Zero-valent Fe confined mesoporous silica nanocarriers (Fe(0) @ MCM-41) for targeting experimental orthotopic glioma in rats.

Mesoporous silica nanoparticles (MSNs) impregnated with zero-valent Fe (Fe(0) @ MCM-41) represent an attractive nanocarrier system for drug delivery into tumor cells. The major goal of this work was to assess whether MSNs can penetrate the blood-brain barrier in a glioblastoma rat model. Synthesized MSNs nanomaterials were characterized by energy dispersive X-ray spectroscopy, measurements of X-ray diffraction, scanning electron microscopy and Mössbauer spectroscopy. For the detection of the MSNs by MR and for biodistribution studies MSNs were labeled with zero-valent Fe. Subsequent magnetometry and nonlinear-longitudinal-response-M2 (NLR-M2) measurements confirmed the MR negative contrast enhancement properties of the nanoparticles. After incubation of different tumor (C6 glioma, U87 glioma, K562 erythroleukemia, HeLa cervix carcinoma) and normal cells such as fibroblasts and peripheral blood mononuclear cells (PBMCs) MSNs rapidly get internalized into the cytosol. Intracellular residing MSNs result in an enhanced cytotoxicity as Fe(0) @ MCM-41 promote the reactive oxygen species production. MRI and histological studies indicated an accumulation of intravenously injected Fe(0) @ MCM-41 MSNs in orthotopic C6 glioma model. Biodistribution studies with measurements of second harmonic of magnetization demonstrated an increased and dose-dependent retention of MSNs in tumor tissues. Taken together, this study demonstrates that MSNs can enter the blood-brain barrier and accumulate in tumorous tissues.

[Evidences of Existence of Serotoninergic Nerves, Enhancing Duodenal Motility].

The review is devoted to the mechanism of duodenal motility activation caused by sympathetic nerves. The authors havefound that stimulation of the sympathetic trunk in the thoracic cavity in dogs in most cases provide not inhibitory but excitatory motor responses of the duodenum. Excitatory effects were eliminated during 5HT-receptors blockade by promedol and lysergol. Analysis ofpublications showed that sympathetic trunk contains serotoninergic fibers, providing excitatory motor responses of the duodenum to electrical nerve stimulation. According to histochemical and physiological studies, amount of serotonergic fibers in the sympathetic trunk is several times more than the adrenergic. This means that the body has sertoninergic nerves. Serotoninergic nerve as well as the sympathetic is a collective notion. There are: sympathetic trunks, their ramifications and branches that innervate the internal organs. Since promedol blocks serotonergic nerves, this is plausible cause of constipation in patients after surgical treatment along with the application of this drug.

[SEROTONERGIC REGULATION OF THE DUODENUM CONTRACTIONS].

The review contains an analysis of literature data on enhancement mechanisms of duodenum contractions arising during stimulation of the sympathetic trunk in the right thoracic cavity in dogs. It is established in experiments that There are mostly enhancement, not relaxation of the organ contraction occured. In this case the stimulatory effect due to the excitation of the parasympathetic fibers is excluded. The trimeperedin inhibit the serotonin receptors of autonomic ganglia neurons stimulatory activity during the nerve stimulation. It is concluded that the sympathetic trunk contain the preganglionic serotonergic nerve fibers, whose activation leads to increased bowel contractions. Direct adipinate-serotonin administration increased the bowel contraction that confirm the preganglionic serotonergic nerve fibers presence in the sympathetic trunk. The practical significance of these studies is that the new approach to the development of pharmacological agents to stimulate the motility of the gastrointestinal tract was found. The trimeperedin may inhibit the serotoninergic nerves activity that resulted in the perioperative constipation in surgical patients. Practical recommendation to exclude trimeperedin in preparing the patient for surgery to prevent perioperative constipation is formulated.

[The significance of different 5-HT-receptors in regulation of gastrointestinal motility].

