RESUMEN

Introduction: The close relationship between inflammatory processes and epileptic seizures is already known, although the exact pathophysiological mechanism is unclear. In this study, the anticonvulsant capacity of piroxicam, an anti-inflammatory drug, was evaluated. A rat pentylenetetrazole kindling model was used.Methods: Male Wistar rats, 8-9 weeks old, received piroxicam (0.15 and 0.30 mg/kg), diazepam (2 mg/kg) or saline for 14 days, and PTZ, on alternate days. Intraperitoneal was chosen as the route of administration. The intensity of epileptic seizures was assessed using a modified Racine scale. The open field test and object recognition analysis were performed at the beginning of the study to ensure the safety of the drugs used. At the end of the protocol, the animals were euthanized to measure the levels of inflammatory (TNF-a and IL-6) and anti-inflammatory (IL-10) cytokines in the cortex, hippocampus, and serum.Results:There were no changes in the open field test and object recognition analysis. Piroxicam was found to decrease Racine scale scores at both concentrations. The reported values for IL-6 levels remained steady in all structures, whereas the TNF-alpha level in the cortex was higher in animals treated with piroxicam than in the saline and diazepam subjects. Finally, animals treated with the anti-inflammatory drug presented reduced IL-10 levels in the cortex and hippocampus.onclusions: Using inflammation as a guiding principle, the anticonvulsant effect of PIRO could be associated with the hippocampal circuits, since this structure showed no increase in inflammatory cytokines.

Asunto(s)

Anticonvulsivantes , Modelos Animales de Enfermedad , Excitación Neurológica , Piroxicam , Ratas Wistar , Animales , Piroxicam/farmacología , Masculino , Excitación Neurológica/efectos de los fármacos , Anticonvulsivantes/farmacología , Ratas , Pentilenotetrazol , Convulsiones/tratamiento farmacológico , Citocinas/metabolismo , Diazepam/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/administración & dosificación , Relación Dosis-Respuesta a Droga , Epilepsia/tratamiento farmacológico

RESUMEN

Epilepsy is a chronic disease characterized by an ongoing predisposition to seizures. Although inflammation has emerged as a crucial factor in the etiology of epilepsy, no approaches to anti-inflammatory treatment have been clinically proven to date. Betamethasone (a corticosteroid drug used in the clinic for its anti-inflammatory and immunosuppressive effects) has never been evaluated in attenuating the intensity of seizures in a kindling animal model of seizures. Using a kindling model in male wistar rats, this study evaluated the effect of betamethasone on the severity of seizures and levels of pro-inflammatory interleukins. Seizures were induced by pentylenetetrazole (30 mg/kg) on alternate days for 15 days. The animals were divided into four groups: a control group treated with saline, another control group treated with diazepam (2 mg/kg), and two groups treated with betamethasone (0.125 and 0.250 mg/kg, respectively). Open field test was conducted. Betamethasone treatments were effective in reducing the intensity of epileptic seizures. There were lower levels of Tumor Necrosis Factor-α and interleukin-1ß in the cortex, compared to the saline group, on the other hand, levels in the hippocampus remained similar to the control groups. There was no change in the levels of interleukin-6 in the evaluated structures. Serum inflammatory mediators remained similar. Lower quantities of inflammatory mediators in the central nervous system may have been the key to the reduced severity of seizures on the Racine scale.

Asunto(s)

Betametasona , Epilepsia , Ratas , Animales , Masculino , Betametasona/efectos adversos , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamente , Epilepsia/tratamiento farmacológico , Ratas Wistar , Antiinflamatorios/uso terapéutico , Mediadores de Inflamación/efectos adversos , Modelos Animales de Enfermedad , Anticonvulsivantes/efectos adversos

RESUMEN

Epilepsy is a chronic neurological disorder and there is increasing evidence about the role of inflammation in epileptogenesis. These findings have spurred the search for new immunomodulatory approaches that can improve prognosis. Using an animal model of chemically-induced epileptic seizures, we tested exercise alone as non-pharmacological therapy, and exercise combined with an anti-inflammatory drug. Five groups were used: sedentary, diazepam, aerobic exercise alone, aerobic exercise combined with an anti-inflammatory drug, and naive control. Our goal was to compare the severity of the epileptic seizures between groups as well as seizure latency in a pentylenetetrazole-induced paradigm. Cytokine levels (IL-1ß, TNF-α, and IL-10) were measured. Both exercise groups showed a reduction in seizure severity and lower levels of pro-inflammatory cytokines in the cortex, while the levels of cytokines in the hippocampus remained unaffected.

