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1.
GE Port J Gastroenterol ; 31(5): 370-376, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39360176

RESUMO

Sleeve gastrectomy (SG) can be aided by the addition of a calibration silicone ring, banded SG (BSG). It provides better weight loss than non-banded SG but with higher rate of adverse events. The aim of this case report is to further contribute to the knowledge of how to endoscopically manage these patients by placing a new esophageal stent (Luso-Cor®). A 58-year-old female with grade III obesity (weight 110 kg, BMI: 45.2 kg/m2) underwent SG in 2013. Due to the limited weight loss, a surgical calibration silicon ring was placed in 2017. In the following months, she developed recurrent and abundant postprandial regurgitation, achieving a minimum weight of 66 kg (BMI: 27.1 kg/m2). Gastroesophageal transit showed a stricture at the junction of the gastric corpus and antrum, causing gastric outlet obstruction. Endoscopy identified a regular luminal stenosis with normal mucosa, which allowed easy passage of the endoscope with slight pressure. Two sessions of endoscopic dilatation were performed, first with an 18-mm through-the-scope balloon and later with a 30-mm pneumatic balloon without symptomatic relief. A two-step endoscopic therapeutic approach was proposed to first promote intragastric ring erosion by placing a new partially covered metallic stent, Luso-Cor® esophageal stent 30/20/30 × 240 mm, and subsequently retrieve the stent, followed by cutting and retrieval of the ring. The proximal flare with a 30 mm diameter was placed in the distal esophagus and the distal edge in the prepyloric antrum. However, 2 weeks later, she complained of vomiting and abdominal fullness. Complete migration of the proximal flare of the stent into the remnant gastric fundus was seen on the contrast study. Endoscopy was performed, and the stent was easily removed. A blue calibration ring, partially eroded into the gastric lumen, was observed at the site of gastric tube stenosis. After stent removal, the patient was asymptomatic, and so conservative follow-up was decided. A follow-up endoscopy, performed 5 months later, showed complete reepithelization of the eroded ring. The patient remains asymptomatic after 3 years of follow-up and has regained weight up to 76 kg (BMI: 31.2 kg/m2). The efficacy of endoscopy on the management of ring-related adverse events has been previously reported. Small-case series describe the use of multiple pneumatic dilations or the deployment of plastic or covered metallic stents to cause erosion of the overlying mucosa, followed by cutting and retrieval of the ring. In conclusion, we believe that the mural pressure exerted by the Luso-Cor® esophageal stent, in the limited period it remained in situ, was sufficient to relieve the luminal pressure of the silicon ring, realigning the ring with the remnant gastric tube. This rare clinical entity highlights the potential role of specific metallic stents in the management of these patients.


A cirurgia bariátrica de gastrectomia vertical (sleeve gástrico) pode ser complementada pela adição de um anel restritivo de silicone ­ sleeve gástrico com anel de silastic. O acréscimo deste anel promove uma maior perda de peso, no entanto está associado a maior risco de eventos adversos. O objetivo da apresentação deste caso é contribuir para as diferentes técnicas úteis no tratamento das complicações relacionadas com o anel, através da utilização de uma prótese esofágica (Luso-Cor®).Uma doente de 58 anos, com obesidade grau III (peso 110 kg, IMC 45,2 kg/m2), foi submetida a um sleeve gástrico em 2013. Não apresentou perda de peso favorável e, em 2017, foi colocado um anel de silicone rodeando o tubo gástrico. Nos meses seguintes desenvolveu regurgitação pós-prandial recorrente e abundante, alcançando um peso mínimo de 66 kg (IMC 27,1 kg/m2). Realizou um trânsito gastroesofágico que revelou uma estenose na junção do corpo com o antro gástrico, com evidência de obstrução do esvaziamento gástrico. A endoscopia digestiva alta identificou uma estenose regular recoberta por mucosa sem lesões, com passagem do aparelho após pressão ligeira. Foram realizadas duas sessões de dilatação, inicialmente com balão trough-the-scope de 18 mm e posteriormente com balão pneumático de 30 mm. Os sintomas persistiram e, por esse motivo, foi decidido uma abordagem em dois tempos: primeiro promover a erosão intragástrica da banda para depois a seccionar e remover intraluminalmente. Nesse sentido, foi colocada uma prótese metálica esofágica parcialmente coberta, Luso-Cor® 30/20/30 × 240 mm. O segmento proximal da prótese com 30 mm de diâmetro foi colocado no esófago e o bordo distal da prótese ficou no antro pré-pilórico. No entanto, duas semanas depois, a doente queixou-se de vómitos e enfartamento precoce. O estudo radiográfico com contraste revelou migração distal da prótese, com deslocamento do segmento proximal para o corpo gástrico remanescente. A prótese foi removida endoscopicamente sem dificuldade e, na região da estenose, foi observado o anel de silicone parcialmente erosionado para o lúmen gástrico. Após remoção da prótese a doente evoluiu favoravelmente, sem novos sintomas, e, por esse motivo, foi decido seguimento sem novas intervenções. A endoscopia de seguimento, realizada cinco meses após, demonstrou reepitelização completa do anel parcialmente erosionado. A doente permanece assintomática após três anos de seguimento e voltou a ganhar peso (peso atual 76 kg, IMC 31,2 kg/m2). A eficácia da resolução endoscópica de estenoses relacionadas com anel de silicone no sleeve gástrico já foi relatada. Pequenas séries de casos utilizaram múltiplas sessões de dilatação com balão pneumático ou colocação de próteses plásticas ou metálicas cobertas para promover erosão intragástrica do anel e sua remoção. Acreditamos que a pressão mural exercida pela prótese Luso-Cor®, no curto tempo em que permaneceu in situ, foi suficiente para aliviar a obstrução, realinhando o seu diâmetro com o restante tubo gástrico. Através do relato desta entidade clínica rara, esperamos contribuir para o conhecimento das próteses metálicas específicas para o manejo destes doentes.