Serotonergic mechanisms are involved in many, if not all digestive functions of the gastrointestinal tract. A special role is played by serotoninergic structures in the neuronal control of motor activity. The study of these structures is of particular interest due to the widespread occurrence of irritable bowel syndrome, covering up to 20% of the adult population, which makes the research in this area up to date and in demand. Acute experiments were performed on 102 Wistar rats in 6 series. Experiments were carried out under general anesthesia (Nembutal, 60 mg/kg) and mechanical lung ventilation. Motor responses of the stomach, duodenum and ascending colon were studied to i.a. Serotonin adipate infusion (1 mg/kg) during joint blockade of sympathetic and parasympathetic chains of ANS, as well as on the background of the blockade of various 5-HT-receptors. Infusions of 5-HT-blockers reduce the magnitude of motor responses in stomach, duodenum and colon in varying degrees. Based on these data found 5-HT(1b)-receptors are mainly located in enteric neurons. The distribution of 5-HT(2b-4)-receptor is heterogeneous: 5-HT(2b)-receptors are located in enteric neurons of the stomach and intestinal myocytes; 5-HT3-receptors localized in the ganglia supplying the stomach and colon and 5-HT4-receptors are mainly located in the smooth muscle of the stomach, duodenal and ascendent colon enteric neurons.

Study of the nature of sympathetic trunk nerve fibers enhancing gastric motility.

Stimulation of the sympathetic nerve in the thoracic cavity often does not inhibit, but increases stomach contractions in dogs. Blockade of α- and ß-adrenoceptors potentiates this stimulatory effect, while blockade of S(1,2)-receptors localized mainly in smooth muscle cells eliminates it. It is concluded that sympathetic nerve includes serotonergic fibers stimulating gastric motility.

Catecholamines, α-, and ß-adrenoceptors are not responsible for activation of duodenum motility induced by sympathetic nerve stimulation.

Stimulation of sympathetic nerve in anesthetized dogs not treated with adrenergic blockers more frequently exerted stimulating rather than inhibitory effect on duodenal motility. Blockade of α- and ß-adrenoceptors with phentolamine and propranolol, respectively, did not prevent the excitatory action of the sympathetic nerve stimulation, but even potentiated this effect. The data showed that catecholamines as well as α- and ß-adrenoceptors are not involved in the excitatory effect of sympathetic origin.

Chronotropic and inotropic components of cardiac reflexes in cats.

The relationship between chronotropic and inotropic components of cardiac reflexes were studied in cats using intravenous blood injections, occlusion of the abdominal aorta, pressing on eyeballs (Aschner maneuver), and occlusion of the carotid arteries. Inotropic reactions were characterized by the contractility index DPxHR/MSAP. Different reflexes were shown to be characterized by different ratio of chronotropic and inotropic components, in addition, heart rate and contractility were often altered in opposite directions.

[Antibiotic resistance of gramnegative nosocomial pathogens in Minsk ICUs].

The species pattern and antibiotic resistance of gramnegative isolates from patients with nosocomial infections in Minsk ICUs were studied. Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli were the main pathogens, highly resistant to the antibiotics used. Imipenem, meropenem, polymyxin B, ampicillin/sulbactam, amikacin and cefoperazone/sulbactam were the most active antimicrobials against the isolates. The choice of antimicrobials for empirical therapy of hospital infections in ICUs should be based on the local situation regarding the antibiotic resistance, that makes it obligatory to use regular microbiological monitoring in all hospitals thus providing the policy of the use of antimicrobials in ICUs.

Effect of atropine, propranolol, and atenolol on wave structure of heart rate oscillations in rats.

Were studied the effects of atropine and beta-adrenoblockers on the power of very low (<0.25 Hz), low (0.25-0.70 Hz), and high frequency (0.7-1.8 Hz) waves of the heart rhythm in wakeful rats. Atropine reduced the power of all waves in 100% cases. Propranolol on average decreased the power of very low frequency waves and increased the power of low and high frequency waves, although opposite effects were observed in many cases. Atenolol produced similar effects. Some animals demonstrated spontaneous moderation of respiratory rate to a level corresponding to low-frequency oscillations of the heart rhythm accompanied by elevation of the relative power of low frequency waves. Inconsistency of the effects of beta-adrenoblockers in rats can be related to variability of sympathetic tone and spontaneous deceleration of respiration with the corresponding changes of low frequency waves. Augmentation of the high frequency waves during application of beta-adrenoblockers is not related to their action on CNS.

Chronotropic and dromotropic components of cardiac reflexes in the cat.

