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Iniencephaly (Greek: “inoin” meaning nape of neck) is an extremely rare and uniformly lethal form of neural tube defect. We report a case diagnosed in the first trimester using two-dimensional and three-dimensional ultrasound. The diagnosis was confirmed on postnatal autopsy. This case highlights the importance of diagnosing structural abnormalities in the first trimester itself.

Highlights • Lipoblastoma is rare benign tumour of extremities. • It occurs in infants and early childhood. • It usually involves subcutaneous tissue. • In our case lipoblastoma occurred in adolescent girl and presented as a mass in name of neck involving muscles., Introduction Lipoblastoma usually develops in extremities and trunk during infancy or childhood. Its occurrence in head and neck is rare. Case presentation Here we present a case of lipoblastoma in 14 years old female who developed swelling in the nape of her neck. Initially the diagnosis of lymphangioma was made on the basis MRI findings but histopathology after excisional biopsy confirmed it to be lipoblastoma. Conclusion Lipoblastoma can rarely present as swelling in the nape of neck in adolescents.

Background: Hair loss at the nape of the neck causes embarrassment and psychological stress in a number of patients due to a variety of causes including acne keloidalis nuchae and traction alopecia. Objectives: To report a case of hair transplantation into the nape of the neck as a treatment option for scarring resulting from acne keloidalis nuchae. Methods: 700 grafts where transplanted from the occipital donor area and transplanted by follicular unit extraction (FUE) into the nape area of a male patient with recurrent scarring folliculitis in that area. Results: Hair Restoration was successful with natural looking results. More tumescence than usual and skin traction was necessary to stabilize the skin during graft insertion due to soft skin in the nape area. Conclusions: Hair Restoration Surgery into the nape of the neck is an option for patients with hair loss in that area. FUE is the best method of hair transplantation allowing the selection of 1 and 2 hair FUE grafts in order to achieve a natural looking result in the nape area.

Background: Cannabis use remains a major public health concern, and its use typically begins in adolescence. Chronic administration of ∆9-tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, during adolescence can produce deficits in adult learning and memory, stress reactivity and anxiety. One possible mechanism behind the disruptions in adulthood from adolescent exposure to THC includes changes in social behaviours, such as social play, which has been shown to be critical to socio-cognitive development. Methods: Here, using an established animal model of adolescent THC exposure in male and female Long–Evans rats, we explored the effects of THC on play behaviour during the chronic administration period. Following puberty onset, as indicated by external changes to the genitalia, THC (5mg/kg) was administered for 14 days. Play behaviour was assessed seven days following the onset of the injection period at approximately 1 hour post treatment. The frequency of nape attacks, the likelihood and tactics of defensive behaviour, and pins were scored and analyzed. Results: THC exposure decreased playfulness in adolescent rats including the number of attacks, likelihood of defense and pins compared to control and vehicle treated rats. Conclusion: This suggests that THC suppresses both the attack and defense components of social play. This is an important finding because there is evidence that attack and defense may be mediated by different mechanisms. Furthermore, the effect of THC exposure decreasing playfulness occurred similarly in males and females.

Bioactive N-acylethanolamines (NAEs) are ethanolamides of long-chain fatty acids, including palmitoylethanolamide, oleoylethanolamide and anandamide. In animal tissues, NAEs are biosynthesized from membrane phospholipids. The classical "transacylation-phosphodiesterase" pathway proceeds via N-acyl-phosphatidylethanolamine (NAPE), which involves the actions of two enzymes, NAPE-generating Ca2+-dependent N-acyltransferase (Ca-NAT) and NAPE-hydrolyzing phospholipase D (NAPE-PLD). Recent identification of Ca-NAT as Ɛ isoform of cytosolic phospholipase A2 enabled the further molecular biological approaches toward this enzyme. In addition, Ca2+-independent NAPE formation was shown to occur by N-acyltransferase activity of a group of proteins named phospholipase A/acyltransferases (PLAAT)-1-5. The analysis of NAPE-PLD-deficient mice confirmed that NAEs can be produced through multi-step pathways bypassing NAPE-PLD. The NAPE-PLD-independent pathways involved three members of the glycerophosphodiesterase (GDE) family (GDE1, GDE4 and GDE7) as well as α/β-hydrolase domain-containing protein (ABHD)4. In this review article, we will focus on recent progress made and latest insights in the enzymes involved in NAE synthesis and their further characterization.

Background: The molecular mechanisms underlying itch are constantly being studied to create new opportunities to prevent or alleviate itch. The aim of our study was to determine the spinal gene expression changes induced by compound 48/80 in a mouse itch model.Methods: Mice were divided into saline group (control group, n=12) and compound 48/80 group (48/80 group, n=12). 100 µl saline or compound 48/80 was microinjected intradermally in the nape of the neck. After injection, pruritic behavior was immediately measured every 5 minutes. 30 minutes after injection, tissue was prepared to carry out mRNA profiling microarray and reverse transcription polymerase chain reaction (RT-qPCR) analyses.Results: The total numbers of scratching bout after compound 48/80 injection (100 µg/100 µl) were significantly increased in 48/80 group (190±11.33) as compared with control group (6.83±1.17). We screened the dorsal part of the cervical spinal cord of the mouse itch model for differentially expressed genes. Out of 45037 studied transcripts, the abundance levels of 15 transcripts were altered following compound 48/80 injection. 9 and 6 genes were up- and down-regulated in 48/80 group, respectively. We validated the reliability of the microarray results by RT-qPCR, and found 6 up-regulated mRNA, including Sgk1, Bag4, Fos, Ehd2, Edn3 and Wdfy, were significantly increased, whereas 3 down-regulated mRNA, including Corin, 4921511E18Rik and 4930423020Rik, were significantly decreased.Conclusions: These findings indicate that the alterations of spinal gene expression are involved in acute itch, and provide a translational bridge for spinal drugs targeting their signaling pathway to prevent or alleviate itch. Citation: Zhi-Gang He, Bao-Wen Liu, Zhi-Xiao Li, Cheng Liu, Hong-Bing Xiang. Altered expression profiling of spinal genes modulated by compound 48/80 in a mouse itch model. J Anesth Perioper Med 2017; 4: 220-4. doi:10.24015/JAPM.2017.0020This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

