Mucociliary clearance affected by mucus-periciliary interface stimulations using analytical solution during cough and sneeze.

Assessment of mucus velocity variations under different conditions including viscosity variation and boundary conditions is useful to develop mucosal-based medical treatments. This paper deals with the analytical investigation of mucus-periciliary velocities under mucus-periciliary interface movements and mucus viscosity variations. The results for mucus velocity show that there is no difference between the two cases under the free-slip condition. Therefore, power-law mucus can be substituted with a high viscosity Newtonian fluid since the upper boundary of the mucus layer is exposed to the free-slip condition. However, when the upper boundary of the mucus layer is under nonzero shear stress levels, including cough or sneeze, the assumption of a high viscosity Newtonian mucus layer is invalid. Moreover, mucus viscosity variations are investigated for both Newtonian and power-law mucus layers under sneeze and cough to propose a mucosal-based medical treatment. The results indicate by varying mucus viscosity up to a critical value, the direction of mucus movement changes. The critical values of viscosity in sneezing and coughing for Newtonian and power-law mucus layers are 10-4 and 5 × 10-5 and 0.0263 and 006.024 m2 s-1, respectively. Therefore, the pathogen entry into the respiratory system can be prevented by varying mucus viscosity during sneeze and cough.

Numerical investigation of mucociliary clearance using power law and thixotropic mucus layers under discrete and continuous cilia motion.

Mucus layer movement inside the airway system is an important phenomenon as the first defensive mechanism against pathogens. This research deals with the mucus velocity variations inside the nasal cavity using two different power law and thixotropic mucus layers. The cilia movement is replaced with four cyclic velocity profiles at the lower boundary of the mucus layer, while the upper boundary is exposed to the free-slip condition. The effects of boundary conditions and different fluid parameters are evaluated on the mucus flow. Furthermore, the replacement of power law and thixotropic mucus layers with a high viscous Newtonian mucus is examined under the free-slip condition at the mucus upper boundary. The adaptation rate is used as the criteria for replacing fluids instead of each other. The results show the mucus flow has enough time to adjust the changes from the lower boundary and the recovery stroke does not affect the mucus velocity in the effective stroke. Moreover, it is observed that the mucus flow variations are the same under the influence of recovery, breakdown, and breakdown exponent parameters. However, the effects of the exponent parameter on the mucus flow are more than the other two parameters in the recovery stroke. It is concluded that the assumption for replacing the power law mucus with a high viscous Newtonian one is acceptable. However, this assumption leads to the maximum error of 98.5% for thixotropic mucus in the recovery stroke.

Effects of continuous and discrete boundary conditions on the movement of upper-convected maxwell and Newtonian mucus layers in coughing and sneezing.

Mucociliary clearance is an important phenomenon inside the respiratory system as a first defensive mechanism against pathogens. Therefore, any assumption considered for the mucociliary clearance and affects its functionality must be validated. The present research deals with the effects of boundary conditions on the movement of upper-convected Maxwell and high viscosity Newtonian mucus layers, numerically. Furthermore, the validity of replacing the viscoelastic mucus layer with a high viscosity Newtonian layer is evaluated. The airway surface liquid layer is considered a two-layer model including non-Newtonian mucus and Newtonian periciliary layers. Four cyclic boundary conditions are imposed at the mucus-periciliary interface as the cilia movement to obtain variations of mucociliary clearance. The upper boundary of the mucus layer is also exposed to different shear stress levels including free slip, cough, and sneeze conditions. By investigation of velocity variations inside mucus and periciliary layers, it is concluded the differences between viscoelastic and Newtonian mucus are not negligible. The maximum velocity differences between the two fluids are more than 52% and 215% during cough and sneeze, respectively. The results show there is a high order of dependency between the relaxation time and the imposed boundary conditions at the mucus-periciliary interface that leads to the invalidation of replacing two fluids with each other. Moreover, the results show substituting the viscoelastic mucus with a high viscosity Newtonian one depends on the mucus-periciliary interface boundary condition. If an independent time-varying boundary condition is used, the substitution leads to an error less than 7% under different shear stress levels. However, time-varying boundary condition shows 38% and 88% differences between high viscosity Newtonian and viscoelastic mucus layers. Furthermore, neglecting the recovery stroke leads to a velocity underestimation up to 50% by substituting viscoelastic mucus with a high viscosity Newtonian one. Therefore, replacing the viscoelastic mucus with a high viscosity Newtonian one is not acceptable for numerical simulations.