The relationship between dromotropic and chronotropic components of various cardiac reflexes was studied in cats. Intravenous infusion of blood was mainly accompanied by unidirectional negative chronotropic and dromotropic effects, but the dynamics of these effects was different. Clumping of the carotid arteries in most animals induced unidirectional negative chronotropic and dromotropic effects. Their dynamics was also different and differed from that observed during intravenous blood infusion. Pulsatile increase in blood pressure in the carotid artery was accompanied by a unidirectional negative effect in the majority of animals. The opposite chronotropic and dromotropic effects with similar temporal dynamics were revealed in 1/3 animals. The ratio of positive and negative effects was similar during clumping of the abdominal aorta (1/3 unidirectional, 1/3 opposite, and 1/3 isolated chronotropic and dromotropic effects). Aschner test was characterized by the prevalence of isolated chronotropic effect (negative effect in the majority of animals; positive effect in 1/3 animals). Hence, different cardiac reflexes are characterized by different ratio between chronotropic and dromotropic components.

Effect of polysaccharides on the blood system in rats.

Natural plant polysaccharides stimulated hemopoiesis, increased the content of some macroglobulins in blood plasma, modulate the weight and cellular composition of lymphoid and hemopoietic organs, activated lymphopoiesis, and enhanced enzyme activity in healthy animals.

Effect of pentobarbital on spectral characteristics and phase ratios of wave oscillations of cardiac contraction period and time of atrioventricular conduction in cats.

Effects of pentobarbital on spectral characteristics and phase ratios of wave oscillations of the cardiac contraction period (RR interval) and time of atrioventricular conduction (AV interval) were studied in experiments of cats. Pentobarbital moderately reduced the mean values of both intervals and significantly reduced their standard deviations and spectral powers in all frequency bands (high-frequency, low-frequency, and very low-frequency). Pentobarbital treatment led to deceleration of breathing, the frequency range of respiratory oscillations of RR and AV intervals shifted in some cases from high to low frequencies; evaluation of spectral power in the intermittent band corresponding to respiration frequency (instead of standard fixed high-frequency band) showed that pentobarbital suppressed the respiratory oscillations in these bands. Pentobarbital induced inversion of phase ratio between respiratory oscillations of RR and AV intervals: oscillations of both intervals before pentobarbital coincided by phase, while after pentobarbital injection they were in antiphase. The mechanisms of the latter phenomenon deserve further investigation.

Chronodromotropic coordination in cats.

The coordinated nervous influences on HR and atrioventricular conduction velocity (chronodromotropic coordination) were examined in wakeful cats. The wave structure and reflex reactions of RR and atrioventricular (AV) intervals to stress noise stimulation were studied under normal conditions and during the action of blockers of peripheral receptors in ANS. Variations of both intervals had similar wave structure (power spectrum) and similar reactions to noise stimulus. Atropine pronouncedly decreased all components of the spectra in the high, low, and very low frequency ranges. It eliminated the reactions of both intervals to noise stimulation. In RR intervals, the high-frequency spectrum component decreased more strongly than the low-frequency ones. By contrast, in AV intervals atropine most greatly decreased the very-low-spectrum component, while the high frequency was decreased less of all. Propranolol produced no effect on the response to noise. It did not decrease components of the wave structure in both intervals, except for the very-low-frequency peak of AV interval. The nervous chronotropic and dromotropic influences were largely coordinated, although they were not obligatorily parallel.

Experimental gastric ulcer: gastro- and duodenoprotective effects of sibusol.

We studied the influence of pretreatment with chemical mildronate analogue sibusol on the course of experimental gastric ulcer in rats. Sibusol produced a protective effects on the stomach and duodenum.

Mechanism of synergism between sympathetic and parasympathetic autonomic nervous systems in the regulation of motility of the stomach and sphincter of Oddi.

The mechanisms of stimulatory effect of the sympathetic trunk on gastric motor activity and vagal inhibitory effect on electromotor activity of the sphincter of Oddi were studied. Gastric contractions were augmented by preganglionic serotoninergic fibers related synaptically to serotoninergic neurons, while inhibition of electromotor activity of the sphincter of Oddi was elicited by activation of alpha- and beta-adrenoceptors.

[The role of the lipid and phospholipid tissue composition in the synergism of vegetative nervous system parts]. / Rol' lipidnogo i fosfolipidnogo sostava tkanei v sinergizme otdelov vegetativnoi nervnoi sistemy.

The role of the lipid and phospholipid composition of tissue homogenates of the vagus nerve, cervicothoracic ganglion, heart, liver, erythrocytes and blood plasma of rabbits was studied in the synergism of vegetative nervous system parts. It was demonstrated that, when the vagus inhibition of the heart performance increased, the animals used to have a higher concentration of choline-containing phospholipids, and their erythrocyte membranes were more permeable.