Mechanism of Activation of Enteric Nociceptive Neurons via Interaction of TLR4 and TRPV1 Receptors.

Evidence obtained by immunohistochemical double labeling and confocal laser scanning microscopy suggests that capsaicin, a ligand of the TRPV1 nociceptive vanilloid receptor, increases the number of TLR4-positive neurons in the rat colon myenteric plexus. In colitis caused by trinitrobenzene sulfonate, an increase in TRPV1 expression was more significant in both plexuses. Specific inhibitor of the TLR4 (C34) pattern-recognition receptor reduces TRPV1 expression in enteric neurons of both intact rats and rats with induced acute colitis. Thus, stimulation of nociceptive neurons by means of direct activation of their receptors of innate immunity (TLR4) is one of the possible mechanisms underlying the visceral pain in bacterial invasion and inflammatory bowel diseases.

[Allergic bronchopulmonary aspergillosis in patients with asthma: Results of a prospective study]. / Allergicheskii bronkholegochnyi aspergillez u bol'nykh bronkhial'noi astmoi: rezul'taty prospektivnogo issledovaniia.

AIM: To estimate the frequency of fungal sensitization and the incidence of allergic bronchopulmonary aspergillosis (ABPA) in asthmatic patients. SUBJECTS AND METHODS: A total of 140 asthmatic patients were examined. They underwent allergologic (skin tests for fungal allergens, estimation of total and fungal allergen-specific IgE levels) and mycological (microscopy and inoculation of respiratory biosubstrates) examinations. Chest computed tomography, when indicated, was done. A group of patients with ABPA and that of patients with severe asthma and fungal sensitization were identified. RESULTS: The frequency of fungal sensitization in asthmatic patients was 36%; the main allergenic fungi were Aspergillus and Alternaria. The incidence of ABPA was as high as 4% in the patients with asthma and 11% in those with severe asthma and fungal sensitization. CONCLUSION: The given current diagnostic criteria will assist practitioners to identify ABPA, to prevent its progression, and to initiate specific anti-inflammatory and antifungal therapy in due time.

[Common variable immunodeficiency in adults]. / Obshchaya variabel'naya immunnaya nedostatochnost' u vzroslykh.

The paper analyzes 7 cases of common variable immune deficiency (CVID), a primary immunodeficiency disease. All the cases were detected in outpatients over the age of 40 years. The diagnosis was based on their history data and general clinical findings with due regard for the results of previously conducted functional studies, expert opinions, and the results of immunological studies including the quantitative and functional indices of T and B cells, phagocytes and the levels of immunoglobulins. The analysis showed that the early signs of impaired immunity in all the patients were seen by physicians of various specialties in both outpatient and inpatient settings. Generalizing of all information about the patient could become the basis for a simple and accessible practical public-health study of immunoglobulins levels significantly sooner than this diagnosis being verified. This testifies that the physicians of various specialties are partially aware of the clinical signs of immunodeficiency states and that there is a need for a clinical immunologist in adult healthcare facilities. This is especially important since the early clinical manifestations of both primary immunodeficiency disorders that are increasingly frequently detected and nonhereditary - secondary ones can be very similar. The timely verification of the diagnosis is necessary for prescribing adequate therapy with intravenous immunoglobulins to prevent severe chronic pyoinflammatory lung disease and disability in patients with CVID.

Expression of Pattern Recognition Receptors by Nociceptive Metasympathetic Neurons.

Immunohistochemical assay with double label and confocal laser scanning microscopy showed that innate immunity receptor TLR4 is expressed predominantly in neurons of the intestinal Auerbach (myenteric) plexus, while vanilloid nociceptive receptor TRPV1 is expressed by neurons of Meissner (submucous) plexus. Immunohistochemical analysis with triple labeling revealed coexpression of TLR4 and TRPV1 in enteric neurons of rat colon. The results attest to a possibility of functional interaction between Toll-like and vanilloid receptors in the neuron level.

[Participation of peripheral sensory structures of autonomic nervous system in the mechanisms of neuroimmune interactions].

