scholarly journals PEA-OXA Mitigates Oxaliplatin-Induced Painful Neuropathy through NF-κB/Nrf-2 Axis

2021 ◽  
Vol 22 (8) ◽  
pp. 3927
Author(s):  
Michela Campolo ◽  
Marika Lanza ◽  
Irene Paterniti ◽  
Alessia Filippone ◽  
Alessio Ardizzone ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Spinal Cord ◽  
Neurotrophic Factors ◽  
Dorsal Root ◽  
Painful Neuropathy ◽  
Glia Cells ◽  
Beneficial Effects ◽  
Pathway Activation ◽  
Dose Dependent ◽  
Ultramicronized Palmitoylethanolamide

Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics, such as oxaliplatin (L-OHP). The aim of the present work was to evaluate the potential beneficial effects of 2-pentadecyl-2-oxazoline (PEA-OXA) in a murine model of oxaliplatin-induced peripheral neuropathy (OIPN). OIPN was induced by an intraperitoneally injection of L-OHP in rats on five consecutive days (D0–4) for a final cumulative dose of 10 mg/kg. PEA-OXA and ultramicronized palmitoylethanolamide (PEAum), both 10 mg/kg, were given orally 15–20 min prior (L-OHP) and sacrifice was made on day 25. Our results demonstrated that PEA-OXA, more than PEAum, reduced the development of hypersensitivity in rats; this was associated with the reduction in hyperactivation of glia cells and the increased production of proinflammatory cytokines in the dorsal horn of the spinal cord, accompanied by an upregulation of neurotrophic factors in the dorsal root ganglia (DRG). Moreover, we showed that PEA-OXA reduced L-OHP damage via a reduction in NF-κB pathway activation and a modulation of Nrf-2 pathways. Our findings identify PEA-OXA as a therapeutic target in chemotherapy-induced painful neuropathy, through the biomolecular signaling NF-κB/Nrf-2 axis, thanks to its abilities to counteract L-OHP damage. Therefore, we can consider PEA-OXA as a promising adjunct to chemotherapy to reduce chronic pain in patients.

Short-Term Ultramicronized Palmitoylethanolamide Therapy in Patients with Myasthenia Gravis: a Pilot Study to Possible Future Implications of Treatment

2019 ◽  
Vol 18 (3) ◽  
pp. 232-238 ◽  
Author(s):  
Emanuela Onesti ◽  
Vittorio Frasca ◽  
Marco Ceccanti ◽  
Giorgio Tartaglia ◽  
Maria Cristina Gori ◽  
...  
Keyword(s):  
Pilot Study ◽  
Myasthenia Gravis ◽  
Repetitive Nerve Stimulation ◽  
Beneficial Effects ◽  
Antibody Titers ◽  
The Stability ◽  
Ultramicronized Palmitoylethanolamide ◽  
Open Pilot

Background: The cannabinoid system may be involved in the humoral mechanisms at the neuromuscular junction. Ultramicronized-palmitoylethanolamide (μm-PEA) has recently been shown to reduce the desensitization of Acetylcholine (ACh)-evoked currents in denervated patients modifying the stability of ACh receptor (AChR) function. <p> Objective: To analyze the possible beneficial effects of μm-PEA in patients with myasthenia gravis (MG) on muscular fatigue and neurophysiological changes. <p> Method: The duration of this open pilot study, which included an intra-individual control, was three weeks. Each patient was assigned to a 1-week treatment period with μm-PEA 600 mg twice a day. A neurophysiological examination based on repetitive nerve stimulation (RNS) of the masseteric and the axillary nerves was performed, and the quantitative MG (QMG) score was calculated in 22 MG patients every week in a three-week follow-up period. AChR antibody titer was investigated to analyze a possible immunomodulatory effect of PEA in MG patients. <p> Results: PEA had a significant effect on the QMG score (p=0.03418) and on RNS of the masseteric nerve (p=0.01763), thus indicating that PEA reduces the level of disability and decremental muscle response. Antibody titers did not change significantly after treatment. <p> Conclusion: According to our observations, μm-PEA as an add-on therapy could improve muscular response to fatigue in MG. The possible modulation of AChR currents as a means of eliciting a direct effect from PEA on the conformation of ACh receptors should be investigated. The co-role of cytokines also warrants an analysis. Given the rapidity and reversibility of the response, we suppose that PEA acts directly on AChR, though further studies are needed to confirm this hypothesis.

