The purpose of this study was to investigate the effect of an egg white hydrolysate (EWH) to protect white adipose tissue damage from cardiometabolic changes induced by severe hypertension. Male ...Wistar rats were uninephrectomised and divided: SHAM (weekly subcutaneous vehicle (mineral oil + propylene glycol, 1:1)), SHAM + EWH (subcutaneous vehicle plus EWH via gavage, 1 g/kg per day), DOCA (deoxycorticosterone acetate diluted in vehicle subcutaneously weekly in subsequent doses of 20 mg/kg -1st week, 12 mg/kg - 2–3th week, and 6 mg/kg -4–8th week, respectively, plus 1 % NaCl and 0·2 % KCl in drinking water), and DOCA + EWH. Body weight gain, food and water intake, glucose and lipid metabolism were evaluated. Oxidative stress was assessed by biochemical assay and immunofluorescence for NOX-1, nuclear factor kappa B (NFκB), and caspase-3 in retroperitoneal white adipose tissue (rtWAT). Proinflammatory cytokines (IL-6 and 1β), CD163+ macrophage infiltration, and immunohistochemistry for TNFα and uncoupling protein-1 were evaluated, as well as histological analysis on rtWAT. Glutathione peroxidase and reductase were also determined in plasma. EWH showed hypocholesterolemic, antioxidant, anti-inflammatory, and anti-apoptotic properties in the arterial hypertension DOCA-salt model. The results demonstrated the presence of functional changes in adipose tissue function by a decrease in macrophage infiltration and in the fluorescence intensity of NFκB, NOX-1, and caspase-3. A reduction of proinflammatory cytokines and restoration of antioxidant enzymatic activity and mitochondrial oxidative damage by reducing uncoupling protein-1 fluorescence intensity were also observed. EWH could be used as a potential alternative therapeutic strategy in the treatment of cardiometabolic complications associated with malignant secondary arterial hypertension.
Background and Objectives
The efficacy of COVID‐19 convalescent plasma (CP) associates with high titres of antibodies. ConPlas‐19 clinical trial showed that CP reduces the risk of progression to ...severe COVID‐19 at 28 days. Here, we aim to study ConPlas‐19 donors and characteristics that associate with high anti‐SARS‐CoV‐2 antibody levels.
Materials and Methods
Four‐hundred donors were enrolled in ConPlas‐19. The presence and titres of anti‐SARS‐CoV‐2 antibodies were evaluated by EUROIMMUN anti‐SARS‐CoV‐2 S1 IgG ELISA.
Results
A majority of 80.3% of ConPlas‐19 donor candidates had positive EUROIMMUN test results (ratio ≥1.1), and of these, 51.4% had high antibody titres (ratio ≥3.5). Antibody levels decline over time, but nevertheless, out of 37 donors tested for an intended second CP donation, over 90% were still EUROIMMUN positive, and nearly 75% of those with high titres maintained high titres in the second sample. Donors with a greater probability of developing high titres of anti‐SARS‐CoV‐2 antibodies include those older than 40 years of age (RR 2.06; 95% CI 1.24–3.42), with more than 7 days of COVID‐19 symptoms (RR 1.89; 95% CI 1.05–3.43) and collected within 4 months from infection (RR 2.61; 95% CI 1.16–5.90). Male donors had a trend towards higher titres compared with women (RR 1.67; 95% CI 0.91–3.06).
Conclusion
SARS‐CoV‐2 CP candidate donors' age, duration of COVID‐19 symptoms and time from infection to donation associate with the collection of CP with high antibody levels. Beyond COVID‐19, these data are relevant to inform decisions to optimize the CP donor selection process in potential future outbreaks.
