Tumour adaptation to immune factors: old and new ideas for cancer immunotherapy.

The tumour is fully functional in the zone of action of immune mediators. Moreover, the tumour needs immune system mediators to survive. "Adaptation" refers to a tumour's ability to withstand the effect of harmful elements. This gives birth to a new form of antitumour therapy: blocking tumour adaptability pathways. In this review, we will look at (i) tumour adaptation mechanisms as a result of pro-tumour immunoediting, (ii) how understanding tumour-adaptive mechanisms has led to ideas for developing cancer immunotherapies, and (iii) prospects for using the adaptation theory to substantiate new approaches to tumour growth inhibition. By considering the cancer problem through the lens of adaptability, a unique strategy for enhancing the efficacy of immunotherapy was proposed. The new approach is to utilise antisense treatment to erase the structural trace of adaptation in tumour cells or to disadapt tumour cells by "turning off" the immune system before initiating immunotherapy.

Chronic Effects of Modeled Myocardial Infarction, Thoracic Trauma, and Denervation of Hind Limb on Rheographic Parameters of Rat Femoral Arteries In Situ.

In experiments on narcotized male rats (n=85), the mean electroimpedance Z and peak-to-peak magnitudes (the swing ranges) of passive (ΔZp) and active (ΔZa) pulsatile electroimpedance oscillations of isolated segment of femoral arteries were determined in situ. These rheographic parameters (RP) were measured in intact animals and in those with modeled chronic myocardial infarction, chronic denervation of the right hind leg, as well as in rats subjected to sham operations to mimic denervation or infarction (with thoracic trauma). The rats with modeled myocardial infarction demonstrated decreasing trends of all RP. In sham-operated rats with thoracic trauma, ΔZp increased significantly on postsurgery months 2-4 by 4.3 times in comparison with the control. No essential correlation was found in denervated rats between RP of any femoral artery and severity of neuropathic pain syndrome assessed by autotomy of the operated leg. In these rats, the mean electroimpedance Z of any femoral artery was significantly greater than the control level. They demonstrated especially high values of ΔZp with significant difference between ΔZp of innervated and denervated hind leg. In denervated rats, ΔZa was significantly greater than the control value without significant difference between ΔZa of both femoral arteries. The paradoxically great increase of ΔZp (100- and 50-fold for innervated and denervated legs, respectively) and a significant 3-fold increment of ΔZa in both hind legs provoked by denervation of one of them are discussed in relation to searching for the ways of systemic influences on vascular network in clinics and experiments.

Anticonvulsant Effects of Combined Treatment with Citicoline and Valproate on the Model of Acute Generalized Convulsions Induced by Pentylenetetrazole in Wistar Rats.

We studied anticonvulsant effects of combined treatment with citicoline, a nootropic substance with neuroregenerative and neuroprotective activities, and valproate, an antiepileptic agent widely used in the treatment of epilepsy, on the model of pentylenetetrazole-induced (75 mg/kg, intraperitoneally) acute generalized convulsions in male Wistar rats. Combined treatment with citicoline and valproate in minimum effective doses (70 and 300 mg/kg, respectively) potentiated the anticonvulsant properties of both agents.

Аnticonvulsant effects of citicoline and diazepam at their combined application on model of the acute generalized convulsions induced by pentylenetetrazole in Wistar rats.

The purpose: Studying of efficiency of the combined application of the citicoline possessing nootropic and anticonvulsive action and antiepileptic drug of diazepam on the acute generalized convulsions (AGC) caused by a convulsant pentylentetrazole (PTZ). Methods: Experiments are executed on the male Wistar rats (n = 68) weighing 160-190 g on the AGС model caused by of PTZ in a dose of 80 mg/kg, intraperitoneally (i.p.). For studying of efficiency of the combined use of drugs determined the minimum anticonvulsive action of a citicoline (Tserakson, «Nicomed Ferrer Internacional, S.A.¼) and diazepam (Relanium, Warsaw pharmaceutical plant of Polf AO, Warsaw, Poland). For this citicoline were administered i.p. in doses 500 and 300 mg/kg 1 hour before the PTZ and diazepam - in doses of 0,5 and 0,25 mg/kg 30 min before administration of PTZ. Control animals were injected with saline to the same extent and under the same experimental conditions. Results: It is shown that the combined administration of a citicoline and diazepam in minimum active doses (300 and 0.25 mg/kg respectively), increases anticonvulsive properties of both drugs. Conclusion: The combined administration of citicoline with diazepam in minimally active doses enhances anticonvulsant properties of both drugs, thereby reducing the risk of development of side effects. In addition, the research may serve as experimental justification for the use of drugs in case of convulsions for the purpose beneficial effect on cognitive function and delays of progressing of neurodegenerative processes.

