Neuroendocrine Factors Research Articles

Amygdala neural ensemble mediates mouse social investigation behaviors.

Innate social investigation behaviors are critical for animal survival and are regulated by both neural circuits and neuroendocrine factors. Our understanding of how neuropeptides regulate social interest, however, is incomplete at the current stage. In this study, we identified the expression of secretin (SCT) in a subpopulation of excitatory neurons in the basolateral amygdala. With distinct molecular and physiological features, BLASCT+ cells projected to the medial prefrontal cortex and were necessary and sufficient for promoting social investigation behaviors, whilst other basolateral amygdala neurons were anxiogenic and antagonized social behaviors. Moreover, the exogenous application of secretin effectively promoted social interest in both healthy and autism spectrum disorder model mice. These results collectively demonstrate a previously unrecognized group of amygdala neurons for mediating social behaviors and suggest promising strategies for social deficits.

Amelioration effect of Lactobacillus plantarum KFY02 on low-fiber diet-induced constipation in mice by regulating gut microbiota.

This study aimed to examine the ameliorating effect of Lactobacillus plantarum (LP) KFY02 on low-fiber diet-induced constipation in mice. LP-KFY02 was isolated from the natural fermented yogurt in Korla of Xinjiang. The mice with low-fiber diet-induced constipation in experimental groups were administered 1 × 109 CFU/kg LP-KFY02 (KFY02H) and 1 × 108 CFU/kg LP-KFY02 (KFY02L). After LP-KFY02 treatment with constipation mice, the mice fecal water content, intestinal transit ability and defecation time of constipated mice were improved. The mice fecal flora diversity, abundance and structure of the intestinal flora were regulated to the balanced state. The mice serum levels of gut motility related neuroendocrine factors have been increased, the intestinal mucosal barrier function and gut motility related gene expression were regulated in mice colon tissues. At the same time, the mice colon tissue damage were improved. These parameters in the KFY02H group were close to the normal group. These results suggested that LP-KFY02 could be considered as a potential probiotic to help alleviate low-fiber diet-induced constipation. They also provided a theoretical basis for the study of probiotics to relieve constipation by regulating intestinal flora.

Neuroendocrine regulations in tissue-specific immunity: From mechanism to applications in tumor.

Immune responses in nonlymphoid tissues play a vital role in the maintenance of homeostasis. Lots of evidence supports that tissue-specific immune cells provide defense against tumor through the localization in different tissue throughout the body, and can be regulated by diverse factors. Accordingly, the distribution of nervous tissue is also tissue-specific which is essential in the growth of corresponding organs, and the occurrence and development of tumor. Although there have been many mature perspectives on the neuroendocrine regulation in tumor microenvironment, the neuroendocrine regulation of tissue-specific immune cells has not yet been summarized. In this review, we focus on how tissue immune responses are influenced by autonomic nervous system, sensory nerves, and various neuroendocrine factors and reversely how tissue-specific immune cells communicate with neuroendocrine system through releasing different factors. Furthermore, we pay attention to the potential mechanisms of neuroendocrine-tissue specific immunity axis involved in tumors. This may provide new insights for the immunotherapy of tumors in the future.

Early Life Trauma and Social Processing in HIV: The Role of Neuroendocrine Factors and Inflammation.

