PEA Levels Research Articles

Circulating Endocannabinoids in Canine Cutaneous Mast Cell Tumor.

A cutaneous mast cell tumor (cMCT) is among the most common tumors in dogs. Endocannabinoids (eCBs) belong to the endocannabinoid system (ECS), which involves also cannabinoid receptors and an enzymatic system of biosynthesis and degradation. In this study, plasma levels of N-arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA) were evaluated in 17 dogs with MCTs of varying histological grades and clinical stages, as well as in a control group of 11 dogs. Dogs affected by cMCT had higher plasma levels of 2-AG (p = 0.0001) and lower levels of AEA (p = 0.0012) and PEA (p = 0.0075) compared to the control group, while no differences were observed at the OEA level between healthy and cMCT dogs (p = 0.9264). The ability of eCBs to help discriminate between healthy and cMCT dogs was interrogated through the area under the ROC curve (AUC). An accuracy of 0.98 (95% confidence interval [CI], 0.94-1.02) was found for 2-AG, of 0.85 (95% CI, 0.71-0.99) for AEA, and of 0.81% for PEA (95% CI, 0.64-0.69). Values > 52.75 pmol/mL for 2-AG showed 94% sensitivity and 90% specificity in distinguishing cMCT. This is the first study to demonstrate alterations in plasmatic levels of eCBs in dogs affected by MCTs, suggesting the significance of these biomarkers in the tumorigenic process and their potential use as biomarkers in the future.

Determinants of smallholder membership in farmers’ groups in the pigeon pea-based farming system in Uganda

BackgroundMembership in farmers’ group (FGs) is an important social aspect of agricultural development. Little is known about the relative importance and benefits from participation in FGs in Uganda, specifically for pigeon pea smallholders in northern Uganda.MethodsWe conducted a cross-sectional survey with 257 smallholders to examine the factors that motivate farmer’s group membership and its influence on pigeon pea yield and technical efficiency (TE) in northern Uganda. We applied the Stochastic Production Frontier (SPF) model and complementary models to assess membership impact on pigeon pea yield and TE determinants, respectively. TE is defined as the degree to which smallholders use the minimum feasible farm inputs to produce a given level of pigeon pea grain.ResultsResults show that FG members were generally older and more experienced, and had better access to extension services (76%) and credit (43%) compared to non-members. Smallholders’ age, access to agricultural training, extension services, and the distance travelled to market centres were statistically significant (p < 0.05), thus limiting the likelihood of FG membership. TE for both groups was low and quite similar, at 63% and 59% for members and non-members, respectively, implying that both groups did not use the available farm resources to maximize pigeon pea yield.ConclusionOur results confirm that FG membership enhances smallholder’s access to extension, agricultural training services and credit. For northern Uganda, the study provides recommendations for increased government investment in the human, financial and physical capacity of extension agents as a strategy for rural development and improved livelihoods. In addition, policy incentives can encourage farmers to seek membership in farmers’ groups and related associations.

Cannabinoid receptor 1 positive allosteric modulator ZCZ011 shows differential effects on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice.

The cannabinoid receptor type 1 (CB1R) is a promising therapeutic target for various neurodegenerative diseases, including HIV-1-associated neurocognitive disorder (HAND). However, the therapeutic potential of CB1R by direct activation is limited due to its psychoactive side effects. Therefore, research has focused on indirectly activating the CB1R by utilizing positive allosteric modulators (PAMs). Studies have shown that CB1R PAMs (ZCZ011 and GAT211) are effective in mouse models of Huntington's disease and neuropathic pain, and hence, we assess the therapeutic potential of ZCZ011 in a well-established mouse model of neuroHIV. The current study investigates the effect of chronic ZCZ011 treatment (14 days) on various behavioral paradigms and the endocannabinoid system in HIV-1 Tat transgenic female and male mice. Chronic ZCZ011 treatment (10 mg/kg) did not alter body mass, locomotor activity, or anxiety-like behavior regardless of sex or genotype. However, differential effects were noted in hot plate latency, motor coordination, and recognition memory in female mice only, with ZCZ011 treatment increasing hot plate latency and improving motor coordination and recognition memory. Only minor effects or no alterations were seen in the endocannabinoid system and related lipids except in the cerebellum, where the effect of ZCZ011 was more pronounced in female mice. Moreover, AEA and PEA levels in the cerebellum were positively correlated with improved motor coordination in female mice. In summary, these findings indicate that chronic ZCZ011 treatment has differential effects on antinociception, motor coordination, and memory, based on sex and HIV-1 Tat expression, making CB1R PAMs potential treatment options for HAND without the psychoactive side effects.

