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"Alessio, F."
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Oral Ultramicronized Palmitoylethanolamide: Plasma and Tissue Levels and Spinal Anti-hyperalgesic Effect
Palmitoylethanolamide (PEA) is a pleiotropic lipid mediator with established anti-inflammatory and anti-hyperalgesic activity. Ultramicronized PEA (PEA-um) has superior oral efficacy compared to naïve (non-micronized) PEA. The aim of the present study was two-fold: (1) to evaluate whether oral PEA-um has greater absorbability compared to naïve PEA, and its ability to reach peripheral and central tissues under healthy and local inflammatory conditions (carrageenan paw edema); (2) to better characterize the molecular pathways involved in PEA-um action, particularly at the spinal level. Rats were dosed with 30 mg/kg of [ 13 C] 4 -PEA-um or naïve [ 13 C] 4 -PEA by oral gavage, and [ 13 C] 4 -PEA levels quantified, as a function of time, by liquid chromatography/atmospheric pressure chemical ionization/mass spectrometry. Overall plasma levels were higher in both healthy and carrageenan-injected rats administered [ 13 C] 4 -PEA-um as compared to those receiving naïve [ 13 C] 4 -PEA, indicating the greater absorbability of PEA-um. Furthermore, carrageenan injection markedly favored an increase in levels of [ 13 C] 4 -PEA in plasma, paw and spinal cord. Oral treatment of carrageenan-injected rats with PEA-um (10 mg/kg) confirmed beneficial peripheral effects on paw inflammation, thermal hyperalgesia and tissue damage. Notably, PEA-um down-regulated distinct spinal inflammatory and oxidative pathways. These last findings instruct on spinal mechanisms involved in the anti-hyperalgesic effect of PEA-um in inflammatory pain.
Journal Article
Topical Application of Adelmidrol + Trans-Traumatic Acid Enhances Skin Wound Healing in a Streptozotocin-Induced Diabetic Mouse Model
Impaired wound healing is considered to be one of the severe complications associated with diabetes. Adelmidrol and trans-traumatic acid are commonly called Nevamast
. This gel consists precisely of 2% adelmidrol and 1% trans-traumatic acid. Thanks to its components, it is capable of favoring the natural process of skin re-epithelialization. This study tests the theory that topical usage of adelmidrol + trans-traumatic acid has important effects on the healing and closure of diabetic wounds in a streptozotocin (STZ)-induced diabetic mouse model. Diabetes was induced by intraperitoneal injection of STZ (60 mg/kg) in 0.01 M citrate buffer (pH 4.5) administrated for 5 consecutive days. After diabetes induction, two longitudinal incisions were made on the dorsum of the mice. The animals were killed between 6 and 12 days from wound induction. We found that diabetic mice compared to control mice presented: a retarded wound closure, characterized by an important reduction in the levels of transforming growth factor-β, plus an important increase of vascular endothelial growth factor and endothelial-type nitric oxide synthase expression, together with a reduction of adhesion molecules such as intercellular adhesion molecule-1 and P-selectin and a prolonged elevation of the levels of matrix metalloproteinase-9 and matrix metalloproteinase-2 in wound tissues. This study demonstrates that topical application of adelmidrol + trans-traumatic acid has important effects on the healing and closure of diabetic wounds in an STZ-induced diabetic mouse model.
Journal Article
Protective Effects of Xyloglucan in Association with the Polysaccharide Gelose in an Experimental Model of Gastroenteritis and Urinary Tract Infections
Acute infectious gastroenteritis (GE) and urinary tract infection (UTI) are common diseases and are normally perceived as mild and limiting illnesses. Xyloglucan is a natural plant polymer with protective barrier properties, also known as “mucosal protectors”, which is the main ingredient of medical devices developed for the management of different diseases, such as gastrointestinal diseases, urinary tract infections, or respiratory allergic diseases. The aim of this study was to evaluate the protective effect of xyloglucan in association with gelose (also called agar) in an experimental model of bacterial GE and UTI in rats. Two kinds of infection were induced by oral administration of Salmonella enterica and Enterococcus hirae for three days. Two days before the bacterial administration, preventive oral treatment with xyloglucan + gelose (10 mg/kg + 5 mg/kg) was performed daily until the seventh day. Twenty-four hours after the last treatment, rats were sacrificed and urinary tracts and intestines for different analysis were collected. The results showed that xyloglucan plus gelose was able to reduce intestinal morphological changes (p < 0.05 for both), tight junctions (TJ) permeability (p < 0.001 for both), and neutrophil infiltration (p < 0.05 for both) induced by bacterial infections, highlighting its barrier proprieties. Moreover, the compound reduced the number of bacterial colonies in the urinary tract favoring elimination by feces. The results obtained in the present study suggest that the protective barrier properties of xyloglucan plus gelose allow the prevention of GE and UTI in models of infections in rats.