Early life trauma (ELT) and HIV are associated with social processing deficits. In people with HIV (PWH), we examined whether facial emotion identification accuracy differs by ELT and whether neuroendocrine factors including cortisol, oxytocin (OT), and arginine vasopressin, and/or immune system measures play a role in the ELT-performance association. We used secondary data from the placebo condition of a pharmacologic challenge study in PWH. Presence of ELT was measured with the Childhood Trauma Questionnaire (at least moderate experiences of sexual, physical, and/or emotional abuse). Social processing was measured with the Facial Emotion Perception Test (FEPT). Salivary immune system measures and cortisol were sampled across a 5-hour study session. Blood was collected at study session start (12 pm ) to measure OT and arginine vasopressin. We examined the association of ELT with FEPT and five biological moderators (from principal components analysis of 12 biomarkers) of ELT-FEPT associations. Of 58 PWH (42 men; mean [standard deviation] age = 33.7 [8.9] years), 50% endorsed ELT. ELT-exposed PWH demonstrated lower identification accuracy across all emotional expressions (unstandardized β [ B ] = 0.13; standard error [SE] = 0.05; p = .021, d = 0.63) and had higher OT levels compared with ELT-unexposed PWH ( t(1,56) = 2.12, p = .039; d = 0.57). For total accuracy, an OT/C-reactive protein factor moderated the ELT-FEPT association ( B = 0.14; SE = 0.05; p = .014); accuracy was lower in ELT-exposed PWH versus ELT-unexposed PWH when the factor was low but not when high. Similar results were obtained for fearful, neutral, and happy faces ( p values < .05). Regardless of ELT, a myeloid migration (MCP-1/MMP-9) factor was associated with reduced accuracy ( p values < .05). Our pilot findings suggest that ELT may alter social processing in PWH, and OT and C-reactive protein may be a target for improving social processing in ELT-exposed PWH, and myeloid migration markers may be a target in PWH more generally.

Signaling pathways activated by sea bass gonadotropin-inhibitory hormone peptides in COS-7 cells transfected with their cognate receptor.

Results of previous studies provided evidence for the existence of a functional gonadotropin-inhibitory hormone (GnIH) system in the European sea bass, Dicentrarchus labrax, which exerted an inhibitory action on the brain-pituitary-gonadal axis of this species. Herein, we further elucidated the intracellular signaling pathways mediating in sea bass GnIH actions and the potential interactions with sea bass kisspeptin (Kiss) signaling. Although GnIH1 and GnIH2 had no effect on basal CRE-luc activity, they significantly decreased forskolin-elicited CRE-luc activity in COS-7 cells transfected with their cognate receptor GnIHR. Moreover, an evident increase in SRE-luc activity was noticed when COS-7 cells expressing GnIHR were challenged with both GnIH peptides, and this stimulatory action was significantly reduced by two inhibitors of the PKC pathway. Notably, GnIH2 antagonized Kiss2-evoked CRE-luc activity in COS-7 cells expressing GnIHR and Kiss2 receptor (Kiss2R). However, GnIH peptides did not alter NFAT-RE-luc activity and ERK phosphorylation levels. These data indicate that sea bass GnIHR signals can be transduced through the PKA and PKC pathways, and GnIH can interfere with kisspeptin actions by reducing its signaling. Our results provide additional evidence for the understanding of signaling pathways activated by GnIH peptides in teleosts, and represent a starting point for the study of interactions with multiple neuroendocrine factors on cell signaling.

Editorial introductions

Editorial introductions

Comprehensive genetic analysis of histological components of combined small cell carcinoma.

BackgroundCombined small‐cell lung cancer (cSCLC) is a rare type of small‐cell lung cancer (SCLC) that includes both SCLC and non‐small‐cell lung cancer (NSCLC). The molecular biological mechanisms underlying the heterogeneity of histological types in combined or metachronously transformed SCLC (mtSCLC) remain unclear. This study aimed to investigate the relationship between genetic alterations and each histological component heterogeneously detected in cSCLC and mtSCLC.MethodsThis study included four cSCLC cases and one mtSCLC case. Formalin‐fixed and paraffin‐embedded sections of each histological component of these tumors were subjected to next‐generation sequencing (NGS) and quantitative reverse transcription‐polymerase chain reaction to investigate the genetic mutations and expression levels of neuroendocrine cell‐specific transcription factors (achaete‐scute homolog‐1 [ASCL1], brain‐2 [BRN2] also known as POU domain class 3 transcription factor 2, nuclear factor 1 B [NF1B], insulinoma‐associated protein 1 [INSM1], and thyroid transcription factor‐1 [TTF‐1]).ResultsNGS analysis revealed that SCLC and NSCLC components share the same somatic mutations detected most frequently in TP53, and also in RB1 and EGFR. Gene expression analysis showed ASCL1 expression was significantly lower in the NSCLC component than in the SCLC component.ConclusionWe conclude that the morphological evolution of heterogeneous histological components in cSCLC may be associated with differences in ASCL1 expression levels, but not in acquired somatic gene mutations.

