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Continuous human metastin 45-54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-releasing hormone release monitored indirectly in the juvenile male Rhesus monkey (Macaca mulatta): a finding with therapeutic implications.

The effect of continuous administration of the C-terminal fragment of metastin, the ligand for the G protein-coupled receptor, GPR54, on GnRH-induced LH secretion was examined in three agonadal, juvenile male monkeys whose responsiveness to GnRH was heightened by pretreatment with a chronic pulsatile iv infusion of synthetic GnRH. After bolus injection of 10 microg human (hu) metastin 45-54 (equivalent to kisspeptin 112-121), the GPR54 agonist was infused continuously at a dose of 100 microg/h and elicited a brisk LH response for approximately 3 h. This rise was then followed by a precipitous

The influence of inflammation on the expression of neuropeptides in the ileum-projecting primary sensory neurones in the pig.

In the present study the ELISA test was used to investigate the influence of chemically-induced ileitis on the dorsal root ganglia (DRG) neurons in the pig. The preliminary retrograde fluorescent tracing study revealed that ileum-projecting sensory neurones (IPN) are located in the thoracic ganglia (Th; Th8-Th13). The ileum wall in experimental (E) pigs was subjected to multiple injection with 4% paraformaldehyde to induce inflammation, while in the control (C) animals the organ was injected with 0.1 M phosphate buffer. Three days later the DRGs (Th8-Th13) collected from all the animals were e

Changes in the mRNA expression pattern, with special reference to calcitonin gene-related peptide, after axonal injuries in rat motoneurons depends on age and type of injury.

The axotomy reaction in motoneurons after a peripheral nerve transection in the adult animal is characterized by a robust upregulation of al … e normalized within the 1st postoperative week, while GAP-43 mRNA was still upregulated at 3 weeks. Galanin message-associated peptide (GMAP) mRNA became upregulated preferentially in motoneurons subjected to ventral root avulsion, while nitric oxide synthase (NOS) mRNA was expressed exclusively after the latter type of injury. In the immature animal, alp …

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration.

INTRODUCTION: Bisphenol A (BPA) is used in the chemical industry for manufacturing plastics which are used as food packaging. Data indicate … uropeptides which modulate neuronal responses: cocaine and amphetamine regulated transcript (CART), galanin (GAL), calcitonin gene-regulated peptide (CGRP) and substance P (SP). MATERIALS AND METHODS: Fifteen young swine at 8 weeks of age were used as experimental models of the juvenile human liver. The pigs were divided into 3 groups and received capsul …

GALR1 methylation in vaginal swabs is highly accurate in identifying women with endometrial cancer.

Endometrial cancer has become the most common gynecological cancer in developed countries. Postmenopausal bleeding is indicative of the disease in only 1 of 10 women with this symptom. A noninvasive tool to identify women with cancer would be highly desirable. We analyzed more than 27,000 CpGs in normal endometrial tissue (n = 23) and endometrial cancers (n = 64) and found that DNA methylation of GALR1 is among the most frequent epigenetic alterations in this cancer. We then developed a real-time polymerase chain reaction-based GALR1 methylation test and applied this test to vaginal swabs from

Tumor cell expression of immune inhibitory molecules and tumor-infiltrating lymphocyte count predict cancer-specific survival in pancreatic and ampullary cancer.

Understanding the mechanisms of immune resistance in pancreatic and ampullary cancers is crucial for the development of suitable biomarkers and effective immunotherapeutics. Our aim was to examine the expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM, IDO and HLA-G, as well as CD8+ and FoxP3+ tumor infiltrating lymphocytes (TIL), in pancreatic and ampullary cancers, and to relate their individual, as well as their combined expression, to cancer survival. Tumor tissue from 224 patients with resected pancreatic (n = 148) and ampullary (n = 76) cancer was used to construct tis

Epidemic and virulence characteristic of Shigella spp. with extended-spectrum cephalosporin resistance in Xiaoshan District, Hangzhou, China.

BACKGROUND: Shigellae have become increasingly resistant to the extended-spectrum cephalosporin (ESC) worldwide and pose a great challenge to anti-infection treatment options. The purpose of this study was to determine the resistance, cephalosporin resistance mechanisms, virulence characteristic and genotype of ESC-resistant Shigella. METHODS: From 2008 to 2012, Shigella isolates collected from diarrhea patients were detected for antibiotics sensitivity by disk diffusion, cephalosporin resistance determinants and virulence genes using polymerase chain reaction (PCR) and genotyping through ent

Signals triggering the induction of leukemia inhibitory factor in sympathetic superior cervical ganglia and their nerve trunks after axonal injury.

