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Jewish Rural Settlements in the Light of the Peasant Survey of 1814: The Perception of Jews and the Socio-Economic Reality at the Beginning of the Nineteenth Century In 1814 the government launched the Peasant Survey, aimed at collecting local elites’ opinions on the best ways of improving the living conditions of peasants. The 140 responses, almost all of them containing comments on Jews, are a rich source of knowledge about the rural Jews of that period. This paper analyzes the Jewish theme in the survey: the predominant critical perception of Jews and various accusations against them as well as proposed reforms. The comparison with the results of the 1819 census of rural Jews in the Kraków voivodeship, including their occupational structure, demonstrates the gap between the elites’ judgement and the reality.

Wood pellets are a commonly used biomass for energy production. However, due to the growing demand, many entrepreneurs have begun to produce non-wood biomass pellets. During experimental research, the process of combusting pellets of forest and agricultural origin at different furnace temperatures and different oxidizing atmospheres in a two-phase flow with the use of inert material modelling conditions in the upper zone of the fluidized bed reactor was analyzed. Inert material caused very significant differences in the time and mechanism of forest and agro biomass combustion. These differences are mainly associated with problematic phenomena during combustion, including sintering of ashes. The inert material accelerated the mass loss of forest biomass pellets at all temperatures by about 50–60%. In the case of agro biomass, the combustion time at the temperatures of 650 °C and 750 °C was shortened by about 20–30%, and in the case of the temperature of 850 °C, it was extended by about 10%. Increasing the value of the inert material stream resulted in a reduction of the combustion time at all temperatures. Increasing the concentration of oxidant in the atmosphere of combustion caused the reduction of the combustion time of all tested fuels.

PK20 is an anti-inflammatory hybrid compound, composed of an endomorphin-2-like and neurotensin-like fragments. The aim of the present study is to assess the contribution of particular pharmacophores to the activity of the hybrid tested. For this purpose, airway hyperresponsiveness, accumulation of inflammatory cells in bronchoalveolar lavage fluid (BALF), concentration of mouse mast cell protease, malondialdehyde and secretory phospholipase 2 activity in lung tissue, as well as production of pro-inflammatory cytokines in BALF and lung were determined by using murine model of non-atopic asthma. Blocking either neurotensin receptors or mu opioid receptors did not alter the potential of PK20 in reducing airway hyperresponsiveness. In studies of inflammatory cells, the beneficial effect of the entire peptide occurs to be mediated by the stimulation of neurotensin receptors. However, regarding cytokine and biochemical assays, pretreatment with both receptor antagonists resulted in a different effect on its activity depending on the parameter studied. To conclude, the activation of both the opioid and neurotensin receptors seems to be necessary to induce the full anti-inflammatory activity of the hybrid compound.

Natan M. Meir, Stepchildren of the Shtetl: The Destitute, Disabled, and Mad of Jewish Eastern Europe, 1800–1939, Stanford University Press, Stanford 2020, ss. 360.

Opioids are the most potent widely used analgesics, primarily, but not exclusively, in palliative care. However, they are associated with numerous side effects, such as tolerance, addiction, respiratory depression, and cardiovascular events. This, in turn, can result in their overuse in cases of addiction, the need for dose escalation in cases of developing tolerance, and the emergence of dose-related opioid toxicity, resulting in respiratory depression or cardiovascular problems that can even lead to unintentional death. Therefore, a very important challenge for researchers is to look for ways to counteract the side effects of opioids. The use of peptides and their related compounds, which have been shown to modulate the effects of opioids, may provide such an opportunity. This short review is a compendium of knowledge about the most important and recent findings regarding selected peptides and their modulatory effects on various opioid actions, including cardiovascular and respiratory responses. In addition to the peptides more commonly reported in the literature in the context of their pro- and/or anti-opioid activity—such as neuropeptide FF (NPFF), cholecystokinin (CCK), and melanocyte inhibiting factor (MIF)—we also included in the review nociceptin/orphanin (N/OFQ), ghrelin, oxytocin, endothelin, and venom peptides.

