Characterization of FimH adhesins expressed by Salmonella enterica serovar Gallinarum biovars Gallinarum and Pullorum: reconstitution of mannose-binding properties by single amino acid substitution

Recombinant FimH adhesins of type 1 fimbriae from Salmonella enterica serovar Gallinarum biovars Gallinarum and Pullorum, in contrast to those of Salmonella enterica serovar Typhimurium, did not bind to high-mannose oligosaccharides or to human colon carcinoma HT-29 cells. However, mutated FimH proteins from biovar Gallinarum and biovar Pullorum, in which the isoleucine at position 78 was replaced by the threonine found in S. enterica serovar Typhimurium, bound well to glycoproteins carrying high-mannose oligosaccharides and colon carcinoma cells. The loss of sugar-binding properties by biovar Gallinarum and biovar Pullorum FimH adhesins, which are a part of the type 1 fimbriae, is most probably the result of a single T78I mutation, as was proven by site-directed mutagenesis of FimH proteins.     

Differential cytokine profile in children with cystic fibrosis

The previously observed occurrence of antineutrophil cytoplasmic autoantibodies (ANCA) in patients who have cystic fibrosis (CF), together with the reported decrease in IgG2, a Th1-controlled isotype, suggests a potential for Th1/Th2 imbalance in CF patients with a possible Th2 predominance. 48 CF patients and 16 controls had levels of IFNgamma, IL-4, and IL-10 measured in supernatants of whole blood cell cultures stimulated by lipopolysaccharide (LPS) and phytohemaglutinine (PHA). The patients were divided into 2 groups: "low responders", having negligible secretion of cytokines (IFNgamma: 10.0-200.0 pg/ml, IL-4: 0.0-0.3 pg/ml) and "high responders", producing high levels of both IFNgamma (500.0-2000.0 pg/ml) and IL-4 (1.0-200.0 pg/ml). There was a statistically significant (P < 0.01) deterioration of lung function measured by an FEV(1) decline by 11.2% over 3 years in the "low responder" group. 10 of 16 "low responders" had chronic lung infections with P. aeruginosa while such infection was less prevalent in the "high responder" group where only 13 of 32 CF patients had positive cultures. A shift towards Th2 response was observed in the "high responder" group as children chronically infected with P. aeruginosa had greater IL-4 production than non-infected CF patients within the same cohort. ANCA autoantibodies were found only in the "high responder" group. Th2 immune response predominance in a subset of CF patients is associated with chronic P. aeruginosa infection.     

Changes in the extracellular profiles of neuroactive amino acids in the rat striatum at the asymptomatic stage of hepatic failure

Rats were treated with a hepatotoxin thioacetamide (TAA) and examined 21 days later, when they showed moderate fatty metamorphosis of the liver and morphological changes in brain indicative of excitotoxic neuronal damage, but no evident biochemical or neurophysiological symptoms of hepatic encephalopathy (HE). High-performance liquid chromatography (HPLC) analysis of extracellular amino acids in striatal microdialysates of TAA-treated rats revealed a significant increase in the excitatory amino acids glutamate (Glu) and aspartate (Asp) and their amino acid metabolites glutamine (Gln) and alanine (Ala). Microdialysis in the presence of 50 mM K+ triggered in TAA-treated rats an accumulation of Asp and Glu, and diminished the accumulation of Gln. These effects were virtually absent in control rats. None of the treatments affected the accumulation of the nontransmitter amino acid leucine (Leu). The above changes mirror those previously described in symptomatic HE and are likely to contribute to excitotoxic damage. The basal microdialysate content of taurine (Tau), an amino acid with antioxidant and volume regulatory properties, was 60% lower in TAA-treated rats than in control rats despite its increased blood-to-brain transport. The decrease in extracellular Tau may thus reflect Tau redistribution to adjacent central nervous system (CNS) cells manifesting a cell-protective response. Stimulation with 50 mM K+ increased extracellular Tau in control rats by 182% and in TAA-treated rats by 322%. Stimulation with 100 microM N-methyl-D-aspartate (NMDA) increased extracellular Tau in control rats by 27 % and in TAA-treated rats by as much as 250%. The increase of K+- or NMDA-dependent Tau release may reflect improved cell volume regulation and neuroprotection and contribute to attenuation of neurologic symptoms in rats with liver failure.     

