Analysis of the Intensity of Nitric Oxide Production in Different Parts of the Spinal Cord after Modeling Combined Cerebral and Spinal Injury.

Using the method of electron paramagnetic resonance spectroscopy, we showed that NO production decreases by 60% (p<0.05) in the region located rostral to the spinal cord injury 7 days after combined injury to the brain and spinal cord. At the same time, NO production did not change in the site of spinal cord injury and caudal to the injury.

Alkaloid-Based Isoxazolylureas: Synthesis and Effect in Combination with Anticancer Drugs on C6 Rat Glioma Model Cells.

Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor activity, in combination with the commonly used five anticancer drugs, namely cyclophosphane, fluorouracil, etoposide, cisplatin, ribomustine with different mechanisms of action, was investigated. Based on the quantum chemical calculations data and molecular docking, hypotheses have been put forward to explain their mutual influence when affecting C6 rat glioma model cells.

Investigation of NO Role in Neural Tissue in Brain and Spinal Cord Injury.

Nitric oxide (NO) production in injured and intact brain regions was compared by EPR spectroscopy in a model of brain and spinal cord injury in Wistar rats. The precentral gyrus of the brain was injured, followed by the spinal cord at the level of the first lumbar vertebra. Seven days after brain injury, a reduction in NO content of 84% in injured brain regions and 66% in intact brain regions was found.

Effect of the isotiazole adjuvants in combination with cisplatin in chemotherapy of neuroepithelial tumors: experimental results and modeling.

Chemotherapy is one of the main treatment options for cancer, but it is usually accompanied with negative side effects. The classical drugs combination with synergistic adjuvants can be the solution to this problem, allowing reducing therapeutic dose. Elucidating the mechanism of adjuvant action is of key importance for the selection of the optimal agent.

Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model.

Immunotherapy in the form of anticancer vaccination relies on the mobilization of the patient's immune system against specific cancer antigens. Instead of focusing on an autologous cell lysate, which is not always available in clinical practice, the present study investigates vaccines utilizing xenogeneic foetal tissue that are rich in oncofoetal antigens. Lewis lung carcinoma (LLC)-challenged C57BL/6 mice were treated with either a xenogeneic vaccine made from chicken whole embryo, or a xenogeneic vaccine made from rat embryonic brain tissue, supplemented with a protein fraction as an adjuvant.

Bacterial ghosts as adjuvants in syngeneic tumour cell lysate-based anticancer vaccination in a murine lung carcinoma model.

Instead of relying on external anticancer factors for treatment, immunotherapy utilizes the host's own immune system and directs it against given tumour antigens. This study demonstrated that it is possible to overcome the documented immunosuppressive properties of tumour cell lysate by supplementing it with appropriate adjuvant. Lewis lung carcinoma (LLC)‑challenged C57BL/6 mice were treated with LLC cryo‑lysate mixed with either bacterial ghosts (BGs) generated from E.

The influence of heterocyclic compound-PAMAM dendrimer complexes on evoked electrical responses in slices of hypoxic brain tissue.

We used complexes between a fourth generation polyamidoamine (PAMAM) dendrimer and one of two heterocyclic compounds - 1-(6-hydroxyhexyl)-3-(5-phenyl-isoxazole-3-yl)-urea or 5-phenyl-isoxazole-3-carboxylic acid - to reduce oxygen consumption in transverse slices of the hippocampus taken from 4-week old male rats. In vitro electrophysiological experiments revealed that the inhibitory effect of the hypoxic state on the evoked responses was enhanced in the presence of the complexes. The data were analyzed in terms of the potential antitumor effects of these complexes.

Lipopolysaccharide-induced neuronal activation in the paraventricular and dorsomedial hypothalamus depends on ambient temperature.

Systemic inflammatory response syndrome is associated with either fever or hypothermia, but the mechanisms responsible for switching from one to the other are unknown. In experimental animals, systemic inflammation is often induced by bacterial lipopolysaccharide (LPS). To identify the diencephalic and brainstem structures involved in the fever-hypothermia switch, we studied the expression of c-Fos protein, a marker of neuronal activation, in rats treated with the same high dose of LPS (0.

