Effects of fatty acid metabolites on nocturia.

Dysregulation of circadian rhythm can cause nocturia. Levels of fatty acid metabolites, such as palmitoylethanolamide (PEA), 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), and 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid (4-HDoHE), are higher in the serum of patients with nocturia; however, the reason remains unknown. Here, we investigated the circadian rhythm of fatty acid metabolites and their effect on voiding in mice. WT and Clock mutant (ClockΔ19/Δ19) mice, a model for nocturia with circadian rhythm disorder, were used. Levels of serum PEA, 9-HODE, and 4-HDoHEl were measured every 8 h using LC/MS. Voiding pattern was recorded using metabolic cages after administration of PEA, 9-HODE, and 4-HDoHE to WT mice. Levels of serum PEA and 9-HODE fluctuated with circadian rhythm in WT mice, which were lower during the light phase. In contrast, circadian PEA and 9-HODE level deteriorated or retreated in ClockΔ19/Δ19 mice. Levels of serum PEA, 9-HODE, and 4-HDoHE were higher in ClockΔ19/Δ19 than in WT mice. Voiding frequency increased in PEA- and 4-HDoHE-administered mice. Bladder capacity decreased in PEA-administered mice. The changes of these bladder functions in mice were similar to those in elderly humans with nocturia. These findings highlighted the novel effect of lipids on the pathology of nocturia. These may be used for development of biomarkers and better therapies for nocturia.

Pcyt2 deficiency causes age-dependant development of nonalcoholic steatohepatitis and insulin resistance that could be attenuated with phosphoethanolamine.

The mechanisms of NASH development in the context of age and genetics are not fully elucidated. This study investigates the age-dependent liver defects during NASH development in mice with heterozygous deletion of Pcyt2 (Pcyt2+/-), the rate limiting enzyme in phosphatidylethanolamine (PE) synthesis. Further, the therapeutic potential of Pcyt2 substrate, phosphoethanolamine (PEtn), is examined. Pcyt2+/- were investigated at 2 and 6-8 months (mo) of age and in addition, 6-mo old Pcyt2+/- with developed NASH were supplemented with PEtn for 8 weeks and glucose and fatty acid metabolism, insulin signaling, and inflammation were examined. Heterozygous ablation of Pcyt2 causes changes in liver metabolic regulators from young age, prior to the development of liver disease which does not occur until adulthood. Only older Pcyt2+/- experiences perturbed glucose and fatty acid metabolism. Older Pcyt2+/- liver develops NASH characterized by increased glucose production, accumulation of TAG and glycogen, and increased inflammation. Supplementation with PEtn reverses Pcyt2+/- steatosis, inflammation, and other aspects of NASH, showing that was directly caused by Pcyt2 deficiency. Pcyt2 deficiency is a novel mechanism of metabolic dysregulation due to reduced membrane ethanolamine phospholipid synthesis, and the metabolite PEtn offers therapeutic potential for NASH reversion.

N-oleoylethanolamine - phosphatidylcholine complex loaded, DSPE-PEG integrated liposomes for efficient stroke.

Causing more and more deaths, stroke has been a leading cause of death worldwide. However, success in clinical stroke trials has remained elusive. N-oleoylethanolamine (OEA) was an endogenous highly hydrophobic molecule with outstanding neuroprotective effect. In this article, hydrogen bonds were successfully formed between OEA and soybean phosphatidylcholine (SPC). The synthetic OEA-SPC complex and DSPE-PEG were self-assembled into liposomes (OEA NPs), with OEA-SPC loaded in the core and PEG formed a hydrophilic shell. Hence, highly hydrophobic OEA was loaded into liposomes as amorphous state with a drug loading of 8.21 ± 0.18 wt%. With fairly uniform size and well-distributed character, the OEA NPs were systemically assessed as an intravenous formulation for stroke therapy. The results indicated that the administration of OEA NPs could significantly improve the survival rate and the Garcia score of the MCAO rats compared with free OEA. The TTC-stained brain slices declared that the cerebral infarct volume and the edema degree induced by MCAO could be decreased to an extremely low level via the administration of OEA NPs. The Morris water maze (MWM) test suggested that the spatial learning and memory of the MCAO rats could also be ameliorated by OEA NPs. The immunofluorescence assay stated that the apoptosis of the neurons and the inflammation within the brain were greatly inhibited. The results suggest that the OEA NPs have a great chance to develop OEA as a potential anti-stroke formulation for clinic application.