Leukemia inhibitory factor (LIF) plays an important role in regulating neuropeptide expression in sympathetic and sensory neurons after axonal transection. By 2 h after axotomy, LIF mRNA increased in nonneuronal cells in sympathetic ganglia and peripheral nerve. In addition, within 1 h of explanting sympathetic ganglia or segments of sympathetic nerve trunks, a protein factor(s) that was able to induce LIF mRNA both in sympathetic cultures and in intact ganglia in vivo was released. This factor(s) appeared to be present in sympathetic ganglia and their nerve trunks under normal conditions and

Pituitary prolactin-secreting tumor formation: recent developments.

Prolactinoma is the most common type of primary pituitary tumors. It occurs more frequently in women than in men. Dopaminergic agonists are … dopamine, GABA, or brain-gut peptides (such as cholecystokinin, vasoactive intestinal polypeptide, galanin, angiotensin, opioid peptide, gastrin, gastrin-releasing peptide, pancreatic polypeptide, and adrenocorticotropic hormone) results in some of the pathological changes that may lead to hyperprolactinemia and/or prolactinoma development. Dysregulation …

Молекулярная и клеточная основа физиологических изменений беременности и ее последствий для нейрологовых и офтальмических патологий.

Беременность олицетворяет глубокие неврологические, гормональные и анатомические преобразования в материнском мозге, подготавливая их к уходу и сближению младенцев. Нейроимация свидетельствует о таких структурных изменениях, как сокращение содержания серых веществ и реорганизация белых веществ во время беременности, за которыми следует частичное послеродовое выздоровление. Эти адаптации модернизируются изменяющимися уровнями эстрадиола, прогестерона, пролактина и окситоцина, которые координируют нейропластичность и поведенческий уровень готовности. На молекулярном и клеточном уровнях гормоны б

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… In rodents, steroid hormones enhance maternal responsiveness to offspring by modulating galanin-expressing neurons in the medial preoptic area (mPOA) of the hypothalamus. … Galanin-expressing neurons in the mPOA are observed to be involved in regulating the motor, motivational, hormonal, and social components of parenting [ 12 ]. …

Satellite glia not DRG neurons constitutively activate EGFR but EGFR inactivation is not correlated with axon regeneration.

To test the possibility that phosphorylated epidermal growth factor receptor (pEGFR) mediates axon growth inhibition, we determined if pEGFR levels were raised in dorsal root ganglia (DRG) after non-regenerating dorsal column (DC) lesions and suppressed in regenerating sciatic nerve (SN) and preconditioning (P) SN+DC lesioned DRG. Levels of EGFR mRNA and protein in DRG were unchanged between control and all injury models. Satellite glia and not DRG neurons (DRGN) constitutively contained pEGFR and, only in PSN+DC rats, were levels significantly reduced in these cells. In vitro, siRNA mediated

Common genetic variants in GAL, GAP43 and NRSN1 and interaction networks confer susceptibility to Hirschsprung disease.

Hirschsprung disease (HSCR) is a severe multifactorial genetic disorder. Microarray studies indicated GAL, GAP43 and NRSN1 might contribute to the altered risk in HSCR. Thus, we focused on genetic variations in GAL, GAP43 and NRSN1, and the gene-gene interactions involved in HSCR susceptibility. We recruited a strategy combining case-control study and MassArray system with interaction network analysis. For GAL, GAP43 and NRSN1, a total of 18 polymorphisms were assessed in 104 subjects with sporadic HSCR and 151 controls of Han Chinese origin. We found statistically significant differences betw

Altered expression of neprilysin family members in the pituitary gland of sleep-disturbed rats, an animal model of severe fatigue.

Alterations of the expression of some peptidases in the pituitary gland of a fatigued rat model were identified. Rats were kept in a cage filled with water to a height of 1.5 cm to disturb deep sleep. After 24-h sleep disturbance, expression of neutral endopeptidase 24.11 (neprilysin) mRNA was increased in the intermediate lobe of the pituitary gland, whereas the mRNA expression of another family member, damage-induced neuronal endopeptidase, which is normally expressed in a subgroup of anterior pituitary cells, was significantly suppressed. These alterations were demonstrated by RT-PCR, north

Distribution of the regulatory peptide alarin in the eye of various species.

Alarin is a recently discovered regulatory peptide with vasoconstrictive properties in murine skin. Control of vasoconstriction/-relaxation is essential for ocular blood flow and hence the eye's homeostasis, and regulatory peptides are involved in regulation of ocular blood flow. Here we describe the existence and distribution of alarin in the eye of human and potential experimental animals (rat, mouse). Eyes of rat, mouse, and human were prepared for immunohistochemistry against murine and human alarin, respectively. Additionally, double staining experiments for alarin and CD31 were performed

Identification of novel genes in Hirschsprung disease pathway using whole genome expression study.