N-acylethanolamines (NAEs), a class of lipid mediators, are produced from N-acyl-phosphatidylethanolamine (NAPE) by several pathways, including the direct release by NAPE-specific phospholipase D (NAPE-PLD) or the multistep pathway via sn-glycero-3-phospho-N-acylethanolamine (Gp-NAE). Using liquid chromatography-tandem mass spectrometry, we compared peripheral tissue levels of NAPE, Gp-NAE and NAE in NAPE-PLD-deficient (NAPE-PLD-/-) and wild type (WT) mice. NAPE-PLD was suggested to play a major role in the NAPE degradation in heart, kidney, and liver, but not in jejunum, because the NAPE levels except jejunum were significantly higher in NAPE-PLD-/- mice than in WT mice. The deletion of NAPE-PLD failed to alter the NAE levels of these tissues, suggesting its limited role in the NAE production. The enzyme assays with tissue homogenates confirmed the presence of NAPE-PLD-independent pathways in these peripheral tissues. Gp-NAE species having an acyl moiety with 22 carbons and 6 double bonds was enriched in these peripheral tissues. As for sn-2 acyl species of NAPE, 18:2-acyl-containing NAPE species were predominant over 18:1-containing species in heart, liver, and jejunum. Our results show that both molecular species composition of NAPE, NAE and Gp-NAE and their dependencies on Napepld are different among the peripheral tissues, suggesting that each tissue has distinct metabolic pathways and these NAE-containing lipids play tissue-specific roles.

A cross-fostering design was used to assess the relative involvement of genetic variability and early postnatal experiences on differential levels of playfulness in juvenile Fischer 344 (F344) and Lewis (LEW) rats and the extent to which strain differences in anxiety may influence play in these two strains. F344 dams were found to lick and groom their pups less than LEW dams and this was not dependent upon the strain of the pups in the litter. As expected, F344 rats were less playful than LEW rats as demonstrated by fewer playful contacts directed to the nape of a Sprague-Dawley (SD) partner and a decreased likelihood of rotating completely to a supine position when their nape was contacted by the SD partner. These differences could not be readily explained by parallel strain differences in anxiety. The pattern of effects on play as a function of cross-fostering depended on both the genetic background of the pup and the motivational state of the pup prior to testing. Whereas in-fostered LEW pups solicited more play as isolation prior to testing increased from 4 to 24 hours, cross-fostered pups of both strains as well as in-fostered F344 pups were relatively insensitive to the motivational modulation of play solicitation. Responsiveness to play solicitations in pups of both strains reared by F344 dams was insensitive to prior isolation whereas pups reared by LEW dams were less likely to respond with a complete rotation to a supine position when solicited as isolation increased from 4 to 24 hours prior to testing. These data suggest that the overall level of playfulness in a particular strain of rat is fairly resistant to cross-fostering and may be particularly sensitive to genetic variation whereas how this urge is titrated and modified by motivational factors may be influenced more by epigenetic factors.

The dropped head syndrome (DHS) is a rare clinical syndrome with a broad differential diagnosis. The basic manifestation is inappropriate kyphosis of the cervico-thoracic link, usually caused by weakness of the extensor muscles of the nape. DHS is a source of significant discomfort and reduces quality of life (visual impairment, dysphagia, secondary pain, etc.).

N-Acylphosphatidylethanolamines (NAPEs) are a class of glycerophospholipids, which are known as precursors for different bioactive N-acylethanolamines. We previously reported that phospholipase A/acyltransferase-1 (PLAAT-1), which was originally found in mammals as a tumor suppressor, catalyzes N-acylation of phosphatidylethanolamines to form NAPEs. However, recent online database suggested the presence of an uncharacterized isoform of PLAAT-1 with an extra sequence at the N terminus. In the present study, we examined the occurrence, intracellular localization, and catalytic properties of this longer isoform, as well as the original shorter isoform from humans and mice. Our results showed that human tissues express the longer isoform but not the short isoform at all. In contrast, mice expressed both isoforms with different tissue distribution. Unlike the cytoplasmic localization of the shorter isoform, the long isoform was found in both cytoplasm and nucleus, inferring that the extra sequence harbors a nuclear localization signal. As assayed with purified proteins, neither isoform required calcium for full activity. Moreover, the overexpression of each isoform remarkably increased cellular NAPE levels. These results conclude that the new long isoform of PLAAT-1 is a calcium-independent N-acyltransferase existing in both cytoplasm and nucleus and suggest a possible formation of NAPEs in various membrane structures including nuclear membrane. J. Lipid Res. 2016. 57: 2051–2060.

