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OBJECTIVE: The aim of this study was to investigate the surface roughness of lithium disilicates (LS2s) polished using various polishing systems. MATERIALS AND METHODS: Two types of LS2 (A, Amber Mill and E, IPS e.max CAD) were polished using LS2-specific polishing systems (L-Edenta, L-Jota), a zirconia-specific polishing system (Z-Jota), and a conventional ceramic polishing system (P-Shofu) (n = 8 per group). The compositions of different polishing systems were analyzed using EDS. Surface roughness was measured using confocal laser scanning microscopy and analyzed using EDS and SEM. ANOVA and Tukey's tests were used for the statistical analyses (p = 0.05). RESULTS: The polishing systems were mainly composed of C, O, and Si. The L-Jota group exhibited rougher surfaces than the other groups. Amber Mill exhibited higher surface roughness than IPS e.max CAD (p⟨0.001). Among the polishing systems, the L-Jota group presented the highest roughness value (pp⟨0.001). The surface roughness of the AL-Jota group was higher than that of the other groups. CONCLUSIONS: A sufficiently smooth surface can be achieved without a LS2-specific polishing system. Further, the same polishing system can have different effects depending on the type of LS2.
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Ámbar , Pulido Dental , Cerámica , Diseño Asistido por Computadora , Porcelana Dental , Ensayo de Materiales , Propiedades de SuperficieRESUMEN
AIM: To compare the performance and reading time of different readers using automatic artificial intelligence (AI)-powered computer-aided detection (CAD) to detect lung nodules in different reading modes. MATERIALS AND METHODS: One hundred and fifty multidetector computed tomography (CT) datasets containing 340 nodules ≤10 mm in diameter were collected retrospectively. A CAD with vessel-suppressed function was used to interpret the images. Three junior and three senior readers were assigned to read (1) CT images without CAD, (2) second-read using CAD in which CAD was applied only after initial unassisted assessment, and (3) a concurrent read with CAD in which CAD was applied at the start of assessment. Diagnostic performances and reading times were compared using analysis of variance. RESULTS: For all readers, the mean sensitivity improved from 64% (95% confidence interval [CI]: 62%, 66%) for the without-CAD mode to 82% (95% CI: 80%, 84%) for the second-reading mode and to 80% (95% CI: 79%, 82%) for the concurrent-reading mode (p<0.001). There was no significant difference between the two modes in terms of the mean sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for both junior and senior readers and all readers (p>0.05). The reading time of all readers was significantly shorter for the concurrent-reading mode (124 ± 25 seconds) compared to without CAD (156 ± 34 seconds; p<0.001) and the second-reading mode (197 ± 46 seconds; p<0.001). CONCLUSION: In CAD for lung nodules at CT, the second-reading mode and concurrent-reading mode may improve detection performance for all readers in both screening and clinical routine practice. Concurrent use of CAD is more efficient for both junior and senior readers.
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Inteligencia Artificial , Neoplasias Pulmonares/diagnóstico por imagen , Tomografía Computarizada Multidetector/métodos , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , TiempoAsunto(s)
Adenocarcinoma/secundario , Neoplasias del Colon/patología , Neoplasias Primarias Múltiples/patología , Neoplasias de la Parótida/secundario , Adenocarcinoma/cirugía , Anciano , Colectomía , Neoplasias del Colon/cirugía , Femenino , Humanos , Neoplasias Primarias Múltiples/cirugía , Neoplasias de la Parótida/cirugíaRESUMEN
OBJECTIVES: Cord blood (CB) has been established to be an alternative source of haematopoietic stem/progenitor cells (HPC) for transplantation. The number of HPC per CB unit is limited, which results in engraftment delay. Ex vivo expansion of HPC improvement must overcome this. MATERIALS AND METHODS: Flow cytometry was used to extensively phenotype HPC pre- and post-expansion and CFDA-SE staining was used to track cell divisions. The NSG mouse model was employed in transplantation studies to determine long and short term repopulation in human cells. Gene array analysis was used to evaluate signalling pathways regulated following ex vivo expansion of HPC. RESULTS: expansion of CD34(+) HPC impaired their regenerative function. In this xenograft transplantation model we showed that repopulating activity of CB cells declined following expansion. Expanded HPC had delayed engraftment at early and late stages post-transplant. High resolution division tracking revealed that the cultured HPC had reduced expansion and self-renewal probability and increased differentiation rate compared to non-expanded cells. Gene expression analysis exposed significant modulation of a complex network of genes and pathways that normally maintain HPC proliferation and limit their differentiation. CONCLUSIONS: The decline in short-term engraftment is consistent with the loss of rapid SCID repopulating ability r(SRA) by expanded CD34(+) CD38(+) cells recently reported. Our data raise concerns for future clinical applications of expanded HPC alone in transplantation.
