihilar area of both lung. Microbial pathogens were not found on sputum, BAL flued and tissues taken by TBLB. In transbronchial lung biopsy specimen, interstitial infiltrates with lymphocytes were distributed on peribronchiolar regions. A pathlolgic diagnosis of NSIP was suggested, he received symptomatic treatment. The follow-up chest X-ray showed near complete resolution.
Subject(s)
Humans , Middle Aged , Biopsy , Cough , Developed Countries , Diagnosis , Diagnosis, Differential , Dyspnea , Follow-Up Studies , Korea , Lung , Lung Diseases , Lung Diseases, Interstitial , Lymphocytes , Prevalence , Respiratory Sounds , Sputum , ThoraxABSTRACT
Functional upper airway obstruction due to vocal cord dysfunction is being increasingly recognized and has been variously described as "Munchausen's stridor", "Emotional laryngeal wheezing", "Nervous asthma". It's features are symptoms of acute reversible recurrent dyspnea associated with an inspiratory stridor, normal anatomy of the upper airway, demonstration of variable severe exthrathoracic upper airways obstruction with pathologic adduction of the vocal cord at bronchoscopy. The patients with this condition are frequently misdiagnosed as asthma and the diagnosis is often delayed. So they can present a serious medical problem and are exposed to the complication of treatment and investigation. We report a case of functional upper airway obstruction due to vocal cord dysfunction who showed paradoxical vocal cord motion at bronchoscopy and typical features of variable exthrathoracic obstruction on Flow-volume loop during a symptomatic period.
Subject(s)
Humans , Airway Obstruction , Asthma , Bronchoscopy , Diagnosis , Dyspnea , Respiratory Sounds , Vocal Cord Dysfunction , Vocal CordsABSTRACT
BACKGROUND: Asthma is an inflammatory disease because there are many inflammatory changes in the asthmatic airways. Axon reflex mechanisms may be involved in the pathogenesis of asthma. Sensory neuropeptides are involved in this inflammation, which is defined as neurogenic inflammation. Substance p, neurokinin A, and neurokinin B may be main neuropeptides of neurogenic inflammation in airways. These tachykinins act on neurokinin recptors. Three types of neurokinin receptors, such as NK1, NK2, and NK3, are currently recognized, at which substance p,neurokinin A, and neurokinin B may be the most relvant natural agonist of neurogenic inflammation in airways. The receptor subtypes present in several tissues have been characterized on the basis of differential sensitivity to substance p, neurokinin A, and neurokinin B. Plasma extravasation and vasodilation are induced by substance p more potently than by neurokinin A, indicating NK1 receptors on endothelial cells mediate the response. But airway contraction is induced by neurokinin A more potently than by substance P, indicating the NK2 receptors in airway smooth muscles. These receptors are used to evaulate the pathogenesis of brochial asthma. FK224 was identified from the fermentation products of Streptomyces violaceoniger. FK224 is a dual antagonist of both NK1 and NK2 recptors. PURPOSE: For a study of pathogenesis of bronchial asthma, the effect of FK224 on plasma extravasation induced by vagal NANC electrical stimulation was evaluated in rat airway. METHOD: Male Sprague-Dawley rats weighing 180~450gm were anesthetized by i.p. injection of urethane. Plasma extravasation was induced by electrical stimulation of cervical vagus NANC nerves with 5Hz, 1mA, and 5V for 2 minutes(NANC2 group) and for sham operation without nerve stimulation(control group). To evaluate the effect of FK224 on plasma extravasation in neurogenic inflammation, FK224(lmg/kg, Fujisawa Pharmaceutical Co., dissolved in dimethylsul- phoxide; DMSO, Sigma Co.) was injected 1 min before nerve stimulation(FK224 group). To assess plasma exudation, Evans blue dye(20mg/kg,dissolved in saline) was used as a plasma marker and was injected before nerve stimulation. After removal of intravascular dye, the evans blue dye in the tissue was extracted in formamide(37degreesC, 24h) and quantified spectrophotometrically by measuring dye absorbance at 629nm wavelength. Tissue dye content was expressed as ng of dye per mg of wet weight tissue. The amount of plasma extravasation was measured on the part of airways in each groups. RESULTS: 1) Vagus nerve(NANC) stimulation significantly increased plasma leakage in trachea, main bronchus, and peripheral bronchus compared with control group, 14.1 +/-1.6 to 49.7+/-2.5, 17.5 +2.0 to 38.7 +/-2.8, and 12.7+/-2.2 to 19.1 +/-1.6ng of dye per mg of tissue(mean +/- SE), respectively(p0.05) 2) FK224 had significant inhibitory effect upon vagal nerve stimulation-induced airway plasma leakage in any airway tissues of rat,such as trachea, main bronchus, and peripheral bronchus compared with vagus nerve stimulation group, 49%, 58%, and 70%, respectively(p<0.05). Inhibitory effect of FK224 on airway plasma leakage in neurogenic inflammation was revealed the more significant in peripheral bronchus, but no significant in lung parenchyma. CONCLUSION: These results suggest that FK224 is a selective NK receptor antagonist which effectively inhibits airway plasma leakage induced by the endogenous neurotransmitters relased by neurogenic inflammation in rat airway. Tachykinin receptor antagonists may be useful in the treatment of brochial asthma.