Background Cortical neuronal dysfunction has been proposed to underlie the psychopathology and cognitive dysfunction of schizophrenia. Previously we have reported altered sphingolipid and N-acylphosphatidylserine (NAPS) metabolism in the frontal cortex in schizophrenia. We continue to expand these investigations to define the biochemical basis for these critical neuropathologies. Methods We undertook a targeted high resolution mass spectrometric analysis to validate our previous reports of elevated sphingolipids and NAPS in the frontal cortex of a new cohort of schizophrenia subjects. Furthermore we expanded these analyses to include ceramides, N-acylphosphatidylethanolamines (NAPE), and N-acylethanolamines (NAE). In the same tissue samples we examined N-acetylaspartylglutamate (NAAG), a modulator of excitatory amino acid transmission, hypothesized to be involved in the pathology of schizophrenia. Results We repeated our observations of elevated sulfatides in the frontal cortex in schizophrenia. An in-depth analysis of other sphingolipids revealed decrements in ceramide levels and increased levels of lactosylceramides. NAPS also were found to be augmented in schizophrenia as we previously reported. In addition, levels of NAPES, established biomarkers of neuronal stress, were elevated while their metabolites, NAEs were decreased. With regard to excitatory amino acid neurotransmission, NAAG levels were decreased by 50% while the metabolic precursor, N-acetylaspartate was unaltered. Conclusions Our data support the concept of cortical neuronal dysfunction in schizophrenia as indicated by altered metabolism of structural sphingolipids and NAAG, a modulator of excitatory amino acid neurotransmission.

Introduction Current markers of Parkinson’s disease (PD) fail to detect the early progression of disease state. Conversely, current omics techniques allow the investigation of hundreds of molecules potentially altered by disease conditions. Based on evidence previously collected by our group in a mouse model of PD, we speculated that a particular set of circulating lipids might be significantly altered by the pathology. Objectives The aim of current study was to evaluate the potential of a particular set of N-acyl-phosphatidylethanolamines (NAPEs) as potential non-invasive plasma markers of ongoing neurodegeneration from Parkinson’s disease in human subjects. Methods A panel of seven NAPEs were quantified by LC–MS/MS in the plasma of 587 individuals (healthy controls, n = 319; Parkinson’s disease, n = 268); Random Forest classification and statistical modeling was applied to compare Parkinson’s disease versus controls. All p-values obtained in different tests were corrected for multiplicity by controlling the false discovery rate (FDR). Results The results indicate that this panel of NAPEs is able to distinguish female PD patients from the corresponding healthy controls. Further to this, the observed downregulation of these NAPEs is in line with the results in plasma of a mouse model of Parkinson’s (6-OHDA). Conclusions In the current study we have shown the downregulation of NAPEs in plasma of PD patients and we thus speculate that these lipids might serve as candidate biomarkers for PD. We also suggest a molecular mechanism, explaining our findings, which involves gut microbiota. Electronic supplementary material The online version of this article (10.1007/s11306-019-1536-z) contains supplementary material, which is available to authorized users.

In patients with melanomas on the upper back or nape, axillary sentinel lymph node (SLN) biopsy (SLNB), when performed in the traditional supine position, is often disturbed by scattered radiation emitted from the primary tumor site. The results from the present study suggestthat axillary SLNB performed in the prone position can solve this problem. We compared two consecutive groups of patients with melanomas of the dorsal trunk or nape who received axillary SLNB performed either in the supine (

International audience; Selective serotonin reuptake inhibitor medications (SSRIs) are prescribed to up to 10% of pregnant women to treat maternal mood disorders. Exposure to these medications in-utero has raised concerns about altered neurobehavioral outcomes; most recently those related to peer-to-peer social interactions and play. While clinical data show that both perinatal SSRIs (pSSRI) and maternal stress can contribute to social behavioral changes in children, minimal animal work has investigated the effects of pSSRIs in relevant models of maternal stress or the long-term implications of these effects. Therefore the aim of this work was to investigate the long-term effects of pSSRI exposure to fluoxetine on social behaviors, the hypothalamic pituitary adrenal system (HPA) and hippocampal plasticity in adult male and female rat offspring using a model of pre-gestational maternal stress. Adult Sprague-Dawley female and male rat offspring from the following four groups were utilized 1. Control + Vehicle, 2. Control + Fluoxetine, 3. Pre-gestational Stress + Vehicle, 4. Pre-gestational Stress + Fluoxetine (n = 8-16/female/age groups, n = 8-14/male/age groups). Main findings show pSSRIs increased social investigation in adult females and increased social play (pouncing, nape attacks) in adult males. Perinatal SSRIs also had sexually differentiated effects on hippocampal neurogenesis and GR density. Pre-gestational stress had enduring effects by decreasing social investigation and hippocampal neurogenesis in adult males. Thus pSSRIs, as well as pre-gestational maternal stress, have significant long-term effects on social neurobehavioral outcomes which differ in males and females. This suggests that it would be valuable to consider fetal-sex specific treatments for maternal mental illness.