Clay raw materials are diverse in terms of their mineral composition, as well as the content of colouring oxides and their physical properties. Determining the suitability of raw materials for various purposes requires comprehensive studies on their properties, as well as their appropriate correction, which is possible through the use of appropriate modification techniques. One of the most commonly used technologies for the enrichment of clay raw materials is to subject them to high temperatures, which, depending on the temperature regime used in the technological process, may cause the decomposition and removal of some addditional components (e.g., carbonates), as well as the removal of water and dehydroxylation of clay minerals, reversible structural changes, and the complete and permanent reconstruction of the mineral phases. This paper presents a new application for fluidization technology in the calcination of clay raw materials. The results of the experiment show that the fluidization method is competitive compared to the technologies that have been used so far, as a result of, inter alia, the much shorter time period required to carry out the calcination process and, consequently, the much lower energy expenditure, the high efficiency of burning coal, and the lower CO2 emissions resulting from the mixing taking place in the reactor.

We report the facile preparation of polypyrrole microcapsules with a hydrophobic liquid core that is loaded with gold nanoparticles. Through the oxidative polymerization of pyrrole, the polymer is deposited onto the surface of the droplets, which results in the encapsulation of both the liquid phase and the metal nanoparticles. We demonstrate the preparation of the microcapsules loaded with organic solvents (toluene, hexane) or 2-oxoheptyl isothiocyanate (new promising anticancer agent) as the liquid cores and stable or radioactive gold nanoparticles (Au-197 or Au-198 isotopes). The resulting microcapsules have been demonstrated as promising agents for medical applications such as computed tomography or gamma imaging. Moreover, the capsules can be applied as drug carriers, which has been shown in vitro on cancer and normal cell cultures.

This review analyses the knowledge about the incidence of transient apnoeic spells, induced by substances which activate vagal chemically sensitive afferents. It considers the specificity and expression of appropriate receptors, and relevant research on pontomedullary circuits contributing to a cessation of respiration. Insight is gained into an excitatory drive of 5-HT1A serotonin receptors in overcoming opioid-induced respiratory inhibition.

Inhalations with brine solutions are old but underestimated add-ons to pharmacological treatments of inflammatory lung diseases. Although widely used, not all features underlying their action on the respiratory system have been explored. The aim of the present study was to elucidate the mechanism of the beneficial action of inhalations of brine solution from the &lsquo, Wieliczka&rsquo, Salt Mine, a Polish health resort, in a murine model of non-atopic asthma. Asthma was induced in BALB/c mice by skin sensitization with dinitrofluorobenzene followed by an intratracheal challenge of cognate hapten. All animals underwent 12 inhalation sessions with brine solution, pure water or physiological saline. Control mice were not inhaled. We found that brine inhalations reduced, as compared to non-inhaled mice, the typical asthma-related symptoms, like airway hyperreactivity (AHR), the infiltration of pro-inflammatory cells into the bronchial tree, and the inflammation of the airways at the level of pro-inflammatory cytokines IL-1&alpha, IL-1&beta, and IL-6. The level of the anti-inflammatory IL-10 was elevated in brine-inhaled mice. Inhalations with pure water increased AHR, whereas saline had no influence, either on AHR or cytokine concentrations. These observations indicate that inhalations with a brine solution from the &lsquo, Salt Mine diminish the asthma-related symptoms, mostly by reducing the inflammatory status and by decreasing AHR.

