P2X receptors as targets for the treatment of status epilepticus.

Prolonged seizures are amongst the most common neurological emergencies. Status epilepticus is a state of continuous seizures that is life-threatening and prompt termination of status epilepticus is critical to protect the brain from permanent damage. Frontline treatment comprises parenteral administration of anticonvulsants such as lorazepam that facilitate γ-amino butyric acid (GABA) transmission. Because status epilepticus can become refractory to anticonvulsants in a significant proportion of patients, drugs which act on different neurotransmitter systems may represent potential adjunctive treatments. P2X receptors are a class of ligand-gated ion channel activated by ATP that contributes to neuro- and glio-transmission. P2X receptors are expressed by both neurons and glia in various brain regions, including the hippocampus. Electrophysiology, pharmacology and genetic studies suggest certain P2X receptors are activated during pathologic brain activity. Expression of several members of the family including P2X2, P2X4, and P2X7 receptors has been reported to be altered in the hippocampus following status epilepticus. Recent studies have shown that ligands of the P2X7 receptor can have potent effects on seizure severity during status epilepticus and mice lacking this receptor display altered seizures in response to chemoconvulsants. Antagonists of the P2X7 receptor also modulate neuronal death, microglial responses and neuroinflammatory signaling. Recent work also found altered neuronal injury and inflammation after status epilepticus in mice lacking the P2X4 receptor. In summary, members of the P2X receptor family may serve important roles in the pathophysiology of status epilepticus and represent novel targets for seizure control and neuroprotection

Influencia de la concentración de la salmuera en la difusión de azúcares y cloruro de sodio durante el procesamiento de aceitunas verdes variedad Arauco

The green olive variety Arauco were debittered using lye concentrations of, 2.50% NaOH.They were then subjected to two rinsing processes with tap water. Next, the olives were cured with brines at 7%, 10% and 13% sodium chloride concentration. During this curing process, the loss of reducing sugars from the olives, and the diffusion of sodium chloride into the olives were quantified. Effective diffusion coefficients of both solutes in the skin and the flesh were calculated for this period using a diffusion model for a composite hollow sphere. The skin effective diffusion coefficients for both solutes ranged from entre 8,27x10-14- m2/s to 4,04x10-13 m2/s. The flesh coefficients varied from 2,92x10-9 m2/s to 3,99x10-9 m2/s for sodium chloride and from 9,76x10-11 m2/s to 2,22x10-10 m2/s for reducing sugars.Aceitunas verdes variedad Arauco fueron tratadas con soluciones de hidróxido de sodio al 2,5%. Estas fueron luego sometidas a dos procesos de lavado con agua corriente. Posteriormente, las aceitunas fueron curadas en salmueras con concentraciones de 7%, 10% y 13% de cloruro de sodio. Durante este proceso de curado, se cuantificó la pérdida de azúcares reductores desde, y la difusión de cloruro de sodio hacia el interior de las aceitunas. Durante este período se calcularon los coeficientes efectivos de difusión de ambos solutos en la piel y la pulpa, utilizando un modelo de difusión en una esfera hueca compuesta. Los coeficientes efectivos de difusión de ambos solutos en la piel estuvieron en un rango entre 8,27x10-14- m2/s y 4,04x10-13 m2/s. Los coeficientes de la pulpa variaron entre 2,92x10-9 m2/s y 3,99x10-9 m2/s para el cloruro de sodio, y entre 9,76x10-11 m2/s y 2,22x10-10 m2/s para los azúcares reductores

Foliar and root comparative metabolomics and phenolic profiling of Micro-Tom tomato (Solanum lycopersicum L.) plants associated with a gene expression analysis in response to short daily UV treatments

Tomato (Solanum lycopersicum L.) is globally recognised as a high-value crop both for commercial profit and nutritional benefits. In contrast to the extensive data regarding the changes in the metabolism of tomato fruit exposed to UV radiation, less is known about the foliar and root metabolome. Using an untargeted metabolomic approach through UHPLC-ESI-QTOF-MS analysis, we detected thousands of metabolites in the leaves (3000) and roots (2800) of Micro-Tom tomato plants exposed to 11 days of short daily UV radiation, applied only on the aboveground organs. Multivariate statistical analysis, such as OPLS-DA and volcano, were performed to allow a better understanding of the modifications caused by the treatment. Based on the unexpected modulation to the secondary metabolism, especially the phenylpropanoid pathway, of which compounds were down and up accumulated respectively in leaves and roots of treated plants, a phenolic profiling was carried out for both organs. The phenolic profile was associated with a gene expression analysis to check the transcription trend of genes involved in the UVR8 signalling pathway and the early steps of the phenolic biosynthesis. The retention of the modifications at metabolic and phenolic levels was also investigated 3 days after the UV treatment, showing a prolonged effect on the modulation once the UV treatment had ceased