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Sangre Fetal/citología , Células Madre Hematopoyéticas/metabolismo , Transducción de Señal , Animales , Antígenos CD34/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Citometría de Flujo , Regulación de la Expresión Génica , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/citología , Humanos , Inmunofenotipificación , Ratones , Factores de Tiempo , Trasplante HeterólogoAsunto(s)
Apendicectomía , Apendicitis/cirugía , Laparoscopía , Adulto , Humanos , Masculino , Recurrencia , Tomografía Computarizada por Rayos XRESUMEN
AIMS: As little is currently known about acid-sensing ion channels (ASICs) in intestinal epithelial cells, the aims of the present study were to investigate the expression and function of ASICs in intestinal epithelial cells, particularly their physiological role in the acid-stimulated duodenal mucosal bicarbonate secretion (DMBS). METHODS: RT-PCR and digital Ca²(+) imaging were used to determine the expression and function of ASICs in HT29 cells and SCBN cells, intestinal epithelial crypt cell lines. The acid-stimulated DMBS was measured in C57 black mice in vivo to study the role of ASICs in this physiological process. RESULTS: ASIC1a mRNA expression was detected in the duodenal mucosa stripped from mice and epithelial cell lines, in which cytoplasmic free Ca²(+) ([Ca²(+) ](cyt)) in response to extracellular acidosis was also increased. In Ca²(+) -containing solutions, acidosis (pH 6.0-5.0) raised [Ca²(+) ](cyt) in both HT29 cells and SCBN cells in a similar pH-dependent manner. Acidosis-induced increase in [Ca²(+) ](cyt) was markedly inhibited by amiloride (an ASICs blocker), SK&F96365 (a blocker for non-selective cation channels), or in Ca²(+) -free solutions; but was abolished by amiloride in Ca²(+) -free solutions. However, acidosis-induced increase in [Ca²(+) ](cyt) was slightly affected by U73122 (a PLC inhibitor), or nifedipine (a voltage-gated Ca²(+) channel blocker). After acidosis raised [Ca²(+) ](cyt) , stimulation of purinergic receptors with ATP further increased [Ca²(+) ](cyt) , but acidosis-induced increase in [Ca²(+) ](cyt) was not altered by suramin. Moreover, acid-stimulated murine DMBS was significantly attenuated by amiloride. CONCLUSION: Therefore, ASICs are functionally expressed in intestinal epithelial cells, and may play a role in acid-stimulated DMBS through a Ca²(+) signalling pathway.
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Bicarbonatos/metabolismo , Duodeno/metabolismo , Células Epiteliales/metabolismo , Mucosa Intestinal/citología , Proteínas del Tejido Nervioso/metabolismo , Canales de Sodio/metabolismo , Canales Iónicos Sensibles al Ácido , Amilorida/metabolismo , Animales , Calcio/metabolismo , Línea Celular , Células Epiteliales/citología , Humanos , Concentración de Iones de Hidrógeno , Ratones , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/genética , Transducción de Señal/fisiología , Bloqueadores de los Canales de Sodio/metabolismo , Canales de Sodio/genética , Suramina/metabolismoRESUMEN
Glycogen Synthase Kinase 3 beta (GSK3ß) is a serine-threonine kinase originally identified for its role in the conversion of glucose to glycogen. Pharmacological inhibition can be achieved by drug binding to ATP or magnesium binding sites on the enzyme. Pharmaceutical companies have developed several small molecule GSK3ß inhibitors for diabetes research. Additionally, GSK3ß inhibitors are being clinically tested as therapeutics for neurological diseases, however, the mechanisms of involvement are unclear. Several studies have shown that the therapeutic effect of GSK3ß inhibition is associated with the inhibition of inflammation. Similarly, the mechanisms underlying the anti-inflammatory function of GSK3ß inhibition are not well understood. GSK3ß inhibition attenuates activation of the pro-inflammatory transcription factor NFκB, and activates the immuno-modulatory transcription factor ß-catenin. GSK3ß inhibition has also been shown to induce secretion of the anti-inflammatory cytokine IL-10. In addition, pharmacological inhibition of GSK3ß suppressed alloreactive T-cell responses. The combined anti-proliferative and anti-inflammatory properties of small molecule inhibitors of GSK3ß make them an attractive treatment modality towards the control of inflammation.
