RESUMEN

The stochastic nonlinear Schrödinger model (SNLSM) in (1+1)-dimension with random potential is examined in this paper. The analysis of the evolution of nonlinear dispersive waves in a totally disordered medium depends heavily on the model under investigation. This study has three main objectives. Firstly, for the SNLSM, derive stochastic precise solutions by using the modified Sardar sub-equation technique. This technique is efficient and intuitive for solving such models, as shown by the generated solutions, which can be described as trigonometric, hyperbolic, bright, single and dark. Secondly, for obtaining numerical solutions to the SNLSM, the algorithms described here offer an accurate and efficient technique. Lastly, investigate the phase plane analysis of the perturbed and unperturbed dynamical system and the time series analysis of the governing model. The results show that the numerical and analytical techniques can be extended to solve other nonlinear partial differential equations in physics and engineering. The results of this study have a significant impact on how well we comprehend how solitons behave in physical systems. Additionally, they may serve as a foundation for the development of improved numerical techniques for handling challenging nonlinear partial differential equations.

Asunto(s)

Algoritmos , Ingeniería , Simulación por Computador , Intuición , Examen Físico

RESUMEN

Carbon dioxide laser-assisted posterior cordotomy (LAPC) is an effective technique for the treatment of Bilateral Vocal Cord Paralysis (BVCP). For our case series we included 34 patients of BVCP from combined military hospitals of Rawalpindi, Lahore, Malir and Quetta and compiled the results of carbon dioxide LAPC which they underwent under general anesthesia between December 2009 to January 2017. Assessment of voice quality and breathing difficulty was carried out before and six weeks after the operation and graded according to scales. The complications after surgery were also noted. In the study, there were 10 (29.4%) males and 24 (70.6%) females. The mean age of the sample was 39.1 } 13.2 years. Overall, there was an improvement in breathing and mild worsening of voice quality after LAPC. The common complications after LAPC were dysphagia, revision surgery, and post-operative pain in 11.8%, 17.6%, and 17.6% respectively. The study concluded that carbon dioxide LAPC was associated with an improvement in breathing but resulted in a poor voice quality among patients with BVCP, along with a few side effects.

Asunto(s)

Obstrucción de las Vías Aéreas/cirugía , Laringoscopía/métodos , Terapia por Láser/métodos , Láseres de Gas/uso terapéutico , Complicaciones Posoperatorias/epidemiología , Parálisis de los Pliegues Vocales/cirugía , Adulto , Anciano , Obstrucción de las Vías Aéreas/etiología , Trastornos de Deglución/epidemiología , Disnea/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/epidemiología , Reoperación , Ruidos Respiratorios/etiología , Traqueostomía , Resultado del Tratamiento , Parálisis de los Pliegues Vocales/complicaciones , Calidad de la Voz , Adulto Joven

RESUMEN

Background: Chronic rhinosinusitis (CRS) is an inflammatory disease of the nose and the paranasal sinuses, often associated with an infection by Staphylococcus aureus (S. aureus). Disturbance in the function of ion channels is regarded as an etiological factor for pathogenesis of CRS. Aims: The study aims to measure the mRNA expression of the ENaC and CFTR ion channels in nasal epithelial cells (NECs) and to investigate the effect of both the budesonide and S. aureus on these ion channels. Materials and method: NECs biopsies obtained from healthy volunteers and patients with CRS. NECs were infected with S. aureus strains and/or budesonide to study the mRNA expression levels of the ENaC and CFTR ion channels. Results: The mRNA expression level of CFTR was increased while that of ENaC was decreased. S. aureus infection and budesonide treatment induced a significant modulation of ENaC and CFTR ion channels expression. Conclusion: The CFTR and ENaC ion channel physiology are of importance in the pathogenesis of CRS. Exposure to S. aureus infection and treatment with budesonide modulated the mRNA expression of CFTR and ENaC ion channels. Significance: Better understanding of the pathophysiology of CRS.

