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1.
Glia ; 72(12): 2217-2230, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39188024

RESUMO

Astrocytes play a multifaceted role regulating brain glucose metabolism, ion homeostasis, neurotransmitters clearance, and water dynamics being essential in supporting synaptic function. Under different pathological conditions such as brain stroke, epilepsy, and neurodegenerative disorders, excitotoxicity plays a crucial role, however, the contribution of astrocytic activity in protecting neurons from excitotoxicity-induced damage is yet to be fully understood. In this work, we evaluated the effect of astrocytic activation by Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) on brain glucose metabolism in wild-type (WT) mice, and we investigated the effects of sustained astrocyte activation following an insult induced by intrahippocampal (iHPC) kainic acid (KA) injection using 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) positron emission tomography (PET) imaging, along with behavioral test, nuclear magnetic resonance (NMR) spectroscopy and histochemistry. Astrocytic Ca2+ activation increased the 18F-FDG uptake, but this effect was not found when the study was performed in knock out mice for type-2 inositol 1,4,5-trisphosphate receptor (Ip3r2-/-) nor in floxed mice to abolish glucose transporter 1 (GLUT1) expression in hippocampal astrocytes (GLUT1ΔGFAP). Sustained astrocyte activation after KA injection reversed the brain glucose hypometabolism, restored hippocampal function, prevented neuronal death, and increased hippocampal GABA levels. The findings of our study indicate that astrocytic GLUT1 function is crucial for regulating brain glucose metabolism. Astrocytic Ca2+ activation has been shown to promote adaptive changes that significantly contribute to mitigating the effects of KA-induced damage. This evidence suggests a protective role of activated astrocytes against KA-induced excitotoxicity.


Assuntos
Astrócitos , Hipocampo , Ácido Caínico , Camundongos Endogâmicos C57BL , Animais , Ácido Caínico/toxicidade , Astrócitos/metabolismo , Astrócitos/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Camundongos , Masculino , Cálcio/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/genética , Agonistas de Aminoácidos Excitatórios/toxicidade , Glucose/metabolismo , Camundongos Knockout , Fluordesoxiglucose F18/metabolismo
2.
Pediatr Allergy Immunol ; 34 Suppl 28: e13854, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37186333

RESUMO

Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.


Assuntos
Hipersensibilidade , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Alérgenos , Imunoglobulina E
3.
Planta Med ; 89(4): 364-376, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36130709

RESUMO

Numerous preclinical studies provide evidence that curcumin, a polyphenolic phytochemical extracted from Curcuma longa (turmeric) has neuroprotective, anti-inflammatory and antioxidant properties against various neurological disorders. Curcumin neuroprotective effects have been reported in different animal models of epilepsy, but its potential effect attenuating brain glucose hypometabolism, considered as an early marker of epileptogenesis that occurs during the silent period following status epilepticus (SE), still has not been addressed. To this end, we used the lithium-pilocarpine rat model to induce SE. Curcumin was administered orally (300 mg/kg/day, for 17 days). Brain glucose metabolism was evaluated in vivo by 2-deoxy-2-[18F]Fluoro-D-Glucose ([18F]FDG) positron emission tomography (PET). In addition, hippocampal integrity, neurodegeneration, microglia-mediated neuroinflammation, and reactive astrogliosis were evaluated as markers of brain damage. SE resulted in brain glucose hypometabolism accompanied by body weight (BW) loss, hippocampal neuronal damage, and neuroinflammation. Curcumin did not reduce the latency time to the SE onset, nor the mortality rate associated with SE. Nevertheless, it reduced the number of seizures, and in the surviving rats, curcumin protected BW and attenuated the short-term glucose brain hypometabolism as well as the signs of neuronal damage and neuroinflammation induced by the SE. Overall, our results support the potential adaptogen-like effects of curcumin attenuating key features of SE-induced brain damage.