Asunto(s)

Epilepsia , Pentilenotetrazol , Animales , Antiinflamatorios/efectos adversos , Citocinas/metabolismo , Diazepam/uso terapéutico , Modelos Animales de Enfermedad , Epilepsia/tratamiento farmacológico , Ejercicio Físico , Hipocampo/metabolismo , Interleucina-10 , Pentilenotetrazol/toxicidad , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

The gut microbiota is a complex community composed by several microorganisms that interact in the maintenance of homeostasis and contribute to physiological processes, including brain function. The relationship of the taxonomic composition of the gut microbiota with neurological diseases such as autism, Parkinson's, Alzheimer's, anxiety, and depression is widely recognized. The immune system is an important intermediary between the gut microbiota and the central nervous system, being one of the communication routes of the gut-brain axis. Although the complexity of the relationship between inflammation and epilepsy has not yet been elucidated, inflammatory processes are similar in many ways to the consequences of dysbiosis and contribute to disease progression. This study aimed to analyze the taxonomic composition of the gut microbiota of rats treated with prednisolone in a kindling model of epilepsy. Male Wistar rats (90 days, n = 24) divided into four experimental groups: sodium chloride solution 0.9 g%, diazepam 2 mg/kg, prednisolone 1 mg/kg, and prednisolone 5 mg/kg administered intraperitoneally (i.p.) for 14 days. The kindling model was induced by pentylenetetrazole (PTZ) 25 mg/kg i.p. on alternate days. The taxonomic profile was established by applying metagenomic DNA sequencing. There was no change in alpha diversity, and the composition of the gut microbiota between prednisolone and diazepam was similar. The significant increase in Verrucomicrobia, Saccharibacteria, and Actinobacteria may be related to the protective activity against seizures and inflammatory processes that cause some cases of epilepsy. Further studies are needed to investigate the functional influence that these species have on epilepsy and the inflammatory processes that trigger it.

Asunto(s)

Microbioma Gastrointestinal , Pentilenotetrazol , Animales , Masculino , Prednisolona , Ratas , Ratas Wistar , Convulsiones/inducido químicamente

RESUMEN

BACKGROUND AND PURPOSE: Oxidative stress (OS) is defined as an excessive production of reactive oxygen species that cannot be neutralized by the action of antioxidants, but also as an alteration of the cellular redox balance. The relationship between OS and epilepsy is not yet fully understood. The objective of this study was to evaluate the effect of dexamethasone on OS levels and memory in the kindling model induced by pentylenetetrazole. METHODS: The animals were divided in six groups: control group that received no treatment, vehicle group treated with vehicle, diazepam group, and groups treated with dexamethasone (1, 2 and 4 mg/kg). Treated animals received pentylenetetrazole in alternated days for 15 days. Inhibitory avoidance test was conducted in 2 hours and OS was evaluated after animal sacrifice. RESULTS: Regarding the treatment with dexamethasone, there was no significant difference when compared to the control groups in relation to the inhibitory avoidance test. On OS levels, there was a decrease in catalase activity levels in the hippocampus and an increase in thiobarbituric acid reactive substances and glutathione peroxidase levels in the hippocampus. CONCLUSIONS: The anticonvulsant effect of dexametasone remains uncertain. Immunological mechanisms, with the release of cytokines and inflammatory mediators, seem to be the key to this process. The mechanisms that generate OS are probably related to the anticonvulsant effects found.