AIM: This study aims to identify new genes not described previously that may be relevant in the etiology or pathophysiology of patients with Hirschsprung disease (HD). This was done by identifying differences in gene expression between normal and abnormal segments of bowel in HD patients compared with controls. METHODS: Full-thickness colonic tissue samples were taken from HD patients, both from the diseased (Ds) and normal segment of the colon (Nr), and from controls (Ct). Samples were further dissected into mucosa (MUC) and muscle (MUS). RNA was extracted and analyzed on Affymetrix Gene Chi

Regulation and function of neuronal GTP-Ras in facial motor nerve regeneration.

Activation of Ras into the GTP-binding, 'ON' state is a key switch in the neurotrophin-mediated neuronal survival and neurite outgrowth, in vitro as well as in vivo. In the current study we explored changes in GTP-Ras levels following facial nerve injury and the ensuing regeneration and the effects of perturbing these changes in vivo using synapsin-promoter mediated neuronal expression of constitutively active Val12H-Ras (synRas). Quantification of GTP-Ras and total Ras revealed a precipitous drop in the relative GTP-Ras levels in the axotomized facial motor nucleus, to 40% of normal levels at

Insulin resistance versus insulin deficiency in non-insulin-dependent diabetes mellitus: problems and prospects.

A definitive assessment of the relative roles of insulin resistance and insulin deficiency in the etiology of NIDDM is hampered by several p … tion: amyloid deposits in the pancreas (126), changes in insulin secretagogues (amylin, GLP-1, GIP, galanin) (127-130), early intrauterine malnutrition (131). Finally, the predictive power of early changes in insulin secretion for the development of typical NIDDM is generally lower than that of insulin

Preparation and pharmacological activities of homolupinanoyl anilides.

On the pattern of well known dialkylaminoacyl anilides, a set of N-homolupinanoyl anilides was prepared and subjected to a broad pharmacological screening with in vivo and in vitro assays. As expected most compounds exhibited a strong antiarrhythmic activity, often comparable or superior to that of lidocaine and quinidine. Compound 1 exhibited an unusual profile as antiarrhythmic, being devoid of local anesthetic activity, calcium channel and beta adrenoceptor antagonism. Calcium channel blocking activity was seen in all aminobenzophenone derivatives, but not in the simpler anilides. Noteworth

Колокольчик коерулус на перекрестке воспаления и нейродегенерации в множестве склерозов.

Множественный склероз (MS) все чаще признается в качестве системного расстройства, включающего повреждения серой материи, разрыв сети и нейропсихиатрические симптомы наряду с демиелинацией. В этих рамках Colus coeruleus (LC), являющийся основным источником норадреналина (NA) в центральной нервной системе, появляется в качестве надежного центра регулирования в рамках распределенной моноаминергической сети. Основные элементы: С помощью ЛК формируется микроглиальная и астроцитическая реактивность, окислительный стресс, митохондриальная функция, дифференциация олигодендроцитов и устойчивость мозго

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… Regulation of neurological and neuropsychiatric phenotypes by locus coeruleus-derived galanin. Brain Res. 2016;1641(Pt B):320–37. 26607256 10.1016/j.brainres.2015.11.025 PMC4874918 35. … Neuronal diversity of neuropeptide signaling, including galanin, in the mouse locus coeruleus. Proc Natl Acad Sci U S A. 2023;120(31):e2222095120. 37487094 10.1073/pnas.2222095120 PMC10401028 36. …

Autonomic control of ventricular function in health and disease: current state of the art.

PurposeCardiac autonomic dysfunction is one of the main pillars of cardiovascular pathophysiology. The purpose of this review is to provide an overview of the current state of the art on the pathological remodeling that occurs within the autonomic nervous system with cardiac injury and available neuromodulatory therapies for autonomic dysfunction in heart failure.MethodsData from peer-reviewed publications on autonomic function in health and after cardiac injury are reviewed. The role of and evidence behind various neuromodulatory therapies both in preclinical investigation and in-use in clini

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… In addition to NE-mediated beta-adrenergic effects, sympathetic responses are enhanced by the release of sympathetic co-transmitters, such as neuropeptide Y (NPY) and galanin (Fig. 1 ). … Galanin is also co-released by sympathetic nerves, although at lower levels than NPY [ 33 ]. Galanin’s effects appear to be similar to NPY, as it can also inhibit acetylcholine release by binding to galanin receptors (GalR1) on parasympathetic neurons [ 33 ]. …