[INDICATORS OF PHAGOCYTIC ACTIVITY OF MONOCYTES AND CYTOKINE PROFILE IN PATIENTS WITH ERYSIPELAS OF VARYING SEVERITY].

Erysipelas (PB) ­ a serious disease that is accompanied by severe complications and high lethality. The immunological investigations were carry out in 51 patients who were treated at the clinic for erysipelas with an immunomodulator application. Marked changes in the indices of phagocytic activity of monocytes (PHAM) and the cytokine profile in patients with erysipelas were note. Application in complex treatment of immunomodulator give the positive effect on the indices of PHAM.

Increase of the seizure threshold in C57BL/6 mice after citicoline administration.

We studied the dose-dependent effect of preventive intraperitoneal injection of citicoline (cytidine 5'-diphosphocholine) on acute generalized epileptiform activity in C57Bl/6 mice. The duration of citicoline action was also evaluated. Administration of citicoline in doses of 500 and 1000 mg/kg 1 h before treatment with the convulsant agent pentylenetetrazole produced an anticonvulsant effect. This effect was manifested in an increase of the threshold of clonic seizures and tonic phase of seizures with lethal outcome. Moreover, the latency of seizure development was elevated under these conditions. The anticonvulsant effect of citicoline persisted for 6 h after its injection.

[Ecologically-dependent vitamin-minerals insufficiency in the sportsmen's organism].

The authors revealed the reduction of saturation of iron, copper, zinc, E and B2 vitamins in sportsmen's organism under high physical exercise. The negative effect was associated with the duration of training - competition cycles. The reduced vitamin-mineral saturation of the organism was associated with the low ferritin level and an imbalance in the hormonal regulation of erythropoiesis. The state of erythropoiesis can be a criterion performance of athletes, whereas a degree of saturation of the body with minerals and vitamins can be the criterion for prenosological diagnosis of their health and professional relevance.

[Neuroimmunological aspects of the pathogenesis of epilepsy].

The review is devoted to the analysis of neuroimmunological aspects of the pathogenesis of epilepsy. Discuss the pathogenetic role of proinflammatory cytokines, antibodies to antigens of the nervous tissue and neurotransmitters, such as dopamine, serotonin, glutamate and GABA in the pathogenesis of epilepsy. The focus of the review is given to clinical research, devoted to the interrelation of the severity of the disease and changes of immunological indices. Disorders of the immune system are most pronounced in drug-resistant forms of epilepsy. Describes the clinical and experimental research, which shows that the use of antiepileptic drugs improves immunity. The use of immunotherapy in combination with anti-epileptics drugs leads to positive results. Thus, the analysis of the immune status of patients with epilepsy can serve as an important criterion for determining the severity of the disease and the appointment of adequate treatment. The authors analyze their own data of anticonvulsant activity of antibodies to glutamate and opposite proconvulsant effect of antibodies to GABA.

[Vitamin and mineral status of oarsmen during the training-competition cycles].

Vitamin and minerals status of 30 sportsmen aged 16.8 +/- 0.2 years (trained in boat racing 5.0 +/- 0.3 years) during the training--competition cycles in autumn and winter has been studied. A significant decrease of vitamin A level in the range of reference limits was found in 30.8% of sportsmen during autumn season, but such decrease was revealed in 100% of examined sportsmen during winter Vitamin B1 and B2 deficiency has been detected in both seasons. The portion of persons with vitamin B2 deficiency increased during training cycles. A significant decrease of magnesium (in 56.3% of sportsmen) and sodium level (in 33.3% of sportsmen) was detected during autumn season. Irrespective of the season a significant decrease of blood serum of calcium (in 40.0-66.7% of sportsmen); potassium (in 53.3-66.7% of sportsmen according to both absolute and individual data); chlorides (in 50.0-90.0% of sportsmen), and iron (in 53.3-60.0% of sportsmen) has been revealed. The data obtained indicate the need for diagnostics and correction of vitamin and minerals status in sportsmen.

Effects of antibodies to glutamate on focal penicillin-induced epileptic activity.

The effects of intranasal pretreatment with antibodies against glutamate on focal penicillin-induced epileptic activity were studied by recording electrocorticogram in non-anesthetized freely moving male Wistar rats. Anticonvulsant effects of intranasal administration of anti-glutamate antibodies (300 µg/kg) 1 h before application of penicillin (30,000 U/ml) on the sensorimotor cortex was demonstrated: the latency of ictal discharges increased and their frequency decreased.