RESUMEN

Epilepsy is a chronic neurological condition that affects 1%-2% of the world population. Although research about the disease is advancing and a wide variety of drugs is available, about 30 % of patients have refractory epilepsy which cannot be controlled with the most common drugs. This highlights the need for a better understanding of the disorder and new types of treatment for it. Against this backdrop, a growing body of evidence has reported that inflammation may play a role both in the origin and in the progression of seizures. It has shown a tendency to be both the root and the result of epilepsy. This investigation aimed to assess the impact of prednisolone, a steroidal anti-inflammatory drug, in an animal model of pentylenetetrazole (PTZ)-induced seizures, at 1 mg/kg and 5 mg/kg doses. We also examined the degree of seizure severity and the modulation of pro-inflammatory cytokines in the treated animals. Four treatment groups were used (saline, diazepam, prednisolone 1 mg/kg, and prednisolone 5 mg/kg) and, in addition to their own daily treatments, subconvulsant doses of pentylenetetrazole (25 mg/kg) were administered every other day during a test protocol that lasted 14 days. After treatment, the cytokines interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) were measured in the animals' sera, hippocampi, and prefrontal cortices. Animals treated with prednisolone presented less severe seizures than the animals in the saline group, and there was a decrease in pro-inflammatory cytokine levels in central structures, but not peripheral ones. In short, an animal model of chemically-induced epileptic seizures was used, in which the animals were treated with doses of prednisolone, and these animals presented less severe seizures than the negative control group (saline), in addition to showing decreased levels of pro-inflammatory cytokines IL-6, IL-1ß and TNF-α, in the hippocampi and prefrontal cortices, but not the sera.

Asunto(s)

Antiinflamatorios/uso terapéutico , Mediadores de Inflamación/antagonistas & inhibidores , Locomoción/efectos de los fármacos , Pentilenotetrazol/toxicidad , Prednisolona/uso terapéutico , Convulsiones/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Mediadores de Inflamación/metabolismo , Locomoción/fisiología , Masculino , Prednisolona/farmacología , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Convulsiones/metabolismo , Resultado del Tratamiento

RESUMEN

Introduction: Several studies in the literature have evaluated the role of oxidative stress and adjuvant therapies for X-linked adrenoleukodystrophy (X-ALD). Here, we investigated whether n-acetyl-L-cysteine (NAC) and rosuvastatin (RSV) could influence the generation of reactive species, redox status and nitrative stress in fibroblasts from asymptomatic patients with X-ALD. Methods: Skin biopsy samples were cultured and treated for 2 hours (37 °C) with NAC and RSV. Results: X-ALD fibroblasts generated high levels of reactive oxygen species. These levels were significantly lower in fibroblasts treated with NAC and RSV relative to untreated samples. The X-ALD fibroblasts from asymptomatic patients also had higher catalase activity, and only NAC was able to increase enzyme activity in the samples. Conclusions: Our results indicated that NAC and RSV were able to improve oxidative stress parameters in fibroblasts from asymptomatic patients with X-ALD, showing that adjuvant antioxidant therapy may be a promising treatment strategy for asymptomatic patients with this disease. (AU)

Asunto(s)

Humanos , Masculino , Femenino , Acetilcisteína , Estrés Oxidativo , Adrenoleucodistrofia/terapia , Rosuvastatina Cálcica , Fibroblastos

