To analyse potential biomarkers for vibration-induced nerve damage in a population-based, observational study.
Prospective cohort study.
Malmö Diet Cancer Study (MDCS), Malmö, Sweden.
In a subcohort of 3898 individuals (recruited 1991-1996) from MDCS (baseline examination in 28 449 individuals; collection of fasting blood samples in a cardiovascular subcohort of MDCS of 5540 subjects), neuropathy-relevant plasma biomarkers were analysed during follow-up after filling out questionnaires, including a question whether work involved hand-held vibrating tools, graded as \'not at all\', \'some\' or \'much\'.
The neuropathy-relevant plasma biomarkers vascular endothelial growth factor (VEGF)-A, VEGF-D, VEGF receptor 2, galanin, galectin-3, HSP27, ß-nerve growth factor, caspase-3, caspase-8, transforming growth factor-α and tumour necrosis factor were analysed. Data were analysed by conventional statistics (Kruskal-Wallis test; post hoc test Mann-Whitney U test; Bonferroni correction for multiple testing) and in a subanalysis for galanin using two linear regression models (unadjusted and adjusted).
Among participants, 3361 of 3898 (86%) reported no work with hand-held vibrating tools, 351 of 3898 (9%) reported some and 186 of 3898 (5%) much work. There were more men and smokers in vibration-exposed groups. Galanin levels were higher after much vibration exposure (arbitrary units 5.16±0.71) compared with no vibration exposure (5.01±0.76; p=0.015) with no other observed differences.
Higher plasma levels of galanin, possibly related to magnitude, frequency, acceleration and duration, as well as to severity of symptoms of vibration exposure, may be found in individuals working with hand-held vibrating tools.

Colorectal cancer (CRC) represents around 10% of all cancers, with an increasing incidence in the younger age group. The gut is considered a unique organ with its distinctive neuronal supply. The neuropeptide, human galanin, is widely distributed in the colon and expressed in many cancers, including the CRC. The current study aimed to explore the role of galanin at different stages of CRC. Eighty-one CRC cases (TNM stages I - IV) were recruited, and formalin-fixed paraffin-embedded samples were analyzed for the expression of galanin and galanin receptor 1 (GALR1) by immunohistochemistry (IHC). Galanin intensity was significantly lower in stage IV (n= 6) in comparison to other stages (p= 0.037 using the Mann-Whitney U test). Whole transcriptomics analysis using NGS was performed for selected samples based on the galanin expression by IHC [early (n=5) with high galanin expression and late (n=6) with low galanin expression]. Five differentially regulated pathways (using Absolute GSEA) were identified as drivers for tumor progression and associated with higher galanin expression, namely, cell cycle, cell division, autophagy, transcriptional regulation of TP53, and immune system process. The top shared genes among the upregulated pathways are AURKA, BIRC5, CCNA1, CCNA2, CDC25C, CDK2, CDK6, EREG, LIG3, PIN1, TGFB1, TPX2. The results were validated using real-time PCR carried out on four cell lines [two primaries (HCT116 and HT29) and two metastatic (LoVo and SK-Co-1)]. The current study shows galanin as a potential negative biomarker. Galanin downregulation is correlated with advanced CRC staging and linked to cell cycle and division, autophagy, transcriptional regulation of TP53 and immune system response.

Sudden unexpected death in epilepsy (SUDEP) is typically unwitnessed but can be preceded by seizures in the period prior to death. Peri-ictal respiratory dysfunction is a likely mechanism for some SUDEP, and central apnea has been shown following amygdala stimulation. The amygdala is enriched in neuropeptides that modulate neuronal activity and can be transiently depleted following seizures. In a postmortem SUDEP series, we sought to investigate alterations of neuropeptidergic networks in the amygdala, including cases with recent poor seizure control.
In 15 SUDEP cases, 12 epilepsy controls, and 10 nonepilepsy controls, we quantified the labeling index (LI) for galanin, neuropeptide Y (NPY), and somatostatin (SST) in the lateral, basal, and accessory basal nuclei and periamygdala cortex with whole slide scanning image analysis. Within the SUDEP group, seven had recent generalized seizures with recovery 24 hours prior to death (SUDEP-R).
Galanin, NPY, and SST LIs were significantly lower in all amygdala regions in SUDEP cases compared to epilepsy controls (P < .05 to P < .0005), and galanin LI was lower in the lateral nucleus compared to nonepilepsy controls (P < .05). There was no difference in the LI in the SUDEP-R group compared to other SUDEP. Higher LI was noted in epilepsy controls than nonepilepsy controls; this was significant for NPY in lateral and basal nuclei (P < .005 and P < .05).
A reduction in galanin in the lateral nucleus in SUDEP could represent acute depletion, relevant to postictal amygdala dysfunction. In addition, increased amygdala neuropeptides in epilepsy controls support their seizure-induced modulation, which is relatively deficient in SUDEP; this could represent a vulnerability factor for amygdala dysfunction in the postictal period.