On the basis of the electrophysiological research carried out with immunohystochemical methods on rats, it is found, that introduction of products of mast cell degranulation into blood as well as endogenous release of mast cell mediators with either the compound 48/80 or introduction of egg albumin to presensitized rats, enhances activity of mesenteric afferent nerve fibers. The obtained data provide evidence that intestinal afferents contribute an early signal to the brain regarding potential pathogens. The question of whether or not the intrinsic enteric neurons are involved in these processes, however, has not been carefully studied. So we investigated this problem and found that the enteric neurons express receptor of innate immunity TLR4 and nociceptive vanilloid receptor TRPV1, by means ofimmunohistochemical method. The analysis of neurons distribution revealed that vanilloid receptors are expressed by neurons localized mainly in myenteric plexus whereas TLR4-immunoreactive neurons generally are present in submucous plexus. It is also established coexpression of both receptors in the single intrinsic enteric neuron. In conclusion, our findings indicate that sensory terminals of external afferent fibers as well as intrinsic neurons of intestine can modulate reactions of the organism to endotoxins and thus may be involved in reception of inflammatory and immune responses.

[An overview of the pulmonary sensory receptors].

The optimum realization to respiratory function depends on varied sensory feedbacks from ensemble of the sources of the body. Pulmonary sensory receptors are the initiating sites for lung reflexes. The information arriving from lungs and airways information is one of the most important feedbacks that provide the adaptation of the respiratory centre for producing of the pattern optimal in terms of work and force of breathing. In article the review of data existing currently about morphology and functional characteristics of three types of the pulmonary structures is presented: slowly adapting stretch receptors, rapidly adapting receptors, C-fiber receptors and neuroepithelial bodies.

[Modern concepts of coding mechanisms of the visceral pain stimuli].

The review of the existing concepts on visceral pain mechanisms and mechanisms of processing nociceptive stimuli on the level of the sensory neurons of superficial segments of the dorsal cornus of the spinal cord was presented. Also the information on ion channels and receptors, which participate in transduction of pain signals are discussed.

[The role of visceral receptors in the mechanisms of neuroimmune interactions in mammalian small intestine].

Exogenous administration of mast cell degranulation products into blood as well as their endogenous release induced by compound 48/80 or repeated egg albumin administration to sensitized rats proved to increase activity of mesenteric afferent nerve fibers in the small intestine. In addition, the primary contact with a foreign protein triggered a cascade of chemical processes mobilizing antioxidant systems and increasing nitric oxide production in the small intestinal tissues. Interleukin-1beta or Escherichia coli lipopolysaccharide injections also had a long-term stimulating effect on intestinal receptors. Indometacin inhibited the effects induced by the bacterial endotoxin and interleukin-1beta. The obtained data suggest that small intestinal interoceptors can monitor chemical environment and modulate body's responses to foreign antigens. Interleukins-1beta acts as a signal transmitter between immune cells and interoceptors, which is mediated by the production of secondary signal substances, in particular, prostaglandin-2 and histamine.

Changes in afferent impulse activity of small intestine mesenteric nerves in response to antigen challenge.

Sprague-Dawley rats (weight 130-150 g) were sensitized by an intraperitoneal injection of 1 mg chicken egg albumin with 0.25 ml Freund's adjuvant to stimulate immunoglobulin E antibody production. Leukocyte migration inhibitory factor was used as an indicator of animal sensitization. In acute electrophysiological experiments on sensitized animals, an intra-arterial or intraluminal chicken egg albumin (100 microg) challenge evoked a 10% enhancement of the activity of mesenteric nerves of the small intestine, regardless of the injection site chosen. Afferent nerve activity in control animals was not changed during the chicken egg albumin challenge. Morphometry at the light microscope level showed activation of mast cell degranulation after the antigen challenge to presensitized rats. Intraluminal injections of a stimulator of mast cell degranulation, compound 48/80 (20-30 mg), were found to increase afferent discharges in intact rats. An antagonist of H1 histamine receptors, clemastine, reduced the effect of compound 48/80. The results obtained provide direct evidence for the stimulation of sensory nerve endings by mast cell mediators released during mast cell degranulation.

[Cost benefit of detection and treatment patients with tuberculosis in Ivanovo region, Russian Federation]. / Stoimost' vyiavleniia i lecheniia bol'nykh tuberkulezom v Ivanovskoi oblasti Rossiiskoi Federatsii.

To execute the tuberculosis control programme in the Ivanovo Region, the authors calculated the cost of detection of a tuberculosis case at patients' referrals to a therapeutical-and-prophylactic institution for medical aid and during prophylactic X-ray fluographic examinations and the cost of tuberculosis cure while treating the patient at a hospital in the intensive treatment phase (2-3 months) and in the outpatient setting or at a day hospital by the intermittent method in the continued treatment phase. The costs calculated were compared with those obtained by early approaches. The cost of detection of a tuberculosis case was 1580.8 for referrals in 1996 and 4000 for X-ray fluographic prophylactic examinations. The costs of hospital tuberculosis cure (85% cure rates) only in the intensive treatment phase (for 2-3 months) and outpatient intermittent treatment (for 2-4 months) with and without meals were 2415.34 and 2142.17 respectively. If the efficiency is equal, the introduction of new approaches to organizing the detection and treatment tuberculosis cases may save 3877.7 for each cured tuberculosis case and 2419.2 for each patient detected.