2.
Arq Bras Cir Dig ; 37: e1819, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39230119

RESUMO

Insulinomas are rare neoplasms of the endocrine pancreas. Minimally invasive treatment options for insulinomas have gained prominence, replacing surgical resection due to its associated morbidity and mortality. Radiofrequency ablation (RFA) has emerged as a relevant treatment option. We present a case of a female patient with neuroglycopenic symptoms and severe hypoglycemic crises. The abdominal magnetic resonance imaging (MRI) showed a small nodular lesion in the pancreatic body. Laparotomy was performed, followed by RFA using a 15-mm active-tipped needle. No complications transpired, and no hypoglycemic episodes were observed during 12 months of follow-up.


Assuntos
Insulinoma , Laparotomia , Neoplasias Pancreáticas , Ablação por Radiofrequência , Humanos , Insulinoma/cirurgia , Insulinoma/diagnóstico por imagem , Feminino , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/diagnóstico por imagem , Ablação por Radiofrequência/métodos , Pessoa de Meia-Idade
3.
Artigo em Inglês | MEDLINE | ID: mdl-39332496

RESUMO

CLINICAL IMPLICATIONS: Female X-linked chronic granulomatous disease (XL-CGD) carriers may develop severe clinical disease including infections with CGD-defining pathogens and inflammatory disorders. Similar to males with XL-CGD, female carriers warrant ongoing evaluation and prophylaxis where indicated.