RGD-Labeled Hemocytes With High Migration Activity Display a Potential Immunomodulatory Role in the Pacific Oyster Crassostrea gigas.

Immunocyte migration to infection sites is important for host cellular defense, but the main types of migrating hemocytes and their mechanisms against pathogen invasions are unclear in invertebrates. In the present study, a population of hemocytes in the Pacific oyster Crassostrea gigas labeled with a fluorescein isothiocyanate (FITC)-conjugated Arg-Gly-Asp (RGD)-containing peptide was sorted. RGD+ hemocytes were characterized by a smaller cell size and cytoplasmic-nucleo ratio, fewer cytoplasmic granules, and higher levels of myeloperoxidase, reactive oxygen species, and intracellular free calcium concentration. RGD+ hemocytes exhibited a high level of migration activity, which was further induced after V. splendidus infection. Transcriptome analysis revealed that RGD+ hemocytes highly expressed a series of migration-related genes, which together with migration-promoting genes were significantly upregulated after V. splendidus infection. The neuroendocrine system was also proven to regulate the migration activity of RGD+ hemocytes, especially with the excitatory neuroendocrine factor dopamine, which promoted migration activity as confirmed by receptor blocking assays. Meanwhile, RGD+ hemocytes could highly express immunomodulatory factor interleukin (IL)-17s and their receptor genes, which was positively related to the production of antimicrobial peptides in whole hemocytes after V. splendidus infection. Collectively, this study identified a specific hemocyte population, i.e., RGD+ hemocytes, that shows high migration activity in response to pathogen infection and exerts a potential immunomodulatory role by highly expressing IL-17s that might enhance the hemocytes’ antimicrobial peptide production in oysters.

A conceptual understanding of intimate partner violence behaviors in men: Implications for research and intervention

Intimate Partner Violence (IPV) is a significant public health concern globally with substantial impact on the health of victims. Although research on IPV has increased substantially over the past several decades, effective evidence-based interventions to address IPV behaviors by men remain limited. The IPV field has lacked a comprehensive review of the status of research across the broad areas that have been found to be associated with use of IPV behaviors. This paper reviewed quantitative research studies of the genetic, neurocognitive, neuroendocrine, and selected environmental underpinnings of IPV behavior in men to develop a conceptual model. To date, environmental studies have been the most extensive with focus on early life adversity, trauma, attachment and substance misuse. Head injuries and neuropsychological impacts have indicated deficits in cognitive flexibility and executive functioning related to the prefrontal cortex are common in men who use IPV. Fewer studies have examined neuroendocrine or hormonal factors impacting IPV behavior but there is some evidence that cortisol and testosterone may play a role. Genetics factors have been the least explored, although there is emerging evidence of genetic heritability, and gene by environment interactions. A more comprehensive understanding of biological, psychological, and social factors will advance future IPV research and intervention.

Haven't lost the positive feeling: a dose-response, oral alcohol challenge study in drinkers with alcohol use disorder.

Models of addiction are based on neurobiological, behavioral, and pharmacological studies in animals, but translational support from human studies is limited. Studies are lacking in examining acute responses to alcohol in drinkers with alcohol use disorder (AUD), particularly in terms of relevant intoxicating doses and measurement of stimulating and rewarding effects throughout the breath alcohol concentration (BrAC) time curve. Participants were N = 60 AUD drinkers enrolled in the Chicago Social Drinking Project and examined in three random-order and blinded sessions for subjective and physiological responses to a beverage containing 0.0 g/kg, 0.8 g/kg, and 1.2 g/kg alcohol. BrAC in the alcohol sessions at 60 min was 0.09 g/dL and 0.13 g/dL, respectively. Both doses of alcohol produced significant biphasic effects on subjective measures of stimulation, euphoria, reward (liking and wanting), sedation, and neuroendocrine and cardiovascular factors. Increased pleasurable effects of alcohol were pronounced during the rising limb-to-peak BrAC and sedating effects emerged during the declining limb. Alcohol dose-dependently increased feel drug ratings and rewarding effects at peak BrAC or early declining limb, and physiological responses at the rising limb. Thus, rather than the notion of an overall tolerance, results show an alcohol response phenotype characterized by sensitivity to alcohol's stimulating, rewarding and physiological effects. The results of this study may aid in the conceptualization of alcohol addiction as a disorder characterized by the persistence of enhanced hedonic alcohol responses rather than chronic tolerance and reward deficiency.