Anti-inflammatory activity of palmitoylethanolamide ameliorates osteoarthritis induced by monosodium iodoacetate in Sprague-Dawley rats.

Novel treatment strategies are urgently required for osteoarthritis (OA). Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide with analgesic and anti-inflammatory effects. We aimed to examine its effect on OA and elucidate the molecular mechanism of actions in monosodium iodoacetate (MIA)-induced OA Sprague-Dawley rats. The experimental animals were divided into normal control group (injected with saline + treated with phosphate-buffered saline (PBS), NOR), control group (injected with MIA + treated with PBS, CON), 50 or 100 mg/kg body weight (BW)/day PEA-treated group (injected with MIA + treated with 50 or 100 mg of PEA/kg BW/day, PEA50 or PEA100), and positive control group (injected with MIA + treated with 6 mg of diclofenac/kg BW/day, DiC). The changes in blood parameters, body parameters, gene expression of inflammatory mediators and cytokines, knee thickness, and joint tissue were observed. Oral administration of PEA had no adverse effects on the BW, liver, or kidneys. PEA reduced knee joint swelling and cartilage degradation in MIA-induced OA rats. The serum levels of leukotriene B4, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and prostaglandin E2 considerably reduced in the PEA100 group compared with those in the CON group. In the synovia of knee joints, the mRNA expression of iNOS, 5-Lox, Cox-2, Il-1ß, Tnf-α, and Mmp-2, -3, -9, and -13 apparently increased with MIA administration. Meanwhile, Timp-1 mRNA expression apparently decreased in the CON group but increased to the normal level with PEA treatment. Thus, PEA can be an effective therapeutic agent for OA.

Co-Ultra PEALut Enhances Endogenous Repair Response Following Moderate Traumatic Brain Injury.

This study aimed to assess the neuro-regenerative properties of co-ultramicronized PEALut (Glialia®), composed of palmitoylethanolamide (PEA) and the flavonoid luteolin (Lut), in an in vivo model of traumatic brain injury (TBI) and patients affected by moderate TBI. An increase in neurogenesis was seen in the mice at 72 h and 7 d after TBI. The co-ultra PEALut treatment helped the neuronal reconstitution process to restore the basal level of both novel and mature neurons; moreover, it induced a significant upregulation of the neurotrophic factors, which ultimately led to progress in terms of memory recall during behavioral testing. Moreover, our preliminary findings in a clinical trial suggested that Glialia® treatment facilitated neural recovery on working memory. Thus, co-ultra PEALut (Glialia®) could represent a valuable therapeutic agent for intensifying the endogenous repair response in order to better treat TBI.

Scalp application of the antioxidant piroctone olamine reduces hair shedding in an 8-week randomized, double-blind, placebo-controlled clinical study.

OBJECTIVE: Increasing scalp hair fullness is a global unmet consumer need. An approach to decrease hair shedding by reducing scalp stratum corneum oxidation via a combination of antioxidant and barrier-enhancing technologies has been previously demonstrated. The purpose of this study was to test the effectiveness of the individual antioxidant piroctone olamine in two different product forms (shampoo or leave-on product) for activity to improve hair retention. METHODS: Female subjects with self-perceived hair thinning participated in an 8-week, double-blind, placebo-controlled, randomized clinical study to evaluate either a piroctone olamine (PO) containing shampoo or a PO containing leave on treatment, each relative to their corresponding placebo formulation Too many periods. Results for phototrichograms, TEWL, and biomarker analysis of scalp condition for the shampoo treatments are discussed. Phototrichogram results are shared for the assessment of the leave on treatment. RESULTS: Statistically significant increases in hair amount were observed by phototrichogram after use of both PO-containing products versus placebo formulations. The PO shampoo treatment also significantly decreased oxidative stress on the hair and scalp, and improved scalp condition as assessed by TEWL and scalp biomarker values. CONCLUSION: These results illustrate the effectiveness of a cosmetic antioxidant to improve scalp condition thereby improving hair retention. The observed improvements in scalp condition are consistent with previous reports with other antioxidant technologies and suggest that the hair retention effect was achieved by preventing oxidative damage to the scalp.

