Increased prevalence of irritable bowel syndrome in patients with bronchial asthma

AbstractIrritable bowel syndrome (IBS) is one of the most common diseases of the gastrointestinal tract. IBS may represent a primary disorder of gastrointestinal motility, accompanied with motor dysfunction in various extraintestinal sites. Recent studies suggest that IBS is associated with bronchial hyper-responsiveness and bronchial asthma might be more prevalent in IBS patients than in control subjects. The aim of our study was to assess the prevalence of IBS in a cohort of asthmatic patients. We evaluated 150 patients with bronchial asthma (71 males and 79 females, aged 45.1±14.9 years) and two control groups including 130 patients with other pulmonary disorder and 120 healthy subjects. All subjects enrolled (asthmatic and controls) completed the Greek version of the Bowel Disease Questionnaire (BDQ). BDQ is a, previously validated, self-report instrument to measure gastrointestinal symptoms. Diagnosis of IBS was based on Rome II criteria. The IBS prevalence was significantly higher in asthmatics (62/150, 41.3%) than in subjects with other pulmonary disorders (29/130, 22.3%,P <0.001) and healthy ones (25/120, 20.8%, P<0.001). For all subjects studied, the prevalence of IBS was significantly higher in females (78/214, 36.4%) than in males (38/186, 20.4%, P<0.001). The IBS prevalence in asthmatic males was 29.5% vs. 15.2% in male patients with other pulmonary disorders (P=0.002) and 14.2% in male healthy subjects (P=0.002). The IBS prevalence in asthmatic females was 51.8% vs. 28.1% in females patients with other pulmonary disorders (P<0.001) and 26.5% in females healthy subjects (P<0.001). None of the asthma medications were associated with increased or decreased likelihood of IBS. We conclude that patients with bronchial asthma have an increased prevalence of IBS. Further studies are needed to clarify the potential pathogenetic mechanisms underlying the association between IBS and asthma

Tailoring the specificity of the type C feruloyl esterase FoFaeC from Fusarium oxysporum towards methyl sinapate by rational redesign based on small molecule docking simulations

The type C feruloyl esterase FoFaeC from Fusarium oxysporum is a newly discovered enzyme with high potential for use in the hydrolysis of lignocellulosic biomass but it shows low activity towards sinapates. In this work, small molecule docking simulations were employed in order to identify important residues for the binding of the four model methyl esters of hydroxycinnamic acids, methyl ferulate/caffeate/sinapate/p-coumarate, to the predicted structure of FoFaeC. Subsequently rational redesign was applied to the enzyme’ active site in order to improve its specificity towards methyl sinapate. A double mutation (F230H/T202V) was considered to provide hydrophobic environment for stabilization of the methoxy substitution on sinapate and a larger binding pocket. Five mutant clones and the wild type were produced in Pichia pastoris and biochemically characterized. All clones showed improved activity, substrate affinity, catalytic efficiency and turnover rate compared to the wild type against methyl sinapate, with clone P13 showing a 5-fold improvement in catalytic efficiency. Although the affinity of all mutant clones was improved against the four model substrates, the catalytic efficiency and turnover rate decreased for the substrates containing a hydroxyl substitution

Could IFN-γ predict the development of residual pleural thickening in tuberculous pleurisy?

Background. The aim of our study was to identify predictive factors for the development of residual pleural thickening (RPT) in patients with tuberculous pleurisy (TP). Methods. A retrospective study of patients with pleural tuberculosis. The clinical and radiological characteristics, and measurements of microbiological and biochemical parameters or markers such as adenosine deaminase (ADA), interferon-γ (IFN-γ) and vascular endothelial growth factor (VEGF) in pleural fluid were studied. Results. Thirty one patients (24 male and 7 female) with a mean age of 55.9 years were studied. There were 25 (80.6%) patients with RPT > 2 mm and 6 (19.4%) patients without RPT. Ten patients (32.2%) had RPT ≥ 10 mm. The rate of pleural thickening was less in small effusions (p<0.05). IFN-γ was higher in patients with RPT ≥ 10 mm (p < 0.05) in comparison with those with RPT < 10 mm. Conclusions. Pleural fluid IFN-γ may deserve further investigation in order to build up preventive and therapeutic strategies against RPT and its clinical complications