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Antiinflamatorios/uso terapéutico , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Inflamación/tratamiento farmacológico , beta Catenina/química , beta Catenina/uso terapéutico , Antiinflamatorios/química , Antiinflamatorios/farmacología , Glucógeno Sintasa Quinasa 3 beta , Humanos , Transducción de Señal/efectos de los fármacos , Proteínas Wnt/metabolismo , beta Catenina/farmacologíaAsunto(s)
Neoplasias de los Conductos Biliares/etiología , Dermatomiositis/complicaciones , Dermatomiositis/tratamiento farmacológico , Conducto Hepático Común/patología , Tumor de Klatskin/etiología , Anciano , Antiinflamatorios/uso terapéutico , Neoplasias de los Conductos Biliares/patología , Humanos , Tumor de Klatskin/patología , Masculino , Prednisolona/uso terapéuticoRESUMEN
The specific role of endogenous glutathione in response to neuronal degeneration induced by trimethyltin (TMT) in the hippocampus was examined in rats. A single injection of TMT (8 mg/kg, i.p.) produced a rapid increase in the formation of hydroxyl radical and in the levels of malondialdehyde (MDA) and protein carbonyl. TMT-induced seizure activity significantly increased after this initial oxidative stress, and remained elevated for up to 2 weeks post-TMT. Although a significant loss of hippocampal Cornus Ammonis CA1, CA3 and CA4 neurons was observed at 3 weeks post-TMT, the elevation in the level of hydroxyl radicals, MDA, and protein carbonyl had returned to near-control levels at that time. In contrast, the ratio of reduced to oxidized glutathione remained significantly decreased at 3 weeks post-TMT, and the glutathione-like immunoreactivity of the pyramidal neurons was decreased. However glutathione-positive glia-like cells proliferated mainly in the CA1, CA3, and CA4 sectors and were intensely immunoreactive. Double labeling demonstrated the co-localization of glutathione-immunoreactive glia-like cells and reactive astrocytes, as indicated by immunostaining for glial fibrillary acidic protein. This suggests that astroglial cells were mobilized to synthesize glutathione in response to the TMT insult. The TMT-induced changes in glutathione-like immunoreactivity appear to be concurrent with changes in the expression levels of glutathione peroxidase and glutathione reductase. Ascorbate treatment significantly attenuated TMT-induced seizures, as well as the initial oxidative stress, impaired glutathione homeostasis, and neuronal degeneration in a dose-dependent manner. These results suggest that ascorbate is an effective neuroprotectant against TMT. The initial oxidative burden induced by TMT may be a causal factor in the generation of seizures, prolonged disturbance of endogenous glutathione homeostasis, and consequent neuronal degeneration.
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Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Epilepsia/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Degeneración Nerviosa/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Epilepsia/inducido químicamente , Proteína Ácida Fibrilar de la Glía/metabolismo , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Hipocampo/citología , Hipocampo/metabolismo , Homeostasis/efectos de los fármacos , Radical Hidroxilo/metabolismo , Malondialdehído/metabolismo , Degeneración Nerviosa/inducido químicamente , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratas , Ratas Sprague-Dawley , Compuestos de Trimetilestaño/toxicidadRESUMEN
OBJECTIVES AND DESIGN: Various sizes of poly-L-lysine (PLL) and poly-L-arginine (PLA) were tested for their possible effects on airway goblet cell mucin release using primary hamster tracheal surface epithelial (HTSE) cells in an attempt to identify the smallest size of the polycationic peptide to suppress mucin release without cytotoxicity. MATERIALS AND METHODS: HTSE cells were metabolically labeled using 3H-glucosamine and chased in the presence of varying concentrations of various sizes of the polycationic peptides. The amount of 3H-mucin in the spent media was measured by Sepharose CL-4B gel-filtration column chromatography. Possible cytotoxicity of the peptides was assessed by measuring the release of lactic dehydrogenase (LDH) during the treatment period. RESULTS: (1) PLL (MW 78,000) inhibited whereas PLA (MW 92,000) stimulated mucin release. However, these peptides were cytotoxic at the effective concentrations; (2) Both PLL (MW 9,600) and PLA (MW 8,900) could inhibit mucin release in a dose dependent manner without cytotoxicity; (3) Both PLL and PLA were effective in suppressing mucin release in 20-mer but not in either 10-mer or 5-mer; (4) 14-mers of both PLL and PLA also inhibited mucin release without cytotoxicity; (5) PLL and poly-D-lysine (PDL) of 14-mer were equipotent in its ability to suppress mucin release. CONCLUSION: Both PLL and PLA are cytotoxic at 'high' molecular weights, but have an ability to suppress mucin release without cytotoxicity at 'low' molecular weights. 14-mer seems to be the small, effective size, if not the smallest, for both PLL and PLA to suppress mucin release without cytotoxicity. The inhibitory effect of these polycationic peptides seems to be determined by the presence and the absolute number of positive charges and also to be independent of optical isomerism.