In paroxysmal nocturnal hemoglobinuria (PNH), lack of the GPI-anchored terminal complement inhibitor CD59 from erythrocytes renders them susceptible to chronic hemolysis, which is central to the ...signs and symptoms of PNH. Patients are at elevated risk for thrombosis, experience anemia that may require transfusion support, and suffer from fatigue that can be severe. Patients often have a poor quality of life resulting from PNH related symptoms including pain, dyspnea, dysphagia and erectile dysfunction, which negatively impact quality of life. The prevalence and severity of symptoms were explored in the context of a multi-national content validation study, of patients not receiving eculizumab therapy, employing the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) instruments. Symptom questions were asked of 29 PNH patients (19 men, 10 women, mean age 41.2±13.2 years) from the United Kingdom, United States, France and Spain. More than half (52%) had PNH for over 5 years. Most (76%) reported never having had a blood clot, 31% reported not receiving any medication for their PNH, and 59% reported either that they had never been transfused or had not received transfusion within the last year for PNH. Patients viewed overall quality of life, global health, functioning, fatigue, pain, and shortness of breath as important PNH-related signs/symptoms. Both the FACIT-Fatigue and EORTC instruments were relevant and adequate in assessing the level of fatigue and other quality of life measures in PNH. The burden of disease in this multicultural and diverse cohort of patients was significant: 76% were forced to modify their daily activities to manage their PNH and 17% were unemployed due to PNH. Nearly all (96%) complained of fatigue and more than half reported abdominal pain, headache and shortness of breath (Table). Patients also commonly reported dysphagia (41%) and erectile dysfunction (47% in males). Most patients reported these PNH-related symptoms as moderate to very severe, and a substantial majority reported distress associated with the symptoms. Significant disease burden was identified in a diverse population of PNH patients, most of which had minimal or no transfusion requirements and a low incidence of thrombosis. Therapy that controls hemolysis and thereby improves fatigue, pain, shortness of breath, dysphagia and erectile dysfunction may prove beneficial for PNH patients with these disease characteristics.
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Background: Constipation-predominant irritable bowel syndrome (IBS-C) is a common gastrointestinal disorder characterized by abdominal pain and altered bowel habits. Conventional treatments for IBS-C ...often provide limited efficiency, leading to an increasing interest in exploring herbal remedies. This systematic review aims to evaluate the efficacy and safety of herbal remedies in the management of IBS-C. Materials and Methods: A comprehensive search of PubMed, MEDLINE, Embase, Scopus, and the Cochrane Library was conducted to identify relevant studies published up to July 2023 and data extraction was performed independently by two reviewers. Results: Overall, the included studies demonstrated some evidence of the beneficial effects of herbal remedies on IBS-C symptoms, including improvements in bowel frequency, stool consistency, abdominal pain, and quality of life. However, the heterogeneity of the interventions and outcome measures limited the ability to perform a meta-analysis. Conclusion: This systematic review suggests that herbal remedies may have potential benefits in the management of IBS-C. However, the quality of evidence is limited, and further well-designed, large-scale RCTs are needed to establish the efficacy and safety of specific herbal remedies for IBS-C. Clinicians should exercise caution when recommending herbal remedies and consider individual patient characteristics and preferences.
Metabolic Syndrome (MS) is a cluster of metabolic risk factors that come together in a single individual. This condition represents an important health problem nowadays¸ and new treatments to ...counteract it are needed. The evaluation of new successful strategies against MS requires the use of animal models that adequately mimic the corresponding alterations. The animals fed a so called ¨Western Diet¨ can in fact simulate the patients that develop MS in our society. These animals usually are fed with a high-fat/high-sugar diet enriched in fructose or sucrose as the main sugars. However¸ glucose is not considered a good candidate to induce MS. The aim of this study was to establish a new high-fat/high-sugar diet for rodents ¸ with D-glucose (dextrose) as the main sugar¸ to induce in these animals the alterations inherent to MS.Eight-week-old male Wistar rats were used. The rats were randomly divided into four groups (n=7 each): Control (C)¸ high-fat (HF)¸ high-fat/high-fructose (HFF) and high-fat/high-dextrose (HFD). The animals were fed the corresponding diets ad libitum for 18 weeks. Body weight and food intake were recorded on a weekly basis in the different groups. Plasma samples were collected for biochemical analysis at the end of the experimental period. Abdominal circumference and epidydimal adipose tissue¸ liver and hearth weight were also recorded at this point. Moreover¸ samples of epidydimal¸ muscle and interescapular adipose tissues were collected for analyses.Body weight¸ abdominal circumference and epididymal adipose tissue weight were higher in the HFD group than in the other groups. Oxidative stress biomarkers and mitochondrial analyses indicated an increase of oxidative damage in the HFD group. This group also showed increased insulin and glucose plasma levels, even if the HFF animals showed the greatest increase on plasma insulin levels. HF¸ HFF and HFD groups also showed increased plasma levels of triglycerides.Our results indicated a better impact of D-glucose than fructose¸ when combined with a high-fat diet¸ to induce most of the alterations associated with MS in rats. In addition¸ our research facilitates a new animal model to evaluate the different treatments for MS.