Perfil fermentativo, valor nutricional e estabilidade aeróbia de silagens mistas de capim-elefante e cunhã

Abstract The aim was to evaluate the effect of butterfly pea inclusion on the fermentation dynamics, nutritional quality and aerobic stability of mixed elephant grass silages. Butterfly pea levels (0, 20, 40, 60 and 80% on a natural matter basis) were added to elephant grass silages. A completely randomized design was adopted, with 5 treatments and 3 replications, totaling 15 experimental silos, which were opened after 30 days of fermentation. The inclusion of butterfly pea in elephant grass silages resulted in a quadratic effect for permeability, density, maximum pH, final pH, time to reach maximum temperature and aerobic stability (P&lt;0.05). Butterfly pea inclusion levels increased dry matter recovery, pH, dry matter, organic matter, ether extract, crude protein and total digestible nutrients (P&lt;0.001) and reduced gas and effluent losses, mineral matter, neutral detergent fiber, acid detergent fiber, hemicellulose, cellulose, lignin and total carbohydrates (P&lt;0.001). Inclusions of 40, 60 and 80% of butterfly pea provided temperature increases at 10, 20, 30 and 40 hours. The inclusion of butterfly pea with levels of up to 80% reduces fermentation losses, allows for a nutritional increase and increase in aerobic stability of silages.

Endocannabinoid and psychological responses to acute resistance exercise in trained and untrained adults.

This study examined the effects of acute resistance exercise on circulating endocannabinoid (eCB) and mood responses in trained and untrained healthy adults. Thirty-two healthy adults (22.1 ± 2.9 years) were recruited from trained (reporting resistance exercise at least twice per week for ≥ previous three months) and untrained (performing no resistance exercise for ≥ previous three months) groups. Participants (13 male, 19 female) completed three sets of resistance exercise (16 repetitions at 50% 1-repetition max, 12 repetitions at 70% 1-repetition max, 8 repetitions at 80% 1-repetition max). Resistance machines targeted the legs, chest, back, and abdominal muscles. Mood states, affect, and circulating eCB concentrations were evaluated before and after resistance exercise. There were significant decreases in AEA, PEA, and OEA levels following acute resistance exercise (p <0.05; ds = -0.39, -0.48, -0.65, respectively), with no significant group differences or group by time interactions. 2-AG did not change significantly. Positive affect increased significantly following resistance exercise (p = 0.009), while negative affect decreased (p <0.001). Depressive symptoms, anger, confusion, and total mood disturbance decreased significantly (p <0.05), while vigor increased significantly following resistance exercise (p = 0.005). There were no significant group differences or group by time interactions for any psychological outcomes. These results indicate that acute resistance exercise may reduce eCB and related lipid concentrations, which is opposite to the increase in lipids typically observed with acute aerobic exercise. Furthermore, psychological improvements occur after resistance exercise regardless of decreases in eCBs, supporting the notion that psychological changes with exercise likely occur through a wide variety of biological and environmental mechanisms.

Ramulus Cinnamomi essential oil exerts an anti-inflammatory effect on RAW264.7 cells through N-acylethanolamine acid amidase inhibition