Journal Article
The association of adelmidrol with sodium hyaluronate displays beneficial properties against bladder changes following spinal cord injury in mice
The disruption of coordinated control between the brain, spinal cord and peripheral nervous system caused by spinal cord injury (SCI) leads to several secondary pathological conditions, including lower urinary tract dysfunction. In fact, urinary tract dysfunction associated with SCI is urinary dysfunction could be a consequence of a lack of neuroregeneration of supraspinal pathways that control bladder function. The object of the current research was to explore the effects of adelmidrol + sodium hyaluronate, on bladder damage generated after SCI in mice. Spinal cord was exposed via laminectomy, and SCI was induced by extradural compression at T6 to T7 level, by an aneurysm clip with a closing force of 24 g. Mice were treated intravesically with adelmidrol + sodium hyaluronate daily for 48 h and 7 days after SCI. Adelmidrol + sodium hyaluronate reduced significantly mast cell degranulation and down-regulated the nuclear factor-κB pathway in the bladder after SCI both at 48 h and 7days. Moreover, adelmidrol + sodium hyaluronate reduced nerve growth factor expression, suggesting an association between neurotrophins and bladder pressure. At 7 days after SCI, the bladder was characterized by a marked bacterial infection and proteinuria; surprisingly, adelmidrol + sodium hyaluronate reduced significantly both parameters. These data show the protective roles of adelmidrol + sodium hyaluronate on bladder following SCI, highlighting a potential therapeutic target for the reduction of bladder changes.
Journal Article
Corrigendum: Oral ultramicronized palmitoylethanolamide: plasma and tissue levels and spinal antihyperalgesic effect
[This corrects the article DOI: 10.3389/fphar.2018.00249.].
Journal Article
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.
Journal Article
Verticality Perceptions Associate with Postural Control and Functionality in Stroke Patients
Deficits of postural control and perceptions of verticality are disabling problems observed in stroke patients that have been recently correlated to each other. However, there is no evidence in the literature confirming this relationship with quantitative posturography analysis. Therefore, the objectives of the present study were to analyze the relationship between Subjective Postural Vertical (SPV) and Haptic Vertical (HV) with posturography and functionality in stroke patients. We included 45 stroke patients. The study protocol was composed by clinical interview, evaluation of SPV and HV in roll and pitch planes and posturography. Posturography was measured in the sitting and standing positions under the conditions: eyes open, stable surface (EOSS); eyes closed, stable surface (ECSS); eyes open, unstable surface (EOUS); and eyes closed, unstable surface (ECUS). The median PV in roll plane was 0.34° (-1.44° to 2.54°) and in pitch plane 0.36° (-2.72° to 2.45°). The median of HV in roll and pitch planes were -0.94° (-5.86° to 3.84°) and 3.56° (-0.68° to 8.36°), respectively. SPV in the roll plane was correlated with all posturagraphy parameters in sitting position in all conditions (r = 0.35 to 0.47; p < 0.006). There were moderate correlations with the verticality perceptions and all the functional scales. Linear regression model showed association between speed and SPV in the roll plane in the condition EOSS (R2 of 0.37; p = 0.005), in the condition ECSS (R2 of 0.13; p = 0.04) and in the condition EOUS (R2 of 0.22; p = 0.03). These results suggest that verticality perception is a relevant component of postural control and should be systematically evaluated, particularly in patients with abnormal postural control.
Journal Article
Novel concepts for the design of moulds and equipment for expanded polymer bead foams
Metal additive manufacturing is proposed as route for the manufacturing of moulds for expanded polymer parts. The traditional tools used in steam-chest moulding technologies can be replaced by lighter moulds accurately designed and produced by the laser-powder bed fusion technology, with significantly reduced thermal capacity and optimized ability to homogeneously deliver the steam throughout the part volume. The general design approach is described and the performance of the innovative tested solution is presented by the discussion of a case study. The experimental tests carried out on the moulds and moulding equipment prototypes showed remarkable reduction in cycle times and energy consumption when compared to a traditional steam-chest moulding used to print the same product.
Journal Article
Effect of Pea Protein Plus Grape Seed Dry Extract on a Murine Model of Candida Albicans Induced Vaginitis
The objective of this research was to evaluate the antifungal properties of the association between grape seed and pea by using a nonpharmacological medical device that contains them.
A murine model of vulvovaginal candidiasis, induced by Candida albicans infection, was used.
We showed that topical treatment with the device significantly reduced the fungal burden in vagina and preserved vagina tissue architecture from C. albicans infection.
We can support the potential beneficial effect of the association between grape and pea extract present in the medical device. Together these results supported this device as a favorable antifungal agent and a promising synergist with fluconazole in the clinical management of vulvovaginal candidiasis caused by C. albicans biofilms.
Journal Article