Obesity increases the risk for cardiometabolic diseases. N-acyl phosphatidylethanolamines (NAPEs) are precursors of N-acylethanolamides, which are endogenous lipid satiety factors. Incorporating engineered bacteria expressing NAPEs into the gut microbiota retards development of diet induced obesity in wild-type mice. Because NAPEs can also exert anti-inflammatory effects, we hypothesized that administering NAPE-expressing bacteria to low-density lipoprotein receptor (Ldlr)−/− mice fed a Western diet would improve various indices of cardiometabolic disease manifested by these mice. NAPE-expressing E. coli Nissle 1917 (pNAPE-EcN), control Nissle 1917 (pEcN), or vehicle (veh) were given via drinking water to Ldlr−/− mice for 12 weeks. Compared to pEcN or veh treatment, pNAPE-EcN significantly reduced body weight and adiposity, hepatic triglycerides, fatty acid synthesis genes, and increased expression of fatty acid oxidation genes. pNAPE-EcN also significantly reduced markers for hepatic inflammation and early signs of fibrotic development. Serum cholesterol was reduced with pNAPE-EcN, but atherosclerotic lesion size showed only a non-significant trend for reduction. However, pNAPE-EcN treatment reduced lesion necrosis by 69% indicating an effect on preventing macrophage inflammatory death. Our results suggest that incorporation of NAPE expressing bacteria into the gut microbiota can potentially serve as an adjuvant therapy to retard development of cardiometabolic disease.

We report two cases of granular cell tumors (GCTs) arising on rare sites, namely, the nape and umbilicus. While GCTs have a very characteristic histology, their clinical signs and symptoms are non-specific. Therefore, it is extremely difficult to make a diagnosis of GCT on the basis of clinical findings only. The two cases reported here were clinically similar to hypertrophic scars and keloids, respectively. Skin surgeons should remember that GCTs are an important differential diagnosis from hypertrophic scars and keloids.

The narrow-angle parabolic equation (NAPE) provides a robust approach for sound propagation in inhomogeneous media such asthe atmosphere and ocean. Several numerical methods for solving the NAPE in a motionless medium have been developed. The Crank-Nicholson finite-difference method is one of the simplest and readily supports range-dependent environmental processes such as turbulence. The NAPE, boundary condition, and artificial absorbing layer are discretized, and the solution is written in a matrix form. A starting field, which approximates the sound source, is marched forward by solving a matrix equation. Because the matrices involved are triagonal, the solution is highly efficient. For many applications in atmospheric and ocean acoustics, the NAPE needs to be generalized for wide-angle propagation and moving media (winds or currents). Recently derived wide-angle parabolic equations (WAPEs) in moving media are reviewed including the phase errors pertinent to the equations. In the Pade (1,1) and high-frequency approximations, the WAPE in a moving medium with arbitrary Mach numbers is surprisingly simple. It can be implemented numerically with minimal modifications to existing Crank-Nicholson NAPE solvers.

Introduction At Homagama Base Hospital there are approximately 100 patients looked after by the ENT clinic. Among the clinic attendees, paranasal sinusitis with vertigo and nape pain is a common observed phenomenon. In Sri Lanka data on these aspects are rare. Method Cross sectional descriptive study at the ENT Clinic of Base Hospital Homagama. Patients diagnosed as Paranasal Sinusitis amongst the patients attending the ENT clinic, age above 12 years. Patients diagnosed as Paranasal Sinusitis further evaluated for Vertigo and Nape pain. Total 425 patients taken for study. Result Patients diagnosed as Sinusitis, 425, 100% Patients diagnosed as Vertigo, 396 – 93.176% Patients diagnosed as Nape Pain, 322 – 75.76% There were Clinical improvement of Sinusitis – 423, 99.523%, among the research group. Patients with Vertigo – 396, all the symptomatic patients improved. Nape Pain – 322, all the symptomatic patients improved. Conclusion Rhino Sinusitis can cause symptoms like vertigo and nape pain. Whilst treating nape pain and vertigo, sinusitis should be considered in the differential diagnosis.

Macrophages are multi-faceted phagocytic effector cells that derive from circulating monocytes and undergo differentiation in target tissues to regulate key aspects of the inflammatory process. Macrophages produce and degrade a variety of lipid mediators that stimulate or suppress pain and inflammation. Among the analgesic and anti-inflammatory lipids released from these cells are the fatty acid ethanolamides (FAEs), which produce their effects by engaging nuclear peroxisome proliferator activated receptor-α (PPAR-α). Two members of this lipid family, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), have recently emerged as important intrinsic regulators of nociception and inflammation. These substances are released from the membrane precursor, N-acylphosphatidylethanolamine (NAPE), by the action of a NAPE-specific phospholipase D (NAPE-PLD), and in macrophage are primarily deactivated by the lysosomal cysteine amidase, N-acylethanolamine acid amidase (NAAA). NAPE-PLD and NAAA regulate FAE levels, exerting a tight control over the ability of these lipid mediators to recruit PPAR-α and attenuate the inflammatory response. This review summarizes recent findings on the contribution of the FAE-PPAR-α signaling complex in inflammation, and on NAAA inhibition as a novel mechanistic approach to treat chronic inflammatory disorders.