Subject(s)
Animals , Humans , Male , Rats , Asthma , Axons , Bronchi , Dimethyl Sulfoxide , Electric Stimulation , Endothelial Cells , Evans Blue , Fermentation , Inflammation , Lung , Muscle, Smooth , Neurogenic Inflammation , Neurokinin A , Neurokinin B , Neuropeptides , Neurotransmitter Agents , Plasma , Rats, Sprague-Dawley , Receptors, Tachykinin , Reflex , Streptomyces , Substance P , Tachykinins , Trachea , Urethane , Vagus Nerve Stimulation , VasodilationABSTRACT
Effusions arising from acute pancreatitis are usually small, left sided and self limiting. The incidence of pleural effusions in acute pancreatitis is reported between 3% and 17%. In chronic pancreatitis, as a consequence of fistula and pancreatitic pseudocyst formation or by spontaneous rupture of a pancreatic psudocyst directly into thoracic cavity, extremely large effusions may be seen. When the underlying pacreatic disease is asymptomatic, the diagnosis is made by measuring the amylase content of the pleural fluid. We experience a case of left sided pleural effusions caused by pancreatico-pleural fistula associated with pancreatic pseudocyst. The diagnosis was made by measuring of pleural fluid amylase level (80000U/L). Abdominal CT scan revealed pancreatic pseudocyct and pancreatitis with extension to left pleural space through esophageal hiatus and extension to left subdiaphragmatic space. Left pleural effusions were decreased after fasting, total parenteral nutrition and percutaneous pleural fluid catheter drainage. We reported a case of pleural effusions and pacreatico-pleural fistula asssociated with asymptomatic pancreatic disease with review of literatures.
Subject(s)
Amylases , Catheters , Diagnosis , Drainage , Fasting , Fistula , Incidence , Pancreatic Diseases , Pancreatic Pseudocyst , Pancreatitis , Pancreatitis, Chronic , Parenteral Nutrition, Total , Pleural Effusion , Rupture, Spontaneous , Thoracic Cavity , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Noninvasive ventilation has been used extensively for the treatment of patients with neuromuscular weakness or restrictive chest wall disorders complicated by hypoventilatory respiratory failure. Recently, noninvasive positive pressure ventilation has been used in patients with alveolar hypoventilation,chronic obstructive pulmonary disease(COPD),and adult respiratory distress syndrome. Sanders and Kern reported treatment of obstructive sleep apnea with a modification of the standard nasal CPAP device to deliver seperate inspiratory positive airway pressure(IPAP) and expiratory positive airway pressure(EPAP).Bi-level positive airway pressure (BiPAP) unlike nasal CPAP, the unit delivers a different pressure during inspiration from that during expiration The device is similar to the positive pressure ventilator or pressure support ventilation. METHOD AND PURPOSE: Bi-level positive airway pressure(BiPAP) system(Respironics, USA) was applied to seven patients with acute respiratory failure and three patients on conventional mechanical ventilation. RESULTS: 1) Two of three patients after extubation were successfully achieved weaning from conventional mechanical ventilation by the use of BiPAP ventilation with nasal mask. Five of seven patients with acute respiratory failure successfully recovered without use of conventional mechanical ventilation. 2) PaO2 lhour after BiPAP ventilation in acute respiratory failure patients significantly improved more than baseline values(p<0.01)). PaCO2 lhour after BiPAP ventilation in acute respiratory failure patients did not change significantly more than baseline values. CONCLUSION: Nasal mask BiPAP ventilation can be one of the possible alternatives of conventional mechanical ventilation in acute respiratory failure and supportive method for weaning from mechanical ventilation.