Influence on study outcomes of an inpatient study by the behavior of the study staff (PINgPOng): study protocol for a randomized clinical trial

BackgroundThe placebo effect as the symptom improvement following inert treatments is a fixed component of RCTs to differentiate between specific effects of the tested pharmacological substance from other unspecific effects. The PINgPOng study was set up to analyze the influence of a study team trained to either minimize the placebo response and optimize drug-placebo differences or to maximize the placebo response to increase drug efficacy by unspecific factors on the study results of a RCT in a classical early clinical trial setting.Methods/designPINgPOng is a single-center, prospective, randomized, double-blind, placebo-controlled study in a 3-group, 2-sequence, 2-period cross-over design. The study is conducted according to the principles of ICH-GCP and the Declaration of Helsinki on the Phase I-Unit of the University Hospital Bonn. The primary endpoint is the pain intensity in the cold pressor test before and after the administration of 15 mg oxycodone or placebo. The pain intensity is compared between three study conditions: 32 healthy volunteers in each study arm will be treated either by an untrained study team (arm A), by a study team trained to maximize (arm B), or to minimize placebo responses (arm C). Neuroendocrine factors (alpha-amylase activity, salivary cortisol), characteristic traits (anxiety, depression, stress), and somatic reactions are analyzed as covariates of the pain perception.DiscussionThe PINgPOng study will allow to answer the question whether and to what extent the behavior of a trained study team (neutral vs. maximize vs. minimize placebo responses) will differentially affect placebo responses in a setting of a highly standardized early clinical trial. The results will help to control the placebo effects by education of the clinical study team and to avoid unnecessary high placebo effects in clinical development.Trial registrationGerman Clinical Trials Register DRKS00013586. Registered on December 22, 2017.

Mood Disorders in Young People With Acquired Brain Injury: An Integrated Model.

Purpose/ObjectiveYoung people with paediatric acquired brain injury (pABI) are twice as likely to develop a mood disorder as their peers, frequently have significant unmet socio-emotional needs, and are at over double the risk of going on to use adult mental health services. Recent years have seen significant advances in the development of interventions for young people with mood disorders. However, evidence-based approaches to mood disorders in pABI are lacking and surprisingly little work has evaluated clinical and neuro-developmental models of mood disorders in this population.MethodWe review the literature regarding key mechanisms hypothesised to account for the increased vulnerability to mood disorders in pABI: First, we summarise the direct neurocognitive consequences of pABI, considering the key areas of the brain implicated in vulnerability to mood disorders within a neurodevelopmental framework. Second, we outline five key factors that contribute to the heightened prevalence of mood disorders in young people following ABI. Finally, we synthesise these, integrating neuro-cognitive, developmental and systemic factors to guide clinical formulation.Results and ImplicationsWe present a framework that synthesises the key mechanisms identified in our review, namely the direct effects of pABI, neurocognitive and neuroendocrine factors implicated in mood and anxiety disorders, maladaptive neuroplasticity and trauma, structural and systemic factors, and psychological adjustment and developmental context. This framework is the first attempt to provide integrated guidance on the multiple factors that contribute to elevated life-long risk of mood disorders following pABI.