Assuntos
Curcumina , Estado Epiléptico , Ratos , Animais , Curcumina/farmacologia , Curcumina/metabolismo , Ratos Sprague-Dawley , Doenças Neuroinflamatórias , Encéfalo , Hipocampo , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodos , Glucose/farmacologia , Pilocarpina/metabolismo , Pilocarpina/farmacologia , Modelos Animais de Doenças
4.
J Integr Neurosci ; 22(3): 75, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37258443

RESUMO

BACKGROUND: Epilepsy is one of the most common neurologic diseases, and around 30% of all epilepsies, particularly the temporal lobe epilepsy (TLE), are highly refractory to current pharmacological treatments. Abnormal synchronic neuronal activity, brain glucose metabolism alterations, neurodegeneration and neuroinflammation are features of epilepsy. Further, neuroinflammation has been shown to contribute to dysregulation of neuronal excitability and the progression of epileptogenesis. Flufenamic acid (FLU), a non-steroidal anti-inflammatory drug, is also characterized by its wide properties as a dose-dependent ion channel modulator. In this context, in vitro studies have shown that it abolishes seizure-like events in neocortical slices stimulated with a gamma-aminobutyric acid A (GABAA) receptor blocker. However, little is known about its effects in animal models. Thus, our goal was to assess the efficacy and safety of a relatively high dose of FLU in the lithium-pilocarpine rat model of status epilepticus (SE). This animal model reproduces many behavioral and neurobiological features of TLE such as short-term brain hypometabolism, severe hippocampal neurodegeneration and inflammation reflected by a marked reactive astrogliosis. METHODS: FLU (100 mg/kg, i.p.) was administered to adult male rats, 150 min before SE induced by pilocarpine. Three days after the SE, brain glucose metabolism was assessed by 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) positron emission tomography (PET). Markers of hippocampal integrity, neurodegeneration and reactive astrogliosis were also evaluated. RESULTS: FLU neither prevented the occurrence of the SE nor affected brain glucose hypometabolism as assessed by [18F]FDG PET. Regarding the neurohistochemical studies, FLU neither prevented neuronal damage nor hippocampal reactive astrogliosis. On the contrary, FLU increased the mortality rate and negatively affected body weight in the rats that survived the SE. CONCLUSIONS: Our results do not support an acute anticonvulsant effect of a single dose of FLU. Besides, FLU did not show short-term neuroprotective or anti-inflammatory effects in the rat lithium-pilocarpine model of SE. Moreover, at the dose administered, FLU resulted in deleterious effects.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Estado Epiléptico , Ratos , Masculino , Animais , Lítio/efeitos adversos , Pilocarpina/efeitos adversos , Ácido Flufenâmico/metabolismo , Ácido Flufenâmico/farmacologia , Ácido Flufenâmico/uso terapêutico , Ratos Sprague-Dawley , Fluordesoxiglucose F18/metabolismo , Fluordesoxiglucose F18/farmacologia , Fluordesoxiglucose F18/uso terapêutico , Gliose/metabolismo , Doenças Neuroinflamatórias , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/metabolismo , Epilepsia/metabolismo , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/tratamento farmacológico , Hipocampo/metabolismo , Glucose/metabolismo , Anti-Inflamatórios/efeitos adversos , Modelos Animais de Doenças
5.
Int J Mol Sci ; 23(9)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35563370

RESUMO

Plant-food allergy is an increasing problem, with nonspecific lipid transfer proteins (nsLTPs) triggering mild/severe reactions. Pru p 3 is the major sensitizer in LTP food allergy (FA). However, in vivo and in vitro diagnosis is hampered by the need for differentiating between asymptomatic sensitization and allergy with clinical relevance. The basophil activation test (BAT) is an ex vivo method able to identify specific IgE related to the allergic response. Thus, we aimed to establish the value of BAT in a precise diagnosis of LTP-allergic patients. Ninety-two individuals with peach allergy sensitized to LTP, Pru p 3, were finally included, and 40.2% of them had symptoms to peanut (n = 37). In addition, 16 healthy subjects were recruited. BAT was performed with Pru p 3 and Ara h 9 (peanut LTP) at seven ten-fold concentrations, and was evaluated by flow cytometry, measuring the percentage of CD63 (%CD63+) and CD203c (%CD203chigh) cells, basophil allergen threshold sensitivity (CD-Sens), and area under the dose−response curve (AUC). Significant changes in BAT parameters (%CD63+ and %CD203chigh) were found between the controls and patients. However, comparisons for %CD63+, %CD203chigh, AUC, and CD-Sens showed similar levels among patients with different symptoms. An optimal cut-off was established from ROC curves, showing a significant positive percentage of BAT in patients compared to controls and great values of sensitivity (>87.5%) and specificity (>85%). In addition, BAT showed differences in LTP-allergic patients tolerant to peanut using its corresponding LTP, Ara h 9. BAT can be used as a potential diagnostic tool for identifying LTP allergy and for differentiating peanut tolerance, although neither reactivity nor sensitivity can distinguish the severity of the clinical symptoms.