Naturally occurring hypothermia is more advantageous than fever in severe forms of lipopolysaccharide- and Escherichia coli-induced systemic inflammation.

The natural switch from fever to hypothermia observed in the most severe cases of systemic inflammation is a phenomenon that continues to puzzle clinicians and scientists. The present study was the first to evaluate in direct experiments how the development of hypothermia vs. fever during severe forms of systemic inflammation impacts the pathophysiology of this malady and mortality rates in rats.

Improved cellular specificity of plasmonic nanobubbles versus nanoparticles in heterogeneous cell systems.

The limited specificity of nanoparticle (NP) uptake by target cells associated with a disease is one of the principal challenges of nanomedicine. Using the threshold mechanism of plasmonic nanobubble (PNB) generation and enhanced accumulation and clustering of gold nanoparticles in target cells, we increased the specificity of PNB generation and detection in target versus non-target cells by more than one order of magnitude compared to the specificity of NP uptake by the same cells. This improved cellular specificity of PNBs was demonstrated in six different cell models representing diverse molecular targets such as epidermal growth factor receptor, CD3 receptor, prostate specific membrane antigen and mucin molecule MUC1.

Cytotoxic effects of chemotherapeutic drugs and heterocyclic compounds at application on the cells of primary culture of neuroepithelium tumors.

Neuroepithelial tumor cells were cultured in vitro. The biopsy material was taken from 93 children at removal of the brain tumors during neurosurgical operations. The individual features of the cells sensitivity of primary cultures in respect to protocol-approved chemotherapy drugs and changes in the Interleukin-6 (Il-6) level in the culture medium after the application of chemotherapy were established.

NT-ProBNP levels, water and sodium homeostasis in healthy men: effects of 7 days of dry immersion.

Immersion is a useful tool for studying fluid-volume homeostasis. Natriuretic peptides play a vital role in renal, humoral, and cardiovascular regulation under changing environmental conditions. We hypothesized that dry immersion would rapidly induce a new steady state for water and sodium metabolism, and that serum NT-proBNP levels, a proxy measure for brain natriuretic peptide (BNP), would decrease during long-term dry immersion and increase during recovery.

Fourth generation phosphorus-containing dendrimers: prospective drug and gene delivery carrier.

Research concerning new targeting delivery systems for pharmacologically active molecules and genetic material is of great importance. The aim of the present study was to investigate the potential of fourth generation (P4) cationic phosphorus-containing dendrimers to bind fluorescent probe 8-anilino-1-naphthalenesulfonate (ANS), anti-neoplastic drug cisplatin, anti-HIV siRNA siP24 and its capability to deliver green fluorescent protein gene (pGFP) into cells. The interaction between P4 and ANS (as the model drug) was investigated.

Proliferation and survival of rat C6 glioma culture in the presence of implants coated with modified carbon-based films.

The survival of rat C6 glioma decreased in the presence of implants from VT-16 titanium alloy. Diamond-like carbon coating of VT-16 alloy slightly increased cell death on day 5 of the experiment (39.9+/-2.

Impulse flow in sympathetic efferents of the abdominal aortic nerve after intrathecal administration of the substrate and inhibitor of nitric oxide synthase.

Experiments were performed on rats anesthetized with urethane and nembutal. Intrathecal administration of a nitric oxide inhibitor L-NAME (60 mg) into the cerebrospinal fluid of the thoracic spinal cord was followed by a 40-45% decrease in tonic activity of efferent fibers of the abdominal aortic nerves. L-NAME reduced a reflex increase in the rate of efferent impulses, which was induced by tetanic stimulation of afferent C-fibers in the mesenteric nerve.

Metabolism in rats during antiorthostatic hypokinesia.

O2 consumption and CO2 release in 3 groups of awake rats were studied on a MM-100 metabolic monitor system (CWE Inc.). The animals of 2 groups were preadapted to 4-h maintenance in special boxes (2 weeks).

Generation of excitatory postsynaptic potentials in the hippocampus after functional modification of glycosaminoglycans.