WHO in 2016 still shows the average rate of exclusive breastfeeding (ASI) in the new world is around 38%. In Indonesia, although a large number of women (96%) breastfeed their children in their lifetime, only 42% of babies under 6 months of age are exclusively breastfed. By the time children approach their second birthday, only 55% are still being breastfed. When compared with the WHO target of 50%, this figure is still far from the target. Maximum achievement can be applied by applying nape and marmot massage techniques for postpartum mothers so that breast milk can be released more quickly. This study aims to help and explain the combination of nape and marmet massage techniques to speed up the use of breast milk in postpartum mothers in the working area of Ngaglik II Sleman Health Center. This research is Quasi-Experimental research using quantitative and post-test designs, with a sample of 30 respondents divided into groups given intervention and control groups taken by purposive sampling. Univariate and bivariate data analysis. The results showed that the effect of nape massage combination and guinea pig technique on the acceleration of ASI use based on the Mann Whitney Test statistical test showed results (p-value 0,002)

Pthirus pubis usually infests the pubis, inguinal folds, buttocks and perianal region. In hairy males or when the infestation is longstanding, this louse can also occur on the thighs, abdomen, chest, axillae and beard. Eyelashes may be involved in children. The involvement of the scalp is very rare. We describe four girls with P. pubis infestation located exclusively on the scalp which was characterized by a rash on the nape that can suggest a head and neck form of atopic dermatitis.

In this study, the effects of salt stress on the physiological, lipidomic and transcriptomic profiles of halophilic microalga Schizochytrium sp. were investigated. In general, Schizochytrium sp. could survive under high osmotic fermentation medium containing 30 g/L NaCl, and showed a significant increase in C14:0 percentage in total fatty acids. In lipidomic analysis, C14:0 was specifically enriched in phosphatidylcholine (PC), and membrane phospholipids participated in the salt stress response mostly. Specially, one novel signal lipid N-acylphosphatidylethanolamine (NAPE) (18:0/20:3/14:0) was upregulated significantly. Transcriptomic analysis revealed glycerol-3-phosphate acyltransferase (GPAT) and phospholipase ABHD3 (PLABDH3) were involved in C14:0 metabolism and NAPE biosynthesis. Signalling pathways they mediated were activated as evident by high expression level of Myristoyl-CoA: protein N-myristoyltransferase (NMT) and NAPE-hydrolyzing PLD (NAPE-PLD). This study gives us an insight in specific responses to salt stress in Schizochytrium sp. and provides a considerable proportion of novel genes that could commendably be used for engineering modification.

Introduction: Ankylosing Spondylitis (AS) is a sero negative chronic inflammatory arthritis of unknown cause that primarily affects the axial skeleton which usually begins in the second or third decade of life with a male to female ratio of 3:1. The prevalence rate of AS in India is 0.03%. It is clinically correlated to Danda Apatanaka in Ayurveda. It is caused due to the vitiated Vata and Kapha Dosha which enters the Dhamani and causes stiffness of the body. Due to its known complications and its tendency to hamper the quality of life, there is a need for an effective Ayurvedic intervention. This report is based on a case of Ankylosing Spondylitis which presented with pricking pain over nape of the neck and low back associated with stiffness and restricted movements, swelling over nape of neck right shoulder and right side of face, associated with restricted movements of right upper limb. Methods: This case was diagnosed as Danda Apatanaka and was treated with Basti Karma, Abhyanga along with oral medications. Assessment was done before and after treatment using relevant scales. Result: After 2 weeks of treatment pain and swelling over the nape of neck, right shoulder and face resolved completely, pain and stiffness of low back reduced, pain in right upper limb reduced and patient was able to perform normal movements. Stiffness of neck still persisted. Conclusion: Ankylosing spondylitis can be effectively managed by Ayurvedic treatment modalities after proper assessment of the involved Dosha and Dhatus.

Neonatal hypoxic-ischaemic (HI) encephalopathy is among the most serious complications in neonatology. In the present study, we studied the immediate (0 hour), subacute (36 hours) and late (144 hours) responses of the neonatal brain to experimental HI insult in laboratory rats. At the striatal level, the mass spectrometry imaging revealed an aberrant plasma membrane distribution of Na+/K+ ions in the oedema-affected areas. The failure of the Na+/K+ gradients was also apparent in the magnetic resonance imaging measurements, demonstrating intracellular water accumulation during the acute phase of the HI insult. During the subacute phase, compared with the control brains, an incipient accumulation of an array of N-acylphosphatidylethanolamine (NAPE) molecules was detected in the HI-affected brains, and both the cytotoxic and vasogenic types of oedema were detected. In the severely affected brain areas, abnormal distributions of the monosialogangliosides GM2 and GM3 were observed in two-thirds of the animals exposed to the insult. During the late stage, a partial restoration of the brain tissue was observed in most rats in both the in vivo and ex vivo studies. These specific molecular changes may be further utilized in neonatology practice in proposing and testing novel therapeutic strategies for the treatment of neonatal HI encephalopathy.

Play is an important part of normal childhood development and seen in many mammals, including rats. To better understand the interplay between genotype and postnatal experiences, the effects of neonatal handling on play were assessed in Lewis (LEW) and Fischer 344 (F344) rats. Handled litters experienced brief periods of separation during the first two postnatal weeks. F344 rats were less likely to direct nape contacts toward an untreated Sprague-Dawley (SD) partner and less likely to rotate to a supine position in response to a nape contact. When compared to rats from control litters, handled LEW, and F344 rats were more likely to respond to nape contacts with complete rotations, suggesting that handling increased playful responsiveness to a comparable extent in both strains. SD rats paired with handled inbred rats had more nape contacts than those paired with non-handled rats. While handled LEW rats also tended to direct more nape contacts to the SD partner than non-handled LEW rats there was no difference between handled and non-handled F344 rats. These results could not be readily explained by handling-induced changes in either maternal care or anxiety. These data suggest that the behavioral consequences of neonatal handling may not depend to a great extent on the genetic platform that these manipulations are acting on. These data also suggest that the ability to maintain the ebb and flow between playful solicitation and playful responsiveness may be compromised in F344 rats and may contribute to the lower levels of play in this strain.