Reducing delirium and cognitive dysfunction after off-pump coronary bypass: A randomized trial

BackgroundNeuropsychiatric complications of surgical coronary revascularization are inconspicuous but frequent and clinically relevant. So far, attempts to reduce their occurrence, such as the introduction of off-pump coronary artery bypass (OPCAB) grafting method, have not brought the desired results. The aim of this trial was to determine whether using any of the 2 selected modifications of OPCAB could decrease the incidence of these undesired sequelae.MethodsIn this single-center, assessor- and patient-blinded, superiority, randomized controlled trial, 192 patients scheduled for elective isolated OPCAB were randomized to 3 parallel arms. The control arm underwent “conventional” OPCAB with vein grafts. The first study arm underwent anaortic OPCAB (ANA) with total arterial revascularization. The second study arm underwent OPCAB with vein grafts using carbon dioxide surgical field flooding (CO₂FF). Outcomes included the incidence of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD).ResultsThe incidence of PD was 35.9% in the control (OPCAB) arm, 32.8% in the CO₂FF arm, and 12.5% in the ANA arm (χ² [2, N = 191] = 10.17; P = .006). Post hoc tests revealed that the incidence of PD in the ANA arm differed from that in the OPCAB arm (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.68; P = .002). The incidence of ePOCD was 34.4% in the OPCAB arm, 28.1% in the CO₂FF arm, and 9.5% in the ANA arm (χ² [2, N = 191] = 11.58; P = .003). Post hoc tests revealed that the incidence of ePOCD differed between the ANA and OPCAB arms (OR, 0.20; 95% CI, 0.06-0.58; P < .001).ConclusionsPerforming ANA significantly decreases the incidence of PD and ePOCD compared with “conventional” OPCAB with vein grafts, whereas CO₂FF is inconsequential in this regard. These results, which probably reflect decreased delivery of embolic load to the brain in ANA, may have practical applicability in daily practice to improve clinical outcomes.     

Relationship between inflammatory markers and clinical patterns of atrial fibrillation in patients with congestive heart failure

BACKGROUND: Occurence of atrial fibrillation (AF) adversely affects left atrial size and cardiac function. This arrhythmia is also associated with an increase of plasma CRP and fibrinogen concentration. It is not clear whether elevated levels of inflammatory markers in patients with congestive heart failure (CHF) are associated with AF, clinical symptoms or adverse cardiac remodelling. AIM: To investigate the association between levels of inflammatory markers and selected clinical and echocardiographic parameters as well as used treatment in the population of CHF patients with various forms of AF. METHODS: The cross-sectional study included 99 patients with CHF divided into 3 groups. Group I included patients with sinus rhythm. Group II consisted of patients admitted to hospital with AF and discharged with sinus rhythm (the category of paroxysmal and persistent AF). Group III comprised patients with permanent AF. In all patients plasma CRP and fibrinogen concentrations were measured and echocardiographic examination was carried out. Left atrial dimension (LA), ejection fraction (LVEF) and right ventricular systolic pressure (RVSP) were assessed. RESULTS: Mean CRP concentration in group III (5.83+/-5.36 mg/l) was significantly higher than in group I (p=0.001) and group II (p=0.033). In the group with permanent AF mean fibrinogen concentration was elevated to a higher level (391.0+/-77.3 mg/dl) than in group II (p=0.007) and group I (p=0.099). Mean LA and RV dimensions and RVSP in group III were significantly higher than in group I and group II. Multivariable analysis revealed that plasma CRP concentration was significantly associated with the presence of arterial hypertension (p <0.001) and LA enlargement (p=0.007). A significant association between fibrinogen level and CRP level (p=0.038), presence of permanent AF (p=0.045) and metabolic syndrome (p <0.05) was found. Values of ln CRP were significantly correlated with LA diameter (r=0.24; p=0.015). CONCLUSIONS: Increased plasma CRP level in patients with CHF were significantly associated with arterial hypertension and LA enlargement. Permanent form of AF and CRP level have been shown to be significantly associated with increased plasma fibrinogen concentration in the course of CHF.     

The role of neurotrophic factors in the pathology and treatment of multiple sclerosis

Multiple sclerosis (MS) is a chronic demyelinating disease of primary autoimmune origin with essential component of subsequent axonal degeneration. It has been found that inflammatory cells crucial for MS pathogenesis are able to release neurotrophic factors (NFs). Thus the concept of neuroprotective effect of inflammation has arisen. Over recent years, increasing number of studies has revealed that NFs play an important role in MS and its animal model — experimental autoimmune encephalomyelitis (EAE). In the current review the evidence for the role of NFs in MS pathogenesis the same as their remarkable potential in MS therapy is presented.     