4.
Hum Reprod Open ; 2024(3): hoae049, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39188568

RESUMO

STUDY QUESTION: Can human pre- and peri-pubertal testicular cells obtained from childhood cancer patients, previously treated with chemotherapy, form testicular organoids (TOs)? SUMMARY ANSWER: Organoid formation from testicular tissue collected from childhood cancer patients positively correlates with SRY-Box transcription factor 9 (SOX9) expression in Sertoli cells, which in turn negatively correlates with previous exposure to alkylating chemotherapy. WHAT IS KNOWN ALREADY: Pre- and peri-pubertal boys exposed to highly gonadotoxic therapies can only safeguard their fertility potential through testicular tissue cryopreservation. Today, there is no established clinical tool to restore fertility using these testicular samples. Organoids hold promise in providing fundamental early insights in creating such platforms. However, the generation of TOs that closely resemble the innate testis, to enable a thorough monitoring of the necessary steps for germ cell differentiation and somatic functionalities, remains a challenge. STUDY DESIGN SIZE DURATION: We used a Matrigel-based three-layer gradient culture system to generate human TOs and to reveal whether chemotherapy exposure affects TO formation capacity and the functionality of pre- and peri-pubertal testicular somatic cells. Testicular cells of 11 boys (aged 7.7 ± 4.1 (mean ± SD) years) were assessed for TO formation in relation to previous chemotherapy exposure and SOX9 expression in histological sections of paraffin-embedded testicular tissue samples collected on the day of biopsy and compared with testicular tissue samples obtained from 28 consecutive patients (aged 6.9 ± 3.8 (mean ± SD) years). All 39 patients were part of the fertility preservation project NORDFERTIL; an additional 10 samples (from boys aged 5.5 ± 3.5 (mean ± SD) years, without an underlying pathology) in an internal biobank collection were used as controls. PARTICIPANTS/MATERIALS SETTING METHODS: We obtained 49 testicular tissue samples from boys aged 0.8-13.4 years. Fresh samples (n = 11) were dissociated into single-cell suspensions and applied to a three-layer gradient culture system for organoid formation. Histological sections of another 28 samples obtained as part of the fertility preservation project NORDFERTIL, and 10 samples from a sample collection of a pathology biobank were used to evaluate the effects of prior exposure to alkylating agents on testicular samples. Testicular organoid formation was defined based on morphological features, such as compartmentalized structures showing cord formation, and protein expression of testicular cell-specific markers for germ and somatic cells was evaluated via immunohistochemical staining. Hormone secretion was analysed by specific enzyme-linked immunosorbent assays for testosterone and anti-Müllerian hormone (AMH) production. MAIN RESULTS AND THE ROLE OF CHANCE: Our results revealed that 4 out of 11 prepubertal testicular samples formed TOs that showed compartmentalized cord-like structures surrounded by interstitial-like areas and increasing levels of both testosterone as well as AMH over a 7-day culture period. We observed that SOX9 expression was correlated positively with TO formation. Moreover, exposure to alkylating agents before biopsy was inversely correlated with SOX9 expression (P = 0.006). LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: Due to the limited amount of material available, only 11 out of the 39 pre- and peri-pubertal testicular tissue samples could be used for the organoid formation experiments. The testicular tissue samples obtained from a sample collection of the internal biobank of Department of Pathology, Karolinska University Hospital were considered normal and included in the study if no testicular pathology was reported. However, detailed information regarding previous medical treatments and/or testicular volumes of the patients included in this biobank was not available. WIDER IMPLICATIONS OF THE FINDINGS: Our observations suggest that SOX9 expression may serve as a putative indicator of TO formation, indicating a critical role of Sertoli cells in promoting organoid formation, seminiferous tubule integrity, and testicular function in pre- and peri-pubertal testicular tissue. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grants from the Swedish Childhood Cancer Foundation (PR2019-0123; PR2022-0115; TJ2020-0023) (J.-B.S.), Finnish Cancer Society (K.J.), Finnish Foundation for Paediatric Research (K.J.), Swedish Research Council (2018-03094; 2021-02107) (J.-B.S.), and Birgitta and Carl-Axel Rydbeck's Research Grant for Paediatric Research (2020-00348; 2020-00335; 2021-00073; 2022-00317) (J.-B.S. and K.J.). Y.C. and Y.Y. received a scholarship from the Chinese Scholarship Council. J.P.A-L. was supported by a Starting Grant in Medicine and Health (2022-01467) from the Swedish Research Council. R.T.M. was supported by a UKRI Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health was supported by an MRC Centre Grant (MR/N022556/1). The authors declare no competing interests.

5.
ACS Omega ; 9(27): 29499-29515, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39005768

RESUMO

Radiotherapy (RT) is the established noninvasive treatment for glioblastoma (GBM), a highly aggressive malignancy. However, its effectiveness in improving patient survival remains limited due to the radioresistant nature of GBM. Metal-based nanostructures have emerged as promising strategies to enhance RT efficacy. Among them, titanate nanotubes (TNTs) have gained significant attention due to their biocompatibility and cost-effectiveness. This study aimed to synthesize zinc-modified TNTs (ZnTNT) from sodium TNTs (NaTNT), in addition to characterizing the formed nanostructures and evaluating their radiosensitization effects in GBM cells (U87 and U251). Hydrothermal synthesis was employed to fabricate the TNTs, which were characterized using various techniques, including transmission electron microscopy (TEM), energy-dispersive spectroscopy, scanning-transmission mode, Fourier-transform infrared spectroscopy, ICP-MS (inductively coupled plasma mass spectrometry), X-ray photoelectron spectroscopy, and zeta potential analysis. Cytotoxicity was evaluated in healthy (Vero) and GBM (U87 and U251) cells by the MTT assay, while the internalization of TNTs was observed through TEM imaging and ICP-MS. The radiosensitivity of ZnTNT and NaTNT combined with 5 Gy was evaluated using clonogenic assays. Monte Carlo simulations using the MCNP6.2 code were performed to determine the deposited dose in the culture medium for RT scenarios involving TNT clusters and cells. The results demonstrated differences in the dose deposition values between the scenarios with and without TNTs. The study revealed that ZnTNT interfered with clonogenic integrity, suggesting its potential as a powerful tool for GBM treatment.