Respiratory disturbances present in Parkinson’s disease (PD) are not well understood. Thus, studies in animal models aimed to link brain dopamine (DA) deficits with respiratory impairment are needed. Adult Wistar rats were lesioned with injection of 6-hydroxydopamine (6-OHDA) into the third cerebral ventricle. Two weeks after hypoxic test was performed in whole-body plethysmography chamber, phrenic (PHR) and hypoglossal (HG) nerve activities were recorded in normoxic and hypoxic conditions in anesthetized, vagotomized, paralyzed and mechanically ventilated rats. The effects of activation and blockade of dopaminergic carotid body receptors were investigated during normoxia in anesthetized spontaneously breathing rats. 6-OHDA injection affected resting respiratory pattern in awake animals: an increase in tidal volume and a decrease in respiratory rate had no effect on minute ventilation. Hypoxia magnified the amplitude and minute activity of the PHR and HG nerve of 6-OHDA rats. The ratio of pre-inspiratory to inspiratory HG burst amplitude was reduced in normoxic breathing. Yet, the ratio of pre-inspiratory time to total time of the respiratory cycle was increased during normoxia. 6-OHDA lesion had no impact on DA and domperidone effects on the respiratory pattern, which indicate that peripheral DA receptors are not affected in this model. Analysis of monoamines confirmed substantial striatal depletion of dopamine, serotonin and noradrenaline (NA) and reduction of NA content in the brainstem. In bilateral 6-OHDA model changes in activity of both nerves: HG (linked with increased apnea episodes) and PHR are present. Demonstrated respiratory effects could be related to specific depletion of DA and NA.

The behavioral responses exerted by spinal administration of the opioid-neurotensin hybrid peptide, PK23, were studied in adult male rats. The antinociceptive effect upon exposure to a thermal stimulus, as well as tolerance development, was assessed in an acute pain model. The PK23 chimera at a dose of 10 nmol/rat produced a potent pain-relieving effect, especially after its intrathecal administration. Compared with intrathecal morphine, this novel compound was found to possess a favourable side effect profile characterized by a reduced scratch reflex, delayed development of analgesic tolerance or an absence of motor impairments when given in the same manner, though some animals died following barrel rotation as a result of its i.c.v. administration (in particular at doses higher than 10 nmol/rat). Nonetheless, these results suggest the potential use of hybrid compounds encompassing both opioid and neurotensin structural fragments in pain management. This highlights the enormous potential of synthetic neurotensin analogues as promising future analgesics., Graphical abstract PK23 is a bifunctional compound consisting of both opioid and neurotensin fragments fused into one molecule. It mediates dose- and time-dependent antinociceptive responses when administered either centrally or peripherally, likely due to its interaction with μ opioid and neurotensin type 1 (NTS1) receptors.Image 1

The 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD) is one of the most extensively utilized animal models used to study pathogenic processes involved in neuronal loss and behavioral alterations characteristic for parkinsonism. To develop the 6-OHDA model, neurotoxin has to be injected into distinct parts of the animal nigrostriatal pathway: substantia nigra pars compacta, striatum, and medial forebrain bundle. The present review summarizes the main features of the model, its neurochemical characterization, and the mechanisms of neurotoxin-evoked neurotoxicity. Also examined in this chapter are motor impairments produced by 6-OHDA, advances in modeling additional nonmotor features of PD, such as behavioral and systemic alterations recapitulating human PD symptomatology, and advantages and shortcomings of the model. Despite limitations such as the lack of Lewy body inclusions and abrupt neurodegeneration of dopamine cells, it appears that the 6-OHDA lesion remains one of the meaningful neurotoxin models used to study neural mechanism underlying Parkinson's disease.

Regulatory neuropeptides control and regulate breathing in physiological and pathophysiological conditions. While they have been identified in the neurons of major respiratory areas, they can be active not only at the central level, but also at the periphery via chemoreceptors, vagal afferents, or locally within lungs and airways. Some neuropeptides, such as leptin or substance P, are respiratory stimulants; others, such as neurotensin, produce variable effects on respiration depending on the site of application. Some neuropeptides have been implicated in pathological states, such as obstructive sleep apnea or asthma. This article provides a concise review of the possible role and functions of several selected neuropeptides in the process of breathing in health and disease and in lung pathologies.