Rats Fed Diets with Different Energy Contribution from Fat Do Not Differ in Adiposity

Objective: To determine whether rats reaching the same body mass, having been fed either a low-fat (LFD) or a high-fat diet (HFD), differ in white adipose tissue (WAT) deposition. Methods: In experiment 1, 22 Sprague-Dawley rats of the same age were divided into 11 rats with body mass below the batch median and fed a HFD, and 11 above the median and fed a LFD. In experiment 2, 20 Sprague-Dawley rats of the same age and starting body mass were randomised to either a HFD or LFD. When all groups reached similar final body mass, WAT was quantified using magnetic resonance imaging (MRI), dissection, and plasma leptin. Results: In experiment 1, both groups reached similar final body mass at the same age; in experiment 2 the HFD group reached similar final body mass earlier than the LFD group. There were no significant differences in WAT as assessed by MRI or leptin between the HFD and LFD groups in both experiments. Dissection revealed a trend for higher retroperitoneal and epididymal adiposity in the HFD groups in both experiments. Conclusions: We conclude that at similar body mass, adiposity is independent of the macronutrient composition of the feeding regimen used to achieve it

Diagnosis and management of parathyroid carcinoma: a state-of-the-art review

Parathyroid carcinoma is one of the least common endocrine malignancies and accounts for approximately 1% of all patients with primary hyperparathyroidism. A systematic review of peer-reviewed literature published between January 2000 and March 2022 via Medline, Embase, Cochrane Central Register of Controlled Trials, EudraCT, ClinicalTrials.gov, CINAHL and SCOPUS was conducted. Manuscripts were eligible if they included data on adult non-pregnant populations with parathyroid carcinoma. No restrictions regarding interventions, comparators or duration of follow-up were imposed. Single case reports, reviews or meta-analyses were excluded. Outcomes of interest were molecular pathogenesis, clinical presentation, differential diagnosis, treatment, follow-up and overall survival. Study quality was evaluated using the Newcastle-Ottawa Scale for observational studies. This review included 75 studies from 17 countries, reporting on more than 3000 patients with parathyroid carcinoma. CDC73 mutation has been recognised as playing a pivotal role in molecular pathogenesis. Parathyroid carcinoma typically presents with markedly increased calcium and parathyroid hormone levels. The most frequently described symptoms were bone and muscle pain or weakness. En bloc resection remains the gold standard for the surgical approach. The 5-year overall survival ranged from 60 to 93%, with resistant hypercalcaemia a significant cause of mortality. Emerging evidence indicating that targeted therapy, based on molecular biomarkers, presents a novel treatment option. The rarity of PC and need for personalised treatment warrant multidisciplinary management in a 'centre of excellence' with a track record in PC management

Roux-en-Y Gastric Bypass Increases Glycemic Variability and Time in Hypoglycemia in Patients With Obesity and Prediabetes or Type 2 Diabetes: A Prospective Cohort Study

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) is an established treatment for type 2 diabetes and obesity. The study objective was to establish RYGB's effects on glycemic variability (GV) and hypoglycemia. RESEARCH DESIGN AND METHODS: This was a prospective observational study of 10 participants with obesity and prediabetes or type 2 diabetes who underwent RYGB. Patients were studied before RYGB (Pre) and 1 month, 1 year, and 2 years postsurgery with continuous glucose measurement (CGM). A mixed-meal test (MMT) was conducted at Pre, 1 month, and 1 year. RESULTS: After RYGB, mean CGM decreased (at 1 month, 1 year, and 2 years), and GV increased (at 1 year and 2 years). Five of the 10 participants had a percent time in range (%TIR) <3.0 mmol/L (54 mg/dL) greater than the international consensus target of 1% at 1 or 2 years. Peak glucagon-like peptide-1 (GLP-1) and glucagon area under the curve during MMT were positively and negatively associated, respectively, with contemporaneous %TIR <3.0 mmol/L. CONCLUSIONS: Patients undergoing RYGB are at risk for development of postbariatric hypoglycemia due to a combination of reduced mean glucose, increased GV, and increased GLP-1 response

Effect of using reporting guidelines during peer review on quality of final manuscripts submitted to a biomedical journal: masked randomised trial

Objective To investigate the effect of an additional review based on reporting guidelines such as STROBE and CONSORT on quality of manuscripts