6.
Basic Clin Pharmacol Toxicol ; 135(3): 250-270, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38989660

RESUMO

Potassium iodide has demonstrated several therapeutic applications over time, being the choice for shielding the thyroid during radiation emergencies involving radioiodine release. Amidst the ongoing military conflict between Ukraine and Russia and the growing concern regarding the potential deployment of nuclear weapons, there has been a surge in the demand for potassium iodide across Europe. This work aimed to comprehensively review the current knowledge regarding the pharmacology, physiology, adverse effects, the protective role in reducing the risk of thyroid cancer and recommendations for potassium iodide use during radiation emergencies. Evidence on adverse effects is scarce, as potassium iodide is generally well-tolerated. Guidelines for thyroid blocking with potassium iodide during radiation emergencies suggest that, among populations vulnerable to radioiodine exposure, the benefits of potassium iodide outweigh the risks of adverse effects. Controversial topics surrounding the utilization of potassium iodide in radiation emergencies include the prophylaxis in iodine-deficient regions and following the detonation of dirty bombs, whether granule formulations versus tablets should be used and mental health concerns. Although the rise in demand seems to be a justified security measure, it is essential to recognize that potassium iodide protects the thyroid from radioiodine and does not impact the body's absorption of other radioactive materials or defend against external radiation exposure.


Assuntos
Iodeto de Potássio , Iodeto de Potássio/uso terapêutico , Humanos , Ucrânia , Europa (Continente) , Glândula Tireoide/efeitos da radiação , Glândula Tireoide/efeitos dos fármacos , Radioisótopos do Iodo/efeitos adversos , Protetores contra Radiação/uso terapêutico , Neoplasias da Glândula Tireoide , Lesões por Radiação , Animais , Armas Nucleares
8.
Rev Esp Enferm Dig ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767010

RESUMO

Flexible esophagogastroduodenoscopy is the gold standard for removing FB of the upper gastrointestinal tract. However large sharped FB are usually challenging to remove and are the subtype that most often requires surgery. We describe a case of a patient with a dental prothesis impacted in the proximal oesophagus. After a failed conventional approach, we made a successful attempt with two regular scopes with two independent operators.

9.
Pharmaceutics ; 16(4)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38675115

RESUMO

The Serra da Estrela Natural Park (NPSE) in Portugal stands out as a well-preserved region abundant in medicinal plants, particularly known for their pharmaceutical applications in diabetes prevention and treatment. This comprehensive review explores these plants' botanical diversity, traditional uses, pharmacological applications, and chemical composition. The NPSE boast a rich diversity with 138 medicinal plants across 55 families identified as traditionally and pharmacologically used against diabetes globally. Notably, the Asteraceae and Lamiaceae families are prevalent in antidiabetic applications. In vitro studies have revealed their significant inhibition of carbohydrate-metabolizing enzymes, and certain plant co-products regulate genes involved in carbohydrate metabolism and insulin secretion. In vivo trials have demonstrated antidiabetic effects, including glycaemia regulation, insulin secretion, antioxidant activity, and lipid profile modulation. Medicinal plants in NPSE exhibit various activities beyond antidiabetic, such as antioxidant, anti-inflammatory, antibacterial, anti-cancer, and more. Chemical analyses have identified over fifty compounds like phenolic acids, flavonoids, terpenoids, and polysaccharides responsible for their efficacy against diabetes. These findings underscore the potential of NPSE medicinal plants as antidiabetic candidates, urging further research to develop effective plant-based antidiabetic drugs, beverages, and supplements.