Aims Parkinson's disease (PD) patients apart from motor dysfunctions exhibit respiratory disturbances. Their mechanism is still unknown and requires investigation. Our research was designed to examine the activity of phrenic (PHR) and hypoglossal (HG) nerves activity during a hypoxic respiratory response in the 6-hydroxydopamine (6-OHDA) model of PD. Main methods Male adult Wistar rats were injected unilaterally with 6-OHDA (20 μg) or the vehicle into the right medial forebrain bundle (MFB). Two weeks after the surgery the activity of the phrenic and hypoglossal nerve was registered in anesthetized, vagotomized, paralyzed, and mechanically ventilated rats under normoxic and hypoxic conditions. Lesion effectiveness was confirmed by the cylinder test, performed before the MFB injection and 14 days after, before the respiratory experiment. Key findings 6-OHDA lesioned animals showed a significant increase in normoxic inspiratory time. Expiratory time and total time of the respiratory cycle were prolonged in PD rats after hypoxia. The amplitude of the PHR activity and its minute activity were increased in comparison to the sham group at recovery time and during 30 s of hypoxia. The amplitude of the HG activity was increased in response to hypoxia in 6-OHDA lesioned animals. The degeneration of dopaminergic neurons decreased the pre-inspiratory/inspiratory ratio of the hypoglossal burst amplitude during and after hypoxia. Significance Unilateral MFB lesion changed the activity of the phrenic and hypoglossal nerves. The altered pre-inspiratory hypoglossal nerve activity indicates modifications to the central mechanisms controlling the activity of the HG nerve and may explain respiratory disorders seen in PD, i.e. apnea.

Aim Chimeric compound – PK20 despite its therapeutic activity on nociceptive and inflammatory processes may affect respiration and blood pressure. Our objective was to evaluate influence of the hybrid composed of endomorphin-2 and neurotensin fragments on ventilation, heart rate and blood pressure in anesthetized and awake rats. Methods The effects of PK20 (1 mg/kg) were studied either after its intravenous administration in anesthetized rats or intraperitoneal injection in awake state. Tidal volume and the timing components of the breathing pattern, arterial blood pressure, and heart rate were recorded. Results Intravenous administration of PK20 in the neurally intact rats evoked a dose-dependent apnoea followed by a transient insignificant increase in tidal volume and breathing rate. The blood pressure changes were biphasic: transient increase was replaced by prolonged hypotension. Midcervical vagotomy abrogated all post-PK20 respiratory effects. Hypotension was eliminated after blockade of neurotensin NTS 1 receptor, while respiratory changes were reduced by blockade of both: NTS 1 and μ opioid receptors. After PK20 intraperitoneal injection awake rats did not show any significant changes in ventilation and blood pressure. Conclusion This chimeric peptide should be used with care via intravenous administration in anesthetized animals since PK20 may evoke respiratory apnoea and hypotension. Nevertheless, applied intraperitoneally in the same dose in conscious rats induced no adverse effects.

We examined anti-inflammatory potency of hybrid peptide-PK20, composed of neurotensin (NT) and endomorphin-2 (EM-2) pharmacophores in a murine model of non-atopic asthma induced by skin sensitization with 2,4-dinitrofluorobenzene and intratracheal challenge of cognate hapten. Mice received intraperitoneally PK20, equimolar mixture of its structural elements (MIX), dexamethasone (DEX), or NaCl. Twenty-four hours following hapten challenge, the measurements of airway responsiveness to methacholine were taken. Bronchoalveolar lavage (BALF) and lungs were collected for further analyses. Treatment with PK20, similarly to dexamethasone, reduced infiltration of inflammatory cells, concentration of mouse mast cell protease, IL-1&beta, IL-12p40, IL-17A, CXCL1, RANTES in lungs and IL-1&alpha, IL-2, IL-13, and TNF-&alpha, in BALF. Simple mixture of NT and EM-2 moieties was less potent. PK20, DEX, and MIX significantly decreased malondialdehyde level and secretory phospholipase 2 activity in lungs. Intensity of NF-&kappa, B immunoreactivity was diminished only after PK20 and DEX treatments. Neither PK20 nor mixture of its pharmacophores were as effective as DEX in alleviating airway hyperresponsiveness. PK20 effectively inhibited hapten-induced inflammation and mediator and signaling pathways in a manner seen with dexamethasone. Improved anti-inflammatory potency of the hybrid over the mixture of its moieties shows its preponderance and might pose a promising tool in modulating inflammation in asthma.