Role of autonomous and endocrine factors in immunotropic effects of nitrogenous metabolites in patients with chronic pyelonephritis

Background. We have previously shown that nitrogenous metabolites have immunomodulatory effects in healthy rats and humans as well as patients with dysfunction of neuroendocrine-immune complex, encephalopatia and chronic pyelonephritis. The purpose of this study is clarification of the role of neuro-endocrine factors in their immunotropic activity in patients with chronic pyelonephritis. Materials and Methods. The object of observation were 17 men (aged 24-70 years) with chronic pyelonephritis in remission. The plasma levels and urinary excretion of nitrogenous metabolites as well as parameters of immunity and its neuro-endocrine regulation twice (on admission and after balneotherapy at the Truskavets’ Spa) was performed. Results. Judging by the multiple correlation coefficient, uricosuria exhibits maximal neuro-endocrine activity (R=0,780), followed by bilirubinemia (R=0,742), creatinineuria (R=0,692), uricemia (R=0,636), creatinineemia (R=0,632), urea excretion (R=0,536), instead urea plasma correlate with neuro-endocrine parameters insignificantly (R=0,360). Nitrogenous metabolites together determine the state of neuro-endocrine regulation by 94,2%, which, in turn, determine the state of immunity by 99,9%. Conclusion. Nitrogenous metabolites carry out immunomodulation in different ways: directly through aryl hydrocarbon (bilirubin), toll-like and adenosine (uric acid) receptors of immunocytes; through modulation of the activity of neurons of the autonomous nervous system and endocrinocytes with subsequent neuro-endocrine immunomodulation; and also, apparently, due to an off-receptor effect on neurons, endocrinocytes and immunocytes (urea and creatinine).

Molecular Subtypes of Extra-pulmonary Neuroendocrine Carcinomas Identified by the Expression of Neuroendocrine Lineage-Specific Transcription Factors

Extra-pulmonary neuroendocrine carcinomas (EPNEC) represent a group of rare and heterogenous neoplasms with adverse clinical outcome. Their molecular profile is largely unexplored. Our aim was to investigate if the major transcriptional drivers recently described in high-grade pulmonary neuroendocrine carcinomas characterize distinct molecular and clinical subgroups of EPNEC. Gene expression of ASCL1, NEUROD1, DLL3, NOTCH1, INSM1, MYCL1, POU2F3, and YAP1 was investigated in a series of 54 EPNEC (including 10 cases with mixed components analyzed separately) and in a group of 48 pulmonary large cell neuroendocrine carcinomas (P-LCNEC). Unsupervised hierarchical cluster analysis classified the whole series into four major clusters. P-LCNEC were classified into two major clusters, the first ASCL1/DLL3/INSM1-high and the second (including four EPNEC) ASCL1/DLL3-low but INSM1-high. The remaining EPNEC cases were sub-classified into two other clusters. The first showed INSM1-high and alternative ASCL1/DLL3 or NEUROD1 high expression. The second was characterized mainly by MYCL1 and YAP1 overexpression. In the ten cases with mixed histology, ASCL1, DLL3, INSM1, and NEUROD1 genes were significantly upregulated in the neuroendocrine component. Higher gene-expression levels of NOTCH1 and INSM1 were associated with lower pT stage and negative nodal status. Low INSM1 gene expression was associated with shorter overall survival in the entire case series (p = 0.0017) and with a trend towards significance in EPNEC, only (p = 0.06). In conclusion, our results show that EPNEC possess distinct neuroendocrine-lineage-specific transcriptional profiles; moreover, low INSM1 gene expression represents a novel potential unfavorable prognostic marker in high-grade NECs including those in extra-pulmonary location.

Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a cholangiopathy caused by genetic and microenvironmental changes, such as bile homeostasis disorders and microbiota dysbiosis. Therapeutic options are limited, and proven surveillance strategies are currently lacking. Clinically, PSC presents as alternating strictures and dilatations of biliary ducts, resulting in the typical “beaded” appearance seen on cholangiography. The pathogenesis of PSC is still unclear, but cholangiocytes play an essential role in disease development, wherein a reactive phenotype is caused by the secretion of neuroendocrine factors. The liver–gut axis is implicated in the pathogenesis of PSC owing to the dysbiosis of microbiota, but the underlying mechanism is still poorly understood. Alterations in cholangiocyte responses and related signalling pathways during PSC progression were elucidated by recent research, providing novel therapeutic targets. In this review, we summarise the currently known underlying mechanisms of PSC pathogenesis caused by the dysbiosis of microbiota and newly reported information regarding cholangiocytes in PSC. We also summarise recently reported in vitro and in vivo models for studying the pathogenesis of PSC.

