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 ◽  
...  

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.

2003 ◽  
Vol 36 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Aluízio Prata ◽  
Mario Léon Silva-Vergara ◽  
Laércio Costa ◽  
Ademir Rocha ◽  
Alejandro Krolewiecki ◽  
...  

The present open pilot study was conducted to assess the efficacy of azithromycin for the treatment of patients with cutaneous leishmaniasis in Araçuaí and Varzelândia, MG. Twenty-four patients with less of six months of disease evolution were treated after clinical examination, Montenegro test and a biopsy. The treatment schemes consisted of oral doses of 500 mg per day for 3, 5 and 10 days and of 1000 mg for two days. A clinical control was performed monthly and treatment cycles were repeated when necessary until full reepithelialization of the lesions. On the occasion of the final evaluation, 20 patients had completed the study and 17 of them (85%) were cured. The time to obtain a cure was 60 days ifor 6 (30%) patients, 90 days for 7 (35%), and 120 for 4 (20%). The three patients with treatment failure received a pentavalent antimonial for 20 days. No adverse reactions to the medication were observed and a 14 month follow-up did not show recurrence in any patient. These results suggest that azithromycin can be a good therapeutic option for the treatment of cutaneous leishmaniasis caused by Leishmania Viannia brasiliensis.


Author(s):  
Anne-Michelle Tessier ◽  
Karen Jesney

Smolensky & Goldrick (2016) first made the case for Gradient Symbolic Representations (GSRs) as the inputs to phonological grammar using the phenomena of French liaison. Under this view, many common French words are stored underlyingly with partially-activated word-final consonants, and others with gradient blends of partially-activated word-initial consonants. In this paper, we follow up some of that view's predictions and consequences, focusing on the acquisition of French liaison using GSRs. We compare our simulations of error-driven GSR learning with observed errors made by French-learning children, and find the results to be encouragingly similar. We also compare predictions about the end state of GSR learning with a pilot study reporting adult French speakers' use of liaison in nonce words, where we find a rather less good explanatory fit. The paper emphasizes the role of word and collocation frequency in the development of phonological patterns by a GSR learner, and outlines many future avenues for research. 


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 60-60
Author(s):  
Noelia Sanmamed ◽  
Rachel Glicksman ◽  
John Thoms ◽  
Alexandre Zlotta ◽  
Antonio Finelli ◽  
...  

60 Background: Pre-operative radiotherapy (PreORT) improves local control in various cancer types, and has become an established oncologic treatment strategy. During 2001-2004, we conducted a phase I pilot study assessing the role of short-course PreORT for men with unfavourable intermediate- and high-risk localized prostate cancer (PCa). We present long-term follow-up toxicity and oncologic outcomes. Methods: Eligible patients had histologically proven PCa, cT1-T2N0M0, PSA > 15-35 ng/ml with any Gleason score, or PSA 10-15 ng/ml with Gleason score ≥7. Patients received 25 Gy in five consecutive daily fractions to the prostate, followed by radical prostatectomy (RadP) within 14 days after RT completion. Primary outcomes were intra-operative morbidity, and late genitourinary (GU) and gastrointestinal (GI) toxicities. Acute toxicity was assessed during radiotherapy treatment on daily basis using RTOG grade scoring scale. Patients were assessed post-RadP clinically and with PSA at 1 and 6 months, and every 6 months. Intra- and Post-RadP toxicity was documented prospectively and scored as per Common Terminology Criteria for Adverse Events v4.0. Biochemical failure (BF) was determined based on two consecutive post-RadP PSA > 0.2 ng/ml. Results: Fifteen patients were enrolled; 14 patients completed PreORT followed by RadP, which also included bilateral lymph node dissections in 13 cases. Median follow-up was 12.2 years (range 6.7-16.3 years). Late GU toxicity was common, with 2 patients (14.3%) experiencing G2 toxicity, and 6 patients (42.8%) G3 toxicity. There were no G4-5 late GU toxicity. Late GI toxicity was infrequent, with only 1 patient (7.1%) experiencing transient G2 proctitis. At last follow-up, 8 (57.1%) and 6 (42.8%) patients experienced BF and metastatic disease recurrence, respectively. Conclusions: The use of PreORT in men with high-risk PCa is associated with unexpected high-rates of late GU toxicity. Future studies examining the role of RT pre-RadP must cautiously select RT technique and dose schedule. Importantly, long-term follow-up data is essential to fully determine the therapeutic index of PreORT in the management of localized PCa. Clinical trial information: NCT00252447.


2018 ◽  
Vol 25 (16) ◽  
pp. 1818-1836 ◽  
Author(s):  
Massimo D`Archivio ◽  
Beatrice Scazzocchio ◽  
Rosaria Vari ◽  
Carmela Santangelo ◽  
Claudio Giovannini ◽  
...  