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Células Epiteliales/metabolismo , Mucinas/metabolismo , Péptidos/farmacología , Polilisina/farmacología , Sistema Respiratorio/metabolismo , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cricetinae , Células Epiteliales/efectos de los fármacos , Células Epiteliales/enzimología , L-Lactato Deshidrogenasa/metabolismo , Masculino , Mesocricetus , Peso Molecular , Sistema Respiratorio/citología , Sistema Respiratorio/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
Previously we have reported that astrocytes deprived of glucose were highly vulnerable to peroxynitrite (Choi and Kim, J. Neurosci. Res. 54 (1998) 870; Neurosci. Lett. 256 (1988) 109; Ju et al., J. Neurochem. 74 (2000) 1989). Here we report that ciclopirox, which is clinically used as an anti-fungal agent, completely prevents the increased death in glucose-deprived astrocytes exposed to 3-morpholinosydnonimine (SIN-1, a peroxynitrite-releasing reagent). The increased vulnerability was in good correlation with the peroxynitrite-evoked decrease of mitochondrial transmembrane potential (MTP) in astrocytes. A simultaneous exposure to glucose deprivation and SIN-1 rapidly depolarized MTP and depleted ATP in astrocytes. Inclusion of ciclopirox initially increased the MTP, maintained it high, and blocked the ATP depletion in glucose-deprived SIN-1-treated astrocytes. However, ciclopirox did not prevent the depletion of reduced glutathione in glucose-deprived SIN-1-treated astrocytes. Consistently, ciclopirox did not scavenge various kinds of oxidants including peroxynitrite, nitric oxide, superoxide anion, hydrogen peroxide and hydroxyl radical. Ciclopirox has been experimentally used as a cell cycle G1/S phase transition blocker (Hoffman et al., Cytometry 12 (1991) 26). Flow cytometry analysis, however, showed that the cytoprotective effect of ciclopirox was not attributed to its inhibition of the cell cycle progression. The present results indicate that ciclopirox protects astrocytes from peroxynitrite cytotoxicity by attenuating peroxynitrite-induced mitochondrial dysfunction.
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Astrocitos/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Molsidomina/análogos & derivados , Fármacos Neuroprotectores/farmacología , Ácido Peroxinitroso/antagonistas & inhibidores , Ácido Peroxinitroso/toxicidad , Piridonas/farmacología , Adenosina Trifosfato/metabolismo , Animales , Ciclo Celular/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Células Cultivadas , Ciclopirox , Citometría de Flujo , Glutatión/metabolismo , Peróxido de Hidrógeno/metabolismo , Radical Hidroxilo/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Potenciales de la Membrana/efectos de los fármacos , Molsidomina/farmacología , Óxido Nítrico/metabolismo , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley , Rodaminas , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/metabolismo , Superóxidos/metabolismo , Tirosina/metabolismoRESUMEN
Pretreatment of interferon-gamma and lipopolysaccharides made C6 glioma cells highly vulnerable to glucose deprivation. Neither 12 h of glucose deprivation nor 2-day treatment with interferon-gamma (100 U/ml) and lipopolysaccharides (1 microg/ml) altered the viability of C6 glioma cells. However, significant death of immunostimulated C6 glioma cells was observed after 5 h of glucose deprivation. The augmented death was prevented by dehydroepiandrosterone (DHEA) treatment during immunostimulation, but not by DHEA treatment during glucose deprivation. DHEA reduced the rise in nitrotyrosine immunoreactivity, a marker of peroxynitrite, and superoxide production in glucose-deprived immunostimulated C6 glioma cells. DHEA, however, did not protect glucose-deprived C6 glioma cells from the exogenously produced peroxynitrite by 3-morpholinosydnonimine. Further, DHEA did not alter the production of total reactive oxygen species and nitric oxide in immunostimulated C6 glioma cells. Superoxide dismutase (SOD) and the synthetic SOD mimetic Mn(III)tetrakis (4-benzoic acid) porphyrin inhibited the death of glucose-deprived immunostimulated C6 glioma cells. In addition, a superoxide anion generator paraquat reversed the protective effect of DHEA on the augmented death. The data indicate that DHEA prevents the glucose deprivation-evoked augmented death by inhibiting the production of superoxide anion in immunostimulated C6 glioma cells.
