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.     

Parallel-opposed fields versus four fields, and two- versus three-dimensional radiotherapy planning in thin patients with gynecological malignancies

Conformal radiotherapy constitutes the standard management of pelvic malignancies, yet its role in thin patients remains debatable. This study compares dose distribution for 2D and 3D treatment techniques for cobalt (60Co) and high energy photons from linear accelerator (LA) in cervical and endometrial cancer patients with antero-posterior diameter of less than 20 cm. CT-based 3D treatment planning and 2D simulation were performed in 10 patients. Particular techniques were compared in terms of treatment portal areas, coverage of planning target volume (PTV) and sparing of critical organs. For 60Co beams, PTV was not covered adequately with 2D fields in nine patients and with conformal fields in seven. For LA, PTV was not adequately covered with 2D two-field and 2D four-field ("box") technique in three and one patients, respectively. Mean bladder dose was comparable for all plans. Both 2D "box" and 3D "box" technique spared additional portion of the rectum volume included in 95% isodose, compared to two-field plan. 3D treatment planning better protected the small intestine. Use of multiple field techniques and 3D planning allows for some improvement of PTV coverage and normal tissue sparing, although the magnitude of this benefit must be weighted against savings of time and labour related to use of simpler treatment techniques.     

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.