Assuntos
Teste de Degranulação de Basófilos , Hipersensibilidade Alimentar , Alérgenos/metabolismo , Arachis , Teste de Degranulação de Basófilos/métodos , Basófilos , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/metabolismo , Humanos , Imunoglobulina E/metabolismo
6.
J Sci Food Agric ; 102(1): 407-416, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34143900

RESUMO

BACKGROUND: Hydric stress affects the production of wheat (Triticum aestivum L.) worldwide, making some tools necessary to cope with the decrease in rainfall. A sustainable alternative is the use of arbuscular mycorrhizal fungi (AMF) as biofertilisers. Here, we analysed the effects of AMF strains adapted or non-adapted to hyper-arid conditions on the phenolic profiles and antioxidant activities of wheat grains from two cultivars with contrasting tolerance to osmotic stress (Ilustre, moderately tolerant; and Maxi, tolerant) grown with and without hydric stress. RESULTS: Eight phenolic compounds were detected, apigenin-C-pentoside-C-hexoside I being the most abundant and showing an increase of 80.5% when inoculated with the fungus Funneliformis mosseae (FM) obtained from Atacama Desert under normal irrigation with respect to non-mycorrhizal (NM) plants. NM treatments were associated with higher grain yields. FM showed a noticeable effect on most phenolic compounds, with an increase up to 30.2% in apigenin-C-pentoside-C-hexoside III concentration under hydric stress with respect to normal irrigation, being also responsible for high antioxidant activities such as ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and DPPH (2,2-diphenyl-1-picrylhydrazyl) activities. CONCLUSION: Inoculation with FM adapted to hydric stress produced improvements in phenolics composition and antioxidant activities in grains from wheat plants growing under hydric stress conditions, improving their food quality and supporting the development of further studies to determine whether the use of adapted AMF could be a realistic tool to improve grain quality in a scenario of increasing hydric stress conditions. © 2021 Society of Chemical Industry.


Assuntos
Inoculantes Agrícolas/fisiologia , Antioxidantes/química , Fungos/fisiologia , Micorrizas/fisiologia , Fenóis/química , Sementes/química , Triticum/crescimento & desenvolvimento , Antioxidantes/metabolismo , Fenóis/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Sementes/microbiologia , Triticum/química , Triticum/metabolismo , Triticum/microbiologia
7.
Allergy ; 76(8): 2433-2446, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33655502

RESUMO

Sensitization to one or more non-specific lipid transfer proteins (nsLTPs), initially thought to exist mainly in southern Europe, is becoming accepted as a cause of allergic reactions to plant foods across Europe and beyond. The peach nsLTP allergen Pru p 3 is a dominant sensitizing allergen and peaches a common food trigger, although multiple foods can be involved. A frequent feature of reactions is the requirement for a cofactor (exercise, alcohol, non-steroidal anti-inflammatory drugs, Cannabis sativa) to be present for a food to elicit a reaction. The variability in the food and cofactor triggers makes it essential to include an allergy-focused diet and clinical history in the diagnostic workup. Testing on suspected food triggers should also establish whether sensitization to nsLTP is present, using purified or recombinant nsLTP allergens such as Pru p 3. The avoidance of known trigger foods and advice on cofactors is currently the main management for this condition. Studies on immunotherapy are promising, but it is unknown whether such treatments will be useful in populations where Pru p 3 is not the primary sensitizing allergen. Future research should focus on the mechanisms of cofactors, improving diagnostic accuracy and establishing the efficacy of immunotherapy.