Experiments on hippocampal slices form 4-week-old rats (n=28) showed that addition of lidase (1.0 and 10.0 U/ml) to the perfusion solution (artificial cerebrospinal fluid) was accompanied by the impaired generation or blockade of excitatory postsynaptic potentials and population spikes in the hippocampal CA1 region during stimulation of Schaffer collaterals.

Ongoing activity in trigeminal wide-dynamic range neurons is driven from the periphery.

Ongoing activity of spinal trigeminal neurons is observed under various conditions and suggested to be responsible for ongoing headache. It can be spontaneous, i.e.

Bilateral splanchnicotomy does not affect lipopolysaccharide-induced fever in rats.

Intraperitoneal capsaicin desensitizes sensory fibers traveling within both the vagus and splanchnic nerves. Because capsaicin desensitization blocks the first phase of lipopolysaccharide (LPS) fever, whereas surgical vagotomy does not, splanchnic mediation of the first phase was proposed. However, all phases of the febrile response of splanchnicotomized rats to intravenous LPS (10 microg/kg) were similar to those of sham-operated controls.

Platelet-activating factor: a previously unrecognized mediator of fever.

Lipopolysaccharide (LPS)-induced systemic inflammation is accompanied by either hypothermia (prevails when the ambient temperature (Ta) is subneutral) or fever (prevails when Ta is neutral or higher). Because platelet-activating factor (PAF) is a proximal mediator of LPS inflammation, it should mediate both thermoregulatory responses to LPS. That PAF possesses hypothermic activity and mediates LPS-induced hypothermia is known.

Role for the cholecystokinin-A receptor in fever: a study of a mutant rat strain and a pharmacological analysis.

The involvement of the cholecystokinin (CCK)-A receptor in fever was studied. The polyphasic febrile responses to lipopolysaccharide (LPS; 10 microg kg-1, I.V.

NO-ergic mechanisms are implicated in a disturbed cardiac rhythm after systemic application of lipopolysaccharide E. coli to rats.

In acute experiments on nembutal-urethan-anaesthetized rats, a slow infusion of subseptic dose of lipopolysaccharide (LPS) Escherichia coli (1 mg/ml) via the right jugular vein immediately led to bradycardia and extrasystoles. Preliminary administration of 20 mg/kg N(G)-nitro-L-arginine methyl ester (L-NAME) or 30 mg/kg aminoguanidine hydrochloride prevented the LPS-induced extrasystoles but did not affect the pattern of bradycardia. We conclude that nitric oxide (NO)-ergic mechanisms are involved in provoking electrical instability of the heart in conditions of endotoxemia.

Central and peripheral mechanisms of nociceptive reflexes in conditions of acute phase reaction.

Since Elie Mechnikoff discovered the main principles of local acute phase reaction (APR), many new regularities of the development of both local and systemic inflammatory responses have been found. The time has come to examine anew the neurohumoral mechanisms of APR and especially those central and peripheral mechanisms that provide the formation of nociceptive responses aimed at maintaining homeostasis and surviving under unfavourable factors. The review analyses the neurohumoral mechanisms of nociceptive response generation in the course of APR.

Does obesity affect febrile responsiveness?

Background And Objective: A decreased resistance to infection and impairments of immunity are common in obese humans and in rodents with hereditary obesity. Since brown fat thermogenesis is also suppressed in obese rodents, we hypothesized that obesity leads to a decreased febrile responsiveness.

Methods: We compared the fever responses to intravenous E.

Multiple neural mechanisms of fever.

In rats, fevers induced by moderate-to-high doses of intravenous lipopolysaccharide consist of three phases (phases 1, 2 and 3) with body temperature peaks at approximately 1, 2, and 5 h postinjection, respectively. In this study, the effects of bilateral truncal subdiaphragmatic vagotomy and intraperitoneal capsaicin desensitization on febrile phases 1-3 were assessed in adult Wistar rats. Surgical vagotomy was performed approximately 30 d before the experiment; this procedure interrupts both afferent and efferent vagal fibers.