Randomized clinical trial "olfactory dysfunction after COVID-19: olfactory rehabilitation therapy vs. intervention treatment with Palmitoylethanolamide and Luteolin": preliminary results.

OBJECTIVE: Approximately 30% of patients with confirmed COVID-19 report persistent smell or taste disorders as long-term sequalae of infection. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with inflammatory changes to the olfactory bulb, and treatments with anti-inflammatory properties are hypothesized to attenuate viral injury and promote recovery of olfaction after infection. Our study investigated the efficacy of a supplement with Palmitoylethanolamide (PEA) and Luteolin to support recovery of olfaction in COVID-19 patients. PATIENTS AND METHODS: We conducted a randomized-controlled pilot study in outpatients with history of confirmed COVID-19 with post-infection olfactory impairment that persisted ≥ 90 days after SARS-CoV-2 negative testing. Patients were randomized to two times a day olfactory rehabilitation alone or weekly olfactory rehabilitation plus daily oral supplement with PEA and Luteolin. Subjects with preexisting olfactory disorders were excluded. Sniffin' Sticks assessments were performed at baseline and 30 days after treatment.  Data on gender, age, and time since infection were collected. Kruskal-Wallis (KW) test was used to compare variances of Sniff scores between groups over time, and Spearman's correlation coefficients were calculated to assess for correlations between Sniff Score and gender or duration of infection. RESULTS: Among 12 patients enrolled (n=7, supplement; n=5, controls), patients receiving supplement had greater improvement in olfactory threshold, discrimination, and identification score versus controls (p=0.01). Time since infection was negatively correlated with Sniff Score, and there was no correlation between gender. CONCLUSIONS: Treatment combining olfactory rehabilitation with oral supplementation with PEA and Luteolin was associated with improved recovery of olfactory function, most marked in those patients with longstanding olfactory dysfunction. Further studies are necessary to replicate these findings and to determine whether early intervention including olfactory rehabilitation and PEA+Luteolin oral supplement might prevent SARS-CoV-2 associated olfactory impairment.

Efficacy of a fixed combination of palmitoylethanolamide and acetyl-l-carnitine (PEA+ALC FC) in the treatment of neuropathies secondary to rheumatic diseases.

BACKGROUND: The neurologic complications of rheumatic diseases (RDs) are highly variable, and their manifestations are linked to the pathogenesis and clinical phenotype of the specific RDs. In rheumatoid arthritis, for example, the peripheral nervous system is most commonly involved and mononeuritis multiplex, nerve entrapment and vasculitic sensorimotor neuropathies are not uncommon. Often the therapy for these disorders is not easy and is characterized by the use of different drugs. Palmitoylethanolamide (PEA) has been tested in a wide variety of animal models and has been evaluated in several clinical studies for nerve compression syndromes, demonstrating that PEA acts as an effective and safe analgesic compound. Acetyl-L-Carnitine (ALC) has also been shown to be an effective and safe treatment in painful peripheral neuropathy. In the last years the synergistic effect between PEA and ALC has been demonstrated. The aim of our study was to evaluate the efficacy of supplementation of standard therapy (STh) with Kalanit® (Chiesi Italia Spa; Parma, Italy) in patients with peripheral neuropathy secondary to RDs. METHODS: Patients at the time of enrollment were affected by RDs with neuropathy from <12 months, documented by electromyography. The analyzed patients were treated with the STh chosen according to their rheumatic disease (RA or SpA) and for their neuropathy (e.g. analgesic, NSAIDs, pregabalin or gabapentin) as per clinical practice. The sample was divided into 2 groups: group 1, patients treated with STh, to which a fixed combination of PEA (600 mg) + ALC (500 mg) (Kalanit®) was added twice a day for 2 weeks and then once a day for 6 months; group 2, patients treated only with STh. Each patient underwent clinical evaluations and questionnaires were administered in order to evaluate their neuropathy and the efficacy of the therapy. RESULTS: In group 1, 18 patients suffering from sciatic pain, 16 patients from carpal tunnel syndrome and 8 patients with peripheral neuropathy of the lower limbs were included and PEA + ALC FC was added to STh. These patients were compared with patients from group 2, who had the same pathology and demographic characteristics: 20 patients with sciatic pain, 15 with carpal tunnel syndrome and 5 with peripheral neuropathy of the lower limbs, respectively; this group was treated with STh only. Patients treated with PEA + ALC FC had a significant improvement in pain VAS compared to patients treated with group 2 in all the diseases analyzed (P value: sciatic pain 0.032, carpal tunnel syndrome 0.025 and lower limbs neuropathy 0.041). Patients in group 1 showed a significant improvement compared to patients treated in group 2 also from a specific score. Specifically, LBP-IQ showed significant improvement in group one (P value: 0.031), as did CHFD (P=0.011) and NPQ (P=0.025). CONCLUSIONS: The synergistic effect of PEA and ALC seems to have a further advantage in the treatment of this type of pathology, including the anti-inflammatory effect but also in terms of therapy optimization and therefore of better adherence to treatments. Our study shows that it is important to identify the type of pain to follow an accurate diagnostic algorithm, considering the clinical characteristics of the patient and carefully evaluate the indication, preferring a multimodal approach.