Neste trabalho o método da equação parabólica (PE) é usado para abordar problemas de radiopropagação. O principal objetivo é obter um modelo de propagação, baseado na solução numérica de SSPE (Split Step Parabolic Equation), que garante a precisão e eciente predição de cobertura radioelétrica. O algoritmo de SSPE é implementado computacionalmente fornecendo solução para duas abordagens denominadas: NAPE (Narrow Angle Parabolic Equation) e WAPE (Wide Angle Parabolic Equation), onde a segunda abordagem apresenta-se como um aprimoramento da primeira para condições especícas de análise. A solução numérica do método PE permite a consideração de efeitos atmosféricos e fatores de terrenos no modelo de canal. O método de DMFT (Discrete Mixed Fourier Transform) inclui-se dentro do algoritmo de SSPE para tratar a análise de ambientes com perdas de propagação devido a condições de impedância nas superfícies, tornando-se em uma abordagem DMFT-SSPE para analisar este tipo de problemas. O algoritmo de SSPE é aplicado em testes canônicos e casos práticos. Este trabalho também propõe estudos comparativos com o objetivo de avaliar os resultados obtidos via NAPE e WAPE. Os estudos de caso analisados têm como referência resultados obtidos com outras técnicas numéricas, e nos casos práticos as referências são medições. Ao longo deste trabalho o método de SSPE é apresentado como uma alternativa que garante uma convergência razoável de resultados, demonstrando precisão e notável eciência em tempo total de simulação para estimar cobertura radioelétrica. In this work, the parabolic equation (PE) method is used to solve radiopropagation problems. The main objective is to obtain a propagation model, based on the numerical solution of SSPE (Split Step Parabolic Equation), that guarantees the precision and ecient prediction of radioelectric coverage. SSPE algorithm is computationally implemented, providing a solution for two approaches: NAPE (Narrow Angle Parabolic Equation) and WAPE (Wide Angle Parabolic Equation), where the second method is presented as an improvement of the rst approach for specic conditions of analysis. The numerical solution of the PE method allows the consideration of atmospheric effects and terrain factors in the channel model. In order to study environments with propagation losses due to impedance conditions on the surfaces, the DMFT (Discrete Mixed Fourier Transform) method is included within the SSPE algorithm, becoming a DMFT-SSPE approach to solve this type of problems. SSPE algorithm is applied in canonical tests and real scenarios. This work also proposes comparative studies with the objective of evaluating the results obtained through NAPE and WAPE. The case studies analyzed use as reference results obtained with other numerical techniques, and in practical cases, the references are measurements. Throughout this work the SSPE method is presented as an alternative that guarantees a reasonable convergence of results, demonstrating precision and notable computational eciency to estimate radioelectric coverage.

Acupuncture has been used in traditional Chinese medicine for over 2500 years. Clinical evidence supports the efficacy of acupuncture in the treatment of itch. In particular, acupuncture can relieve histamine-induced itch, refractory uremic pruritus and neurogenic pruritus. However, very little clinical evidence is available as to how acupuncture can assist in itch. Preclinical investigations into itch typically use rodents, in which scratching behavior reliably serves as a behavioral readout of itch. Typically, researchers count the numbers of hindlimb scratch bouts at the site of an injected pruritogen in the nape of the neck. Using murine models of itch, we have demonstrated that EA at Hegu (LI4) and Quchi (LI11) or cold stimulation at LI11 significantly attenuates pruritogen-induced scratching behavior. This chapter discusses evidence suggesting that this effect is mediated by the inhibition of microglial activation in the spinal cord.

is missing (Short communication)

N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is a membrane-associated zinc enzyme that catalyzes the hydrolysis of N-acylphosphatidylethanolamines (NAPEs) into fatty acid ethanolamides (FAEs). Here, we describe the identification of the first small-molecule NAPE-PLD inhibitor, the quinazoline sulfonamide derivative 2,4-dioxo-N-[4-(4-pyridyl)phenyl]-1H-quinazoline-6-sulfonamide, ARN19874.

Objective To observe the clinical efficacy of nape cluster acupuncture in treating migraine.

N-Acyl phospholipids are atypical components of cell membranes that bear three acyl chains and serve as potential biosynthetic precursors for lipid mediators such as endocannabinoids. Biochemical studies have implicated ABHD4 as a brain N-acyl phosphatidylethanolamine (NAPE) lipase, but in vivo evidence for this functional assignment is lacking. Here, we describe ABHD4(-/-) mice and their characterization using untargeted lipidomics to discover that ABHD4 regulates multiple classes of brain N-acyl phospholipids. In addition to showing reductions in brain glycerophospho-NAEs (GP-NAEs) and plasmalogen-based lyso-NAPEs (lyso-pNAPEs), ABHD4(-/-) mice exhibited decreases in a distinct set of brain lipids that were structurally characterized as N-acyl lysophosphatidylserines (lyso-NAPSs). Biochemical assays confirmed that NAPS lipids are direct substrates of ABHD4. These findings, taken together, designate ABHD4 as a principal regulator of N-acyl phospholipid metabolism in the mammalian nervous system.

