Involvement of capsaicin-sensitive afferent nerves and cholecystokinin 2/gastrin receptors in gastroprotection and adaptation of gastric mucosa to Helicobacter pylori-lipopolysaccharide

Lipopolysaccharide (LPS) is one of the virulence factors in the Helicobacter pylori (Hp)-infected stomach, but it remains unknown whether single and prolonged pretreatment with Hp-LPS can affect the course of gastric damage induced by aspirin (ASA). We compared the effects of Hp-LPS with those induced by LPSs isolated from intestinal Bacteroides fragilis, Yersinia enterocolitica, and Campylobacter jejuni applied for 4 days on acute ASA-induced gastric lesions in rats. The area of ASA-induced gastric lesions, gastric blood flow (GBF), expression of mRNA and protein of leptin and plasma leptin, gastrin, interleukin-1beta, and tumor necrosis factor-alpha levels were examined. Single (once) or repeated (five times) i.p. injections of Hp-LPS (1 mg/kg) or intestinal LPSs failed to produce macroscopic gastric damage and did not affect the GBF when compared with vehicle. Hp-LPS injected repeatedly suppressed the gastric acid secretion, up-regulated leptin mRNA and protein, and increased plasma leptin and gastrin levels. Hp-LPS significantly reduced the ASA-induced gastric damage and the accompanying decline in the GBF, and these effects were significantly attenuated by capsaicin denervation and selective antagonism of cholecystokinin-B (CCK2) receptors by RPR-102681 [N-(metoxy-3 phenyl) N-(N-methyl N-phenyl-carbamylmethyl) carbamoylmethyl]-3 ureido]-3 phenyl]-2 propronique] but not by loxiglumide, an antagonist of CCK1 receptors. We conclude that 1) daily application of Hp-LPS enhances gastric mucosal resistance against ASA damage due to the increase of GBF and the expression and release of leptin and gastrin exerting trophic and gastroprotective effects, and 2) this enhanced resistance to ASA damage in Hp-LPS-adapted stomach is mediated by the sensory afferents and specific CCK2/gastrin receptors.     

Asbestos in the sputum, crackles in the lungs, and radiologic changes in women exposed to asbestos

In a rural community in South Africa historically exposed to asbestos environmentally and occupationally, 200 women who had worked with asbestos and applied for medical examination to determine compensable asbestos disease were evaluated. Clinical and radiologic evaluation, sputum collection, and microscopic analysis were done. A questionnaire elicited type of exposure, duration, decade of first work exposure, and environmental exposure. Crackles were present in the lungs of 166 women and asbestos fibers and ferruginous bodies were present in 122. Asbestosis was identified in 26 and plural plaques in 62. Auscultation for crackles (rales) is useful in the initial examination of former asbestos workers in rural communities of developing countries.     

Synthesis and in vitro cytostatic activity of some new 1,3-(oxytetraethylenoxy)-cyclotriphosphazatriene derivatives

A series of cyclophosphazene crown ether derivatives bearing aziridinyl (ethylene imine) units and also 2-naphthyl or anthraquinone groups as co-substituents has been synthesized and their cytostatic activity against the panel of eight cancer cells in vitro has been studied. The substituents used exhibit different activities: alkylation (aziridinyl groups) and intercalation (naphtyl, anthraquinone groups) against DNA. These both interactions are supposed to enhance the efficiency of the cyclophosphazene crown ether derivatives studied as cytotoxic agents.     

Synthesis and cytotoxic effect of carbocyclic potential minor groove binders

New carbocyclic potential minor groove binders were synthesised, using 3-nitrobenzoyl chloride and aliphatic alpha,omega-diamines with three, four and five methylene fragments. The half structures, compounds IV-VI can be compared to bis-amidines, compounds X-XII to bis-netropsin. All of the compounds were investigated antiproliferative and cytotoxic effects in the standard cell line of mammalian tumour MCF-7.     

Effect of antagonists of adrenergic and cholinergic receptors on ion transport in the isolated rabbit caecum wall

A hypothesis was tested in this study that antagonists of adrenergic and cholinergic receptors affect sodium and chloride ion transport in the rabbit caecum. A modified Ussing chamber was used in the experiment. It was demonstrated that isolated caecum responded to a mechanical stimulus, which consisted in gentle rinsing of the mucous surface, with changes in transepithelial electrical potential difference. An application of ion transport inhibitors, amiloride for sodium and bumetanide for chloride ions, demonstrated that both sodium and chloride ion transport in part determined the response. Pharmaceuticals that are antagonistic at neural receptors (alpha- and beta-adrenergic, nicotinic, and muscarinic), applied both for incubation and stimulation, reduced electrical potential and inhibited responses to mechanical stimuli. Basing on the results of this experiment and literature data, one can presume that analogical responses occur in vivo, and the physiological role of the autonomic system includes regulation of the thickness and consistence of mucus that separates fecal masses from the caecum walls.     