10.
Food Res Int ; 181: 114083, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38448094

RESUMO

Malnutrition is considered one of the major public health problems worldwide and negatively affects the growth, development and learning of schoolchildren. This study developed and evaluated a fermented milk drink with added Umbu (Spondias tuberosa) pulp in the weight gain and renutrition of mice submitted to malnutrition by calorie restriction, and in malnourished children. The supplementation with this fermented milk drink contributed to an increase of 7.2 % in body weight, and 64.3 % in albumin, and a reduction of 35 % in cholesterol in malnourished mice. In humans, a group of nine malnourished children consumed a daily 200 mL serving of the milk drink (for 60 days). For humans, the fermented milk drink allowed an increase of 16.5 % in body weight, and 20.9 % in body mass index in malnourished children. In conclusion, fermented milk drink has a positive effect on the re-nutrition of malnourished mice and helps to improve the nutritional status of malnourished children.


Assuntos
Anacardiaceae , Desnutrição , Criança , Humanos , Animais , Camundongos , Soro do Leite , Leite , Estado Nutricional , Proteínas do Soro do Leite , Aumento de Peso , Peso Corporal
11.
Nat Protoc ; 19(4): 1149-1182, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38302732

RESUMO

Human primordial germ cells (hPGCs), the precursors of eggs and sperm, start their complex development shortly after specification and during their migration to the primitive gonads. Here, we describe protocols for specifying hPGC-like cells (hPGCLCs) from resetting precursors and progressing them with the support of human hindgut organoids. Resetting hPGCLCs (rhPGCLCs) are specified from human embryonic stem cells (hESCs) transitioning from the primed into the naive state of pluripotency. Hindgut organoids are also derived from hESCs after a sequential differentiation into a posterior endoderm/hindgut fate. Both rhPGCLCs and hindgut organoids are combined and co-cultured for 25 d. The entire procedure takes ~1.5 months and can be successfully implemented by a doctoral or graduate student with basic skills and experience in hESC cultures. The co-culture system supports the progression of rhPGCLCs at a developmental timing analogous to that observed in vivo. Compared with previously developed hPGCLC progression protocols, which depend on co-cultures with mouse embryonic gonadal tissue, our co-culture system represents a developmentally relevant model closer to the environment that hPGCs first encounter after specification. Together with the potential for investigations of events during hPGC specification and early development, these protocols provide a practical approach to designing efficient models for in vitro gametogenesis. Notably, the rhPGCLC-hindgut co-culture system can also be adapted to study failings in hPGC migration, which are associated with the etiology of some forms of infertility and germ cell tumors.


Assuntos
Endoderma , Sêmen , Humanos , Masculino , Animais , Camundongos , Células Germinativas , Diferenciação Celular , Organoides
13.
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1532970

RESUMO

O livro "Educação Física Menor" problematiza e propõe alternativas diante do chamado currículo cultural ou pós-crítico de Educação Física. Faz isso, a partir de dois gestos: problematizando algumas acepções culturalistas e almejando a singularização ou a minoração das perspectivas "maiores" do componente, a partir de uma conceitualização das filosofias de pensadores como Foucault, Deleuze e Guattari.


The book "Minor Physical Education" problematizes and proposes alternatives to the so-called cultural or post-critical curriculum of Physical Education. It does this from two gestures: problematizing some culturalist acceptations and aiming at the singularization or the minimization of the "major" perspectives of the component, from a conceptualization of the philosophies of thinkers such as Foucault, Deleuze and Guattari.


El libro "Educación Física Menor" problematiza y propone alternativas al llamado currículo cultural o postcrítico de la Educación Física. Lo hace a través de dos gestos: problematizando algunos conceptos culturalistas y apuntando a singularizar o disminuir las perspectivas "mayores" del componente, a partir de una conceptualización de las filosofías de pensadores como Foucault, Deleuze y Guattari.

14.
Rev. bras. entomol ; Rev. bras. entomol;68(3): e20240017, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1576061

RESUMO

ABSTRACT Xylem sap-feeding auchenorrhynchans, e.g. sharpshooters and spittlebugs (Hemiptera: Cicadellinae and Cercopoidea, respectively), are considered potential vectors of the xylem-limited bacterium Xylella fastidiosa, which is associated with olive leaf desiccation syndrome, a severe disease affecting olive orchards (Olea europaea L.) in the Mantiqueira mountain range region, southeastern Brazil. We evaluated, through faunal analysis, the composition and predominance of Cicadellinae and Cercopoidea species collected fortnightly over two years with yellow sticky cards in eight olive orchards distributed along an altitudinal gradient in the states of São Paulo and Minas Gerais. A high diversity of Cicadellinae (64 species) and Cercopoidea (10 species) was found in the orchards, with 20 of them considered predominant. Clastoptera sp. 1, Macugonalia cavifrons, and Scopogonalia paula were the most representative among the predominant species. We also found out that the trap position on the olive tree canopy at a height of 0.8 m above ground is more efficient than at 1.6 m for capturing the majority of Cicadellinae and Cercopoidea species associated with olive orchards.