Neuroendocrine Regulation of Plasma Cortisol Levels During Smoltification and Seawater Acclimation of Atlantic Salmon

Diadromous fishes undergo dramatic changes in osmoregulatory capacity in preparation for migration between freshwater and seawater. One of the primary hormones involved in coordinating these changes is the glucocorticoid hormone, cortisol. In Atlantic salmon (Salmo salar), cortisol levels increase during the spring smoltification period prior to seawater migration; however, the neuroendocrine factors responsible for regulating the hypothalamic-pituitary-interrenal (HPI) axis and plasma cortisol levels during smoltification remain unclear. Therefore, we evaluated seasonal changes in circulating levels of cortisol and its primary secretagogue—adrenocorticotropic hormone (ACTH)—as well as transcript abundance of the major regulators of HPI axis activity in the preoptic area, hypothalamus, and pituitary between migratory smolts and pre-migratory parr. Smolts exhibited higher plasma cortisol levels compared to parr across all timepoints but circulating ACTH levels were only elevated in May. Transcript abundance of preoptic area corticotropin-releasing factor b1 and arginine vasotocin were ~2-fold higher in smolts compared to parr in February through May. Smolts also had ~7-fold greater hypothalamic transcript abundance of urotensin 1 (uts-1a) compared to parr in May through July. When transferred to seawater during peak smolting in May smolts rapidly upregulated hypothalamic uts-1a transcript levels within 24 h, while parr only transiently upregulated uts-1a 96 h post-transfer. In situ hybridization revealed that uts-1a is highly abundant in the lateral tuberal nucleus (NLT) of the hypothalamus, consistent with a role in regulating the HPI axis. Overall, our results highlight the complex, multifactorial regulation of cortisol and provide novel insight into the neuroendocrine mechanisms controlling osmoregulation in teleosts.

Neuroendocrine tumor theranostics.

Theranostics is a term coined by combining the words “therapeutics” and “diagnostics,” referring to single chemical entities developed to deliver therapy and diagnosis simultaneously. Neuroendocrine tumors are rare cancers that occur in various organs of the body, and they express neuroendocrine factors such as chromogranin A and somatostatin receptor. Somatostatin analogs bind to somatostatin receptor, and when combined with diagnostic radionuclides, such as gamma‐emitters, are utilized for diagnosis of neuroendocrine tumor. Somatostatin receptor scintigraphy when combined with therapeutic radionuclides, such as beta‐emitters, are effective in treating neuroendocrine tumor as peptide receptor radionuclide therapy. Somatostatin receptor scintigraphy and peptide receptor radionuclide therapy are some of the most frequently used and successful theranostics for neuroendocrine tumor. In Japan, radiopharmaceuticals are regulated under a complex law system, creating a significant drug lag, which is a major public concern. It took nearly 10 years to obtain the approval for somatostatin receptor scintigraphy and peptide receptor radionuclide therapy use by the Japanese government. In 2021, 111Lu‐DOTATATE (Lutathera), a drug for peptide receptor radionuclide therapy, was covered by insurance in Japan. In this review, we summarize the history of the development of neuroendocrine tumor theranostics and theranostics in general, as therapeutic treatment for cancer in the future. Furthermore, we briefly address the Japanese point of view regarding the development of new radiopharmaceuticals.

Identifying the Interaction of the Brain and the Pituitary in Social – and Reproductive – State of Tilapia by Transcriptome Analyses