Ethnopharmacological relevanceRamulus Cinnamomi, the dried twig of Cinnamomum cassia (L.) J.Presl., is a traditional Chinese medicine (TCM) with anti-inflammatory effects. The medicinal functions of Ramulus Cinnamomi essential oil (RCEO) have been confirmed, although the potential mechanisms by which RCEO exerts its anti-inflammatory effects have not been fully elucidated. Aim of the studyTo investigate whether N-acylethanolamine acid amidase (NAAA) mediates the anti-inflammatory effects of RCEO. Materials and methodsRCEO was extracted by steam distillation of Ramulus Cinnamomi, and NAAA activity was detected using HEK293 cells overexpressing NAAA. N-Palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA), both of which are NAAA endogenous substrates, were detected by liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). The anti-inflammatory effects of RCEO were analyzed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and the cell viability was measured with a Cell Counting Kit-8 (CCK-8) kit. The nitric oxide (NO) in the cell supernatant was measured using the Griess method. The level of tumor necrosis factor-α (TNF-α) in the RAW264.7 cell supernatant was determined using an enzyme-linked immunosorbent assay (ELISA) kit. The chemical composition of RCEO was assessed by gas chromatography-mass spectroscopy (GC-MS). The molecular docking study for (E)-cinnamaldehyde and NAAA was performed by using Discovery Studio 2019 software (DS2019). ResultsWe established a cell model for evaluating NAAA activity, and we found that RCEO inhibited the NAAA activity with an IC50 of 5.64 ± 0.62 μg/mL. RCEO significantly elevated PEA and OEA levels in NAAA-overexpressing HEK293 cells, suggesting that RCEO might prevent the degradation of cellular PEA and OEA by inhibiting the NAAA activity in NAAA-overexpressing HEK293 cells. In addition, RCEO also decreased NO and TNF-α cytokines in lipopolysaccharide (LPS)-stimulated macrophages. Interestingly, the GC-MS assay revealed that more than 93 components were identified in RCEO, of which (E)-cinnamaldehyde accounted for 64.88%. Further experiments showed that (E)-cinnamaldehyde and O-methoxycinnamaldehyde inhibited NAAA activity with an IC50 of 3.21 ± 0.03 and 9.62 ± 0.30 μg/mL, respectively, which may represent key components of RCEO that inhibit NAAA activity. Meanwhile, docking assays revealed that (E)-cinnamaldehyde occupies the catalytic cavity of NAAA and engages in a hydrogen bond interaction with the TRP181 and hydrophobic-related interactions with LEU152 of human NAAA. ConclusionsRCEO showed anti-inflammatory effects by inhibiting NAAA activity and elevating cellular PEA and OEA levels in NAAA-overexpressing HEK293 cells. (E)-cinnamaldehyde and O-methoxycinnamaldehyde, two components in RCEO, were identified as the main contributors of the anti-inflammatory effects of RCEO by modulating cellular PEA levels through NAAA inhibition.

Fermentation dynamics and quality of maize silage with Pigeon pea

Tropical legumes are used to prepare mixed silages to enrich the crude protein (CP) content. In This context, objective of this study was to evaluate the dynamics of fermentation and quality of maize silage with different levels of Pigeon pea. The experimental design was entirely randomized, with four repetitions. The treatments comprised maize silages with six levels of added Pigeon pea (0, 20, 40, 60, 80, and 100%), calculated based on natural matter. The maize hybrid and Pigeon pea varieties used were B 2800 PWU and Cajanus cajan cv. BRS Mandarin, respectively. For the silage, the maize and Pigeon pea were harvested when they reached 335.7 g kg-1 dry matter (DM) and 281.3 g kg-1 DM, respectively. The results revealed that the added of up to 40% Pigeon pea in maize silages promote nutritive increment without compromising their fermentative profile of the silage. Exclusive Pigeon pea silage (100%) undergoes fermentative losses that compromise the silage quality. Therefore, mixed silages of maize with Pigeon pea, with appropriate levels of addition, are a viable alternative to increase the nutritive value of silages, mainly the CP content, contributing to reducing the cost of acquisition of protein salts.

Liquid Chromatographic Determination of &lt;i&gt;o&lt;/i&gt;-Phosphoethanolamine in Human Plasma Using Fluorescent Derivatization

In this study, an HPLC analysis method using pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) was developed for the determination of o-phosphoethanolamine (PEA), which is a potential biomarker for the diagnosis of major depressive disorder, in human plasma sample. After PEA was derivatized with AQC under mild conditions, the obtained derivative was subjected to purification with a titanium dioxide-modified monolithic silica spin column (MonoSpin® TiO). The eluate from the MonoSpin® TiO was directly injected into an amide-type hydrophilic interaction liquid chromatography (HILIC) column-equipped HPLC system, and the resulting derivative could be separated on the column under alkaline mobile phase conditions and subsequently detected fluorometrically at excitation and emission wavelengths of 250 and 395 nm, respectively. The limit of detection and limit of quantification for a 10 µL injection volume of PEA were 0.052 and 0.17 µM, respectively. The method was validated at 0.2, 1.0, and 5.0 nmol/mL levels in plasma sample, and the precision values were 2.0-6.6% as relative standard deviation and the correlation coefficient (r) of the calibration curve was 0.9995. Furthermore, applicability of this method was demonstrated by analyzing PEA levels in plasma samples from mental illness patients.