Background: Scientific evidence has been accumulated about the effects of polyunsaturated fatty acids (PUFAs) on human health. The hypothesis that n-3 PUFAs might improve the efficiency of anticancer drugs has recently been considered. The role of n-6 PUFAs, in contrast, needs to be better assessed. However, the effective mechanisms of action of PUFAs have not been fully clarified yet. This review aims to report the most updated evidence on the role of n-6 and n-3 PUFAs in the development and treatment of human cancers, focusing on the potential mechanisms by which PUFAs exert their effects. Methods: We undertook a structured search in PubMed on February 17th 2017 for peer-reviewed research articles published from 2013. The search syntax used was: PUFA or PUFAs and cancer. Results: Contradictory results were found, most likely due to the genetic background, the different dietary sources used, the interaction among different nutrients, and the tumor subtypes. However, the more recent findings strongly support the use of n-3 PUFAs in cancer prevention and treatment. On the other hand, n-6 PUFAs are often associated with an increased risk of cancer, even if recently their beneficial effects have also been highlighted. Conclusion: N-3 PUFAs may represent a potential therapeutic agent contributing to treat at least some type of human cancers. However, studies with larger sample sizes and longer follow-up times are still needed. To increase the knowledge about how food and nutrition can improve human health it is advisable to deliver an open access nutritional database.


1987 ◽  
Vol 60 (2) ◽  
pp. 555-560 ◽  
Author(s):  
Lionel Collet ◽  
Jean Cottraux ◽  
Robert Ladouceur

A multiple-baseline design with counterdemands instructions was used to evaluate the efficacy of cognitive therapy in five depressed patients. Depression measures (MMPI, Hamilton, and Beck Depression Inventory) showed that all the patients were improved at the end of treatment and therapeutic benefits were maintained at a 1-yr. follow-up. These results confirmed the beneficial effects for depressive patients of cognitive therapy with stringent methodological controls.


Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 125
Author(s):  
Abhinav B. Swaminathan ◽  
Vishal M. Gohil

Copper is essential for the stability and activity of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Copper is bound to COX1 and COX2, two core subunits of CcO, forming the CuB and CuA sites, respectively. Biogenesis of these two copper sites of CcO occurs separately and requires a number of evolutionarily conserved proteins that form the mitochondrial copper delivery pathway. Pathogenic mutations in some of the proteins of the copper delivery pathway, such as SCO1, SCO2, and COA6, have been shown to cause fatal infantile human disorders, highlighting the biomedical significance of understanding copper delivery mechanisms to CcO. While two decades of studies have provided a clearer picture regarding the biochemical roles of SCO1 and SCO2 proteins, some discrepancy exists regarding the function of COA6, the new member of this pathway. Initial genetic and biochemical studies have linked COA6 with copper delivery to COX2 and follow-up structural and functional studies have shown that it is specifically required for the biogenesis of the CuA site by acting as a disulfide reductase of SCO and COX2 proteins. Its role as a copper metallochaperone has also been proposed. Here, we critically review the recent literature regarding the molecular function of COA6 in CuA biogenesis.


2020 ◽  
Vol 8 (9) ◽  
pp. 4310-4316
Author(s):  
Rajni Kanojiya ◽  
Shreyes. S ◽  
Yogitha Bali M.R

Background: Stanyakshaya is the common problem noticed in about 40% patients in our clinical practice. Due to adaptation of Western culture, women get exposed to stress and strain. Lactation is the process as-sociated with psychosomatic condition and lifestyle. Breast milk is the perfect food for a normal neonate. It is the best gift a mother can give her baby. Breast feeding is the ideal form of infant feeding and is cru-cial for lifelong health and wellbeing. Design: This was a single pilot study. 10 patients(lactating mothers, both primi and multi gravida) who ful-filled the eligibility criteria were selected for the study and the assessments were made before the treatment on the 1st day and after the treatment on the 30th day and follow up was done on 20th day after the comple-tion of treatment. Intervention: Karpasabeejachurna (6gms) was administered with lukewarm water as the Anupana after food twice a day for one month and follow up carried out on 20th day after the completion of treatment. Results: Karpasabeejachurna showed statistically significant results in the Stanamlanata, Stana/milk ejec-tion, breast feeding, weight of the baby and breast engorgement with p<0.001. Conclusion: Karpasabeejachoorna showed to be effective in increasing the Stanya and it is a Stan-yajanakadravya.


2014 ◽  
Vol 36 (4) ◽  
pp. 599-605 ◽  
Author(s):  
Jin-Sung Park ◽  
Hye-Gyung Kim ◽  
Jin-Hong Shin ◽  
Young-Chul Choi ◽  
Dae-Seong Kim

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