scholarly journals Serine Proteases Degrade Airway Mucins in Cystic Fibrosis

2011 ◽  
Vol 79 (8) ◽  
pp. 3438-3444 ◽  
Author(s):  
Markus O. Henke ◽  
Gerrit John ◽  
Christina Rheineck ◽  
Shashi Chillappagari ◽  
Lutz Naehrlich ◽  
...  

ABSTRACTAirway mucins are the major molecular constituents of mucus. Mucus forms the first barrier to invading organisms in the airways and is an important defense mechanism of the lung. We confirm that mucin concentrations are significantly decreased in airway secretions of subjects with cystic fibrosis (CF) who have chronicPseudomonas aeruginosainfection. In sputum from CF subjects without a history ofP. aeruginosa, we found no significant difference in the mucin concentration compared to mucus from normal controls. We demonstrate that mucins can be degraded by synthetic human neutrophil elastase (HNE) andP. aeruginosaelastase B (pseudolysin) and that degradation was inhibited by serine proteases inhibitors (diisopropyl fluorophosphates [DFP], phenylmethylsulfonyl fluoride [PMSF], and 1-chloro-3-tosylamido-7-amino-2-heptanone HCl [TLCK]). The mucin concentration in airway secretions from CF subjects is similar to that for normal subjects until there is infection byP. aeruginosa, and after that, the mucin concentration decreases dramatically. This is most likely due to degradation by serine proteases. The loss of this mucin barrier may contribute to chronic airway infection in the CF airway.

1991 ◽  
Vol 74 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Juha Öhman ◽  
Antti Servo ◽  
Olli Heiskanen

✓ A prospective series of 265 patients with aneurysmal subarachnoid hemorrhage (SAH) of Grades I to III (Hunt and Hess classification) upon admission were evaluated as to neurological outcome and computerized tomography (CT) findings 1 to 3 years (mean 1.4 years) after the SAH and surgery. A total of 73 patients underwent acute surgery (within 72 hours after the bleed: Days 0 to 3), 86 were operated on subacutely (between Days 4 and 7), and 91 had late surgery (on Day 8 or later). Fifteen patients died before surgery was undertaken and another 20 patients died during the follow-up period. A total of 104 patients received nimodipine and the rest of the patients received either placebo (109 patients) or no medication (52 patients). A logistical regression analysis revealed the following prognostic factors for cerebral infarction, in order of importance: the amount of blood on the primary CT scan; postoperative angiographic vasospasm; the timing of the operation; and a history of hypertension. The use of nimodipine was associated with a significant reduction of cerebral infarcts visualized by CT scanning in patients who received intermediate or late surgery. In patients who underwent acute surgery no significant difference between the incidence of cerebral infarcts was observed.


PEDIATRICS ◽  
1977 ◽  
Vol 60 (2) ◽  
pp. 146-152
Author(s):  
John W. Wong ◽  
Thomas G. Keens ◽  
Eleanor M. Wannamaker ◽  
Douglas N. Crozier ◽  
Henry Levison ◽  
...  

A noninvasive, radionuclide imaging technique for measuring the rate of mucus clearance in the trachea (RT), was used to study gravitational effects on mucus clearance in 13 patients with cystic fibrosis (CF), average age 17 years; 7 normal, nonsmoking adults, average age 26 years; and a normal subject who was recovering from an acute upper respiratory tract infection (URTI). In the upright position, nine of the CF patients and the subject with URTI demonstrated abnormal tracheal mucus clearance which approached normal when they were placed in a 25° headdown position. The normal subjects and two of the CF patients showed no significant difference in the RT measured in the two positions. The results of the study indicate that the force of gravity can be a major influence on tracheal mucus clearance in CF and URTI subjects. This conclusion supports the use of postural drainage as an effective form of therapy in patients with cystic fibrosis.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Houra Mohseni ◽  
Shirin Amini ◽  
Behnaz Abiri ◽  
Mojtaba Kalantar