The effect of adding different levels of local grass pea on some qualitative traits of Japanese quail eggs

This experiment was conducted in the poultry field of the research station at the College of Agriculture and the Marshes of Thi-Qar University, from 1/11/2021 to 1/4/2022, to determine the effect of replacement different levels of grass pea seeds instead of soybean meal in the diet, and their effect on the growth parameters of Japanese quail (Coturnix coturnix). A total of 216 Japanese quail birds of 45 days old were used, distributed randomly to four experimental treatments and three replicates (18 birds/replicate). The treatments were as follows: T1: control transaction; T2: The birds were fed a diet containing 20% soybean meal with 10% local grass pea seeds; T3: The birds were fed a diet containing 10% soybean with 20% local grass pea seeds; T4: The birds were fed a diet containing 30% local grass pea seeds. The results of the study indicated that the addition of 20% grass pea seeds powder led to a significant improvement on the qualitative traits of Japanese quail eggs (yolk and albumin height, relative weight of yolk, albumin and shell, shell thickness, yolk and albumin index and Hough unit), compared to the level of addition of 30% of crushed safflower seeds.&#x0D; Keywords: local grass pea, eggs qualitative, Japanese quail.

Development of an enzyme-linked immunosorbent assay for the quantification of O-Phosphoethanolamine in human plasma

O-Phosphoethanolamine (PEA) is an endogenous substance that is attracting interest as a biomarker for depression, and thus there is a need to develop a simple analytical method that specifically measures PEA. Therefore, this study aimed to develop a simple and specific enzyme-linked immunosorbent assay (ELISA) for PEA.Anti-PEA antibody was obtained by immunizing mice with an antigen conjugated with mercaptosuccinyl bovine serum albumin using m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester (MBS). In this assay, the PEA to be quantified is chemically modified by benzoyl chloride that is allowed to compete with a PEA-MBS-HRP conjugate for binding to a limited amount of an anti-PEA antibody, which was used to coat the wells of a microtiter plate. This ELISA shows a linear range of detection of 0.11–27 μM, and a limit of quantification of 0.144 μM. The anti-PEA antibody showed high affinity for benzoyl PEA. No detectable cross-reactivity was found with benzoyl 2-aminoethanol, O-phospho-l-tyrosine or benzoyl sphingosine-1-phosphate. The values of plasma PEA levels measured by this ELISA were comparable to those measured by HPLC, and a strong correlation was observed between the values determined by the two methods. The developed ELISA should provide a valuable new tool for the quantification of PEA in human plasma.

Comparative Evaluation of Salicylic Acid (SA) and 2,4-Dichloro-6-{(E)-[(3methoxyphenyl)imino]methyl} Phenol (DPMP) on Growth and Salt Stress Tolerance in Forage Pea (Pisum sativum L. arvense)

Alleviation of salt stress is becoming one of the urgent needs of agricultural production. Even though enhancement of tolerance levels with genetic variation is a common approach, exogenous applications of various compounds are a newly emerging field. Here, the effects of two different plant elicitors, salicylic acid (SA) and 2,4-dichloro-6-{(E)-[(3methoxyphenyl)imino]methyl} phenol (DPMP) on growth and stress tolerance levels of forage pea (Pisum sativum ssp. arvense L.) were evaluated. Plants were exposed to salt stress (100 mM) in addition to DPMP, SA, or DMSO (Solvent) foliar spraying. The results revealed contrasting effects for each elicitor. Under non-stressed conditions, DPMP applied plants had higher values in plant height, shoot dry weight (SDW), and taproot length, while SA applied plants had significantly higher shoot fresh weight (SFW), and DMSO applied plants had higher values in root fresh (RFW) and dry (RDW) weights, and root/shoot ratios. When we evaluated stress tolerance index (STI) levels, DPMP applied plants had higher STI values in SFW, SDW, RFW, and RDW. DPMP improved STI and biomass allocation better than SA and DMSO. These elicitors may have significant potential in abiotic stress tolerance, in addition to their well-known biotic stress eliciting roles. There is a need for further research to define appropriate doses and application times.