Failure to Recognize Nontuberculous Mycobacteria Leads to Misdiagnosis of Chronic Pulmonary Tuberculosis

BACKGROUND: Nontuberculous mycobacterial (NTM) infections cause morbidity worldwide. They are difficult to diagnose in resource-limited regions, and most patients receive empiric treatment for tuberculosis (TB). Our objective here is to evaluate the potential impact of NTM diseases among patients treated presumptively for tuberculosis in Mali. METHODS: We re-evaluated sputum specimens among patients newly diagnosed with TB (naïve) and those previously treated for TB disease (chronic cases). Sputum microscopy, culture and Mycobacterium tuberculosis drug susceptibility testing were performed. Identification of strains was performed using molecular probes or sequencing of secA1 and/or 16S rRNA genes. RESULTS: Of 142 patients enrolled, 61 (43%) were clinically classified as chronic cases and 17 (12%) were infected with NTM. Eleven of the 142 (8%) patients had NTM disease alone (8 M. avium, 2 M. simiae and 1 M. palustre). All these 11 were from the chronic TB group, comprising 11/61 (18%) of that group and all were identified as candidates for second line treatment. The remaining 6/17 (35.30%) NTM infected patients had coinfection with M. tuberculosis and all 6 were from the TB treatment naïve group. These 6 were candidates for the standard first line treatment regimen of TB. M. avium was identified in 11 of the 142 (8%) patients, only 3/11 (27.27%) of whom were HIV positive. CONCLUSIONS: NTM infections should be considered a cause of morbidity in TB endemic environments especially when managing chronic TB cases to limit morbidity and provide appropriate treatment

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives:We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT(&gt; MIC) (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving beta-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of &gt;= 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025].Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections

A holistic approach to factors affecting depression in haemodialysis patients

Depression in dialysis populations is affected by co-morbid diseases, such as cardiovascular disease, diabetes, and immune dysfunction, and it also includes high suicide risk and frequent hospitalizations. Depressive disorders have a close association with malnutrition and chronic inflammation, as well as with cognitive impairment. Impaired cognitive function may be manifested as low adherence to dialysis treatment, leading to malnutrition. Additionally, chronic pain and low quality of sleep lead to high rates of depressive symptoms in haemodialysis patients, while an untreated depression can cause sleep disturbances and increased mortality risk. Depression can also lead to sexual dysfunction and non-adherence, while unemployment can cause depressive disorders, due to patients’ feelings of being a financial burden on their family. The present review provides a holistic approach to the factors affecting depression in haemodialysis, offering significant knowledge to renal professionals. © 2018, Springer Science+Business Media B.V., part of Springer Nature

Drug-Induced Skin Adverse Reactions: The Role of Pharmacogenomics in Their Prevention

Adverse drug reactions (ADRs) affect many patients and remain a major public health problem, as they are a common cause of morbidity and mortality. It is estimated that ADRs are responsible for about 6% of hospital admissions and about 9% of hospitalization costs. Skin is the organ that is most frequently involved in ADRs. Drug-induced skin injuries vary from mild maculopapular eruptions (MPE) to severe cutaneous adverse reactions (SCARs) that are potentially life threatening. Genetic factors have been suggested to contribute to these SCARs, and most significant genetic associations have been identified in the major histocompatibility complex (MHC) genes. Common drugs associated with SCARs connected with strong genetic risk factors include antiepileptic drugs (AEDs), allopurinol, abacavir, nevirapine, sulfonamides, dapsone, non-steroidal anti-inflammatory drugs (NSAIDs), and analgesic drugs. However, genetic associations vary between different ethnic populations. Differences may in part be explained by the different prevalence of HLA (human leukocyte antigen) alleles among ethnic groups. In this review, we present and discuss the recent advances in genetic associations with ADRs in the skin. Many of these ADRs are now preventable with pharmacogenetic screening. © 2018, Springer International Publishing AG, part of Springer Nature