Introduction: As in all vertebrates, reproduction in fish is regulated by gonadotrophin-releasing hormone (GnRH) control on gonadotrophic hormones (GtHs) activity. However, the neuroendocrine factors that promote GnRH and GtH activity are unknown. In Nile tilapia (Oreochromis niloticus), sexual activity and reproduction ability depend on social rank; only dominant males and females reproduce. Here, this characteristic of dominant fish allows us to compare brain and pituitary gene expression in animals that do and do not reproduce, aiming to reveal mechanisms that regulate reproduction. Methods: An extensive transcriptome analysis was performed, combining two sets of transcriptomes: a novel whole-brain and pituitary transcriptome of established dominant and subordinate males, together with a cell-specific transcriptome of luteinizing hormone (LH) and follicle-stimulating hormone cells. Pituitary incubation assay validated the direct effect of steroid application on chosen genes and GtH secretion. Results: In most dominant fish, as determined behaviorally, the gonadosomatic index was higher than in subordinate fish, and the leading upregulated pituitary genes were those coding for GtHs. In the brain, various neuropeptide genes, including isotocin, cholecystokinin, and MCH, were upregulated; these may be related to reproductive status through effects on behavior and feeding. In a STRING network analysis combining the two transcriptome sets, brain aromatase, highly expressed in LH cells, is the most central gene with the highest number of connections. In the pituitary incubation assay, testosterone and estradiol increased the secretion of LH and specific gene transcription. Conclusions: The close correlation between behavioral dominance and reproductive capacity in tilapia allows unraveling novel genes that may regulate the hypothalamic-pituitary-gonadal axis, highlighting aromatase as the main factor affecting the brain and pituitary in maintaining a sexually active organism.

Neuro-endocrine mechanism of specific balneoeffects of sulfate-chloride sodium-magnesium mineral waters

Background. Earlier we showed that the newly created sulfate-chloride sodium-magnesium drinking mineral waters “Myroslava” (5 g/L) and “Khrystyna” (10 g/L) have favorable effects on neuroendocrine-immune complex and metabolism of patients with their violations. At the same time, the influence of both waters on one constellation of parameters is similar, despite the twofold difference in mineralization, while on the other constellation it is different. The aim of this study was to elucidate the neuroendocrine mechanism of specific effects. Materials and Methods. The object of clinical-physiological observation were 22 men aged 23-70 years, who underwent rehabilitation treatment of chronic pyelonephritis and cholecystitis in remission in the Truskavets’ spa. The examination was performed twice, before and after a 7-10-day course of balneotherapy. All patients received bioactive water Naftussya, however, 11 men additionally drank water "Khrystyna", and the other 11 men - water "Myroslava". The subject of the study were the parameters of the neuroendocrine-immune complex and metabolism. Results. The method of canonical analysis shows that the changes in neuroendocrine factors (LF and VLF bands HRV; beta- and delta-rhythm-generating nerve structures, cortisol and aldosterone determine changes in the parameters of immunity, microbiota, metabolism and cholekinetics by 99,5-98,6%. Conclusion. The primary effects of mineral waters are the modulation of the activity of the structures of the central and autonomic nervous and endocrine systems, which, in turn, have a regulatory modulating effect on the immune system, microbiota, metabolism, cholekinetics and blood pressure.

Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome.

Abnormalities of mast cell structure or function may play prominent roles in irritable bowel syndrome (IBS) symptom genesis. Mast cells show close apposition to sensory nerves and release bioactive substances in response to varied stimuli including infection, stress, and other neuroendocrine factors. Most studies focus on patients who develop IBS after enteric infection or who report diarrhea‐predominant symptoms. Three topics underlying IBS pathogenesis have been emphasized in recent investigations. Visceral hypersensitivity to luminal stimulation is found in most IBS patients and may contribute to abdominal pain. Mast cell dysfunction also may disrupt epithelial barrier function which alters mucosal permeability potentially leading to altered bowel function and pain. Mast cell products including histamine, proteases, prostaglandins, and cytokines may participate in hypersensitivity and permeability defects, especially with diarrhea‐predominant IBS. Recent experimental evidence indicates that the pronociceptive effects of histamine and proteases are mediated by the generation of prostaglandins in the mast cell. Enteric microbiome interactions including increased mucosal bacterial translocation may activate mast cells to elicit inflammatory responses underlying some of these pathogenic effects. Therapies to alter mast cell activity (mast cell stabilizers) or function (histamine antagonists) have shown modest benefits in IBS. Future investigations will seek to define patient subsets with greater potential to respond to therapies that address visceral hypersensitivity, epithelial permeability defects, and microbiome alterations secondary to mast cell dysfunction in IBS.