Phenethylamine is a substrate of monoamine oxidase B in the paraventricular thalamic nucleus

Monoamine oxidase (MAO) is a key enzyme responsible for the degradation of neurotransmitters and trace amines. MAO has two subtypes (MAO-A and MAO-B) that are encoded by different genes. In the brain, MAO-B is highly expressed in the paraventricular thalamic nucleus (PVT); however, its substrate in PVT remains unclear. To identify the MAO-B substrate in PVT, we generated Maob knockout (KO) mice and measured five candidate substrates (i.e., noradrenaline, dopamine, 3-methoxytyramine, serotonin, and phenethylamine [PEA]) by liquid chromatography tandem mass spectrometry. We showed that only PEA levels were markedly elevated in the PVT of Maob KO mice. To exclude the influence of peripheral MAO-B deficiency, we developed brain-specific Maob KO mice, finding that PEA in the PVT was increased in brain-specific Maob KO mice, whereas the extent of PEA increase was less than that in global Maob KO mice. Given that plasma PEA levels were elevated in global KO mice, but not in brain–specific KO mice, and that PEA passes across the blood–brain barrier, the substantial accumulation of PEA in the PVT of Maob KO mice was likely due to the increase in plasma PEA. These data suggest that PEA is a substrate of MAO-B in the PVT as well as other tissues.

Genetic Blockade of NAAA Cell-specifically Regulates Fatty Acid Ethanolamides (FAEs) Metabolism and Inflammatory Responses.

N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme responsible for the hydrolysis of fatty acid ethanolamides (FAEs). However, the role of NAAA in FAEs metabolism and regulation of pain and inflammation remains mostly unknown. Here, we generated NAAA-deficient (NAAA-/-) mice using CRISPR-Cas9 technique, and found that deletion of NAAA increased PEA and AEA levels in bone marrow (BM) and macrophages, and elevated AEA levels in lungs. Unexpectedly, genetic blockade of NAAA caused moderately effective anti-inflammatory effects in lipopolysaccharides (LPS)-induced acute lung injury (ALI), and poor analgesic effects in carrageenan-induced hyperalgesia and sciatic nerve injury (SNI)-induced mechanical allodynia. These data contrasted with acute (single dose) or chronic NAAA inhibition by F96, which produced marked anti-inflammation and analgesia in these models. BM chimera experiments indicated that these phenotypes were associated with the absence of NAAA in non-BM cells, whereas deletion of NAAA in BM or BM-derived cells in rodent models resulted in potent analgesic and anti-inflammatory phenotypes. When combined, current study suggested that genetic blockade of NAAA regulated FAEs metabolism and inflammatory responses in a cell-specifical manner.

The effect of adding different levels of local grass pea on some qualitative traits of Japanese quail eggs

The effect of adding different levels of local grass pea on some qualitative traits of Japanese quail eggs

Alterations of the endocannabinoid system and circulating and peripheral tissue levels of endocannabinoids in sarcopenic rats.

BackgroundActivation of the endocannabinoid system (ECS) is associated with the development of obesity and insulin resistance, and with perturbed skeletal muscle development. Age‐related sarcopenia is a progressive and generalized skeletal muscle disorder involving an accelerated loss of muscle mass and function, with changes in skeletal muscle protein homeostasis due to lipid accumulation and anabolic resistance. Hence, both obesity and sarcopenia share a common set of pathophysiological alterations leading to skeletal muscle impairment. The aim of this study was to characterize how sarcopenia impacts the ECS and if these modifications were related to the loss of muscle mass and function associated with aging in rats.MethodsSix‐month‐old and 24‐month‐old male rats were used to measure the contractile properties of the plantarflexors (isometric torque–frequency relationship & concentric power–velocity relationship) and to evaluate locomotor activity, motor coordination, and voluntary gait by open field, rotarod, and catwalk tests, respectively. Levels of endocannabinoids (AEA & 2‐AG) and endocannabinoid‐like molecules (OEA & PEA) were measured by LCF‐MS/MS in plasma, skeletal muscle, and adipose tissue, while the expression of genes coding for the ECS were investigated by quantitative reverse transcription PCR (RT‐qPCR).ResultsSarcopenia in old rats was exemplified by a 49% decrease in hindlimb muscle mass (P < 0.01), which was associated with severe impairment of isometric torque, power, voluntary locomotor activity, motor coordination, and gait quality. Sarcopenia was associated with (1) increased 2‐AG (+32%, P = 0.07) and reduced PEA and OEA levels in the plasma (−25% and −40%, respectively, P < 0.01); (2) an increased content of AEA, PEA, and OEA in subcutaneous adipose tissue (P < 0.01); and (3) a four‐fold increase of 2‐AG content in the soleus (P < 0.01) and a reduced OEA content in EDL (−80%, P < 0.01). These alterations were associated with profound modifications in the expression of the ECS genes in the adipose tissue and skeletal muscle.ConclusionsTaken together, these findings demonstrate that circulating and peripheral tissue endocannabinoid tone are altered in sarcopenia. They also demonstrate that OEA plasma levels are associated with skeletal muscle function and loss of locomotor activity in rats, suggesting OEA could be used as a circulating biomarker for sarcopenia.