Elevation of seizure threshold after intranasal administration of anti-glutamate antibodies to C57BL/6 mice.

The dose-dependent effect of intranasal administration of antibodies to glutamate on acute generalized epileptic activity was studied in C57Bl/6 mice. It was shown that pretreatment with antibodies in doses of 100, 300, and 500 µg/kg 1 h before titration with convulsant pentylenetetrazole had anticonvulsant effects. This treatment was followed by an increase in the thresholds of clonic and tonic seizures with fatal outcome and lengthening of seizure latency. The most pronounced effect was observed in doses of 300 and 500 µg/kg. Comparison of the anticonvulsant effect of antibodies in active immunization with glutamate-BSA conjugate and systemic intraperitoneal administration of purified anti-glutamate antibodies revealed advantages of intranasal administration.

[Improvement of method for detecting volatile fatty acids in air].

The authors demonstrated possible use of capillary columns to detect volatile fatty acids in air. Tenax TA as adsorbent is recommended.

[Cancer risk assessment in a group of traffic officers].

Air-pollution studies in the area where the traffic officers of the road-patrol service of the State Inspectorate for Road Traffic Safety, who patrol road traffic safety, breathe at the stationary militia inspection stations (MIS) and in the areas of the heaviest motor traffic highways of a city ascertained the cancer risk from exposure to carcinogenic agents, such as benzo(a)pyrene, benzene, and formaldehyde. The mean concentrations of these substances do not exceed the hygienic limits. In terms of the hazard index (1.04) and the individual's cancer risk index (4.8 x 10(-5)), the cancer risk for the traffic officers of MIS may be considered acceptable. Both indices (1.28 and 1.3 x 10(-4), respectively) for traffic officers and traffic controllers are suggestive of an increased cancer risk, which constitutes a potential threat to a rise in cancer morbidity in this occupational group and needs preventive measures to be undertaken.

Effect of cesium radioisotope on humoral immune status in Ukrainian children with clinical symptoms of irritable bowel syndrome related to Chernobyl disaster.

UNLABELLED: The aim of this study is to determine humoral immune status in Ukrainian children with clinical symptoms of irritable bowel syndrome 23 years after the Chernobyl disaster. METHOD AND MATERIAL: The test population consisted of 95 participants: 75 rural patients aged 4-18, who lived in a contaminated area exposed to natural environmental radiation (falling under three groups) and 20 healthy urban participants from Kiev aged 5-15 as a control group. Internal radiation activity has been measured by gamma-ray spectrometry. B-lymphocytes population was analyzed with monoclonal antibody against antigen CD22(+). Serum immunoglobulins were evaluated by enzyme-linked immunosorbent assay (ELISA) method. p < 0.05 was considered significant. RESULT: The percentage of CD22(+) in study groups is increased significantly in comparison to control group at p < 0.05. Reduced serum immunoglobulins levels have developed in the majority of the participants. CONCLUSION: Humoral immune status of study groups with clinical symptom of irritable bowel syndrome residing in a contaminated area has changed.

[Influence of antibodies to the glutamate on convulsive reaction to mice C57Bl/6 in term of chronic epileptogenesis].

It was shown that the preliminary single i.p. injection of antibodies (AB) to glutamate (GLU) 1,5 hours prior to the first injection pentylenetetrazole (prior to the beginning of kindling) did not have an effect on latency period of appearance and the severity of convulsive reactions in the mice of C57Bl/6. The administrations of AB to GLU at the different stages of kindling animals with different severity of seizures did not have an effect on their severity. Thus, AB to GLU did not posses antiepileptic effect. However, AB to GLU posses anticonvulsive action on the acute seizures reaction, inducing an increase in the thresholds of clonic seizures and tonic phase seizures with lethal outcome as well as an extended latency period of occurrance these seizures in mice with enhanced kindling-producing convulsive readiness of the brain. This effect was revealed at the different stages of kindling in animals with the severity of seizures 2-3 and 4-5 marks. Possible to assume, that the mechanisms of chronic epileptogenesis (in this case, in the form kindling-dependent enhanced convulsive readiness of the brain) and those of the acute convulsive reaction are not similar.

[Autoantibodies to glutamate, GABA, dopamine and serotonin in the dynamics of development of chronic brain epileptization in mice C578l/6].