Dorsal Root Crush in Adult Mice to Study Spinal Cord Regeneration

BIO-PROTOCOL ◽  
2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Hyukmin Kim ◽  
Harun Noristani ◽  
Seung Han ◽  
Young-Jin Son
Keyword(s):  
Spinal Cord ◽  
Dorsal Root ◽  
Spinal Cord Regeneration ◽  
Adult Mice

Microanatomy of the Origin of the Cervical Plexus at the Spinal Cord, Nerve Root Cuffs, and Dorsal Root Ganglia Levels

2022 ◽  
pp. 93-125
Author(s):  
Irene Riquelme ◽  
Miguel Angel Reina ◽  
André P. Boezaart ◽  
Francisco Reina ◽  
Virginia García-García ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Root Ganglia ◽  
Nerve Root ◽  
Dorsal Root ◽  
Cervical Plexus

scholarly journals Quantitative Sensory Testing of Spinal Cord and Dorsal Root Ganglion Stimulation in Chronic Pain Patients

2021 ◽  
Author(s):  
Vishwanath Sankarasubramanian ◽  
Srinivas Chiravuri ◽  
Ehsan Mirzakhalili ◽  
Carlos J. Anaya ◽  
John Ryan Scott ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Quantitative Sensory Testing ◽  
Sensory Testing ◽  
Chronic Pain Patients ◽  
Pain Patients

scholarly journals Ultramicronized Palmitoylethanolamide (um-PEA): A New Possible Adjuvant Treatment in COVID-19 patients

2021 ◽  
Vol 14 (4) ◽  
pp. 336
Author(s):  
Annalisa Noce ◽  
Maria Albanese ◽  
Giulia Marrone ◽  
Manuela Di Lauro ◽  
Anna Pietroboni Zaitseva ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Pulmonary Involvement ◽  
In Vivo Studies ◽  
Pharmacological Treatments ◽  
Beneficial Effects ◽  
Coronavirus Infection ◽  
Ultramicronized Palmitoylethanolamide ◽  
Potential Use

The Coronavirus Disease-19 (COVID-19) pandemic has caused more than 100,000,000 cases of coronavirus infection in the world in just a year, of which there were 2 million deaths. Its clinical picture is characterized by pulmonary involvement that culminates, in the most severe cases, in acute respiratory distress syndrome (ARDS). However, COVID-19 affects other organs and systems, including cardiovascular, urinary, gastrointestinal, and nervous systems. Currently, unique-drug therapy is not supported by international guidelines. In this context, it is important to resort to adjuvant therapies in combination with traditional pharmacological treatments. Among natural bioactive compounds, palmitoylethanolamide (PEA) seems to have potentially beneficial effects. In fact, the Food and Drug Administration (FDA) authorized an ongoing clinical trial with ultramicronized (um)-PEA as an add-on therapy in the treatment of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. In support of this hypothesis, in vitro and in vivo studies have highlighted the immunomodulatory, anti-inflammatory, neuroprotective and pain-relieving effects of PEA, especially in its um form. The purpose of this review is to highlight the potential use of um-PEA as an adjuvant treatment in SARS-CoV-2 infection.

scholarly journals N-acetyl-L-cysteine Improves the Developmental Competence of Bovine Oocytes and Embryos Cultured In Vitro by Attenuating Oxidative Damage and Apoptosis