Alterations of plasma endocannabinoid levels in MCI and dementia patients

AbstractBackgroundThere is growing evidence that alterations in the endocannabinoid system (ECS) co‐occur with dementia pathophysiology. Currently, limited literature is available on components of the peripheral ECS as diagnostic markers for dementia.MethodsIn the present study we analysed the concentrations of the endocannabinoids (eCBs) anandamide (AEA) and 2‐Arachidonoylglycerol (2‐AG), and their lipid congeners N‐palmitoylethanolamide (PEA) and N‐oleoylethanolamide (OEA) in plasma and serum using LC‐MS/MS. Samples were collected from healthy controls, participants with mild cognitive impairment (MCI), Alzheimer’s disease (AD) and other dementia subtypes (OD).ResultsStatistical analysis revealed significantly lower concentrations of plasma AEA (p: 0.0017), PEA (p: 0.0056) and OEA (p: 0.0015) in MCI vs. OD groups, and lower OEA levels in MCI vs. healthy controls (p: 0.0099). Plasma PEA levels in AD patients were lower compared to healthy controls (p: 0.0409) and OD groups (p: 0.0307). Additionally, plasma 2‐AG levels correlated positively with age and body mass index (p&lt;0.0001), and negatively with ACE‐III scores (p&lt;0.0011).ConclusionsThese results suggest that peripheral levels of eCBs vary with age and cognitive decline, and may be beneficial in differential diagnosis of dementia. Further, plasma eCB levels may be indicative of early stages of cognitive impairment like MCI, which currently is difficult to diagnose.

Urinary phenylethylamine metabolites as potential markers for sports drug testing purposes.

The misuse of 2-phenylethylamine (PEA) in sporting competitions is prohibited by the World Anti-Doping Agency. As it is endogenously produced, a method is required to differentiate between naturally elevated levels of PEA and the illicit administration of the drug. In 2015, a sulfo-conjugated metabolite [2-(2-hydroxyphenyl)acetamide sulfate (M1)] was identified, and pilot study data suggested that the ratio M1/PEA could be used as a marker indicating the oral application of PEA. Within this project, the required reference material of M1 was synthesized, single and multiple dose elimination studies were conducted and 369 native urine samples of athletes were analyzed as a reference population. While the oral administration of only 100 mg PEA did not affect urinary PEA concentrations, an increase in urinary concentrations of M1 was observed for all volunteers. However, urinary concentrations of both PEA and M1 showed relatively large inter-individual differences and establishing a cut-off-level for M1/PEA proved difficult. Consequently, a second metabolite, phenylacetylglutamine, was considered. Binary logistic regression demonstrated a significant (P < 0.05) correlation of the urinary M1 and phenylacetylglutamine concentrations with an oral administration of PEA, suggesting that assessing both analytes can assist doping control laboratories in identifying PEA misuse.

N-Acylethanolamine Acid Amidase Inhibition Potentiates Morphine Analgesia and Delays the Development of Tolerance