In experiments on mice C57Bl/6 was studied the possibility of production of glutamate, GABA, dopamine and serotonin autoantibodies in the dynamics of development of chronic brain epileptization--pharmacological kindling, induced by daily administration of pentylenetetrazol in subconvulsive dose (30 mg/kg) during 24 days. 14 days after the start of the kindling autoantibodies to glutamate was detected in all experimental animals, to CABA--in 60% of mice, to serotonine--in 70%, and to dopamine--in 90%. After 24 days--the number of animals with autoantibodies to glutamate and dopamine was decreased, to serotonin--increased, and to GABA--was not altered. It was shown the relationship between detection neurotransmitters autoantibodies and severity of the convulsive reaction.

Low internal radiation alters innate immune status in children with clinical symptom of irritable bowel syndrome.

Adverse health effect of low radiation is clear. The aim of this study was to determine effect of internal low radiation on innate immune status in Ukrainian children with spastic colitis as a result of Chernobyl disaster. The test population consisted of 95 participants: 75 rural participants with clinical symptom of irritable bowel syndrome, aged 4 to 18, who lived in a contaminated area exposed to radio nucleotide due to the disaster in reactor in Chernobyl nuclear power plant (categorized in three groups) and 20 healthy urban participants from Kiev, aged 5 to 15, as the control group. Internal radiation activity has been measured by gamma-ray spectrometry. Peripheral blood leukocytes were analyzed for CD16(+) subset, serum concentration of circulation immune complex was measured by the polyethylene glycol method. Phagocytic activity function was assessed by using latex article and phagocytic index were calculated. p < 0.05 was considered significant. Percent of CD16(+) cell in groups II and III increased significantly in comparison to control group (p < 0.05). Concentration of circulating immune complexes increased significantly in all study groups compared to control group (p < 0.001). Phagocytes activity and phagocyte index decreased significantly in all study groups in comparison to control group (p < 0.001). The innate immune status of study groups has changed. Our data have demonstrated that this change may be related to radioactivity from technogenic pollution due to the disaster in reactor in Chernobyl nuclear power plant.

Affects of ionizing radiation on T-cell population lymphocyte: a risk factor of irritable bowel syndrome.

Irritable bowel syndrome is observed mostly in Ukrainian children and may be related to adverse health effects as a result of the Chernobyl disaster. The aim of this study was to determine status of T-cell population lymphocytes in children with clinical symptom of irritable bowel syndrome. The test population consisted of 95 participants: 75 rural patients aged 4 to 18 who lived in a contaminated area exposed to natural environmental radiation with clinical symptom of irritable bowel syndrome (categorized in three groups) and 20 healthy urban participants from Kiev aged 5 to 15 as control group. Internal radiation activity has been measured by gamma-ray spectrometry. Peripheral blood leukocytes were analyzed for T-lymphocytes subset such as T-lymphocytes (CD3(+)), T-helper (CD4(+)) and T-cytotoxic (CD8(+)) and then CD4/CD8 ratio was calculated. Percentage of CD3(+) and CD4(+) in all study groups decreased significantly in comparison to control group (p < 0.001). Percentage of CD8(+) increased significantly in all study groups in comparison to control group (p < 0.05). The CD4/CD8 ratio decreased significantly all study groups in comparison to control group (p < 0.001). Cellular immune status of study groups that are residing in a contaminated area has changed. Our data have demonstrated that this change may be related to a higher incidence of children with irritable bowel syndrome.

[Expression of gene recA of Deinococcus radiodurans in Escherichia coli cells].

Plasmids pKS5 and pKSrec30 carrying normal and mutant alleles of Deinococcus radiodurans recA gene controlled by the lactose promoter slightly increase radioresistance of Escherichia coli cells with mutations at genes recA and ssb. The RecA protein of D. radiodurans is expressed in E. coli cells, and its synthesis can be supplementary induced. The radioprotective effect of the xenologic protein does not exceed 1.5 times and is essentially to the contribution of plasmid pUC 19-recA1.1 harboring the E. coli recA+ gene in the recovery of resistance of the deltarecA deletion mutant. These data suggest that the expression of D. radiodurans recA gene in E. coli cells does not complement mutations at gene recA in the chromosome possibly due to structural and functional peculiarities of the D. radiodurans RecA protein.

[Sanitary and chemical control over workplace air in production of acrylic acid and its aethers].

The authors specified highly sensitive method based on capillary gas chromatography to detect acryl compounds in workplace air. The method is designed for industrial laboratories assessing quality of workplace air in acrylic acid and its aethers production.