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Adyuvantes Inmunológicos/farmacología , Astrocitos/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Muerte Celular/efectos de los fármacos , Deshidroepiandrosterona/farmacología , Glucosa/deficiencia , Molsidomina/análogos & derivados , Estrés Oxidativo/inmunología , Tirosina/análogos & derivados , Adyuvantes Inmunológicos/metabolismo , Animales , Astrocitos/inmunología , Astrocitos/metabolismo , Encéfalo/inmunología , Encéfalo/metabolismo , Encéfalo/fisiopatología , Isquemia Encefálica/inmunología , Isquemia Encefálica/metabolismo , Muerte Celular/inmunología , Citocinas/inmunología , Citocinas/metabolismo , Deshidroepiandrosterona/metabolismo , Inhibidores Enzimáticos/farmacología , Depuradores de Radicales Libres/farmacología , Glioma , Herbicidas/farmacología , Humanos , Interferón gamma/farmacología , Lipopolisacáridos/farmacología , Metaloporfirinas/farmacología , Molsidomina/farmacología , Neuronas/efectos de los fármacos , Neuronas/inmunología , Neuronas/metabolismo , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Paraquat/farmacología , Ácido Peroxinitroso/metabolismo , Superóxido Dismutasa/farmacología , Células Tumorales Cultivadas , Tirosina/efectos de los fármacos , Tirosina/metabolismoRESUMEN
Glucocorticoids have been implicated in the exacerbation of several types of neurotoxicity in various neuropathological situations. In this study, we investigated the effect of a glucocorticoid dexamethasone on glucose deprivation induced cell death of immunostimulated rat primary astrocytes, which is dependent on the production of peroxynitrite from the immunostimulated cells [Choi et al. Glia, 31(2001) 155-164; J. Neuroimmunol. 112 (2001) 55-62]. Glucose deprivation in immunostimulated rat primary astrocytes results in the release of lactate dehydrogenase (LDH) after 5 h and co-treatment with dexamethasone (1-1000 nM) dose-dependently increased LDH release. Treatment of the exogenous peroxynitrite generator SIN-1 (20 microM), plus glucose deprivation, also increased LDH release after 6 h and co-treatment with dexamethasone dose-dependently increased LDH release. A glucocorticoid receptor antagonist, RU-486, reversed the potentiation of cell death by dexamethasone. Glucose deprivation in immunostimulated cells decreased the intracellular ATP levels, which preceded LDH release from the cell, and co-treatment with dexamethasone dose-dependently potentiated the depletion of intracellular ATP levels. In addition, dexamethasone further deteriorated SIN-1 plus glucose deprivation-induced decrease in mitochondrial transmembrane potential in rat primary astrocytes, which was reversed by RU-486. The results from the present study suggest that glucocorticoids may be detrimental to astrocytes in situations where activation of glial cells are observed, including ischemia and Alzheimer's disease, by mechanisms involving depletion of intracellular ATP levels and deterioration of mitochondrial transmembrane potentials.
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Astrocitos/citología , Muerte Celular/efectos de los fármacos , Dexametasona/farmacología , Glucocorticoides/farmacología , Glucosa/farmacología , Molsidomina/análogos & derivados , Ácido Peroxinitroso/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Antineoplásicos/farmacología , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Muerte Celular/fisiología , Células Cultivadas , Antagonistas de Hormonas/farmacología , Interferón gamma/farmacología , Potenciales de la Membrana/efectos de los fármacos , Mifepristona/farmacología , Mitocondrias/metabolismo , Molsidomina/farmacología , Donantes de Óxido Nítrico/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
1. The putative effects of prenatal exposure to magnetic field (MF) have recently received much interest. In the present study, mice were exposed to a MF of 50 mT during gestation (0-19 days). 2. After the exposure was terminated, mothers and offspring were returned to normal laboratory conditions. We then determined changes in striatal levels of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the offspring. 3. Our results indicate that prenatal exposure to MF increases levels of DA and DOPAC in the striatum at 4, 8 and 12 weeks postnatally.