15.
Cureus ; 15(10): e46723, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38022239

RESUMO

Severe coronavirus disease 2019 (COVID-19) is known to manifest in two phases, with a potential worsening in the second week. The pathophysiology of the first phase is expected to be heavily influenced by viral replication while the second phase is thought to be primarily characterized by systemic inflammation. We present the case of a 42-year-old man hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with a history of Philadelphia-positive chronic myeloid leukemia, diagnosed seven months earlier, proposed to bone marrow allotransplantation after refractory imatinib and dasatinib treatment. After an initial clinical and laboratory improvement, the patient got worse. A pulmonary CT scan showed worsening ground-glass opacities and multiple bilateral consolidations. Neutropenia was resolved, and on the same day, the patient developed progressive respiratory failure with rapidly increasing oxygen demand and distributive shock, requiring mechanical ventilation. Acute respiratory distress syndrome (ARDS) induced by paradoxical COVID-19 immune reconstitution inflammatory syndrome (IRIS) following chemotherapy-induced aplasia was equated. High-dose corticosteroid therapy was rapidly effective. IRIS occurs in patients with severe immunosuppression in response to rapid immune reconstitution and results in an uncontrolled inflammatory response to infectious agents that cause tissue damage. The inflammation associated with both IRIS and COVID-19 shares a common path in terms of immunological response. We hypothesize that in our patient, a hyperinflammation overlap exerted a synergistic effect, leading to the worsening of the disease.

16.
Biomolecules ; 13(8)2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37627238

RESUMO

The intracerebroventricular (icv) injection of amyloid peptides (Aß) models Alzheimer's disease (AD) in mice, as typified by the onset within 15 days of deficits of memory and of hippocampal long-term potentiation (LTP) that are prevented by the blockade of adenosine A2A receptors (A2AR). Since A2AR overfunction is sufficient to trigger memory deficits, we tested if A2AR were upregulated in hippocampal synapses before the onset of memory deficits to support the hypothesis that A2AR overfunction could be a trigger of AD. Six to eight days after Aß-icv injection, mice displayed no alterations of hippocampal dependent memory; however, they presented an increased excitability of hippocampal synapses, a slight increase in LTP magnitude in Schaffer fiber-CA1 pyramid synapses and an increased density of A2AR in hippocampal synapses. A2AR blockade with SCH58261 (50 nM) normalized excitability and LTP in hippocampal slices from mice sacrificed 7-8 days after Aß-icv injection. Fifteen days after Aß-icv injection, mice displayed evident deficits of hippocampal-dependent memory deterioration, with reduced hippocampal CA1 LTP but no hyperexcitability and a sustained increase in synaptic A2AR, which blockade restored LTP magnitude. This shows that the upregulation of synaptic A2AR precedes the onset of deterioration of memory and of hippocampal synaptic plasticity, supporting the hypothesis that the overfunction of synaptic A2AR could be a trigger of memory deterioration in AD.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Regulação para Cima , Doença de Alzheimer/induzido quimicamente , Receptor A2A de Adenosina , Plasticidade Neuronal , Adenosina , Transtornos da Memória/induzido quimicamente
17.
Foods ; 12(14)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37509830

RESUMO

Oligomers are a particular category of non-intentionally added substances (NIAS) that may be present in food contact materials (FCMs), such as polyethylene terephthalate (PET), and consequently migrate into foods. Here, an ultra-high-pressure liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-qTOF-MS) method was developed for the analysis of 1st series cyclic PET oligomers in virgin olive oil (VOO) following a QuEChERS clean-up protocol. Oligomer migration was evaluated with two different migration experiments using bottles from virgin and recycled PET: one with VOO samples stored in household conditions for a year and one using the food simulant D2 (95% v/v ethanol in water) at 60 °C for 10 days. Calibration curves were constructed with fortified VOO samples, with the LOQs ranging from 10 to 50 µg L-1 and the recoveries ranging from 86.6 to 113.0%. Results showed no migration of PET oligomers in VOO. However, in the simulated study, significant amounts of all oligomers were detected, with the migration of cyclic PET trimers from recycled bottles being the most abundant. Additional substances were tentatively identified as linear derivatives of PET oligomers. Again, open trimer structures in recycled bottles gave the most significant signals.