Neurotensin (NT) demonstrates ambiguous activity on inflammatory processes. The present study was undertaken to test the potential anti-inflammatory activity of NT in a murine model of non-atopic asthma and to establish the contribution of NTR1 receptors. Asthma was induced in BALB/c mice by skin sensitization with dinitrofluorobenzene followed by intratracheal hapten provocation. The mice were treated intraperitoneally with NT, SR 142948 (NTR1 receptor antagonist) + NT or NaCl. Twenty-four hours after the challenge, airway responsiveness to nebulized methacholine was measured. Bronchoalveolar lavage fluid (BALF) and lungs were collected for biochemical and immunohistological analysis. NT alleviated airway hyperreactivity and reduced the number of inflammatory cells in BALF. These beneficial effects were inhibited by pretreatment with the NTR1 antagonist. Additionally, NT reduced levels of IL-13 and TNF-&alpha, in BALF and IL-17A, IL12p40, RANTES, mouse mast cell protease and malondialdehyde in lung homogenates. SR 142948 reverted only a post-NT TNF-&alpha, decrease. NT exhibited anti-inflammatory activity in the hapten-induced asthma. Reduced leukocyte accumulation and airway hyperresponsiveness indicate that this beneficial NT action is mediated through NTR1 receptors. A lack of effect by the NTR1 blockade on mast cell activation, oxidative stress marker and pro-inflammatory cytokine production suggests that other pathways can be involved, which requires further research.

Inhalations with brine solutions as an example of climatotherapy-related therapeutic procedures are old but forgotten add-ons to pharmacological treatments of inflammatory lung diseases. The aim of the present study was to elucidate the mechanism of beneficial action of inhalations of brine solution (2%) from the Wieliczka Salt Mine, a Polish health resort, in a murine model of non-atopic asthma. Asthma was induced in BALB/c mice by skin sensitization with dinitrofluorobenzene followed by intratracheal challenge of similar hapten. Then, the animals underwent 12 inhalation sessions with brine solution, pure water or saline in a scheme comparable to the one of physiotherapy departments of health resorts. Control mice were not inhaled. We found that brine inhalations reduced as compared to non-inhaled mice the typical asthma-related symptoms like bronchial hyperreactivity (AHR), infiltration of pro-inflammatory cells including neutrophils into the bronchial tree, and inflammation of the bronchi and lungs at the level of pro-inflammatory cytokines IL-1alpha and IL-6. The level of the anti-inflammatory IL-10 was elevated in brine-inhaled mice. Inhalations with pure water increased AHR whereas saline had no influence nor on AHR nor on cytokine concentrations. These observations indicate that inhalations with a brine solution from the Wieliczka Salt Mine diminish the asthma-related symptoms by reducing the inflammatory status and thus act in anti-inflammatory and relaxing way on the airway muscles. The project was financed by the MINIATURA research grant 2017/01/X/NZ5/00325 of the Polish National Science Centre.