Tolerability profile of topical cannabidiol and palmitoylethanolamide: a compilation of single-centre randomized evaluator-blinded clinical and in vitro studies in normal skin.

BACKGROUND: An increasing number of studies have investigated the adverse effect profile of oral cannabinoids; however, few studies have provided sufficient data on the tolerability of topical cannabinoids in human participants. AIM: To assess the tolerability profile of several commercial topical formulations containing cannabidiol (CBD) and palmitoylethanolamide (PEA) on the skin of healthy human participants. METHODS: Three human clinical trials and one in vitro study were conducted. The potential for skin irritation, sensitization and phototoxicity of several products, were assessed via patch testing on healthy human skin. The products assessed included two formulations containing CBD and PEA, one containing hemp seed oil and four concentrations of CBD alone. Ocular toxicity was tested using a traditional hen's egg chorioallantoic membrane model with three CBD, PEA and hemp seed oil formulations. RESULTS: There was no irritation or sensitization of the products evident via patch testing on healthy participants. Additionally, mild phototoxicity of a hemp seed oil product was found at the 48-h time point compared with the negative control. The in vitro experiment demonstrated comparable effects of cannabinoid products with historically nonirritating products. CONCLUSION: These specific formulations of CBD- and PEA-containing products are nonirritating and nonsensitizing in healthy adults, and further encourage similar research assessing their long-term safety and efficacy in human participants with dermatological diseases. There are some limitations to the study: (i) external validity may be limited as formulations from a single manufacturer were used for this study, while vast heterogeneity exists across unregulated, commercial CBD products on the market; and (ii) products were assessed only on normal, nondiseased human skin, and therefore extrapolation to those with dermatological diseases cannot be assumed.

Micronized / ultramicronized palmitoylethanolamide (PEA) as natural neuroprotector against COVID-19 inflammation.

Coronavirus Disease 2019 (COVID-19) is upsetting the world and innovative therapeutic solutions are needed in an attempt to counter this new pandemic. Great hope lies in vaccines, but drugs to cure the infected patient are just as necessary. In the most severe forms of the disease, a cytokine storm with neuroinflammation occurs, putting the patient's life at serious risk, with sometimes long-lasting sequelae. Palmitoylethanolamide (PEA) is known to possess anti-inflammatory and neuroprotective properties, which make it an ideal candidate to be assumed in the earliest stage of the disease. Here, we provide a mini-review on the topic, pointing out phospholipids consumption in COVID-19, the possible development of an antiphospholipid syndrome secondary to SARS-CoV-2 infection, and reporting our preliminary single-case experience concerning to a 45-year-old COVID-19 female patient recently treated with success by micronized / ultramicronized PEA.

Impaired Duodenal Palmitoylethanolamide Release Underlies Acid-Induced Mast Cell Activation in Functional Dyspepsia.