Infectious and Noninfectious Pulmonary Complications in Patients With Primary Immunodeficiency Disorders.

Primary immunodeficiency disorders (PIDs) are caused by 1 or more defects of the immune system. Patients are more likely to experience recurrent and/or severe infections and tend to develop a wide range of complications. Respiratory diseases are the main and initial manifestation in most cases and the most common complication. Pulmonary complications cause significant morbidity and mortality in patients with PIDs. Early diagnosis and appropriate treatment can prevent or at least slow the development of respiratory complications. Since the spectrum of pulmonary complications in PIDs is broad, we divided pulmonary complications into upper respiratory complications (eg, sinusitis, otitis media, and laryngeal angioedema) and lower respiratory complications (eg, pneumonia, bronchitis, bronchiectasis, interstitial lung diseases, organizing pneumonia, pulmonary adenopathies and malignancies, hyperreactive airway diseases, pulmonary dysgenesis, and adverse reactions to treatment). This review covers the main respiratory manifestations in patients with PIDs.

Evaluation of pulmonary complications in patients with primary immunodeficiency disorders.

SUMMARY: Background. Primary immunodeficiencies (PIDs) are inherited disorders in which one or several components of immune system are defected. Moreover, affected patients are at high risk for developing recurrent infections, particularly pulmonary infections. The spectrum of pulmonary manifestations in PIDs is broad, and includes acute and chronic infection, structural abnormalities (eg, bronchiectasis), malignancy and dysregulated inflammation resulting in tissue damage. In this study, our aims are to evaluate pulmonary complications in PID patients. Patients and Methods. We studied 204 cases with confirmed PID. To evaluate pulmonary complications in these patients, we used pulmonary function test (PFT), high resolution computed tomography (HRCT) scan and bronchoalveolar lavage (BAL). Results. Our results showed that pneumonia was the most frequent clinical manifestations in all PID patients. There were significantly greater numbers of episodes of pneumonia in HIgM, XLA and CVID patients with delayed diagnoses < 6 years. Moreover, of 57.4% CVID patients, 55% XLA patients and 33.3% HIgM patients had abnormal PFT results, and bronchiectasis was showed in 9 (42.9%) of XLA, 6 (11.8%) of HIES, 3 (21.4%) of HIgM and 38 (62.3%) of CVID patients. Conclusion. Pulmonary complications should be considered in cases with PIDs especially in CVID cases.

Infectious and noninfectious pulmonary complications in patients with primary immunodeficiency disorders

Primary immunodeficiency disorders (PIDs) are caused by 1 or more defects of the immune system. Patients are more likely to experience recurrent and/or severe infections and tend to develop a wide range of complications. Respiratory diseases are the main and initial manifestation in most cases and the most common complication. Pulmonary complications cause significant morbidity and mortality in patients with PIDs. Early diagnosis and appropriate treatment can prevent or at least slow the development of respiratory complications. Since the spectrum of pulmonary complications in PIDs is broad, we divided pulmonary complications into upper respiratory complications (eg, sinusitis, otitis media, and laryngeal angioedema) and lower respiratory complications (eg, pneumonia, bronchitis, bronchiectasis, interstitial lung diseases, organizing pneumonia, pulmonary adenopathies and malignancies, hyperreactive airway diseases, pulmonary dysgenesis, and adverse reactions to treatment). This review covers the main respiratory manifestations in patients with PIDs (AU)

Las inmunodeficiencias primarias (PIDs) son enfermedades causadas por uno o más defectos del sistema inmunológico. Estos pacientes presentan con frecuencia infecciones recidivantes y/o severas así como otro tipo de complicaciones. Las patologías respiratorias son la principal y más frecuente manifestación y complicación de las PIDs. Las complicaciones de estas patologías pulmonares constituyen una de las principales causas de morbimortalidad entre los pacientes que sufren PIDs. El diagnóstico temprano y el tratamiento adecuado pueden prevenir, o al menos retrasar, la aparición de las complicaciones respiratorias en estos pacientes. Dado que el espectro de las enfermedades pulmonares es muy amplio, hemos dividido estas complicaciones entre aquellas que afectan a las vías aéreas superiores (sinusitis, otitis media y angioedema laríngeo, etc.) y las que afectan a las vías aéreas bajas (neumonía, bronquitis, bronquiectasias, enfermedades pulmonares intersticiales, neumonía organizada, adenopatías pulmonares y neoplasias, hiperreactividad bronquial, disgenesia pulmonar y las debidas a los efectos secundarios del tratamiento instaurado). Este artículo revisa las manifestaciones respiratorias que se observan más frecuentemente en los pacientes con PIDs (AU)

In vitro expression of HPV16 E7 linked to HMGB1 immunoadjuvant in mammalian cells.