Purpose The coronavirus disease 2019 (COVID-19) is an infectious disease that puts strain on health-care systems. Obesity is considered as a risk factor for the severity of infection. Hypotheses also suggested some nutritional supplements may be useful in COVID-19. This paper aims to assess the role of body mass index (BMI) and nutritional supplements on the severity of COVID-19. Design/methodology/approach This research was conducted on 603 participants (in five groups including: exposure to virus and healthy, COVID-19 positive patients with severity of mild, moderate, severe and death from COVID-19), in age 18 to 65 years. Demographic data and history of nutritional supplements were asked. Anthropometric measurements were measured in a healthy group and in a patient. They were collected by referring to patients' medical records. Findings The mean of BMI in groups with severity symptoms of moderate (27.57 kg/m2), severe (29.70 kg/m2) and death persons (28.13 kg/m2), was significantly higher than healthy (26.70 kg/m2) and mild symptoms (26.57 kg/m2) groups (p = 0.001). The logistic regression shown, the fourth quartile of BMI was significantly associated with occurrence of COVID19, odds ratios (ORs) and 95% confidence intervals (CI): [OR: 1.81, (95% CI: 1.13– 2.89), p-for trend = 0.55]. There was no significant difference in the percentage of vitamin C, D3, Zinc, Iron and multivitamin supplements intake, between groups, in the past six months (p = 0.11). Originality/value This study indicated the role of higher BMI in the occurrence and severity of COVID-19. Researches are not enough to recommend consumption of nutritional supplements for the prevention of COVID-19.


2007 ◽  
Vol 293 (5) ◽  
pp. G1023-G1028 ◽  
Author(s):  
Sudip K. Ghosh ◽  
Peter J. Kahrilas ◽  
Nilesh Lodhia ◽  
John E. Pandolfino

Successful esophageal emptying depends on the generation of a sustained intrabolus pressure (IBP) sufficient to overcome esophagogastric junction (EGJ) obstruction. Our aim was to develop a manometric analysis paradigm that describes the bolus driving pressure difference and the flow permissive time for esophageal bolus transit. Twenty normal subjects were studied with a 36-channel manometry assembly (1-cm spacing) during two 5- and one 10-ml barium swallows and concurrent fluoroscopy. Bolus domain pressure plots were generated by plotting bolus domain pressure (BDP) and EGJ relaxation pressure. BDP was defined as the pressure midway between the peristaltic ramp-up and the proximal margin of the EGJ. The flow permissive time was defined as the period where the BDP was ≥ EGJ relaxation pressure. The mean BDP was 11.7 ± 1.0 mmHg (SE), and the mean flow permissive time was 3.9 ± 0.4 s for 5-ml swallows in normal controls. The mean BDP difference during flow was 4.0 ± 1.0 mmHg. There was no significant difference in the fluoroscopic transit time and the flow permissive time calculated from the BDP plots (5 ml: fluoroscopy 3.4 ± 0.2 s; BDP 3.9 ± 0.4 s, P > 0.05). BDP plots provide a reliable measurement of IBP and its relationship with EGJ relaxation. The time available for flow can be readily delineated from this analysis, and the driving pressure responsible for flow can be accurately described and quantified. This may help predict abnormal bolus transit and the underlying mechanical properties of the EGJ.


2014 ◽  
Vol 02 (01) ◽  
pp. 022-025
Author(s):  
Subhash Vasudeva ◽  
Asha Iyengar ◽  
Nagesh Seetaramaiah

Abstract Purpose: Temporomandibular disorders are among the common musculoskeletal conditions affecting the individual. Modern day lifestyle and work environment may introduce abnormal habits like constant tooth contact habit which may have a role in the pathogenesis of temporomandibular disorder. This study aimed to correlate the prevalence of tooth contact habits in individuals suffering from TMD and compare them with that of normal individuals without any signs and symptoms of TMD. Material and Methods: 505 individuals were included in the study. They were divided into 2 groups. Group 1 consisted of 255 individuals who presented with signs and symptoms of temporomandibular disorders and group 2 consisted of 250 normal individuals. Detailed case history with emphasis on habits of constant tooth contact was recorded. Fischer's t test was used to compare the results between the two groups. Results: In group 1,54.5% of males and 58.02% of females gave a history of tooth contact habit while in group 2 individuals 38.7% males and 39.8% females gave a history of this habit. There was no statistically significant difference between males and females of group 1 with regard to this habit. There was a statistically significant difference between group 1 and group 2 individuals (both males and females combined) with regards to this habit. (p= 0.0003) Conclusion: Individuals with temporomandibular disorders exhibited higher prevalence of tooth contact habit when compared to normal subjects.