Asunto(s)

Budesonida/administración & dosificación , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulación de la Expresión Génica , Rinitis/genética , Sinusitis/genética , Infecciones Estafilocócicas/genética , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Enfermedad Crónica , Canales Epiteliales de Sodio/efectos de los fármacos , Canales Epiteliales de Sodio/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Transporte Iónico , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Valores de Referencia , Rinitis/tratamiento farmacológico , Rinitis/microbiología , Medición de Riesgo , Transducción de Señal/genética , Sinusitis/tratamiento farmacológico , Sinusitis/microbiología , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Regulación hacia Arriba

RESUMEN

BACKGROUND AND OBJECTIVE: Glucocorticoids (GCs) are anti-inflammatory agents, but their use in cystic fibrosis (CF) is controversial. In CF, the early colonization with Pseudomonas aeruginosa is mainly due to nonmucoid strains that can internalize, and induce apoptosis in the epithelial cells. Uptake of P. aeruginosa by the epithelial cells and subsequent apoptosis may prevent colonization of P. aeruginosa in CF airways. In the airway epithelia, several other biological effects, including an anti-secretory role by decreasing intracellular Ca(2+) concentration have been described for this anti-inflammatory drug. However, the effects of GCs on the nonmucoid P. aeruginosa internalization and intracellular Ca(2+) in CF bronchial epithelial cells have not been evaluated. METHODS: We used cultured human CF bronchial airway epithelial cell (CFBE) monolayers to determine P. aeruginosa internalization, apoptosis, and intracellular Ca(2+)concentration in CF bronchial epithelial cells. Cells were treated with IL-6, IL-8, dexamethasone, betamethasone, or budesonide. RESULTS: GCs in co-treatments with IL-6 reversed the effect of IL-6 by decreasing the internalization of P. aeruginosa in the CFBE cells. GCs decreased the extent of apoptosis in CFBE cells infected with internalized P. aeruginosa, and increased the intracellular Ca(2+) concentration. CONCLUSION: These findings suggest that if internalization of P. aeruginosa reduces infection, GC therapy would increase the risk of pulmonary infection by decreasing the internalization of P. aeruginosa in CF cells, but GCs may improve airway hydration by increasing the intracellular Ca(2+) concentration. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out.

Asunto(s)

Bronquios/efectos de los fármacos , Calcio/metabolismo , Fibrosis Quística/metabolismo , Fibrosis Quística/microbiología , Células Epiteliales/efectos de los fármacos , Glucocorticoides/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Bronquios/metabolismo , Bronquios/microbiología , Budesonida/farmacología , Línea Celular , Células Cultivadas , Dexametasona/farmacología , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Epitelio/microbiología , Humanos , Interleucina-6/farmacología , Interleucina-8/farmacología , Infecciones por Pseudomonas

RESUMEN

CONCLUSION: Using a local anesthetic agent before obtaining nasal biopsies by nasal brushing makes the sampling procedure smooth, avoids lacrimation, nasal itching/irritation, and/or sneezing and provides enough viable cells to establish primary cultures. OBJECTIVES: To examine the use of local anesthesia to avoid the irritation experienced by the subject when nasal biopsies are obtained by nasal brushing in order to culture viable nasal epithelial cells. METHODS: Nasal epithelial cells were collected from the mid-part of the inferior turbinate of healthy volunteers by brushing with interdental brushes, after spraying a topical anesthetic on the nasal mucosa. Immunocytochemistry was performed to assess the purity of epithelial cells. RESULTS: Cell samples ranging from 1.16 × 10(5) to 3.06 × 10(5) cells/per sample were obtained. Of 11 samples, 7 formed confluent cultures, while the remaining 4 samples showed only patches of epithelial cells. Neither fungal nor bacterial contamination posed a problem. Immunocytochemistry of the cytospin slides confirmed the presence of epithelial cells in the cultures. No adverse effects were experienced by the volunteers.

Asunto(s)

Anestesia Local , Biopsia/métodos , Técnicas de Cultivo de Célula , Mucosa Nasal/citología , Recuento de Células , Humanos , Inmunohistoquímica/métodos , Queratina-18/análisis