BACKGROUND & AIMS: Acid hypersensitivity is claimed to be a symptomatic trigger in functional dyspepsia (FD); however, the neuroimmune pathway(s) and the mediators involved in this process have not been investigated systematically. Palmitoylethanolamide (PEA) is an endogenous compound, able to modulate nociception and inflammation, but its role in FD has not been assessed. METHODS: Duodenal biopsy specimens from FD and control subjects, and peroxisome proliferator-activated receptor-α (PPARα) null mice were cultured at a pH of 3.0 and 7.4. Mast cell (MC) number, the release of their mediators, and the expression of transient receptor potential vanilloid receptor (TRPV)1 and TRPV4, were evaluated. All measurements also were performed in the presence of a selective blocker of neuronal action potential (tetradotoxin). FD and control biopsy specimens in acidified medium also were incubated in the presence of different PEA concentrations, alone or combined with a selective PPARα or PPAR-γ antagonist. RESULTS: An acid-induced increase in MC density and the release of their mediators were observed in both dyspeptic patients and controls; however, this response was amplified significantly in FD. This effect was mediated by submucosal nerve fibers and up-regulation of TRPV1 and TRPV4 receptors because pretreatment with tetradotoxin significantly reduced MC infiltration. The acid-induced endogenous release of PEA was impaired in FD and its exogenous administration counteracts MC activation and TRPV up-regulation. CONCLUSIONS: Duodenal acid exposure initiates a cascade of neuronal-mediated events culminating in MC activation and TRPV overexpression. These phenomena are consequences of an impaired release of endogenous PEA. PEA might be regarded as an attractive therapeutic strategy for the treatment of FD.

Antibacterial activity of nitric oxide-releasing carboxymethylcellulose against periodontal pathogens.

The prevalence of periodontal disease poses a significant global health burden. Treatments for these diseases, primarily focused on removal and eradication of dental plaque biofilms, are challenging due to limited access to periodontal pockets where these oral pathogens reside. Herein, we report on the development and characterization of nitric oxide (NO)-releasing carboxymethylcellulose (CMC) derivatives and evaluate their in vitro bactericidal efficacy against planktonic Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, two prominent periodontopathogens. Bactericidal exposure assays revealed that three of the synthesized NO-releasing polymers were capable of reducing bacterial viability of both species by 99.9% in 2 hr at concentrations of 4 mg ml-1 or lower, reflecting NO's potent and rapid bactericidal action. The NO-releasing CMCs elicited minimal toxicity to human gingival fibroblasts at their bactericidal concentrations following 24-hr exposure.

Palmitoylethanolamide: A Nutritional Approach to Keep Neuroinflammation within Physiological Boundaries-A Systematic Review.

Neuroinflammation is a physiological response aimed at maintaining the homodynamic balance and providing the body with the fundamental resource of adaptation to endogenous and exogenous stimuli. Although the response is initiated with protective purposes, the effect may be detrimental when not regulated. The physiological control of neuroinflammation is mainly achieved via regulatory mechanisms performed by particular cells of the immune system intimately associated with or within the nervous system and named "non-neuronal cells." In particular, mast cells (within the central nervous system and in the periphery) and microglia (at spinal and supraspinal level) are involved in this control, through a close functional relationship between them and neurons (either centrally, spinal, or peripherally located). Accordingly, neuroinflammation becomes a worsening factor in many disorders whenever the non-neuronal cell supervision is inadequate. It has been shown that the regulation of non-neuronal cells-and therefore the control of neuroinflammation-depends on the local "on demand" synthesis of the endogenous lipid amide Palmitoylethanolamide and related endocannabinoids. When the balance between synthesis and degradation of this bioactive lipid mediator is disrupted in favor of reduced synthesis and/or increased degradation, the behavior of non-neuronal cells may not be appropriately regulated and neuroinflammation exceeds the physiological boundaries. In these conditions, it has been demonstrated that the increase of endogenous Palmitoylethanolamide-either by decreasing its degradation or exogenous administration-is able to keep neuroinflammation within its physiological limits. In this review the large number of studies on the benefits derived from oral administration of micronized and highly bioavailable forms of Palmitoylethanolamide is discussed, with special reference to neuroinflammatory disorders.

The Protective Effects of Pre- and Post-Administration of Micronized Palmitoylethanolamide Formulation on Postoperative Pain in Rats.