Assuntos
Antígenos de Plantas , Hipersensibilidade Alimentar , Alérgenos , Reações Cruzadas , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/terapia , Humanos , Imunoglobulina E , Lipídeos , Proteínas de Plantas
8.
Allergy ; 75(12): 3228-3236, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32535938

RESUMO

BACKGROUND: Patients with peach allergy due to nsLTP sensitization constitute a heterogeneous group in terms of sensitization profile and severity. This could be due to the presence of additional allergies to pollens. The aim of this study was to analyse the clinical characteristics, sensitization profile and severity of reactions in peach-allergic patients sensitized to nsLTP from two Mediterranean areas with different pollen exposure. METHODS: Patients with diagnosis of LTP allergy from the Allergy Unit of Hospital Regional Universitario de Malaga (HRUM) and Hospital Clinic de Barcelona (HCB) were prospectively included and classified into two groups; (a) LTP-monoallergic: those that presented reaction only with peach and (b) LTP-Allergy: those that presented reaction with peach and at least another plant-food containing LTP. RESULTS: A total of 252 patients were included, 235 (93.2%) had LTP-syndrome and 17 (6.8%) were LTP-monoallergic. We found a higher percentage of anaphylaxis and delayed onset of symptoms in the LTP-monoallergic group (P = .02 and P = .04, respectively). Moreover, anaphylaxis was less frequent in patients with profilin sensitization (P = .03). The comparison of patients' data from HRUM with data from HCB showed differences in sensitization to olive tree pollen and profilin (P = .01 and P = .001, respectively). CONCLUSION: This study was undertaken to characterize two large group of subjects from to two regions with differing exposures to pollen. We found that more than 90% of peach-allergic patients in both populations evolved to LTP-Allergy and showed an early onset. Profilin sensitization could be more useful as a severity biomarker than the number of nsLTP, aeroallergen sensitizations or sIgE levels. This could provide clues regarding sensitization and severity patterns that might be relevant in other geographical areas.


Assuntos
Hipersensibilidade Alimentar , Prunus persica , Alérgenos , Antígenos de Plantas , Biomarcadores , Proteínas de Transporte , Reações Cruzadas , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/epidemiologia , Humanos , Proteínas de Plantas
10.
J Sci Food Agric ; 99(5): 2404-2410, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30357837

RESUMO

BACKGROUND: Strawberries are consumed worldwide. In Chile, strawberry production has been established in Andisols, were phosphorus is scarce. Traditional fertilization (TF) and organic fertilization (OF) have both been established there. This study examined their impact on the polyphenolic content of strawberries. RESULTS: Two anthocyanins were identified by high performance liquid chromatography with diode array detection coupled to mass spectrometry (HPLC-DAD-ESI-MS/MS). The average total anthocyanin concentrations were found to be 651 mg kg-1 fresh weight in 100% OF, which represents a 56% increase compared to fruits that were not fertilized. In the case of flavonols, only quercetin-rhamnoside was identified, and its concentration reached 14.6 mg kg-1 with 100% OF. The ascorbic acid concentration reached 0.54 g kg-1 in 50% TF (a 20% increase over fruits without fertilization, WF). The antioxidant activities slightly increased in the fruits subjected to TF and OF in comparison with WF treatment. CONCLUSION: These results support a management strategy for obtaining the best quality and potential beneficial effects in health by increasing anthocyanins and other polyphenols under OF. © 2018 Society of Chemical Industry.