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 860
Author(s):  
Wu-Sheng Sun ◽  
Hoon Jang ◽  
Mi-Ryung Park ◽  
Keon Bong Oh ◽  
Haesun Lee ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Early Stage ◽  
Developmental Competence ◽  
Beneficial Effects ◽  
Developmental Rates ◽  
A Cell ◽  
Bovine Oocytes ◽  
Dose Dependent

Oxidative stress has been suggested to negatively affect oocyte and embryo quality and developmental competence, resulting in failure to reach full term. In this study, we investigated the effect of N-acetyl-L-cysteine (NAC), a cell-permeating antioxidant, on developmental competence and the quality of oocytes and embryos upon supplementation (0.1–10 mM) in maturation and culture medium in vitro using slaughterhouse-derived oocytes and embryos. The results show that treating oocytes with 1.0 mM NAC for 8 h during in vitro maturation attenuated the intracellular reactive oxygen species (ROS) (p < 0.05) and upregulated intracellular glutathione levels (p < 0.01) in oocytes. Interestingly, we found that NAC affects early embryonic development, not only in a dose-dependent, but also in a stage-specific, manner. Significantly (p < 0.05) decreased cleavage rates (90.25% vs. 81.46%) were observed during the early stage (days 0–2), while significantly (p < 0.05) increased developmental rates (38.20% vs. 44.46%) were observed during the later stage (from day 3) of embryonic development. In particular, NAC supplementation decreased the proportion of apoptotic blastomeres significantly (p < 0.05), resulting in enhanced hatching capability and developmental rates during the in vitro culture of embryos. Taken together, our results suggest that NAC supplementation has beneficial effects on bovine oocytes and embryos through the prevention of apoptosis and the elimination of oxygen free radicals during maturation and culture in vitro.

scholarly journals Glatiramer Acetate Treatment in Multiple Sclerosis-Associated Fatigue—Beneficial Effects on Self-Assessment Scales But Not on Molecular Markers

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 393
Author(s):  
Oliver Neuhaus ◽  
Wolfgang Köhler ◽  
Florian Then Bergh ◽  
Wolfgang Kristoferitsch ◽  
Jürgen Faiss ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Neurotrophic Factors ◽  
Common Symptom ◽  
Mrna Levels ◽  
Open Label ◽  
Immunological Parameters ◽  
Beneficial Effects

Although fatigue is a common symptom in multiple sclerosis (MS), its pathomechanisms are incompletely understood. Glatiramer acetate (GA), an immunomodulatory agent approved for treatment of relapsing-remitting MS (RRMS), possesses unique mechanisms of action and has been shown to exhibit beneficial effects on MS fatigue. The objective of this study was to correlate clinical, neuropsychological, and immunological parameters in RRMS patients with fatigue before and during treatment with GA. In a prospective, open-label, multicenter trial, 30 patients with RRMS and fatigue were treated with GA for 12 months. Inclusion criterion was the presence of fatigue as one of the most frequent and disabling symptoms. Before and during treatment, fatigue was assessed using the Fatigue Severity Scale (FSS), the MS-FSS, and the Modified Fatigue Impact Scale (MFIS). In addition, fatigue and quality of life were assessed using the Visual Analog Scales (VAS). Laboratory assessments included screening of 188 parameters using real-time PCR microarrays followed by further analysis of several cytokines, chemokines, and neurotrophic factors. Fatigue self-assessments were completed in 25 patients. After 12 months of treatment with GA, 13 of these patients improved in all three scales (with the most prominent effects on the MFIS), whereas 5 patients had deteriorated. The remaining 7 patients exhibited inconsistent effects within the three scales. Fatigue and overall quality of life had improved, as assessed via VAS. Laboratory assessments revealed heterogeneous mRNA levels of cytokines, chemokines, and neurotrophic factors. In conclusion, we were not able to correlate clinical and molecular effects of GA in patients with RRMS and fatigue.

Sign in / Sign up

Export Citation Format

Share Document