2017 ◽  
Vol 55 (7) ◽  
pp. 2074-2085 ◽  
Author(s):  
B. D. Edwards ◽  
J. Greysson-Wong ◽  
R. Somayaji ◽  
B. Waddell ◽  
F. J. Whelan ◽  
...  

ABSTRACTAchromobacterspecies are increasingly being detected in cystic fibrosis (CF) patients, with an unclear epidemiology and impact. We studied a cohort of patients attending a Canadian adult CF clinic who had positive sputum cultures forAchromobacterspecies in the period from 1984 to 2013. Infection was categorized as transient or persistent (≥50% positive cultures for 1 year). Those with persistent infection were matched 2:1 with age-, sex-, and time-matched controls without a history ofAchromobacterinfection, and mixed-effects models were used to assess pulmonary exacerbation (PEx) frequency and lung function decline. Isolates from a biobank were retrospectively assessed, identified to the species level bynrdAsequencing, and genotyped using pulsed-field gel electrophoresis (PFGE). Thirty-four patients (11% of those in our clinic), with a median age of 24 years (interquartile range [IQR], 20.3 to 29.8 years), developedAchromobacterinfection. Ten patients (29%) developed persistent infection. Persistence did not denote permanence, as most patients ultimately cleared infection, often after years. Patients were more likely to experience PEx at incident isolation than at prior or subsequent visits (odds ratio [OR], 2.7 [95% confidence interval {CI}, 1.2 to 6.7];P= 0.03). Following persistent infection, there was no difference in annual lung function decline (−1.08% [95% CI, −2.73 to 0.57%] versus −2.74% [95% CI, −4.02 to 1.46%];P= 0.12) or the odds of PEx (OR, 1.21 [95% CI, 0.45 to 3.28];P= 0.70). Differential virulence amongAchromobacterspecies was not observed, and no cases of transmission occurred. We demonstrated that incidentAchromobacterinfection was associated with a greater risk of PEx; however, neither transient nor chronic infection was associated with a worsened long-term prognosis. Large, multicenter studies are needed to clarify the clinical impact, natural history, and transmissibility ofAchromobacter.


2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Tamer M. Attia ◽  
Ahmad M. Hamdan

Abstract Background Olfaction is a complex process involving different neurological mechanisms with a correlation between the chemical structure and quality of odors regarding pleasantness. This study aimed to compare the detection of pleasant and unpleasant odors in different grades of hyposmia. A descriptive cross-sectional study was conducted preceded by a preliminary pilot study, including 20 normal subjects without a history of hyposmia. The pilot study was carried out using the University of Pennsylvania Smell Identification Test (UPSIT) with the assessment of pleasantness of odors using a visual analog scale (VAS). Fifty patients diagnosed with organic hyposmia/anosmia were included in the main study and assessed for the degree of hyposmia/anosmia using UPSIT. The number of detected odors out of the five odors with highest VAS for pleasantness and five odors with lowest VAS for pleasantness, as detected by the pilot study, for every patient was assessed and compared. Results There was a significant difference between the detection of pleasant and unpleasant odors in mild, moderate, and severe hyposmia (p value = 0.02, 0.005, and 0.03 respectively) with a highly significant difference in the whole study group ( p < 0.00001) with more loss of ability to detect unpleasant odors compared with pleasant odors. Conclusion The current study showed significantly less ability to detect unpleasant odors compared with pleasant odors in different grades of hyposmia. This finding suggests that the pattern of degeneration of the olfactory sense organ is not uniform with the topographic nature of the olfactory membrane.


2007 ◽  
Vol 293 (1) ◽  
pp. L96-L104 ◽  
Author(s):  
Amit Gaggar ◽  
Yao Li ◽  
Nathaniel Weathington ◽  
Margaret Winkler ◽  
Michele Kong ◽  
...  