BACKGROUND: Postoperative pain (PO) is a common form of acute pain. Inadequate PO treatment is an important health problem, as it leads to worse outcomes, such as chronic post-surgical pain. Therefore, it is necessary to acquire new knowledge on PO mechanisms to develop therapeutic options with greater efficacy than those available today and to lower the risk of adverse effects. For this reason, we evaluated the ability of micronized palmitoylethanolamide (PEA-m) to resolve the pain and inflammatory processes activated after incision of the hind paw in an animal model of PO. METHODS: The animals were subjected to surgical paw incision and randomized into different groups. PEA-m was administered orally at 10 mg/kg at different time points before or after incision. RESULTS: Our research demonstrated that the pre- and post-treatment with PEA-m reduced the activation of mast cells at the incision site and the expression of its algogenic mediator nerve growth factor (NGF) in the lumbar spinal cord. Furthermore, again at the spinal level, it was able to decrease the activation of phospho-extracellular signal-regulated kinases (p-ERK), ionized calcium binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and the expression of brain-derived neurotrophic factor (BDNF). PEA-m also reduced the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) spinal pathway, showing a protective effect in a rat model of PO. CONCLUSION: The results obtained reinforce the idea that PEA-m may be a potential treatment for the control of pain and inflammatory processes associated with PO. In addition, pre- and post-treatment with PEA-m is more effective than treatment alone after the surgery and this limits the time of taking the compound and the abuse of analgesics.

Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma.

Glaucoma, a leading cause of irreversible blindness worldwide, is an optic neuropathy characterized by the progressive death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is recognized as the main risk factor. Despite effective IOP-lowering therapies, the disease progresses in a significant number of patients. Therefore, alternative IOP-independent strategies aiming at halting or delaying RGC degeneration is the current therapeutic challenge for glaucoma management. Here, we review the literature on the neuroprotective activities, and the underlying mechanisms, of natural compounds and dietary supplements in experimental and clinical glaucoma.

Topical Scar Treatment Products for Wounds: A Systematic Review.

BACKGROUND: There is an increasing number of over-the-counter topical products that are said to prevent pathologic scar formation and improve scar cosmesis. However, robust clinical data are lacking to substantiate these claims and to guide selection of topical products. OBJECTIVE: To determine the effectiveness of topical scar management products, including silicone gel, Allium cepa onion extract, vitamin E, trolamine, and microporous tape. METHODS AND MATERIALS: A PubMed search (2005-2019) was performed to identify studies of topical scar management products. Randomized controlled trials (RCTs), quasi-RCTs, meta-analyses, and controlled clinical trials were included for analysis. RESULTS: A total of 34 trials were included in this study. Of the 16 trials investigating silicone gel sheets, numerous high-quality RCTs found that silicone gel sheets and silicone gels significantly improved scar outcomes. Only a limited number of studies supported the effectiveness of onion extract, vitamin E, trolamine, and microporous tape products. CONCLUSION: Silicone gel products are an effective noninvasive treatment to prevent formation of pathologic scars and improve mature scars. Further high-quality studies are needed to elucidate the long-term effectiveness of these therapies.

Looking for a Treatment for the Early Stage of Alzheimer's Disease: Preclinical Evidence with Co-Ultramicronized Palmitoylethanolamide and Luteolin.

BACKGROUND: At the earliest stage of Alzheimer's disease (AD), although patients are still asymptomatic, cerebral alterations have already been triggered. In addition to beta amyloid (Aß) accumulation, both glial alterations and neuroinflammation have been documented at this stage. Starting treatment at this prodromal AD stage could be a valuable therapeutic strategy. AD requires long-term care; therefore, only compounds with a high safety profile can be used, such as the new formulation containing palmitoylethanolamide and luteolin (co-ultra PEALut) already approved for human use. Therefore, we investigated it in an in vivo pharmacological study that focused on the prodromal stage of AD. METHODS: We tested the anti-inflammatory and neuroprotective effects of co-ultra PEALut (5 mg/Kg) administered for 14 days in rats that received once, 5 µg Aß(1-42) into the hippocampus. RESULTS: Glial activation and elevated levels of proinflammatory mediators were observed in Aß-infused rats. Early administration of co-ultra PEALut prevented the Aß-induced astrogliosis and microgliosis, the upregulation in gene expression of pro-inflammatory cytokines and enzymes, as well as the reduction of mRNA levels BDNF and GDNF. Our findings also highlight an important neuroprotective effect of co-ultra PEALut treatment, which promoted neuronal survival. CONCLUSIONS: Our results reveal the presence of cellular and molecular modifications in the prodromal stage of AD. Moreover, the data presented here demonstrate the ability of co-ultra PEALut to normalize such Aß-induced alterations, suggesting it as a valuable therapeutic strategy.