Mast cell mediators excite the afferents of cat small intestine.

The influence of intra-arterial injections of 5-hydroxytryptamine, histamine and prostaglandin E2 on afferent impulse activity of mesenteric nerves of small intestine was studied. In anaesthetized cats 5-hydroxytryptamine (10(-5)-10(-4) M) and histamine (10(-5)-10(-3) M) were shown to increase the impulse activity in a dose-dependent manner. Metergolin, 5-hydroxytryptamine antagonist, suppressed the effect of 5-hydroxytryptamine. Clemastine and cimetidine, antagonists of H1 and H2 histamine receptors respectively, distinctly diminished excitatory histamine effects. Prostaglandin E2 (10-30 micrograms/kg) enhanced the afferent impulse activity. The results suggest that afferents of the small intestine may be involved in reception of inflammatory and immune responses.

[The effect of the mast-cell mediators histamine and prostaglandins on the afferent nerve fibers of the small intestine in the cat]. / Vliianie mediatorov tuchnykh kletok gistamina i prostaglandinov na afferentnye nervnye volokna tonkoi kishki koshki.

Histamine was shown to increase afferent impulse activity of the small intestine's mesenteric nerves in a dose-dependent manner, the effect being reduced by antagonists of the H1 and H2 histamine receptors. PG E2 and PC D2 also enhanced the afferent impulse activity. Interaction of antigens with the intestinal mast cells seems to participate in immune response.

[The effect of serotonin on the receptors of the cat small intestine]. / Vliianie serotonina na retseptory tonkoi kishki koshki.

5-HT was shown to increase dose-dependently the afferent activity in the cat mesenteric nerves. Metergolin suppressed the effects of serotonin. The data obtained suggest that the small intestine afferents may take part in reception of immune response.

[The morphological characteristics of the parasympathetic innervation of the pyloric sphincter in the cat]. / Morfologicheskie osobennosti parasimpaticheskoi innervatsii piloricheskogo sfinktera u koshki.

The method of axonal transport of horse-radish peroxidase was used to detect the localization of neurons in the dorsal motor nucleus of the vagus nerve sending the axons to the pyloric sphincter. The investigation was carried out in cats. Under study were also morphological features of the nodular ganglion responsible for afferent innervation of the sphincter. The maximum amount of the corresponding cells are found in the dorsomedial part of the dorsal motor nucleus in the area from +1.0 to +2.0 mm (with respect to obex). The afferent neurons to which information comes from interoceptors of the sphincter zone along the vagus nerve fibers, are distributed in the left and right nodular ganglia almost evenly. The major part of these cells have the area of 300-800 mkm2.

Localization of neurons innervating the upper portion of the duodenum in the motor nucleus of the vagus nerve.

Using the method of the retrograde axonal transport of horseradish peroxidase and a microelectrode technique, a population of neurons sending axons to the upper portion of the duodenum was identified in the dorsal motor nucleus of the vagus nerve. It was established that the maximal number of such neurons was located 1.0-2.5 mm rostral to the obex. The effects of their stimulation on the electrical activity of the smooth muscles of the duodenum was studied.

[The localization of neurons in the nodose ganglion of the cat that innervate the rostral portion of the duodenum]. / Lokalizatsiia neironov uzlovatogo gangliia koshki, innerviruiushchikh rostral'nuiu chast' dvenadtsatiperstnoi kishki.

The method of axonal transport of horseradish peroxidase was used for studying the sites of localization and morphological features of sensory neurons of the vagus nerve in the left and right ganglion nodosum innervating the rostral part of the duodenum. Animals under nembutal narcosis were given 90-100 mcl of 33% solution of horseradish peroxidase ("Olaine", Riga RZ 2.7) injected into a limited area (1 x 1 sm) of the muscular layer of the duodenum. Horseradish peroxidase labelled neurons were found bilaterally in the both ganglia. The number of neurons in the left ganglion was 91 +/- 23, in the right one--115 +/- 24. The sensory cells are mainly of the ellipsoid form and of different sizes. Areas of sections of the neurons vary from 100 to 1300 mkm2, most on them having the area from 300 to 700 mkm2. The distribution of neurons according to the sizes of their areas have no substantial differences in the left and right ganglia. It was found that 65% of neurons in the right ganglion and 67% in the left one are localized in its caudal half.