Essential role of choline for pneumococcal virulence in an experimental model of meningitis

Objectives: The goal of the present study was to elucidate the contribution of the newly recognized virulence factor choline to the pathogenesis of Streptococcus pneumoniae in an animal model of meningitis. Results: The choline containing strain D39Cho^– and its isogenic choline‐free derivative D39Cho^–licA64 –each expressing the capsule polysaccharide 2 – were introduced intracisternally at an inoculum size of 10³ CFU into 11 days old Wistar rats. During the first 8 h post infection both strains multiplied and stimulated a similar immune response that involved expression of high levels of proinflammatory cytokines, the matrix metalloproteinase 9 (MMP‐9), IL‐10, and the influx of white blood cells into the CSF. Virtually identical immune response was also elicited by intracisternal inoculation of 10⁷ CFU equivalents of either choline‐containing or choline‐free cell walls. At sampling times past 8 h strain D39Cho^– continued to replicate accompanied by an intense inflammatory response and strong granulocytic pleiocytosis. Animals infected with D39Cho^– died within 20 h and histopathology revealed brain damage in the cerebral cortex and hippocampus. In contrast, the initial immune response generated by the choline‐free strain D39Cho^–licA64 began to decline after the first 8 h accompanied by elimination of the bacteria from the CSF in parallel with a strong WBC response peaking at 8 h after infection. All animals survived and there was no evidence for brain damage. Conclusion: Choline in the cell wall is essential for pneumococci to remain highly virulent and survive within the host and establish pneumococcal meningitis.     

Day/night differences in stress-induced gastric lesions in rats with an intact pineal gland or after pinealectomy

Abstract:  The formation of acute gastric lesions depends upon the balance between the aggressive factors promoting mucosal damage and the natural defense mechanisms. Previous studies have shown that melatonin inhibits gastric acid secretion, enhances the release of gastrin, augments gastric blood flow (GBF), increases the cyclooxygenase-2 (COX-2)–prostaglandin (PG) system and scavenges free radicals, resulting in the prevention of stress-induced gastric lesions. Besides the pineal gland, melatonin is also generated in large amounts in the gastrointestinal tract and due to its antioxidant and anti-inflammatory properties; this indole might serve as local protective endogen preventing the development of acute gastric damage. The results of the present study indicate that stress-induced gastric lesions show circadian variations with an increase in the day time and a decline at night. These changes are inversely related to plasma melatonin levels. Following pinealectomy, stress-induced gastric mucosal lesions were more pronounced both during the day and at night, and were accompanied by markedly reduced plasma melatonin levels with a pronounced reduction in mucosal generation of prostaglandin E₂ (PGE₂), GBF and increased free radical formation and by small rise in plasma melatonin during the dark phase. We conclude that stress-induced gastric ulcerations exhibit a circadian variation with an increase in the day and attenuation at night and that these fluctuations of gastric stress ulcerogenesis occur also after pinealectomy, depending upon the interaction of COX–PG and free radicals, probably mediated by the changes in local gastric melatonin.     

Association of G-174C Polymorphism of the Interleukin-6 Gene Promoter with Graves' Ophthalmopathy

Interleukin-6 (IL-6) may play an important role in the pathogenesis of Graves' ophthalmopathy (GO). The aim of this study was to analyze the association of IL-6 gene promoter polymorphism, at position -174 (G→C, termed as G-174C), which may affect IL-6 production, with the development of GO. The G-174C polymorphism was determined in 279 Polish-Caucasian patients with Graves' disease (GD), of which 108 had clinically evident ophthalmopathy (NOSPECS class III or higher) and 186 healthy Polish adults. In patients with GD, the frequencies of the C allele (45 vs 42%; P=0.35) and C/C genotype (20 vs 15%; P=0.13) were not significantly different compared to controls. Subdividing patients with GD for the presence of eye disease revealed that the C allele (44 vs 45%; P=0.76) and C/C genotype (20 vs 20%; P=0.92) were equally distributed in patients with or without ophthalmopathy. There was also no association between the G-174C polymorphism and the severity of eye changes. Finally, IL-6 genotypes were not associated with laboratory findings (thyroid volume, serum IL-6 and thyroid autoantibodies levels) in patients with GD at diagnosis. Our results suggest that G-174C polymorphism of the IL-6 gene does not contribute to the development and severity of GO.     