Aluminum (Al), which is omnipresent in human life, is a potent neurotoxin. Here, we have tested the potential for Egg White Hydrolysate (EWH) to protect against changes in cognitive function in rats ...exposed to both high and low levels of Al. Indeed, EWH has been previously shown to improve the negative effects induced by chronic exposure to heavy metals. Male Wistar rats received orally: Group 1) Low aluminum level (AlCl
at a dose of 8.3 mg/kg b.w. during 60 days) with or without EWH treatment (1 g/kg/day); Group 2) High aluminum level (AlCl
at a dose of 100 mg/kg b.w. during 42 days) with or without EWH treatment (1 g/kg/day). After 60 or 42 days of exposure, rats exposed to Al and EWH did not show memory or cognitive dysfunction as was observed in Al-treated animals. Indeed, co-treatment with EWH prevented catalepsy, hippocampal oxidative stress, cholinergic dysfunction and increased number of activated microglia and COX-2-positive cells induced by Al exposure. Altogether, since hippocampal inflammation and oxidative damage were partially prevented by EWH, our results suggest that it could be used as a protective agent against the detrimental effects of long term exposure to Al.
Objective
To assess the effectiveness and tolerability of perampanel (PER) monotherapy in routine clinical practice for the treatment of focal onset and generalized tonic‐clonic seizures (GTCS).
...Methods
This multicenter, retrospective, observational study was conducted in patients aged ≥12 years treated with PER as primary monotherapy or converted to PER monotherapy by progressive reduction of background antiepileptic drugs. Outcomes included retention, responder, and seizure‐free rate after 3, 6, and 12 months and tolerability throughout the follow‐up.
Results
A total of 98 patients (mean age = 49.6 ± 21.7 years, 51% female) with focal seizures and/or GTCS were treated with PER monotherapy for a median exposure of 14 months (range = 1‐57) with a median dose of 4 mg (range = 2‐10). The retention rates at 3, 6, and 12 months and last follow‐up were 93.8%, 89.3%, 80.9%, and 71.4%, respectively. The retention rates according to the type of monotherapy (primary vs conversion) did not differ (log‐rank P value = .57). Among the 98 patients, 61.2% patients had seizures throughout the baseline period, with a median seizure frequency of 0.6 seizures per month (range = 0.3‐26). Responder rates at 3, 6, and 12 months were 79.6%, 70.1%, and 52.8%, respectively, and seizure freedom rates at the same points were 62.7%, 56.1%, and 41.5%. Regarding the 33 patients who had GTCS in the baseline period, 87.8% were seizure‐free at 3 months, 78.1% at 6 months, and 55.1% at 12 months. Over the entire follow‐up, PER monotherapy was generally well tolerated, and only 16% of patients discontinued PER due to adverse events (AEs). Female patients were found to be at a higher risk of psychiatric AEs (female vs male odds ratio = 2.85, 95% confidence interval = 1‐8.33, P = .046).
Significance
PER demonstrated good effectiveness and a good safety profile when used as primary therapy or conversion to monotherapy at relatively low doses, in a clinical setting with patients with focal seizures and GTCS.
Objective
Cenobamate is an antiseizure medication (ASM) associated with high rates of seizure freedom and acceptable tolerability in patients with focal seizures. To achieve the optimal cenobamate ...dose for maximal potential effectiveness while avoiding or minimizing drug‐related adverse events (AEs), the administration of cenobamate with other ASMs must be managed through concomitant ASM load reduction. A panel of Spanish epilepsy experts aimed to provide a Spanish consensus on how to adjust the dose of concomitant ASMs in patients with drug‐resistant epilepsy (DRE) in order to improve the effectiveness and tolerability of adjunctive cenobamate.
Methods
A three‐stage modified Delphi consensus process was undertaken, including six Spanish epileptologists with extensive experience using cenobamate. Based on current literature and their own expert opinion, the expert panel reached a consensus on when and how to adjust the dosage of concomitant ASMs during cenobamate titration.
Results
The expert panel agreed that tailored titration and close follow‐up are required to achieve the best efficacy and tolerability when initiating cenobamate in patients receiving concomitant ASMs. When concomitant clobazam, phenytoin, phenobarbital, and sodium channel blockers are taken at high dosages, or when the patient is receiving two or more sodium channel blockers, dosages should be proactively lowered during the cenobamate titration period. Other concomitant ASMs should be reduced only if the patient reports a moderate/severe AE at any stage of the titration period.
Significance
Cenobamate is an effective ASM with a dose‐dependent effect. To maximize effectiveness while maintaining the best tolerability profile, co‐medication management is needed. The recommendations included herein provide practical guidance for proactive and reactive management of co‐medication in cenobamate‐treated patients with DRE and a high drug load.
Plain Language Summary
Patients with epilepsy may continue to have seizures even after treatment with several different antiseizure medications (ASMs). Cenobamate is an ASM that can reduce seizures in these patients. In this study, six Spanish experts in epilepsy discussed the best way to use cenobamate in drug‐resistant epilepsy. They provide practical guidance on when and how the dose of other ASMs might be adjusted to reduce side effects and optimize the use of cenobamate.
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