Summary Background Serotonin is a pruritogenic substance in humans and animals, but the mechanisms of action through which serotonin induces itch response are not yet understood. Aim To examine the possible role of nitric oxide (NO) in the profile of scratching behaviour due to intradermal injection of serotonin in mice. Methods Intradermal injection of serotonin (14.1–235 nmol per site) into the nape of the neck was used to elicit itch in mice. Scratching behaviour was evaluated by counting the number of bouts during 60 min after injection. To determine the possible involvement of the nitrergic system in serotonin-induced scratching, L-NG-nitroarginine methyl ester [L-NAME; a nonselective nitric oxide synthase (NOS) inhibitor], aminoguanidine [a selective inducible (i)NOS inhibitor] and L-arginine (an NO precursor) were administered intraperitoneally to control and serotonin-injected animals. Results Intradermal serotonin caused scratching in mice with a bell-shaped dose–response correlation, and the peak effective dose was 141 nmol per site. The majority of scratching bouts in animals occurred 5–10 min after injection. Ineffective doses of L-NAME (3 mg/kg IP) and aminoguanidine (100 mg/kg IP) decreased the scratching induced by intradermal serotonin injection in animals (P

The endogenous cannabinoid system was first uncovered following studies of the recreational drug Cannabis sativa. It is now recognized as a vital network of signaling pathways that regulate several physiological processes. Following the initial discovery of the cannabinoid receptors 1 (CB1) and 2 (CB2), activated by Cannabis-derived analogs, many endogenous fatty acids termed "endocannabinoids" are now known to be partial agonists of the CB receptors. At present, the most thoroughly studied endocannabinoid signaling molecules are anandamide (AEA) and 2-arachidonylglycerol (2-AG), which are both derived from arachidonic acid. Both AEA and 2-AG are also substrates for the eicosanoid-synthesizing pathways, namely, certain cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes. In the past, research in the endocannabinoid field focused on the interaction of AEA and 2-AG with the COX and LOX enzymes, but accumulating evidence also points to the involvement of CYPs in modulating endocannabinoid signaling. The focus of this review is to explore the current understanding of CYP-mediated metabolism of endocannabinoids.

Phospholipase D (PLD) hydrolyses cellular lipids to produce the important lipid second messenger phosphatidic acid. A PLD enzyme expressed by Pseudomonas aeruginosa (PldA) has been shown to be important in bacterial infection, and NAPE-PLD has emerged as being key in the synthesis of endocannabinoids. In order to better understand the biology and therapeutic potential of these less explored PLD enzymes, small molecule tools are required. Selective estrogen receptor modulators (SERMs) have been previously shown to inhibit mammalian PLD (PLD1 and PLD2). By targeted screening of a library of SERM analogues, additional parallel synthesis, and evaluation in multiple PLD assays, we discovered a novel desketoraloxifene-based scaffold that inhibited not only the two mammalian PLDs but also structurally divergent PldA and NAPE-PLD. This finding represents an important first step toward the development of small molecules possessing universal inhibition of divergent PLD enzymes to advance the field.

The authors have adopted acupuncture at Jľngjiājľ ( ) combined with nape cluster needling in treatment of 100 patients with cervicogenic headache. Nape cluster needling was: Xianaohu ( ) (located in the median depression under occipital bone), Fēngfŭ ( GV 16) and Yamen ( GV 15) were selected longitudinally; horizontally, the part from GV 16 to Wangŭ ( GB 12) was divided into six equal sections, one section was an acupoint, and there were 12 acupoints in total at the left and right sides. Bilateral Jľngjiājľ ( ) points on the second vertebra to the seventh vertebra were selected. The acupuncture was conducted once a day, five days were considered as one course of treatment, and two days were free from treatment between two courses. Four courses of treatment were needed. All the patients were cured clinically. It can be seen that acupuncture at Jľngjiājľ combined with nape cluster needling in treatment of cervicogenic headache has sound effect.

Engineering the gut microbiota to produce specific beneficial metabolites represents an important new potential strategy for treating chronic diseases. Our previous studies with bacteria engineered to produce N-acyl-phosphatidylethanolamines (NAPEs), the immediate precursors of the lipid satiety factors N-acyl-ethanolamides (NAEs), found that colonization of these bacteria inhibited development of obesity in C57BL/6J mice fed a high fat diet. Individual NAE species differ in their bioactivities. Intriguingly, colonization by our engineered bacteria resulted in increased hepatic N-stearoyl-ethanolamide (C18:0NAE) levels despite the apparent inability of these bacteria to biosynthesize its precursor N-stearoyl-phosphatidylethanolamine (C18:0NAPE) in vitro. We therefore sought to identify the factors that allowed C18:0NAPE biosynthesis by the engineered bacteria after colonization of the intestinal tract. We found that the species of NAPE biosynthesized by engineered bacteria depends on the species of dietary fatty acids available in the intestine, suggesting a simple method to fine-tune the therapeutic effects of modified microbiota.