Assuntos
Antocianinas/química , Antioxidantes/química , Produção Agrícola/métodos , Fertilizantes/análise , Flavonóis/química , Fragaria/química , Chile , Cromatografia Líquida de Alta Pressão , Fragaria/crescimento & desenvolvimento , Frutas/química , Frutas/crescimento & desenvolvimento , Agricultura Orgânica/métodos , Polifenóis/química
11.
J Sci Food Agric ; 99(3): 1397-1404, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30120790

RESUMO

BACKGROUND: The main methods used to increase the yield and quality of strawberry fruit produced in acidic soils with low P availability include root colonization by arbuscular mycorrhizal (AM) fungi and adjusting the type of P supplementation by means of traditional (TF) or organic (OF) fertilization, and adjusting nutrient doses. In this study, the antioxidant properties of strawberry fruit were evaluated under different treatments of fertilization (TF or OF) and different doses of P supplied at planting (0, 50 or 100% of the agronomic recommendation) and in the presence or absence of AM fungus as a bioinoculant. RESULTS: Fruits without fertilization treatments and with TF presented with higher anthocyanin concentrations. In general, higher values were obtained without AM colonization. However, spectrophotometric tests showed the highest activity and concentration in the AM-inoculated treatments. It is likely that phenolic compounds other than anthocyanins are present in the extracts. These other compounds could not be identified by the method used but could be detected by the Folin-Ciocalteu method. CONCLUSION: This study provides information that allows for improvements in strawberry fruit quality by agronomic management, with a potential beneficial effect on the health of consumers. © 2018 Society of Chemical Industry.


Assuntos
Inoculantes Agrícolas/fisiologia , Fertilizantes/análise , Fragaria/microbiologia , Frutas/química , Micorrizas/fisiologia , Antocianinas/análise , Antocianinas/metabolismo , Antioxidantes/análise , Antioxidantes/metabolismo , Fragaria/química , Fragaria/crescimento & desenvolvimento , Fragaria/metabolismo , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Nitrogênio/análise , Nitrogênio/metabolismo , Fenóis/análise , Fenóis/metabolismo , Fosfatos/análise , Fosfatos/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/microbiologia
15.
Exp Brain Res ; 233(3): 983-95, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25515088

RESUMO

Fluoxetine (FLX) is prescribed to treat depression and anxiety in adolescent patients. However, FLX has anxiogenic effects during the acute phase of treatment, and caution has been raised due to increased suicidal thinking and behavior. Herein, we sought to study in adolescent (35-day-old) male rats, the effects of short-term FLX treatment (10 mg/kg/day, i.p. for 3-4 days) on hypothalamic-pituitary-adrenal axis activity, serotonin (5-hidroxytriptamine, 5-HT) transporter (SERT) mRNA expression in the dorsal raphe nucleus (DRN), energy balance-related variables and behavioral profiles in the holeboard. Our results revealed that daily FLX administration increased plasma corticosterone (B) concentrations without affecting basal gene expression of corticotrophin releasing hormone in the hypothalamic paraventricular nucleus (PVN) nor of pro-opiomelanocortin in the anterior pituitary. However, FLX had significant effects increasing the mRNA expression of PVN arginine vasopressin (AVP) and reducing SERT mRNA levels in the dorsolateral subdivision of the DRN. In the holeboard, FLX-induced anxiety/emotionality-like behaviors. As expected, FLX treatment was endowed with anorectic effects and reduced body weight gain. Altogether, our study shows that short-term FLX treatment results in physiological, neuroendocrine and behavioral stress-like effects in adolescent male rats. More importantly, considering that the AVP- and 5-HTergic systems: (1) are intimately involved in regulation of the stress response; (2) are regulated by sex hormones and (3) are related to regulation of aggressive behaviors, our results highlight the potential significance of these systems mediating the anxiogenic/emotionality/stress-like responses of adolescent male rats to short-term FLX treatment.


Assuntos
Ansiedade/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Fluoxetina/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , Ansiedade/metabolismo , Corticosterona/sangue , Núcleo Dorsal da Rafe/efeitos dos fármacos , Núcleo Dorsal da Rafe/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo
16.
J Stroke Cerebrovasc Dis ; 24(11): e327-31, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26329361