RESUMEN

Bacteria affect the respiratory epithelium, which is covered by airway surface liquid (ASL) and mucus. Ion concentrations in the ASL are determined by the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial Na(+) channel (ENaC). Neonatal sepsis is a major risk factor for subsequent pulmonary disease in preterm newborns. Predominating are coagulase-negative staphylococci (e.g., Staphylococccus epidermidis and Staphylococccus aureus). The aim of this study was to investigate modulation of CFTR, ENaC, mucins, proinflammatory cytokines, and inducible nitric oxide synthase (iNOS) in respiratory epithelial cells after S. epidermidis 94B080 and S. aureus 90B083 exposure. Bronchial epithelial cells were incubated with S. epidermidis 94B080 and S. aureus 90B083 (neonatal blood isolates) for 1-36 h. Expression of CFTR, ENaC, iNOS, and mucins was analyzed by real-time PCR and Western blotting. Release of cytokines was analyzed by ELISA, and production of NO by the Griess assay. Expression of CFTR significantly decreased after 36 h incubation with S. epidermidis and more prominently with S. aureus, whereas S. epidermidis caused a significant increase in the expression of ß- and γ-ENaC. Expression of iNOS increased, but NO was not detected. Both staphylococci caused a decrease in the intracellular Ca(2+) concentration. S. aureus induced increased secretion of IL-6, IL-8, and transforming nuclear factor (TNF)-α in a time-dependent manner as compared with S. epidermidis. In conclusion, expression of ENaC, CFTR, and iNOS is modulated by exposure to S. aureus 90B083 and S. epidermidis 94B080. S. aureus is more potent in causing release of IL-6, IL-8, and TNF-α by bronchial epithelial cells as compared with S. epidermidis. The mRNA expression for the mucus proteins MUC2, MUC5AC, and MUC5B could not be measured, neither in the presence nor in the absence of bacteria.

Asunto(s)

Bronquios/inmunología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Células Epiteliales/inmunología , Canales Epiteliales de Sodio/genética , Óxido Nítrico Sintasa de Tipo II/genética , Staphylococcus aureus/fisiología , Staphylococcus epidermidis/fisiología , Bronquios/microbiología , Bronquios/patología , Calcio/metabolismo , Línea Celular , Supervivencia Celular , Regulador de Conductancia de Transmembrana de Fibrosis Quística/inmunología , Citocinas/biosíntesis , Citocinas/inmunología , Células Epiteliales/microbiología , Células Epiteliales/patología , Canales Epiteliales de Sodio/inmunología , Regulación de la Expresión Génica/inmunología , Humanos , Recién Nacido , Mucinas/genética , Mucinas/inmunología , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/inmunología , Staphylococcus aureus/aislamiento & purificación , Staphylococcus epidermidis/aislamiento & purificación

RESUMEN

Ambroxol, a mucokinetic anti-inflammatory drug, has been used for treatment of cystic fibrosis (CF). The respiratory epithelium is covered by the airway surface liquid (ASL), the thickness and composition of which is determined by Cl(-) efflux via the cystic fibrosis transmembrane conductance regulator (CFTR) and Na(+) influx via the epithelial Na(+) channel (ENaC). In cells expressing wt-CFTR, ambroxol increased the Cl(-) conductance, but not the bicarbonate conductance of the CFTR channels. We investigated whether treatment with ambroxol enhances chloride transport and/or CFTR and ENaC expression in CF airway epithelial cells (CFBE) cells. CFBE cells were treated with 100 µM ambroxol for 2, 4 or 8 h. mRNA expression for CFTR and ENaC subunits was analysed by real-time polymerase chain reaction (RT-PCR); protein expression was measured by Western blot. The effect of ambroxol on Cl(-) transport was measured by Cl(-) efflux measurements with a fluorescent chloride probe. Ambroxol significantly stimulated Cl(-) efflux from CFBE cells (a sixfold increase after 8 h treatment), and enhanced the expression of the mRNA of CFTR and α-ENaC, and of the CFTR protein. No significant difference was observed in ß-ENaC after exposure to ambroxol, whereas mRNA expression of γ-ENaC was reduced. No significant effects of ambroxol on the ENaC subunits were observed by Western blot. Ambroxol did not significantly affect the intracellular Ca(2+) concentration. Upregulation of CFTR and enhanced Cl(-) efflux after ambroxol treatment should promote transepithelial ion and water transport, which may improve hydration of the mucus, and therefore be beneficial to CF-patients.