Anticancer activity of bacteriophage T4 and its mutant HAP1 in mouse experimental tumour models

BACKGROUND: Previously, we have shown the ability of the bacteriophage T4 and its substrain HAP1 (selected for a higher affinity to melanoma cells) to reveal antimetastatic activity in a mouse melanoma model. Here, we investigated the potential phage anticancer activity in primary tumour models. MATERIALS AND METHODS: Mice were inoculated subcutaneously with B16 or LLC cells (collected from in vitro culture). Bacteriophages T4 and HAP1 were injected intraperitoneally daily (8 x 10(8)pfu/mouse, except the experiment concerning the dose-dependence). RESULTS: Treatment with purified preparations of bacteriophage T4 resulted in significant reduction of tumour size, the effect being dose-dependent. HAP1 was more effective than T4 and its activity was also dose-dependent. Parallel experiments with non-purified bacteriophage lysates resulted in significant stimulation of tumour growth. CONCLUSION: These data suggest that purified bacteriophages may inhibit tumour growth, a phenomenon with potentially important clinical implications in oncology.     

Effects of ischaemia and hypoxia on the development of the nervous system in acardiac foetus

The twin-reversed arterial perfusion (TRAP) sequence and development of an acardius are rare and severe complications in monozygotic twin pregnancy. Haemodynamic disturbances in placental perfusion via abnormal vascular anastomoses allow inter-twin transfusion to occur. Because of blood perfusion, one of the twins is poorly oxygenated and contains metabolic waste products. Retrograde placental perfusion leads to the formation of a non-viable malformed acardiac foetus. We studied the effects of haemodynamic disturbances in acardiac foetus on the development of the nervous system. The acardius was a product of a 32-weeks pregnancy. Caesarean section yielded a skin covered ovoid mass (size, 10 x 8 cm; weight, 220 g). The dissection of the acardiac twin showed a skin with hair and appendages, rudimentary lower limbs, vertebral column and brain mass. The rudimentary brain tissue was considerably disorganised structurally. We distinguished two main morphological forms of various appearances. In the centre, we observed a scarcely vascularised mass of tissue containing mature and immature neurones, glial cells and randomly distributed fibres. The mass of tissue appeared poorly differentiated, although there were some arrangements reminiscent of cerebral structures. Clusters of neurones provided a slight suggestion of nuclear or fibre structure. The cerebellar cortex was the only well recognisable structure. In the other fragment of the tissue, we found a slit cavity with ependymal outline and well-developed choroid plexus, which seemed to represent the 3rd ventricle. The scarcely vascularised disorganised tissue was surrounded by the highly vascularised one. It included many thin-walled sinusoid vessels. In some places, they were so concentrated that they resembled cavernous haemangioma. The spinal cord appeared comparatively well organised with a slightly dilated central canal. The morphological picture of the rudimentary brain tissue was similar to the picture of the cerebrovasculosa area. The effect of ischaemia in the presented case is the anomalous formation of the cerebral structures. The morphological features imply that the failure occurred after neurulation and before the prosencephalic began to grow. The failure of neural tube formation occurred on the 22nd-25th day of gestation. The malformed formation of the nervous system might be caused by impaired induction due to altered gene expression or to the interference of exogenous agents that interrupt normal development. The haemodynamic abnormal placental circulation, which induced lack of oxygen supply and nutritional deficiency, implies the morphological pattern of the anomaly.     

Toll-like receptors in rat brains injured by hypoxic-ischaemia or exposed to staphylococcal alpha-toxin

Some data suggest that the central nervous system (CNS) is the main target of Staphylococcus alpha-toxin. Since this pathogen cannot penetrate the blood-brain barrier (BBB), the exact mechanism by which alpha-toxin affects the CNS remains unclear. Recent studies on the role of the innate immune system have shed light on how bacterial infections initiate inflammatory responses within the CNS. The aim of this study was to investigate the immunoexpression of Toll-like receptors (TLR 2, TLR 4) in brains of young rats systemically exposed to Staphylococcus alpha-toxin or injured by neonatal hypoxia-ischaemia. The study was carried out on 6-week-old Wistar rats. A group of 6-week-old rats with severe brain injury caused by neonatal hypoxia-ischaemia was also studied separately. In all control rats, the immunoexpression of TLR 2 and TLR 4 was not detected. However, the expression of both TLRs was evident in all brains injured by HI or exposed to alpha-toxin. The immunoexpression was localised in the wall of the small brain vessels, cells of ependyma and leptomeninges. In such vessels the spectrum of ultrastructural lesions was found. The presence of TLR4 detected in the nerve cells of the subcortical gray matter of the brain is particularly of interest, but requires further studies. The presence of TLR 4 antigen in the nerve cells of the subcortical gray matter is particularly of interest. In conclusion, the results show that brain microvessels through TLRs may participate in the immune response of brain affected by bacterial infection as well as injured by non-infection insults.