Neurotensin (NTS) is an oligopeptide, which shows ambiguous activity in inflammatory process. The aim of the study was to test potential anti-inflammatory activity of NTS in mice model of non-atopic asthma and establish the contribution of NTS1 receptors. Asthma was induced in BALB/c mice by skin sensitization with dinitrofluorobenzene followed by intratracheal challenge of dinitrobenzene sulfonic acid. After hapten provocation and 8 hr later, mice were treated intraperitoneally with NTS, SR142948 (NTS1 receptor antagonist)+NTS or NaCl. 24 hr after challenge airway responsiveness to nebulized methacholine was measured in plethysmographic chamber. Bronchoalveolar lavage fluid (BALF) and differential cell count was performed. BALF and lung homogenates were used to quantify the levels of cytokines, mouse mast cell protease (mMCP-1) and malondialdehyde (MDA). NTS alleviated bronchial hyperreactivity and reduced number of inflammatory cells in BALF. Administration of NTS1 receptor antagonist inhibited these beneficial effects. Treatment with neurotensin decreased levels of IL-13, TNF-a in BALF and IL-17A, IL-12p40, RANTES, mMCP-1, MDA in lung tissue homogenates. SR142948 blockade reverted only post-neurotensin TNF-a decrease. NTS exhibits anti-inflammatory activity in hapten-induced asthma model. Leukocyte accumulation and bronchial constriction studies indicate, that this beneficial NTS action is mediated through NTS1 receptors. No effect of NTS1 blockade on mast cells activation product, oxidative stress marker and pro-inflammatory cytokine production suggest that NTS2 receptor can be involved. Further research is required. Financial support: National Science Centre, Poland, 2014/13/B/NZ7/02247

Breathing impairments, such as an alteration in breathing pattern, dyspnoea, and sleep apnoea, are common health deficits recognised in Parkinson’s disease (PD). The mechanism that underlies these disturbances, however, remains unclear. We investigated the effect of the unilateral damage to the rat nigrostriatal pathway on the central ventilatory response to hypercapnia, evoked by administering 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB). The respiratory experiments were carried out in conscious animals in the plethysmography chamber. The ventilatory parameters were studied in normocapnic and hyperoxic hypercapnia before and 14 days after the neurotoxin injection. Lesion with the 6-OHDA produced an increased tidal volume during normoxia. The magnified response of tidal volume and a decrease of breathing frequency to hypercapnia were observed in comparison to the pre-lesion and sham controls. Changes in both respiratory parameters resulted in an increase of minute ventilation of the response to CO(2) by 28% in comparison to the pre-lesion state at 60 s. Our results demonstrate that rats with implemented unilateral PD model presented an altered respiratory pattern most often during a ventilatory response to hypercapnia. Preserved noradrenaline and specific changes in dopamine and serotonin characteristic for this model could be responsible for the pattern of breathing observed during hypercapnia.

Present trends in the global energy sector effectively drive the development of technologies using renewable energy sources and the improvement of combustion technology towards increasing its efficiency and removing environmentally harmful flue gases. One solution is to replace fossil energy sources with renewable sources, including biomass. The degree of biomass utilization depends on the size of resources and processing technology. There are more and more different types of biomass on the market. There are many technologies for its energetic use. In recent years, fluidized combustion technology has been considered as one of the main directions of development of professional energy in the world. Many units in the world in fluidized combustion technology use as primary or supplementary fuel: sludge, wood waste and biomass, as well as municipal waste, etc. Fluidized bed boilers also allow the implementation of the dynamically developing oxy-combustion technology, which perfectly fits the prevailing trends due to the key advantages of increased energy conversion, as well as the possibility of direct sequestration of carbon dioxide. During experimental research, the mass loss of biomass pellets of various origins was analyzed in an oxidizing and inert atmosphere in a two-phase flow with the use of inert material. The obtained results allow to state that the large variety of biomass offered by suppliers requires a thorough knowledge of its properties and determination of its impact on the process and installations when used in the power industry.