RESUMO

BACKGROUND: demonstrate the importance of considering limb-shaking syndrome in the differential diagnosis of patients who present to the emergency department (ED) with hyperkinetic movements. METHODS: In this article, we describe a diagnostic challenge in the ED in which a patient presents with hyperkinetic movements that are initially diagnosed as hemichorea-hemiballismus (HCHB) but are subsequently found to be limb-shaking syndrome with important therapeutic opportunities. RESULTS: Following a diagnosis of left carotid obstruction, the patient underwent left carotid endarterectomy 5 days after admission. Six months after surgery, the patient had no further symptoms, and an ultrasound scan and magnetic resonance angiography have confirmed no restenosis. CONCLUSION: Limb shaking is an uncommon form of transient ischemic attack that should be recognized and differentiated from conditions such as focal motor seizures. Recognition will almost invariably indicate carotid artery occlusion, and timely treatment may not only abolish the attacks in patients but also reduce their risk of stroke. HCHB represents a spectrum of hyperkinetic movement disorders varying in the severity of choreic and/or ballistic movements. The presented case includes limb-shaking syndrome in the differential diagnosis and prompts for further investigations to complete the assessment.


Assuntos
Discinesias/etiologia , Extremidades/fisiopatologia , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/diagnóstico , Tremor/complicações , Serviço Hospitalar de Emergência , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
17.
Eur J Pharmacol ; : 177073, 2024 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-39481630

RESUMO

Status epilepticus (SE) is a neurologic emergency characterized by prolonged or rapidly recurring seizures. Increased intracellular calcium concentration ([Ca2+]i) occurring after SE is a key mediator of excitotoxicity that contributes to the brain damage associated with the development of epilepsy. Accumulated evidence indicates that dantrolene, a ryanodine receptor (RyR) blocker may have protective effects against the SE-induced damage. We evaluated whether dantrolene (10 mg/kg, i.p.) administered twice, 5 min and 24 h after the lithium-pilocarpine-induced SE in rats, had neuroprotective effects. Dantrolene by itself had no effects on control rats. However, it exacerbated the signs of damage in rats that underwent SE, increasing brain glucose hypometabolism as measured by PET neuroimaging 3 days after SE. Likewise, the neurohistochemical studies revealed that dantrolene aggravated signs of hippocampal neurodegeneration, neuronal death and microglia-induced neuroinflammation. Besides, the damaging effects were reflected by severe body weight loss. Overall, our results point towards a deleterious effect of dantrolene in the lithium-pilocarpine-induced SE model. Nonetheless, our results are in opposition to the reported neuroprotective effects of dantrolene. Whether the mechanisms underlying [Ca2+]i increase might significantly differ depending on the particularities of the model of epilepsy used and general experimental conditions need further studies. Besides, it is yet to be determined which isoform of RyRs significantly contributes to Ca2+-induced excitotoxicity in the lithium-pilocarpine SE rat model.

18.
Front Immunol ; 15: 1385101, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38725998

RESUMO

Background: Immunopathology in food allergy is characterized by an uncontrolled type 2 immune response and specific-IgE production. Recent studies have determined that group 2 innate lymphoid cells (ILC2) participate in the food allergy pathogenic mechanism and their severity. Our objective was to investigate the role of ILC2 in peach-allergic patients due to non-specific lipid transfer protein (Pru p 3) sensitization. Methods: The immune response in peripheral blood mononuclear cells was characterized in lipid transfer protein-allergic patients and healthy controls. We have analyzed the Pru p 3 uptake on ILC2, the expression of costimulatory molecules, and their involvement on the T-cell proliferative response and cytokine production under different experimental conditions: cytokines involved in group 2 innate lymphoid cell activation (IL-33 and IL-25), Pru p 3 as main food allergen, and the combination of both components (IL-33/IL-25+Pru p 3) using cell sorting, EliSpot, flow cytometry, and confocal microscopy. Results: Our results show that Pru p 3 allergen is taken up by group 2 innate lymphoid cells, regulating their costimulatory molecule expression (CD83 and HLA-DR) depending on the presence of Pru p 3 and its combination with IL-33/IL-25. The Pru p 3-stimulated ILC2 induced specific GATA3+Th2 proliferation and cytokine (IL-4, IL-5, and IL-13) production in lipid transfer protein-allergic patients in a cell contact-dependent manner with no changes in Tbet+Th1- and FOXP3+Treg cell differentiation. Conclusions: The results indicate that in lipid transfer protein-allergic patients, the responsible allergen, Pru p 3, interacts with group 2 innate lymphoid cells, promoting a Th2 cell response. Our results might be of interest in vivo, as they show a role of group 2 innate lymphoid cells as antigen-presenting cells, contributing to the development of food allergy. Consequently, group 2 innate lymphoid cells may be considered as potential therapeutic targets.