Amiodarone induced pneumonitis and hyperthyroidism: case report

Amiodarone is a highly effective antiarrhythmic agent used in life-threatening ventricular and supraventricular arrhythmias. Its long-term use may however lead to several adverse effects, including corneal deposits, liver and thyroid gland dysfunction, lung lesions, bone marrow injury, skin lesions, or neurological abnormalities. The article presents the case of a 56-year-old man with a history of a stroke, who after a few days of amiodarone therapy for an episode of atrial fibrillation was diagnosed with amiodarone-induced hyperthyroidism and interstitial pulmonary lesions. Clinical and laboratory symptoms of hyperthyroidism and radiographic signs of pulmonary involvement did not occur until several weeks after discontinuation of amiodarone therapy. Differential diagnosis of causes of hyperthyroidism and diseases causing nodular pulmonary lesions did not demonstrate any other pathologies. Empirical antibiotic therapy and administration of thiamazole and high doses of propranolol failed to improve the patient's clinical status. It was not until thiamazole was given in combination with glucocorticosteroids, when a slow relief of hyperthyroidism symptoms and resolution of radiographic pulmonary signs were observed. Based on the presented case, the risk of appearance of 2 serious concomitant adverse effects was demonstrated, even following a short-term amiodarone therapy. This paper also contains an overview of adverse effects which may be encountered during or after therapy with this effective antiarrhythmic agent. It was emphasized how important it is to select patients appropriately, and to monitor potential adverse effects during amiodarone therapy.     

Cross-cultural adaptation and validation of the health literacy assessment tool METER in the Portuguese adult population

Objective

We aimed to culturally adapt and validate METER in the Portuguese population, and to define cut-off values for adequate health literacy.

Methods

We used the standard procedure for the adaptation of the words and surveyed health professionals to select the non-words. The instrument was administered to a total sample of 249 participants and retested in a sub-sample of 45 after three months. Cut-offs were defined using the modified Angoff procedure. Construct validity was assessed through association with educational attainment and health-related occupation.

Results

Exploratory factor analysis revealed two dimensions of the instrument, one for words and another for non-words. METER showed a high degree of internal consistency, and acceptable test–retest reliability. Adequate health literacy was defined as scoring at least 35/40 in words and 18/30 in non-words. Physicians scored higher than any other group, followed by health researchers, researchers from other areas and by people with progressively lower levels of education (p < 0.001).

Conclusion

We culturally adapted a brief and simple instrument for health literacy assessment, and showed it was valid and reliable.

Practice implications

The Portuguese version of METER can be used to assess health literacy in Portuguese adults and to explore associations with health outcomes.     

The effect of treatment with risperidone,olanzapine or phenothiazines on cognitive functions in patients with schizophrenia

INTRODUCTION: Theaimofthestudywastocomparetheeffectsofrisperidone, olanzapine and phenothiazines on cognitive functions in schizophrenia during short-term (4 &#45 6 weeks) and long-term (3 &#45 4 months) treatment. METHOD: Seventy patients with schizophrenia were investigated: 30 treated with risperidone, 20 with olanzapine and 20 with phenothiazines, in standard doses. Psychometric measurements were made with the Positive and Negative Syndrome Scale (PANSS), and neuropsychological tests included the Trail Making Test (TMT), the Stroop Test and the Wisconsin Card Sorting Test (WCST). RESULTS: PANSS negative symptoms decreased significantly after risperidone and olanzapine, did not change after short-term, and improved marginally after long-term, phenothiazine treatment. Risperidone treatment resulted in significant amelioration of performance on all neuropsychological tests after both short- and long-term treatment. Olanzapine gave benefit on five out of seven subtests, although in most instances this effect was noted only after long-term treatment. Olanzapine was inferior to risperidone in improving WCST performance. Treatment with phenothiazines brought about improvement on two subtests while the results on three showed significant deterioration. CONCLUSION: The results obtained suggest that novel antipsychotics show differential effect on cognition, with risperidone especially improving working memory; however, their effect on negative symptoms and cognitive functions is better than that of typical neuroleptics.     

Association of CD36 gene polymorphisms with echo- and electrocardiographic parameters in patients with early onset coronary artery disease

Introduction

CD36 plays an important role in long-chain fatty acid homeostasis in skeletal muscle and the myocardium. CD36 deficiency may lead to reduced myocardial uptake of long-chain fatty acid. Therefore, different mutations of the CD36 gene may contribute to the clinical heterogeneity of cardiac hypertrophy.

Material and methods

The objective of the study was to investigate whether there is an association between the sequence changes in CD36 and echocardiographic and electrocardiographic parameters in Caucasian patients with early onset coronary artery disease. The study group comprised 100 patients. Electrocardiography and echocardiography were performed in all patients. Amplicons of exons 4 to 6 including fragments of introns were studied using the denaturing high-performance liquid chromatography technique.

Results

IVS3-6TC (rs3173798) heterozygotes had impaired left ventricle diastolic function. 573GA heterozygotes (rs5956) had higher frequency of pseudonormal left ventricular diastolic function and it was confirmed by the increase in wave A’ in the tissue Doppler. 591AT genotype was associated with borderline higher posterior wall end-diastolic thickness and lower E/A ratio. These results are consistent with electrocardiography parameters which could reflect left ventricular hypertrophy (higher R_V5(6) and R_V5(6) + S_V1(2) parameters, depressed ST segments and tendency to longer Qtc II interval) in 591AT heterozygotes.

Conclusions

Detected variant alleles of CD36 may be associated with features of left ventricular hypertrophy and impaired diastolic function.