Opioids are essential drugs for pain management, although long-term use is accompanied by tolerance, necessitating dose escalation, and dependence. Pharmacological treatments that enhance opioid analgesic effects and/or attenuate the development of tolerance (with a desirable opioid-sparing effect in treating pain) are actively sought. Among them, N-palmitoylethanolamide (PEA), an endogenous lipid neuromodulator with anti-inflammatory and neuroprotective properties, was shown to exert anti-hyperalgesic effects and to delay the emergence of morphine tolerance. A selective augmentation in endogenous PEA levels can be achieved by inhibiting N-acylethanolamine acid amidase (NAAA), one of its primary hydrolyzing enzymes. This study aimed to test the hypothesis that NAAA inhibition, with the novel brain permeable NAAA inhibitor AM11095, modulates morphine’s antinociceptive effects and attenuates the development of morphine tolerance in rats. We tested this hypothesis by measuring the pain threshold to noxious mechanical stimuli and, as a neural correlate, we conducted in vivo electrophysiological recordings from pain-sensitive locus coeruleus (LC) noradrenergic neurons in anesthetized rats. AM11095 dose-dependently (3–30 mg/kg) enhanced the antinociceptive effects of morphine and delayed the development of tolerance to chronic morphine in behaving rats. Consistently, AM11095 enhanced morphine-induced attenuation of the response of LC neurons to foot-shocks and prevented the attenuation of morphine effects following chronic treatment. Behavioral and electrophysiological effects of AM11095 on chronic morphine were paralleled by a decrease in glial activation in the spinal cord, an index of opioid-induced neuroinflammation. NAAA inhibition might represent a potential novel therapeutic approach to increase the analgesic effects of opioids and delay the development of tolerance.

Circulating Endocannabinoids as Diagnostic Markers of Canine Chronic Enteropathies: A Pilot Study.

Chronic enteropathies (CEs) in dogs, according to the treatment response to consecutive trials, are classified as food-responsive (FRE), antibiotic-responsive (ARE), and immunosuppressive-responsive (IRE) enteropathy. In addition to this classification, dogs with loss of protein across the gut are grouped as protein-losing enteropathy (PLE). At present, the diagnosis of CEs is time-consuming, costly and sometimes invasive, also because non-invasive biomarkers with high sensitivity and specificity are not yet available. Therefore, this study aimed at assessing the levels of circulating endocannabinoids in plasma as potential diagnostic markers of canine CEs. Thirty-three dogs with primary chronic gastrointestinal signs presented to Veterinary Teaching Hospitals of Teramo and Bologna (Italy) were prospectively enrolled in the study, and 30 healthy dogs were included as a control group. Plasma levels of N-arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA) were measured at the time of the first visit in dogs with different CEs, as well as in healthy subjects. Plasma levels of 2-AG (p = 0.001) and PEA (p = 0.008) were increased in canine CEs compared to healthy dogs. In particular, PEA levels were increased in the FRE group compared to healthy dogs (p = 0.04), while 2-AG was higher in IRE than in healthy dogs (p = 0.0001). Dogs affected by FRE also showed decreased 2-AG (p = 0.0001) and increased OEA levels (p = 0.0018) compared to IRE dogs. Moreover, dogs with PLE showed increased 2-AG (p = 0.033) and decreased AEA (p = 0.035), OEA (p = 0.016) and PEA (p = 0.023) levels, when compared to dogs affected by CEs without loss of proteins. The areas under ROC curves for circulating 2-AG (0.91; 95% confidence interval [CI], 0.79–1.03) and OEA (0.81; 95% CI, 0.65–0.97) showed a good accuracy in distinguishing the different forms of CEs under study (FRE, ARE and IRE), at the time of the first visit. The present study demonstrated that endocannabinoid signaling is altered in canine CEs, and that CE subtypes showed distinct profiles of 2-AG, PEA and OEA plasma levels, suggesting that these circulating bioactive lipids might have the potential to become candidate biomarkers for canine CEs.

The effect of feeding graded levels of raw pigeon pea seed (Cajanus cajan) meal on the performance, nutrient retention and carcass characteristics of weaner rabbits

An 8-week study was conducted to determine the effect of feeding graded levels of raw pigeonpea seed (Cajanus cajan) meal (PSM) on the performance, nutrient retention and carcass characteristics of weaner rabbits 24 rabbits of initial average liveweight of 600-700g in a completely randomized design (CRD). Four experimental diets were formulated such that diet 1 (control) was maize soybean meal based with 0% PSM. Treatnents 2, 3 and 4 had 10, 20 and 30% PSM, respectively replacing part of maize and soybean in the diets. Results showed that there were no significant differences (P&gt;0.05) between the rabbits fed the raw and control diets in all the performance measurements considered. The diet of 30% PSM significantly reduced (P&lt;0.05) feed cost of weight gain and significantly improved (P&lt;0.05) dry matter (DM) and crude protein (CP) digestibility more than other diets. It was concluded that raw PSM could be included up to 30%, replacing 28.57 and 71.43% of maize and soybean meal, respectively in the rabbits diets without any adverse effect on performance.