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.     

Investigation of local reaction of muscular tissue after injection of polyvinylpyrrolidone preparation

Natural preparations for replenishing of hyaluronic acid of zoogenous origin used till now, are characterized with quit low biocompatibility and also too short effect of their action. Recently worked out synthetic polyvinylpyrrolidone preparation PVP, contains modification constituting internally netting of microgels to improve polymer bioresistance. The introduce modification can, however influence PVP biocompatibility after deposition into tissues of the living organism. The aim of research was evaluation of the local reaction of muscular tissue after PVP infection. The results of research concerned a control group where normal saline was used for infections. The research was carried out on 18 Wistar rats and included macroscopic and histologic observations made in the 3rd, 5th, 7th, 14th and 30th day after PVP injection into thigh muscle. The local reaction of muscular tissue was macroscopically characterized with inflammatory reaction till the 7th day after PVP injection, in later terms the observed changes disappeared. Microscopic research showed that PVP till the 7th day after PVP injection caused rather strong diffuse non-specific inflammatory process, yet without essential participation of neutrophils leading to producing of loose intra-muscular. Connective tissue in a later term. The carried out tests showed presence of PVP in muscular tissue till the 30th day after injection.     

Tissue reaction after injection of polyvinylpyrrolidone (PVP) preparation into knee joint. Experiment

Internally netted miscogelatinated preparation on the basis of polyvinylpyrrolidone PVP desioned for viscosuplementation of joint fluid was worked out. Netted structure of microgel grains presents larger resistance to the degrading action of free radicals than analogical linear polymer chains. Application of zoogeous preparations of hyaluronic acid results in short-term effects of their usage in evoking reaction foreign protein. Replenishment of joint fluid with preparation with higher biostability from biocompatible synthetic polymer-polyvinylpyrrolidone could improve the function of synovial through restoration of its proper viscosity and protection of the joint for a longer period of time. The aim of the experiment was determination of bioresistance and reaction of microgel PVP on the tissues of synovial joint. The tests were carried out on 10 white New Zealand rabbits after injection PVP into the knee joint for 3, 7, 14 and 30 days and submitted to macroscopic and histological evaluation. The results of tests were compared with the data obtained after injection of normal saline. Macroscopically, there were no changes in the limits of articular capsule and cartilage; there was only slight and enlargement of synovial membrane in the first 7 days after PVP injection. In histological tests it was observed that reaction in the knee joint after PVP injection was characterised it single inflammatory chains without essential participation of neutrophils observed only in synovial membrane and limited to places were tested preparation was seen. Microgel PVP was present in diverticula of synovial membrane to 30th day after injection.     

Posterior capsule opacification as a complication of the posterior chamber intraocular lens implantation

PURPOSE: The aim of the study was to evaluate factors possibly effecting the posterior capsule opacification (PCO), after extra-capsular cataract extraction with the posterior chamber intra-ocular lens (IOL) implantation. Age of patients, refractive errors, technique of cataract extraction, intra- and postoperative complications and coexisting diseases were taken into consideration. In 1992-98 posterior laser Nd:YAG capsulotomy was performed in 222 eyes of 222 patients (134 women and 88 men) previously operated in 1st and IInd Eye Clinic. PCO occurred in 5.8% patients, who underwent cataract extraction in this period, in 5.7% patients operated with phacoemulsification method and in 5.8% patients where extra-capsular cataract extraction with nucleus expulsion was performed. PCO was diagnosed in 12.7% patients at the age below 30, in 17% aged 31-40, in 7.8% aged 41-55 and in 5.1% patients older than 55 years. Among the patients, who developed PCO, in 6.3% myopia was present, in 8% primary open angle glaucoma, 16.6% were treated for diabetes mellitus. In 7.6% eyes the intra-operative cortical clean up was not efficient. CONCLUSION: PCO occurred in young patients (under 40) twice as often as in the other groups of age. Technique of cataract extraction had an influence on the incidence of PCO as well.     

Diode laser cyclophotocoagulation--effect on intraocular pressure in comparison with cyclodiathermy under the scleral flap

The aim of this study was to retrospectively analyze intraocular pressure and state of the eyeball in patients treated with diode laser, and to compare the outcomes with a group of patients after cyclodiahtermy under the scleral flap. We analyzed: visual acuity, IOP, percentage of lowering the IOP from the beginning, subjective patients' feelings of pain and complications. Conclusions: TSCPC is safe for patients and may be repeated, if needed. Laser cyclodestruction gives new possibilities in noninvasive IOP lowering with less complications than cyclodiahtermy, without changes in patient's visual functions.