18.
Neurosci Lett ; 808: 137292, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37156440

RESUMO

Caffeic acid is a polyphenolic compound present in a vast array of dietary components. We previously showed that caffeic acid reduces the burden of brain ischemia joining evidence by others that it can attenuate different brain diseases. However, it is unknown if caffeic acid affects information processing in neuronal networks. Thus, we now used electrophysiological recordings in mouse hippocampal slices to test if caffeic acid directly affected synaptic transmission, plasticity and dysfunction caused by oxygen-glucose deprivation (OGD), an in vitro ischemia model. Caffeic acid (1-10 µM) was devoid of effect on synaptic transmission and paired-pulse facilitation in Schaffer collaterals-CA1 pyramidal synapses. Also, the magnitude of either hippocampal long-term potentiation (LTP) or the subsequent depotentiation were not significantly modified by 10 µM caffeic acid. However, caffeic acid (10 µM) increased the recovery of synaptic transmission upon re-oxygenation following 7 min of OGD. Furthermore, caffeic acid (10 µM) also recovered plasticity after OGD, as heralded by the increased magnitude of LTP after exposure. These findings show that caffeic acid does not directly affect synaptic transmission and plasticity but can indirectly affect other cellular targets to correct synaptic dysfunction. Unraveling the molecular mechanisms of action of caffeic acid may allow the design of hitherto unrecognized novel neuroprotective strategies.


Assuntos
Hipocampo , Transmissão Sináptica , Camundongos , Animais , Transmissão Sináptica/fisiologia , Potenciação de Longa Duração/fisiologia , Isquemia , Plasticidade Neuronal/fisiologia
19.
Biomolecules ; 13(4)2023 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-37189461

RESUMO

Adenosine operates a modulation system fine-tuning the efficiency of synaptic transmission and plasticity through A1 and A2A receptors (A1R, A2AR), respectively. Supramaximal activation of A1R can block hippocampal synaptic transmission, and the tonic engagement of A1R-mediated inhibition is increased with increased frequency of nerve stimulation. This is compatible with an activity-dependent increase in extracellular adenosine in hippocampal excitatory synapses, which can reach levels sufficient to block synaptic transmission. We now report that A2AR activation decreases A1R-medated inhibition of synaptic transmission, with particular relevance during high-frequency-induced long-term potentiation (LTP). Thus, whereas the A1R antagonist DPCPX (50 nM) was devoid of effects on LTP magnitude, the addition of an A2AR antagonist SCH58261 (50 nM) allowed a facilitatory effect of DPCPX on LTP to be revealed. Additionally, the activation of A2AR with CGS21680 (30 nM) decreased the potency of the A1R agonist CPA (6-60 nM) to inhibit hippocampal synaptic transmission in a manner prevented by SCH58261. These observations show that A2AR play a key role in dampening A1R during high-frequency induction of hippocampal LTP. This provides a new framework for understanding how the powerful adenosine A1R-mediated inhibition of excitatory transmission can be controlled to allow the implementation of hippocampal LTP.


Assuntos
Potenciação de Longa Duração , Receptor A2A de Adenosina , Adenosina/farmacologia , Hipocampo/metabolismo , Receptor A2A de Adenosina/metabolismo , Transmissão Sináptica , Animais , Camundongos
20.
Cureus ; 15(3): e35687, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37012940

RESUMO

Brugada syndrome (BrS) is a congenital channelopathy associated with an increased risk of malignant ventricular arrhythmias and sudden cardiac death in individuals without any structural cardiopathy. Brugada phenocopies (BrPs) are clinical entities that present electrocardiographic patterns similar to those of BrS that are elicited only under transitory pathophysiological conditions, with normalization of the ECG pattern after the resolution of those conditions. We present a rare case of BrP due to intracranial hemorrhage. We also present and discuss the diagnostic criteria for BrPs and their application to this case.

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