Sulforaphane-modified selenium nanoparticles can be prepared in a simple aqueous-phase redox reaction through reduction of selenite with ascorbic acid. The sulforaphane molecules present in the reaction mixture adsorb on the nanoparticle surface, forming an adlayer. The resulting conjugate was examined with several physicochemical techniques, including microscopy, spectroscopy, x-ray diffraction, dynamic light scattering and zeta potential measurements. As shown in in vivo investigations on rats, the nanomaterial administered intraperitoneally is eliminated mainly in urine (and, to a lesser extent, in feces); however, it is also retained in the body. The modified nanoparticles mainly accumulate in the liver, but the basic parameters of blood and urine remain within normal limits. The sulforaphane-conjugated nanoparticles reveal considerable anticancer action, as demonstrated on several cancer cell cultures in vitro. This finding is due to the synergistic effect of elemental selenium and sulforaphane molecules assembled in one nanostructure (conjugate). On the other hand, the cytotoxic action on normal cells is relatively low. The high antitumor activity and selectivity of the conjugate with respect to diseased and healthy cells is extremely promising from the point of view of cancer treatment.

The objective of the study was to investigate the possibility of modulation of skin inflammation by topical treatment with a novel compound: an opioid-neurotensin hybrid peptide PK20 encompassing endomorphin-2 analog and modified fragment of neurotensin (8–13). Contact sensitivity response was induced in mice by skin sensitization with dinitrofluorobenzene (DNFB) followed by topical hapten application on ears. Mice were treated locally with PK20 or pure cream 2 h after the challenge with DNFB. 2 and 24 h after hapten exposure, ear thickness was determined. Ears were collected for histology and homogenization. Supernatants were used for measurement of contents of cytokines and lipid peroxidation products. Treatment with PK20 reduced significantly the late phase of contact sensitivity response, which was revealed by ear thickness diminution and reduction of inflammatory cell infiltration. The average concentrations of IL-1α, MCP-1, TNF-α and thiobarbituric acid-reactive substances were significantly decreased in the ears treated with the chimera in comparison to the control cream treated ears in DNFB sensitized/DNFB challenged group. We found that PK20 topical treatment alleviates hypersensitivity responses triggered by DNFB challenge and usage of the hybrid peptide may be a novel therapeutic strategy in the treatment of chronic inflammatory diseases. However, the mechanism remains unclear and needs further investigation.

Neurokinin A (NKA) is a peptide neurotransmitter that participates in the regulation of breathing and the cardiovascular system. The purpose of the current study was to determine the cardiorespiratory pattern exerted by the systemic injection of NKA, to look at the contribution of neurokinin NK1 and NK2 receptors, and to establish the engagement of the vagal pathway in mediation of these responses. The effects of intravenous injections of NKA (50 μg/kg) were studied in anaesthetized, spontaneously breathing rats in the following experimental schemes: in neurally intact rats; and vagotomized at either midcervical or supranodosal level. Intravenous injections of NKA in the intact rats evoked sudden and short-lived increase in the respiratory rate concomitant with drop in tidal volume, followed by a prolonged depression, coupled with continuous augmentation of the tidal volume. Respiratory alterations were accompanied by transient tachycardia and prolonged hypotension. Midcervical vagotomy eliminated respiratory rate response and augmentation of tidal volume. Section of supranodosal vagi abrogated all respiratory reactions. NK2 receptor blockade abolished respiratory changes without affecting cardiovascular effects, whereas NK1 receptor blockade significantly reduced hypotension and increase in heart rate with no impact on the respiratory system. These results indicate that NKA induced changes in the breathing resulting from an excitation of the NK2 receptors on the vagal endings. A fall in blood pressure triggered by NKA occurs outside of the vagus nerve and is probably mediated via its direct action on vascular smooth muscles supplied with NK1 receptors.