Asunto(s)

Ambroxol/farmacología , Bronquios/patología , Cloruros/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Fibrosis Quística/patología , Células Epiteliales/metabolismo , Canales Epiteliales de Sodio/metabolismo , Transporte Biológico/efectos de los fármacos , Transporte Biológico/genética , Western Blotting , Calcio/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Células Epiteliales/efectos de los fármacos , Canales Epiteliales de Sodio/genética , Colorantes Fluorescentes/metabolismo , Humanos , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regulación hacia Arriba/efectos de los fármacos

RESUMEN

Since previous studies showed that the endogenous bronchodilator, S-nitrosglutathione (GSNO), caused a marked increase in CFTR-mediated chloride (Cl(-)) efflux and improved the trafficking of CFTR to the plasma membrane, and that also the nitric oxide (NO)-donor GEA3162 had a similar, but smaller, effect on Cl(-) efflux, it was investigated whether the NO-donor properties of GSNO were relevant for its effect on Cl(-) efflux from airway epithelial cells. Hence, the effect of a number of other NO-donors, sodium nitroprusside (SNP), S-nitroso-N-acetyl-DL-penicillamine (SNAP), diethylenetriamine/nitric oxide adduct (DETA-NO), and diethylenetriamine/nitric oxide adduct (DEA-NONOate) on Cl(-) efflux from CFBE (∆F508/∆F508-CFTR) airway epithelial cells was tested. Cl(-) efflux was determined using the fluorescent N-(ethoxycarbonylmethyl)-6-methoxyquinoliniu bromide (MQAE)-technique. Possible changes in the intracellular Ca(2+) concentration were tested by the fluorescent fluo-4 method in a confocal microscope system. Like previously with GSNO, after 4 h incubation with the NO-donor, an increased Cl(-) efflux was found (in the order SNAP>DETA-NO>SNP). The effect of DEA-NONOate on Cl(-) efflux was not significant, and the compound may have (unspecific) deleterious effects on the cells. Again, as with GSNO, after a short (5 min) incubation, SNP had no significant effect on Cl(-) efflux. None of the NO-donors that had a significant effect on Cl(-) efflux caused significant changes in the intracellular Ca(2+) concentration. After 4 h preincubation, SNP caused a significant increase in the mRNA expression of CFTR. SNAP and DEA-NONOate decreased the mRNA expression of all ENaC subunits significantly. DETA-NO caused a significant decrease only in α-ENaC expression. After a short preincubation, none of the NO-donors had a significant effect, neither on the expression of CFTR, nor on that of the ENaC subunits in the presence and absence of L-cysteine. It can be concluded that the effect of GSNO on Cl(-) efflux is, at least in part, due to its properties as an NO-donor, and the effect is likely to be mediated by CFTR, not by Ca(2+)-activated Cl(-) channels.

Asunto(s)

Calcio/metabolismo , Cloruros/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/genética , Células Epiteliales/metabolismo , Canales Epiteliales de Sodio/genética , Donantes de Óxido Nítrico/farmacología , Bronquios/patología , Línea Celular , Fibrosis Quística/metabolismo , Fibrosis Quística/patología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Células Epiteliales/patología , Canales Epiteliales de Sodio/metabolismo , Regulación de la Expresión Génica , ARN Mensajero/metabolismo , Triazoles/farmacología

RESUMEN

Canavan disease (OMIM 271900) is an autosomal recessive lethal neurodegenerative disorder characterized by spongy degeneration of the brain. A highly consanguineous Pakistani family with Canavan disease was enrolled on the basis of diagnosis. All the affected individuals have mental retardation, megalocephaly and degradation of motor skills, poor head control, partial vision loss, weakness of the muscles and raised urinary concentration of N-acetyl aspartic acid in the urine. Blood samples were collected from affected as well as normal siblings and processed for DNA purification. Linkage analysis was performed by typing three short tandem repeat markers D17S1583 (7.19 cM), D17S1828 (10.02 cM) and D17S919 (14.69 cM) for an already-reported gene/locus ASPA at chromosome 17p13.2 causing Canavan disease. During linkage analysis, all the affected individuals were homozygous for short tandem repeat markers while the normal siblings were heterozygous showing co-segregation of the disease. Gene ASPA (NM_000049) was undertaken to sequence for mutation analysis. As a result of sequence analysis, we found missense substitution 740A→G (p.G274R) in exon 6 of gene ASPA. To our knowledge, this is the first report about Canavan disease on a Pakistani family.

Asunto(s)

Amidohidrolasas/genética , Enfermedad de Canavan/enzimología , Enfermedad de Canavan/genética , Mutación Missense/genética , Adolescente , Secuencia de Bases , Niño , Análisis Mutacional de ADN , Familia , Femenino , Homocigoto , Humanos , Masculino , Datos de Secuencia Molecular , Pakistán , Linaje , Adulto Joven