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Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Magnetismo/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Cuerpo Estriado/embriología , Femenino , Feto/metabolismo , Ratones , Ratones Endogámicos C57BL , EmbarazoRESUMEN
AIMS/BACKGROUND: alpha-1 antitrypsin (alpha1AT) is an abundant protease inhibitor in human plasma. Its phenotypic variability has been reported to be associated with pulmonary emphysema and chronic liver diseases. However, alpha1AT deficiency is an uncommon condition in the Chinese population. The aim of this study was to describe the phenotypic distribution of alpha1AT in a southern Chinese population. METHODS: A total of 1085 healthy blood donors underwent alpha1AT phenotyping by isoelectric focusing. RESULTS: Two thirds (66.1%) were homozygous for either M1 or M2, whereas 32.6% were heterozygous for two different M phenotypes. The frequency of allelic variants was only 0.007, and deficiency variants were absent. Compared with earlier studies on southern Chinese populations, this study found a lower frequency of M2, and a higher number of allelic variants, including E, L, N, P, and S. This phenomenon can be attributed to population migration and mixing. CONCLUSIONS: An understanding of the alpha1AT pattern is important for evaluating the predisposition of the population to selected clinical diseases.
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Pueblo Asiatico/genética , alfa 1-Antitripsina/genética , Adolescente , Adulto , Alelos , Femenino , Heterocigoto , Homocigoto , Hong Kong , Humanos , Focalización Isoeléctrica/métodos , Masculino , Persona de Mediana Edad , FenotipoRESUMEN
Adenosine triphosphate (ATP) has been shown to stimulate mucin release by activation of protein kinase C (PKC) following activation of phospholipase C (PLC) coupled to the P2 receptor via G-proteins. The aim of the present study was to investigate pathways downstream to the PKC activation in ATP-induced mucin release from primary hamster tracheal surface epithelial (HTSE) cells. The release of mucin was determined by chromatographic procedure after metabolic labeling of mucin with [3H]-glucosamine. The results were: i) ATP induced the release of arachidonic acid, which caused the release of mucin. Pretreatment with mepacrine (0.3 mM), a phospholipase A2 (PLA2) inhibitor, inhibited the ATP-induced arachidonic acid and mucin release. Oleoyloxyethylphosphocholine, another PLA2 inhibitor, gave similar results. ii) An activator of PKC, 4 beta-phorbol-12 alpha-myristate-13-acetate (PMA, 1 microM) induced mucin release, which was inhibited by mepacrine pretreatment. iii) Downregulation of PKC by prolonged (16 h) PMA treatment caused inhibition of ATP-induced mucin release. Treatment of PKC downregulated HTSE cells with mepacrine did not further decrease the ATP-induced mucin release. These results suggest that PLA2 is involved in ATP-induced mucin release and its activation is sequential to the PLC-PKC pathway.
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Adenosina Trifosfato/farmacología , Células Caliciformes/efectos de los fármacos , Fosfolipasas A/metabolismo , Análisis de Varianza , Animales , Células Cultivadas , Cricetinae , Activación Enzimática , Inhibidores Enzimáticos/farmacología , Células Caliciformes/metabolismo , Masculino , Mesocricetus , Mucinas/metabolismo , Fosfolipasas A/antagonistas & inhibidores , Fosfolipasas A2 , Proteína Quinasa C/metabolismo , Quinacrina/farmacología , Tráquea/efectos de los fármacos , Tráquea/metabolismoRESUMEN
We examined the effects of a non-opioid antitussive, carbetapentane (CB) on kainic acid (KA)-induced neurotoxicity in rats. KA administration (10 mg/kg, i.p.) produced robust behavioral convulsions lasting 4 to 5 h. CB (12.5 and 25 mg/kg. i.p.) pretreatment consistently and in a dose-dependent manner reduced the KA-induced seizures, mortality, and marked loss of cells in regions CA1 and CA3 of the hippocampus. Consistently, CB pretreatment also significantly attenuated the KA-induced increase in Fos-related antigen immunoreactivity in the hippocampus. In contrast, pretreatment with the sigma-1 receptor antagonist BD1047 (1 and 2 mg/kg, i.p.) blocked, in a dose-related manner, the neuroprotection afforded by CB. These results suggest that CB provides neuroprotection against KA insult via sigma-1 receptor modulation.