Food intake induces synthesis of N-acylphosphatidylethanolamines (NAPEs) in the intestinal tract. While NAPEs exert leptin-like (leptogenic) effects, including reduced weight gain and food intake, the mechanisms by which NAPEs induce these leptogenic effects remain unclear. One key question is whether intestinal NAPEs act directly on cognate receptors or first require conversion to N-acylethanolamides (NAEs) by NAPE-hydrolyzing phospholipase D (NAPE-PLD). Previous studies using Nape-pld−/− mice were equivocal because intraperitoneal injection of NAPEs led to nonspecific aversive effects. To avoid the aversive effects of injection, we delivered NAPEs and NAEs intestinally using gut bacteria synthesizing these compounds. Unlike in wild-type mice, increasing intestinal levels of NAPE using NAPE-synthesizing bacteria in Nape-pld−/− mice failed to reduce food intake and weight gain or alter gene expression. In contrast, increasing intestinal NAE levels in Nape-pld−/− mice using NAE-synthesizing bacteria induced all of these effects. These NAE-synthesizing bacteria also markedly increased NAE levels and decreased inflammatory gene expression in omental adipose tissue. These results demonstrate that intestinal NAPEs require conversion to NAEs by the action of NAPE-PLD to exert their various leptogenic effects, so that the reduced intestinal NAPE-PLD activity found in obese subjects may directly contribute to excess food intake and obesity.

Prader-Willi syndrome (PWS), the leading genetic cause of obesity, is characterized by a striking hyperphagic behavior that can lead to obesity, type-2 diabetes, cardiovascular disease and death. The molecular mechanism underlying impaired satiety in PWS is unknown. Oleoylethanolamide (OEA) is alipid mediator involved in the control of feeding, body weight and energy metabolism. OEA produced by small-intestinal enterocytes during dietary fat digestion activates type-α peroxisome proliferator-activated receptors (PPAR-α) to trigger an afferent signal that causes satiety. Emerging evidence from genetic and human laboratory studies suggests that deficits in OEA-mediated signaling might be implicated in human obesity. In the present study, we investigated whether OEA contributes to feeding dysregulation in Magel2m+/p− (Magel2 KO) mice, an animal model of PWS. Fasted/refed male Magel2 KO mice eat more than do their wild-type littermates and become overweight with age. Meal pattern analyses show that hyperphagia in Magel2 KO is due to increased meal size and meal duration rather than to lengthening of the intermeal interval, which is suggestive of a defect in mechanisms underlying satiation. Food-dependent OEA accumulation in jejunum and fasting OEA levels in plasma are significantly greater in Magel2 KO mice than in wild-type controls. Together, these findings indicate that deletion of the Magel2 gene is accompanied by marked changes in OEA signaling. Importantly, intraperitoneal administration of OEA (10 mg/kg) significantly reduces food intake in fasted/refed Magel2 KO mice, pointing to a possible use of this natural compound to control hunger in PWS.

Fatty acyl ethanolamides represent a class of endogenous bioactive lipid molecules and are generally referred to as N-acylethanolamines (NAEs). NAEs include palmitoylethanolamide (anti-inflammatory and analgesic substance), oleoylethanolamide (anorexic substance), and anandamide (endocannabinoid). The endogenous levels of NAEs are mainly regulated by enzymes responsible for their biosynthesis and degradation. In mammalian tissues, the major biosynthetic pathway starts from glycerophospholipids and is composed of two enzyme reactions. The first step is N-acylation of ethanolamine phospholipids catalyzed by Ca(2+)-dependent N-acyltransferase and the second step is the release of NAEs from N-acylated ethanolamine phospholipids by N-acylphosphatidylethanolamine (NAPE)-hydrolyzing phospholipase D (NAPE-PLD). As for the degradation of NAEs, fatty acid amide hydrolase plays the central role. However, recent studies strongly suggest the involvement of other enzymes in the NAE metabolism. These enzymes include members of the HRAS-like suppressor family (also called phospholipase A/acyltransferase family), which were originally discovered as tumor suppressors but can function as Ca(2+)-independent NAPE-forming N-acyltransferases; multiple enzymes involved in the NAPE-PLD-independent multi-step pathways to generate NAE from NAPE, which came to light by the analysis of NAPE-PLD-deficient mice; and a lysosomal NAE-hydrolyzing acid amidase as a second NAE hydrolase. These newly recognized enzymes may become the targets for the development of new therapeutic drugs. Here, we focus on recent enzymological findings in this area.

Anandamide is a well-known agonist for the cannabinoid receptors. Along with endogenous anandamide other non-endocannabinoid N-acylethanolamines are also formed, apparently in higher amounts. These include mainly oleoylethanolamide (OEA), palmitoyelethanolamide (PEA) and linoleoylethanolamide (LEA), and they have biological activity by themselves being anorectic and anti-inflammatory. It appears that the major effect of dietary fat on the level of these molecules is in the gastrointestinal system, where OEA, PEA and LEA in the enterocytes may function as homeostatic signals, which are decreased by prolonged consumption of a high-fat diet. These lipid amides appear to mediate their signaling activity via activation of PPARα in the enterocyte followed by activation of afferent vagal fibers leading to the brain. Through this mechanism OEA, PEA and LEA may both reduce the consumption of a meal as well as increase the reward value of the food. Thus, they may function as homeostatic intestinal signals involving hedonic aspects that contribute to the regulation of the amounts of dietary fat to be ingested.