Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone. MECHANISM OF ACTION: The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals. PHARMACOKINETICS: Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5-9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates. CLINICAL TRIALS: The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure. THERAPEUTIC ADVANCE: Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.

Inappropriate Use of Emergency Services from the Perspective of Primary Care Underutilization in a Local Romanian Context: A Cross-Sectional Study.

Background: The underutilization of primary care services is a possible factor influencing inappropriate emergency service presentations. The objective of this study was to evaluate the proportion and characteristics of patients inappropriately accessing emergency room services from the perspective of primary care underutilization. Methods: This cross-sectional study included patients who visited the emergency room of a County Hospital, initially triaged with green, blue, or white codes, during a 2-week period in May 2017. Two primary care physicians performed a structured analysis to correlate the initial diagnosis in the emergency room with the final diagnosis to establish whether the patient's medical complaints could have been resolved in primary care. Results: A total of 1269 adult patients were included in this study. In total, the medical problems of 71.7% of patients could have been resolved by a primary care physician using clinical skills, extended resources, or other ambulatory care and out-of-hours services. Conclusions: Low awareness of out-of-hours centers and a lack of resources for delivering more complex services in primary care can lead to inappropriate presentations to the emergency services. Future research on this topic needs to be conducted at the national level.

Vitamin D Status in the Adult Population of Romania-Results of the European Health Examination Survey.

BACKGROUND: Vitamin D deficiency is recognized as a general health condition globally and is acknowledged as a public health concern in Europe. In Romania, a national program of examination of the status of vitamin D for high-risk groups has demonstrated a vitamin D deficiency prevalence of 39.83%. No national data on the status of vitamin D in the general adult population are available to date. METHODS: We used the framework of the European Health Examination Survey to analyze vitamin D levels in a sample population of adults aged 25-64 years, from 120 family doctors' patients lists, by using a sequential sampling method. Data were weighted to the Romanian population. Vitamin D deficiency was defined as 25(OH)D < 20 ng/mL. RESULTS: In total, 5380 adults aged 25-64 years were included in this study. The overall prevalence of vitamin D deficiency is 24.8%. Predictors of vitamin D deficiency were found to be obesity, female sex, living in rural areas, lower education level, and lower socioeconomic status. CONCLUSIONS: Specific recommendations for vitamin D screening and supplementation should be issued for women by specialist boards. Further studies are needed to identify seasonal variation and to establish a correlation with nutritional surveys.

Royal Jelly and Fermented Soy Extracts-A Holistic Approach to Menopausal Symptoms That Increase the Quality of Life in Pre- and Post-menopausal Women: An Observational Study.

BACKGROUND: The objective of this study was to determine the effects of royal jelly and fermented soy extracts on menopausal symptoms and on quality of life in pre- and post-menopausal women. MATERIALS AND METHOD: This prospective observational study was carried out in a Clinical Hospital of Brasov, Romania, during June 2020 and December 2021. Eighty pre- and post-menopausal women, aged between 45 and 60 years, were included in two groups. The first group (40 women) received a dietary supplement with fermented soy extract twice a day for eight weeks and the second group (40 women) received the same dietary supplement with fermented soy extracts and 1500 mg of royal jelly capsules for eight weeks. After the treatment, the MENQOL score, DASS-21 score, and the mean number and intensity of daily hot flushes were recorded and compared with baseline values. RESULTS: After eight weeks of treatment, the score of the MENQOL questionnaire and all its domains' scores decreased in comparison with the baseline in both groups (p < 0.001). Also, the DASS-21 score (p < 0.001), depression score (p < 0.001), anxiety score (p < 0.001), and stress score (p < 0.001) improved. The mean number and the intensity of hot flushes decreased in both groups (p < 0.001). Comparing these variables after the treatment in both groups, we observed that the women who received dietary supplements with fermented soy extracts and royal jelly capsules recorded better scores for MENQOL (vasomotor, physical, and psychosocial domains) and a more reduced mean number of daily hot flushes. CONCLUSIONS: This observational study suggests that both dietary fermented soy supplements and royal jelly capsules possess beneficial effects against menopausal symptoms, increase the quality of life in pre- and post-menopausal women, and that the effects might be significantly improved if those dietary supplements are administered in association.

Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders.