Matrix metalloproteases (MMPs) are proteolytic enzymes that regulate extracellular matrix turnover and aid in restoring tissue architecture following injury. There is an emerging role for extracellular matrix destruction in the pathogenesis of chronic neutrophilic lung diseases. In this study, we examined the expression and activity profiles of MMPs in lower airway secretions from cystic fibrosis (CF) patients, patients with acute respiratory failure (ARF), and normal controls. A discrete repertoire of MMP isoforms was found in the CF samples, with robust MMP-9 expression compared with normal controls and ARF. CF samples possessed increased levels of active MMP-9, as well as decreased amounts of tissue inhibitor of metalloprotease-1 (TIMP-1), a natural inhibitor of MMP-9. The CF inpatient samples demonstrated fully active MMP-9 activity compared with CF outpatients, ARF, and normal controls. CF samples also demonstrated increased human neutrophil elastase (HNE) levels compared with ARF and normal controls. To examine potential mechanisms for the protease dysregulation seen in the CF clinical samples, in vitro studies demonstrated that HNE could activate pro-MMP-9 and also degrade TIMP-1; this HNE-based activation, however, was not seen with MMP-8. A strong correlation was seen between HNE and MMP-9 activity in CF inpatient samples. Finally, the dysregulated MMP-9 activity seen in CF inpatient sputum samples could be significantly reduced by the use of MMP-9 inhibitors. Collectively, these findings further emphasize the proposed protease/antiprotease imbalance in chronic neutrophilic lung disease, providing a potential mechanism contributing to this proteolytic dysregulation.


1997 ◽  
Vol 85 (3) ◽  
pp. 851-858 ◽  
Author(s):  
I. Alex Rubino ◽  
Valeria Zanna ◽  
Anna Marino ◽  
Bianca Pezzarossa

A stimulus portraying a mother figure who is leaving a baby alone on the floor (Separation Theme) was presented tachistoscopically at increasing exposure times, according to the method of the Defense Mechanism Test, to three sex-matched groups of 31 normal subjects, 31 patients with bronchial asthma, and 31 patients with Panic Disorder and Agoraphobia. The frequency of several codings was significantly higher in both clinical groups compared with normal controls. Asthma patients were characterized by reports of the child seen as a statue and of contact or fusion between mother and child. Agoraphobic patients employed different strategies, centered on the mother rather than on the child and mainly represented by the denial of mother's action, e.g., she is not leaving, she is entering. The findings support the hypothesis of a difference in defensive organization between neurotic and psychosomatic patients.


2014 ◽  
Vol 16 (4) ◽  
pp. 295-303 ◽  
Author(s):  
Irram Walji ◽  
Vincent Egan ◽  
Andres Fonseca ◽  
Adam Huxley

Purpose – There is an association between the diagnosis of a mental illness and violent behaviour. Individuals diagnosed with severe and enduring mental health difficulties who display violent behaviour have inferior treatment outcomes when compared with those who do not engage in violent behaviour. Violent behaviour within care settings impacts on general functioning, adherence to treatment plans, and inhibits wider recovery goals. The paper aims to discuss these issues. Design/methodology/approach – This research studied 95 inpatients with a primary diagnosis of severe mental illness, with and without a history of violence, and compared how levels of global functioning and risk impacted on recovery. Patients were divided into two groups: those with and without a previous or current history of violence. The two groups were compared on measures of global functioning, symptomatology, and risk at baseline and 12-month follow up. Findings – Both violent and non-violent groups showed increased global functioning over time, with no significant difference between the groups. Neither group showed significant reductions in risk over time. Patients in the violent group had significantly fewer prior and current symptoms of mental ill-health than non-violent individuals. Research limitations/implications – Despite evidence suggesting that historical or current violence leads to impaired outcomes amongst people with diagnoses of mental illness, the findings of this study suggest a history of violent behaviour was not a predictor of poor progress within inpatient settings. Practical implications – Disconfirming previous hypotheses, the paper suggests that in itself, violent behaviour does not always significantly impair outcomes for individuals diagnosed with mental illnesses, and that many other variables contribute to meaningful recovery. Originality/value – Whilst there are previous studies investigating outcomes for inpatients diagnosed with mental illness who have violent histories, there is a dearth of research comparing equivalent groups in the same facility over the same time period. This study directly compared inpatients with or without a history of violence in the same psychiatric rehabilitation settings.


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