Sodium chromo-glycate and palmitoylethanolamide: A possible strategy to treat mast cell-induced lung inflammation in COVID-19.

A novel human coronavirus SARS-CoV-2 (also referred to as CoV-19) that emerged in late 2019 causes Covid-19 disease a respiratory tract infection which provokes about 4 million deaths per year. Unfortunately, to date, there is no specific antiviral treatment for COVID-19. Mast cells (MCs) are immune cells implicated in the pathogenesis of viral infections, where they mediate inflammation. Microbes, including virus, activate MCs through TLR releasing chemical pro-inflammatory compounds and cytokines. Although, in biomedical literature there are only few reports on MCs activation by SARS-CoV-2 infection. The production of pro-inflammatory cytokines by MC viral activation leads to increase pulmonary inflammation and fibrosis. Sodium Chromo-Glycate (SCG) described as a MC stabilizer, prevents the release of inflammatory chemical compounds, improve mouse survival and respiratory pathological changes in lung viral infection and suppresses inflammation. Furthermore, palmitoylethanolamide (PEA) a nuclear factor agonist, an endogenous fatty acid amide, which exerts a variety of biological effects, related to chronic inflammation and pain, is involved also in MCs homeostasis with an inhibitory and protective effect on the respiratory tract during viral infections. Here, we hypothesize for the first time, that SCG and/or PEA suppress MC activation and pro-inflammatory mediators release, playing an anti-inflammatory therapeutic role in the inflamed lung of patients with COVID-19.

Eicosapentaenoic Acid-Enriched Phosphoethanolamine Plasmalogens Alleviated Atherosclerosis by Remodeling Gut Microbiota to Regulate Bile Acid Metabolism in LDLR-/- Mice.

Eicosapentaenoic acid (EPA)-enriched phosphoethanolamine plasmalogens (EPA-PlsEtns) might be retained in the intestine rich in gut microbiota for a long time after treatment. It reminded us that EPA-PlsEtns might affect intestinal microbiota composition and its metabolites, which have been identified as a contributing factor in the development of cardiovascular diseases. In the present study, EPA-PlsEtn administration for 8 weeks significantly reduced the atherosclerotic lesion area in low-density lipoprotein receptor deficient (LDLR-/-) mice. Notably, the serum total cholesterol and low-density lipoprotein cholesterol levels were significantly reduced by 33.6 and 38.2%, respectively, by EPA-PlsEtns instead of EPA in the form of ethyl ester (EPA-EE) treatment compared with the model group. EPA-PlsEtn administration also increased total neutral sterol and bile acids in feces by 92 and 39%, respectively, rather than EPA-EE. Mechanistically, EPA-PlsEtns might affect the abundance of gut microbiota contributing to the alteration of bile acid profiles, which might further accelerate bile acid synthesis via increasing cholesterol 7 α-hydroxylase expression induced by the inhibition of farnesoid X receptor activation.

A Comparison of the Wound Healing Efficacy of Trolamine Emulsion, Manuka Gel, and Polymyxin-Bacitracin Ointment.

OBJECTIVE: To compare the efficacy of three topical agents commonly used in cutaneous wound healing. METHODS: Wound healing was studied in 29 participants, and each participant served as his or her own control. In each participant, three similarly sized and located seborrheic keratoses were removed by curettage. Resultant wounds were treated with either trolamine emulsion, manuka honey gel, or polymyxin-bacitracin ointment until the wounds were fully healed. RESULTS: Wounds treated with trolamine emulsion healed significantly faster than wounds treated with either manuka honey or polymyxin-bacitracin (15 vs 19 days; P < .001). CONCLUSIONS: Trolamine emulsion may be preferred in clinical practice to accelerate the healing time of clean, shallow wounds.