Metformin, a widely prescribed medication for type 2 diabetes, has garnered increasing attention for its potential neuroprotective properties due to the growing demand for treatments for Alzheimer's, Parkinson's, and motor neuron diseases. This review synthesizes experimental and clinical studies on metformin's mechanisms of action and potential therapeutic benefits for neurodegenerative disorders. A comprehensive search of electronic databases, including PubMed, MEDLINE, Embase, and Cochrane library, focused on key phrases such as "metformin", "neuroprotection", and "neurodegenerative diseases", with data up to September 2023. Recent research on metformin's glucoregulatory mechanisms reveals new molecular targets, including the activation of the LKB1-AMPK signaling pathway, which is crucial for chronic administration of metformin. The pleiotropic impact may involve other stress kinases that are acutely activated. The precise role of respiratory chain complexes (I and IV), of the mitochondrial targets, or of the lysosomes in metformin effects remains to be established by further research. Research on extrahepatic targets like the gut and microbiota, as well as its antioxidant and immunomodulatory properties, is crucial for understanding neurodegenerative disorders. Experimental data on animal models shows promising results, but clinical studies are inconclusive. Understanding the molecular targets and mechanisms of its effects could help design clinical trials to explore and, hopefully, prove its therapeutic effects in neurodegenerative conditions.

The Potential Involvement of an ATP-Dependent Potassium Channel-Opening Mechanism in the Smooth Muscle Relaxant Properties of Tamarix dioica Roxb.

Background: Tamarix dioica is traditionally used to manage various disorders related to smooth muscle in the gastrointestinal, respiratory, and cardiovascular systems. This study was planned to establish a pharmacological basis for the uses of Tamarix dioica in certain medical conditions related to the digestive, respiratory, and cardiovascular systems, and to explore the underlying mechanisms. Methods: A phytochemical study was performed by preliminary methods, followed by HPLC-DAD and spectrometric methods. In vivo evaluation of a crude hydromethanolic extract of T.dioica (TdCr) was done with a castor-oil-provoked diarrheal model in rats to determine its antidiarrheal effect. Ex vivo experiments were done by using isolated tissues to determine the effects on smooth and cardiac muscles and explore the possible mechanisms. Results: TdCr tested positive for flavonoids, saponins, phenols, and tannins as methanolic solvable constituents in a preliminary study. The maximum quantity of gallic acid equivalent (GAE), phenolic, and quercetin equivalent (QE) flavonoid content found was 146 ± 0.001 µg GAE/mg extract and 36.17 ± 2.35 µg QE/mg extract. Quantification based on HPLC-DAD (reverse phase) exposed the presence of rutin at the highest concentration, followed by catechin, gallic acid, myricetin, kaempferol, and apigenin in TdCr. In vivo experiments showed the significant antidiarrheal effect of TdCr (100, 200, and 400 mg/kg) in the diarrheal (castor-oil-provoked) model. Ex vivo experiments revealed spasmolytic, bronchodilatory, and vasorelaxant activities as well as partial cardiac depressant activity, which may be potentiated by a potassium channel opener mechanism, similar to that of cromakalim. The potassium channel (KATP channel)-opening activity was further confirmed by repeating the experiments in glibenclamide-pretreated tissues. Conclusions: In vivo and ex vivo studies of T.dioica provided evidence of the antidiarrheal, spasmolytic, bronchodilator, vasorelaxant, and partial cardiodepressant properties facilitated through the opening of the KATP channel.

Botulinum Toxin a Valuable Prophylactic Agent for Migraines and a Possible Future Option for the Prevention of Hormonal Variations-Triggered Migraines.

BACKGROUND: In 1989, Botulinum toxin (BoNT) was accepted by the FDA for the management of some ophthalmic disorders. Although it was initially considered a lethal toxin, in recent times, Botulinum toxin A (BoNT-A), which is the more used serotype, has expanded to cover different clinical conditions, primarily characterized by neuropathic pain, including migraines and headaches. Evidence suggests that migraines are influenced by hormonal factors, particularly by estrogen levels, but very few studies have investigated the prevalence and management strategies for migraines according to the hormonal status. The effects of several therapeutic regimens on migraines have been investigated, but the medications used varied widely in proven efficacies and mechanisms of action. BoNT-A is increasingly used in the management of migraine and several placebo-controlled trials of episodic and chronic migraine are currently underway. This paper is a review of the recently published data concerning the administration of BoNT-A in the prevention of chronic migraines. Considering the lack of population-based studies about the effectiveness of BoNT-A in the alleviation of premenstrual and perimenopausal migraines, this study proposes a new perspective of the therapeutic approach of migraine syndrome associated with menopausal transition and the premenstrual period. METHODS: We selected the reviewed papers from CrossRef, PubMed, Medline, and GoogleScholar, and a total of 21 studies met our inclusion criteria. RESULTS: To date, no specific preventive measures have been recommended for menopausal women with migraines. BoNT-A often reduces the frequency and intensity of migraine attacks per month; the treatment is well tolerated and does not exhibit a significantly higher rate of treatment-related side effects. No population-based studies were conducted in order to highlight the role of BoNT-A in menopause-related migraines, neither in menstrual migraines. CONCLUSION: There is a need for further research in order to quantify the real burden of menstrual and perimenopausal migraines and to clarify if BoNT-A could be used in the treatment of refractory postmenopausal and premenstrual migraines.