BACKGROUND: Melatonin regulates metabolism and metabolism related hormones in mammalians. Castration has some adverse effects on the metabolic hormones of dog. This study was conducted to determine the effects of oral melatonin administration on metabolic hormones, as well as to compare changes of these hormones after administration of melatonin in castrated and intact dogs. Twenty healthy mixed breed mature male dogs were divided randomly into four groups (n = 5): melatonin (3 mg/10 kg(, castrated, castrated and melatonin treated, and negative control. Blood sample was collected from jugular vein weekly for 1 month.
RESULTS: T3 and T4 hormones had a significant decrease within 1 month following administration of melatonin. No significant change was observed in concentration of FT3 and FT4 hormones. Leptin and ghrelin hormones also had a significant decrease in this period. Leptin and ghrelin had a more significant decrease in \"non-castrated and melatonin treated\" group compared to \"castrated and melatonin treated\" group. Galanin had a significant decrease but this neurotransmitter had no significant change in \"non-castrated and melatonin treated\" group in comparison to \"castrated and melatonin treated\" group.
CONCLUSIONS: It seems that daily administration of melatonin capsule in all dogs can probably decrease concentration of T3 and T4 hormones and balance other metabolic hormones following castration.
METHODS: The dogs underwent castration, melatonin treatment and blood sampling.

Around a quarter of neurons in laminae I-II of the dorsal horn are inhibitory interneurons. These play an important role in modulating somatosensory information, including that perceived as pain or itch. Previous studies in rat identified four largely non-overlapping neurochemical populations among these cells, defined by expression of galanin, neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS) or parvalbumin. The galanin cells were subsequently shown to coexpress dynorphin. Several recent studies have used genetically modified mice to investigate the function of different interneuron populations, and it is therefore important to determine whether the same pattern applies in mouse, and to estimate the relative sizes of these populations. We show that the neurochemical organization of inhibitory interneurons in mouse superficial dorsal horn is similar to that in the rat, although a larger proportion of these neurons (33%) express NPY. Between them, these four populations account for ∼75% of inhibitory cells in laminae I-II. Since ∼25% of inhibitory interneurons in this region belong to a novel calretinin-expressing type, our results suggest that virtually all inhibitory interneurons in superficial dorsal horn can be assigned to one of these five neurochemical populations. Although our main focus was inhibitory neurons, we also identified a population of excitatory dynorphin-expressing cells in laminae I-II that are largely restricted to the medial part of the mid-lumbar dorsal horn, corresponding to glabrous skin territory. These findings are important for interpretation of studies using molecular-genetic techniques to manipulate the functions of interneuron populations to investigate their roles in somatosensory processing.

The present study has demonstrated the galaninergic innervation of the endocrine pancreas including sources of the galaninergic nerve fibers, and the influence of galanin receptor agonists on blood glucose level in the zebrafish. For the first time, a very abundant galaninergic innervation of the endocrine pancreas during development is shown, from the second day post-fertilization to adulthood. The fibers originated from ganglia consisting of galanin-IR, non-adrenergic (non-sensory) neurons located rostrally to the pancreatic tissue. The ganglia were found on the dorsal side of the initial part of the anterior intestinal segment, close to the intestinal branch of the vagus nerve. The galanin-IR neurons did not show immunoreactivity for applied antibodies against tyrosine hydroxylase, choline acetyltransferase, and vesicular acetylcholine transporter. Intraperitoneal injections of galanin analog NAX 5055 resulted in a statistically significant increase in the blood glucose level. Injections of another galanin receptor agonist, galnon, also caused a rise in blood glucose level; however, it was not statistically significant. The present findings suggest that, like in mammals, in the zebrafish galanin is involved in the regulation of blood glucose level. However, further studies are needed to elucidate the exact mechanism of the galanin action.