Modified non-motor brainstem ventilatory control might be involved in Parkinson's disease. Our study was designed to investigate the impact of degeneration of the nigrostriatal dopaminergic pathway on resting breathing and hypoxic ventilatory response in conscious rats. The role of central and peripheral dopamine D2 receptors in the modulation of the hypoxic ventilatory response in conditions of dopamine shortage was examined. Adult Wistar rats received a unilateral double 6-hydroxydopamine lesion of the right medial forebrain bundle. After surgery, animals were placed in whole-body plethysmographic chamber and exposed to hypoxia (8% O2). One group of animals received inraperitoneal injections of either haloperidol or domperidone before hypoxia. Levels of dopamine and its metabolite in the brainstem and striatum were assessed. Neurotoxin treatment evoked limb use asymmetry. No effect on the resting normoxic respiration was observed. An increase in tidal volume and a decrease in respiratory rate during respiratory response to hypoxia with short magnification of minute ventilation were predominant effects. Domperidone treatment in intact animals evoked a significant increase in normoxic tidal volume, while haloperidol potentiated tidal volume increase in response to hypoxia. After the lesion, the effects of both antagonists were absent. In rats with Parkinson's, the content of dopamine and its metabolite decreased substantially in the injured striatum. Augmentation of a tidal volume response to hypoxia, and the absence of stimulatory effect of intraperitoneal domperidone on normoxic and haloperidol on hypoxic tidal volume, in lesioned rats indicated altered control of breathing. This could be the result of a dopamine deficiency in the striatum and an increased turnover of DOPAC/DA in the brainstem.

The study investigated the share of vagal input at infra- and supra-nodosal level and the contribution of CCK1 and CCK2 receptors to the cardiorespiratory responses produced by an intravenous injection of sulfated cholecystokinin octapeptide (CCK-8) in anesthetized rats. This compound administered intravenously at a dose of 50μg/kg induced short-lived decline in tidal volume and respiratory rate resulting in depression of minute ventilation. Midcervical vagotomy had no effect on CCK-8-evoked ventilatory changes, whereas supranodosal denervation abolished slowing down of breathing. Cardiovascular response to CCK challenge was characterized by a transient decrease followed by an augmentation in the mean blood pressure (MAP) in the intact animals. Vagotomy performed at both levels abrogated the declining phase of MAP. Blood pressure changes were associated with decreased heart rate present in all neural states. All cardiovascular and respiratory effects were antagonized by pre-treatment with devazepide-CCK1 receptors' antagonist, whereas CI988-antagonist of CCK2 receptors was ineffective. In conclusion, our results indicate that CCK-8 modulates slowing down of respiratory rhythm via CCK1 receptors located in the nodose ganglia (NG) and depresses tidal volume via central CCK1 dependent mechanism. CCK-8-evoked decline in blood pressure may be due to activation of vagal afferents, whereas pressor responses seem to be mediated by an activation of CCK1 receptors in the central nervous system. Bradycardia was probably induced by the direct action of CCK-8 on the heart pacemaker cells.

PK20M (Dmt-D-Lys-Phe-Phe-OH) is a novel modified endomorphin-2 (EM-2) peptide producing strong dose- and time-dependent antinociceptive activity. Yet its prototype, endogenous EM-2, has been reported to trigger respiratory and vascular effects such as apnea and hypotension. The purpose of this study was to investigate the potency of the PK20M to evoke respiratory and cardiovascular responses in comparison to endogenous endomorphins. The engagement of the vagal pathway and μ opioid receptors in mediation of these responses was investigated. The effects of intravenous injections of PK20M, EM-1, and EM-2 were studied in anaesthetized, spontaneously breathing rats. The main dose-dependent effect of all endomorphins in the intact rats was immediate apnea, blood pressure and heart rate decrease. PK20M produced apnea in at least half of the intact animals in a much smaller dose than EM-1 and EM-2. The effects of all compounds were abrogated by pre-treatment with MNLX, a peripherally acting μ receptor antagonist. Cervical vagotomy eliminated arrest of breathing in the case of each tested compound. Hypotension was reduced by vagi section only after EM-1 and EM-2 administration. Our results demonstrated that apnea and bradycardia caused by systemic injection of all endomorphins were mediated via activation of μ vagal opioid receptors. The hypotension depended on intact vagi nerves only in the case of EM-1 and EM-2, whereas PK20M decreased blood pressure via other mechanisms outside vagal innervation. Modified opioid agonist is more potent in evoking extended hypotension; at the same time, it produces an arrest of breathing less frequently than its prototype EM-2.