Morpholinium-based ionic liquids show antimicrobial activity against clinical isolates of Pseudomonas aeruginosa

Pseudomonas aeruginosa is a multi-drug resistant (MDR) pathogen. It is classified by WHO as one of the most life-threatening pathogens causing nosocomial infections. Some of its clinical isolates and their subpopulations show high persistence to many antibiotics that are recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Thus, there is a need for non-traditional classes of antibiotics to fight the increasing threat of MDR P. aeruginosa. Ionic liquids (IL) are one such promising class of novel antibiotics. We selected four strains of P. aeruginosa and studied the growth inhibition and other effects of 12 different ILs. We used the well-characterized P. aeruginosa PAO1 (ATCC 15692) as model strain and compared it to three other isolates from chronic lung infection (LES B58), skin burn infection (UCBPP-PA14) and keratitis infection (39016), respectively. The ILs consisted of either 4,4-didecylmorpholinium [Dec₂Mor]⁺ or 4-decyl-4-ethylmorpholinium [DecEtMor]⁺ cations combined with different anions. We found that the ILs with 4,4-didecylmorpholinium [Dec₂Mor]⁺ cations most effectively inhibited bacterial growth as well as reduced strain fitness and virulence factor production. Our results indicate that these ILs could be used to treat P. aeruginosa infections.     

Postnatal ossification sequences in Acrocephalus scirpaceus and Chroicocephalus ridibundus (Aves: Neognathae): The precocial–altricial spectrum and evolution of compound bones in birds

Although the development of the avian skeleton has attracted considerable attention, most of the studies have been concentrated on the embryonic period, while studies on the postnatal period are rare. We studied the postnatal development of the skeleton in two phylogenetically distant birds, an altricial passerine Acrocephalus scirpaceus and a semiprecocial charadriiform Chroicocephalus ridibundus. The neonates of the former, despite being altricial, have well-ossified skeleton—the degree of development approaches that of the semiprecocial gull. However, after hatching the limb bones (particularly those of the hind limb) ossify earlier in the gull which is probably related to faster acquisition of locomotor abilities. We have observed that, in contrast to previous reports from neognathous birds, in the ankle of the gull, the ascending process fuses with the astragalus rather than with the calcaneum. This type of development is present in palaeognaths and nonavian dinosaurs but has not yet been reported in neognaths. This indicates a greater diversity within Neognathae and suggests a more complex scenario for the evolution of the avian ankle. However, data from a greater number of species are needed to establish the developmental sequence ancestral for neognathous birds. Furthermore, the sequence of bone fusions in the wrist of Acrocephalus is similar to the fossil-documented evolutionary sequence observed in the phylogeny of early birds, with the semilunate carpal and major metacarpal fusing first, followed by the alular metacarpal fusing with the major metacarpal and then the major and minor metacarpal fusing proximally. These data underscore the importance of developmental studies for reconstructing the evolutionary history.     

Predictors of Coronary and Carotid Atherosclerosis in Patients with Severe Degenerative Aortic Stenosis

Background. Patients with degenerative aortic stenosis (AS) exhibit elevated prevalence of coronary artery disease (CAD) and internal carotid artery stenosis (ICAS). Our aim was to investigate prevalence of significant CAD and ICAS in relation to demographic and cardiovascular risk profile among patients with severe degenerative AS.Methods. We studied 145 consecutive patients (77 men and 68 women) aged 49-91 years (median, 76) with severe degenerative AS who underwent coronary angiography and carotid ultrasonography in our tertiary care center. The patients were divided into two groups according to the presence of either significant CAD (n=86) or ICAS (n=22).Results. The prevalence of significant CAD or ICAS was higher with increasing number of traditional risk factors (hypertension, hypercholesterolemia, diabetes, smoking habit) and decreasing renal function. We found interactions between age and gender in terms of CAD (p=0.01) and ICAS (p=0.06), which was confirmed by multivariate approach. With the reference to men with a below-median age, the prevalence of CAD or ICAS increased in men aged >76 years (89% vs. 55% and 28% vs. 14%, respectively), whereas the respective percentages were lower in older vs. younger women (48% vs. 54% and 7% vs. 17%).Conclusions. In severe degenerative AS gender modulates the association of age with coronary and carotid atherosclerosis with its lower prevalence in women aged >76 years compared to their younger counterparts. This may result from a hypothetical “survival bias”, i.e., an excessive risk of death in very elderly women with severe AS and coexisting relevant coronary or carotid atherosclerosis.