Neuropeptide S (NPS) is a regulatory peptide expressed by limited number of neurons in the brainstem. The simultaneous anxiolytic and arousal-promoting effect of NPS suggests an involvement in mood control and vigilance, making the NPS-NPS receptor system an interesting potential drug target. Here we examined, in detail, the distribution of NPS-immunoreactive (IR) fiber arborizations in brain regions of rat known to be involved in the regulation of sleep and arousal. Such nerve terminals were frequently apposed to GABAergic/galaninergic neurons in the ventro-lateral preoptic area (VLPO) and to tyrosine hydroxylase-IR neurons in all hypothalamic/thalamic dopamine cell groups. Then we applied the single platform-on-water (mainly REM) sleep deprivation method to study the functional role of NPS in the regulation of arousal. Of the three pontine NPS cell clusters, the NPS transcript levels were increased only in the peri-coerulear group in sleep-deprived animals, but not in stress controls. The density of NPS-IR fibers was significantly decreased in the median preoptic nucleus-VLPO region after the sleep deprivation, while radioimmunoassay and mass spectrometry measurements showed a parallel increase of NPS in the anterior hypothalamus. The expression of the NPS receptor was, however, not altered in the VLPO-region. The present results suggest a selective activation of one of the three NPS-expressing neuron clusters as well as release of NPS in distinct forebrain regions after sleep deprivation. Taken together, our results emphasize a role of the peri-coerulear cluster in the modulation of arousal, and the importance of preoptic area for the action of NPS on arousal and sleep.

暂无摘要。

It is becoming increasingly evident that genetic variants contribute to the development of opioid addiction. An elucidation of these genetic factors is crucial for a better understanding of this chronic disease and may help to develop novel therapeutic strategies. In recent years, several candidate genes were implicated in opioid dependence. However, most study findings have not been replicated and additional studies are required before reported associations can be considered robust. Thus, the major objective of this study was to replicate earlier findings and to identify new genetic polymorphisms contributing to the individual susceptibility to opioid addiction, respectively. Therefore, a candidate gene association study was conducted including 142 well-phenotyped long-term opioid addicts undergoing opioid maintenance therapy and 142 well-matched healthy controls. In both study groups, 24 single nucleotide polymorphisms predominantly located in pharmacogenetic candidate genes have been genotyped using an accurate mass spectrometry based method. The most significant associations with opioid addiction (remaining significant after adjustment for multiple testing) were observed for the rs948854 SNP in the galanin gene (GAL, p = 0.001) and the rs2236861 SNP in the delta opioid receptor gene (OPRD1, p = 0.001). Moreover, an association of the ATP binding cassette transporter 1 (ABCB1) variant rs1045642 and the Mu Opioid receptor (OPRM1) variant rs9479757 with opioid addiction was observed. The present study provides further support for a contribution of GAL and OPRD1 variants to the development of opioid addiction. Furthermore, our results indicate a potential contribution of OPRM1 and ABCB1 SNPs to the development of this chronic relapsing disease. Therefore it seems important that these genes are addressed in further addiction related studies.

OBJECTIVE: The aim of the present study was to examine whether an association is present between amniotic fluid (AF) galanin and neonatal birth weight (NBW).
METHODS: Prospective observational study.
METHODS: Fetal maternal unit in a tertiary teaching hospital.
METHODS: Fifty women of singleton pregnancy who underwent amniocentesis during the second trimester and delivered after the 37th week of gestation.
METHODS: Amniocentesis 18th-19th gestational week for genetic indication with the use of a 22G needle under real-time sonographic guidance and measurement of galanin concentration in the AF.
METHODS: Association between concentration of AF galanin and NBW at term.
RESULTS: Galanin was isolated in all samples of AF (median concentration 19.95 pg/mL; range: 19.0-21.7). A strong linear correlation between AF galanin and NBW was detected (τ = 0.928; p < 0.001). Non-parametric linear regression analysis revealed that galanin concentration could explain 72.1% of the variance in the NBW, when controlling for gestational week at birth and mother\'s body mass index at delivery.
CONCLUSIONS: AF galanin during the second trimester seems to have a strong linear correlation with NBW of term deliveries in singleton pregnancies, even when controlling for important confounders.