BACKGROUND: E7 is the major transforming protein of human papillomavirus (HPV) that plays important role in maintaining the proliferative state in HPV-infected cells. Furthermore, high mobility group 1 protein (HMGB1) is a highly conserved component of chromatin that can be secreted by macrophages and activated monocytes and thus functions as an inflammation mediator. METHODS: In the current study, cloning of HMGB1 gene and also HPV16E7-HMGB1 was performed in pEGFP-N1 eukaryotic expression vector in order to evaluate their expression in mammalian cells. For this purpose, the HEK-293T cells were transfected by pEGFP-E7, pEGFP-HMGB1 and pEGFP-E7-HMGB1 using TurboFect delivery system. The levels of protein expression were assessed by flow cytometry and fluorescent microscopy at 48 hr after transfection, as well as by western blot analysis using anti-GFP polyclonal antibody. RESULTS: Our data showed a clear band of ~ 684 bp and ~ 981 bp related to HMGB1 and E7-HMGB1 genes in agarose gel, respectively. The expression of HMGB1-GFP and E7-HMGB1-GFP proteins was confirmed for the bands of ~ 53 kDa and ~ 64 kDa in the transfected cells using western blot analysis, respectively. The linkage of HMGB1 gene to E7 could likely neutralize the negative charges of E7, thus a clear band of 64 kDa was detected instead of 76 kDa in western blot analysis. Moreover, the percentage of expression for E7-GFP, HMGB1-GFP and E7-HMGB1-GFP was 76 %, 55 %, and 52 %, in comparison with pEGFP-N1 (~82 %) as a positive control. Indeed, HMGB1 linked to HPV16 E7 gene decreased transfection efficiency of E7 DNA in HEK-293T cells. CONCLUSION: Generally, the electrophoretic mobility of HPV16 E7 was changed due to the linkage of HMGB1 gene. Furthermore, the fusion protein could be efficiently expressed in mammalian cells for the next use in immunotherapy (Fig. 3, Ref. 51).

High total acrosin activity in varicocele individuals.

Varicocele is a common cause of male infertility and reports indicate that varicocelectomy has a beneficial effect on male fertility. The aims of this study were to evaluate and compare the total acrosin activity along with DNA integrity in semen samples obtained from 70 varicocele individuals with male factors infertility presenting grades II and III varicocele before and after the surgery and 30 fertile individuals without any clinical presentation of varicocele. Total acrosin activity, protamine deficiency, DNA fragmentation, and semen parameters including sperm concentration, motility and sperm morphology were assessed by spectrophotometery, CMA3 staining, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and WHO criteria, respectively. Total acrosin activity (P = 0.03), percentage CMA3 positivity (P = 0.00) and TUNEL-positive spermatozoa (P = 0.04) were higher in the varicocele individuals before the surgery compared with the fertile individuals; yet, all the aforementioned criteria decreased significantly after surgery (P < 0.05). The results of this study reveal that DNA fragmentation and protamine deficiency, as negative parameters in fertility, improve post-surgery; however, total acrosin activity as a positive parameter in fertility is higher in the varicocele individuals compared with fertile and decreases to a value close to the fertile control post-surgery. High levels of total acrosin activity in varicocele individuals need more research in future.

Production of superoxide radicals by sheep liver nitrofurantoin reductase: In vitro effects of nitrofurantoin metabolites on DNA.

The reduction of nitrofurantoin by purified liver nitrofurantoin reductase was followed by the production of superoxide radicals, which were detected by the reduction of epinephrine. The conditions for the formation of superoxide radicals were optimized. The maximum superoxide radical formation occurred at approximately 3.5 mug purified reductase, with optimum pH of 7.8 and at 0.05 mm nitrofuran- toin concentration. The K(m) and V(max) values were calculated as 1.95 x 10(-2) mm and 4.81 nmol Superoxide formed per minute. An obliteration of the banding pattern was observed on the agarose gel electrophoresis of sheep liver DNA, which was incubated in the nitrofurantoin-nitrofurantoin reductase system, as a possible consequence of the generation of superoxide radicals during the reduction of nitrofurantoin by nitrofurantoin reductase.