Assuntos
Antígenos de Plantas , Proteínas de Transporte , Hipersensibilidade Alimentar , Imunidade Inata , Humanos , Hipersensibilidade Alimentar/imunologia , Feminino , Antígenos de Plantas/imunologia , Proteínas de Transporte/imunologia , Masculino , Adulto , Citocinas/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Proteínas de Plantas/imunologia , Ativação Linfocitária/imunologia , Adulto Jovem , Pessoa de Meia-Idade
19.
Eur J Pharmacol ; 939: 175453, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36516936

RESUMO

Status epilepticus (SE) triggered by lithium-pilocarpine is a model of epileptogenesis widely used in rats, reproducing many of the pathological features of human temporal lobe epilepsy (TLE). After the SE, a silent period takes place that precedes the occurrence of recurrent spontaneous seizures. This latent stage is characterized by brain glucose hypometabolism and intense neuronal damage, especially at the hippocampus. Importantly, interictal hypometabolism in humans is a predictive marker of epileptogenesis, being correlated to the extent and severity of neuronal damage. Among the potential mechanisms underpinning glucose metabolism impairment and the subsequent brain damage, a reduction of cerebral blood flow has been proposed. Accordingly, our goal was to evaluate the potential beneficial effects of naftidrofuryl (25 mg/kg i.p., twice after the insult), a vasodilator drug currently used for circulatory insufficiency-related pathologies. Thus, we measured the effects of naftidrofuryl on the short-term brain hypometabolism and hippocampal damage induced by SE in rats. 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) neuroimaging along with various neurohistochemical assays aimed to assess brain damage were performed. SE led to both severe glucose hypometabolism in key epilepsy-related areas and hippocampal neuronal damage. Although naftidrofuryl showed no anticonvulsant properties, it ameliorated the short-term brain hypometabolism induced by pilocarpine. Strikingly, the latter was neither accompanied by neuroprotective nor by anti-inflammatory effects. We suggest that naftidrofuryl, by acutely enhancing brain blood flow around the time of SE improves the brain metabolic state but this effect is not enough to protect from the damage induced by SE.


Assuntos
Nafronil , Estado Epiléptico , Humanos , Ratos , Animais , Pilocarpina/farmacologia , Lítio/farmacologia , Nafronil/metabolismo , Nafronil/farmacologia , Vasodilatadores/farmacologia , Neuroproteção , Glucose/metabolismo , Modelos Animais de Doenças , Encéfalo , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/tratamento farmacológico , Hipocampo , Convulsões/metabolismo
20.
Plants (Basel) ; 12(16)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37631184

RESUMO

Potato (Solanum tuberosum) is one of the most important food crops worldwide, and Rhizoctonia solani infection is one of the most common diseases. The objective of this study was to evaluate the antifungal activity of Vitis vinifera byproducts (VIDES) and flesh-coloured potato (FCP) extracts against Rhizoctonia sp. in potato crops. Photosynthetic traits, phenolic profiles, and antioxidant and enzymatic activities were determined. The VIDES extract showed a 151.4% improvement in stomatal conductance and a 258.5% improvement in the photosynthetic rate compared to the plants without infection. Regarding the enzymatic antioxidant activity, the best response was found in the FCP treatments with 30 min of application, with increases of 25%, 161%, and 450% in ascorbate peroxidase, catalase (CAT), and glutathione reductase (GR) activities, respectively, compared to plants without infection. For the VIDES extract, a 15 min application produced an 83% increase in CAT activity, whereas a 181% increase in GR activity compared to plants without infection was produced after a 30 min application. A similar behaviour was observed for antioxidant compounds, where FCP had a higher concentration of compounds and antioxidant activity. This finding suggests that FCP and VIDES promote the synthesis of plant-defence compounds against Rhizoctonia sp. in potato crops, in which the application time is a determining factor.

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