RESUMEN

Introduction: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal metabolic disorder associated with mutations in the ATP-binding cassette sub-family D member1 (ABCD1) gene. Practically all male patients with X-ALD develop adrenocortical insufficiency during childhood and progressive myelopathy and peripheral neuropathy in adulthood. However, some male patients develop a fatal cerebral demyelinating disease named cerebral adrenoleukodystrophy. Although the exact mechanisms underlying brain damage in X-ALD are still poorly elucidated, it is known that hexacosanoic acid (C26:0) accumulation represents a hallmark in the pathogenesis of this disease. In this study, we examined whether an overload of C26:0 injected in Wistar rats was capable of causing behavioral changes in these animals. Methods: Egg lecithin in ethanol was dried under a nitrogen stream and mixed with C26:0 methyl ester. Male Wistar rats at 2-3 weeks of age were obtained from Universidade Federal do Rio Grande do Sul (UFRGS), divided into 8 groups, and submitted to an open field test. We then analyzed line crossings (locomotion and exploration), rearing (orienting and investigatory responses), grooming (anxiety manifestation), and latency to move for each animal. Results: Animals subjected to C26:0 administration presented fewer crossings and rearing episodes and a higher latency to move 45 minutes after C26:0 injection. The present work yields experimental evidence that C26:0, the main accumulated metabolite in X-ALD, can cause behavioral alterations in rats such as the impairment of locomotion and exploratory capabilities, as well as a reduction in orienting and investigatory responses. Conclusion: Although our results are preliminary, they are extremely important for future studies that investigate C26:0 accumulation and locomotor impairment in patients with X-ALD. (AU)

Asunto(s)

Animales , Ratas , Conducta , Ratas Wistar , Adrenoleucodistrofia , Cerebro/efectos de los fármacos , Ácidos Grasos , Actividad Motora/efectos de los fármacos

RESUMEN

X-linked adrenoleukodystrophy (X-ALD) is an inherited neurometabolic disorder caused by disfunction of the ABCD1 gene, which encodes a peroxisomal protein responsible for the transport of the very long-chain fatty acids from the cytosol into the peroxisome, to undergo ß-oxidation. The mainly accumulated saturated fatty acids are hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0) in tissues and body fluids. This peroxisomal disorder occurs in at least 1 out of 20,000 births. Considering that pathophysiology of this disease is not well characterized yet, and glial cells are widely used in studies of protective mechanisms against neuronal oxidative stress, we investigated oxidative damages and inflammatory effects of vesicles containing lecithin and C26:0, as well as the protection conferred by N-acetyl-L-cysteine (NAC), trolox (TRO), and rosuvastatin (RSV) was assessed. It was verified that glial cells exposed to C26:0 presented oxidative DNA damage (measured by comet assay and endonuclease III repair enzyme), enzymatic oxidative imbalance (high catalase activity), nitrative stress [increased nitric oxide (NO) levels], inflammation [high Interleukin-1beta (IL-1ß) levels], and induced lipid peroxidation (increased isoprostane levels) compared to native glial cells without C26:0 exposure. Furthermore, NAC, TRO, and RSV were capable to mitigate some damages caused by the C26:0 in glial cells. The present work yields experimental evidence that inflammation, oxidative, and nitrative stress may be induced by hexacosanoic acid, the main accumulated metabolite in X-ALD, and that antioxidants might be considered as an adjuvant therapy for this severe neurometabolic disease.

Asunto(s)

Acetilcisteína/farmacología , Cromanos/farmacología , Ácidos Grasos/farmacología , Inflamación/patología , Neuroglía/patología , Estrés Nitrosativo , Estrés Oxidativo , Rosuvastatina Cálcica/farmacología , Animales , Antioxidantes/metabolismo , Catalasa/metabolismo , Supervivencia Celular/efectos de los fármacos , Vesículas Citoplasmáticas/metabolismo , Daño del ADN , Interleucina-1beta/metabolismo , Isoprostanos/metabolismo , Neuroglía/metabolismo , Fármacos Neuroprotectores/farmacología , Nitratos/metabolismo , Nitritos/metabolismo , Estrés Nitrosativo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas

RESUMEN

The objective of this study was to evaluate the effect of dexamethasone, on the severity of seizures and levels of pro-inflammatory interleukins in animals with kindling model induced by pentylenetetrazole (20 mg/kg) in alternated days for 15 days of treatment. The animals were divided into five groups: control group given saline, a group treated with diazepam (2 mg/kg) and groups treated with dexamethasone (1, 2 and 4 mg/kg). Open field test was conducted. The treatment with dexamethasone decreased the severity of seizures, also decreased TNF-alpha and Interleukin 1 beta levels in the hippocampus and TNF-alpha level in the serum.

Asunto(s)

Dexametasona/uso terapéutico , Modelos Animales de Enfermedad , Mediadores de Inflamación/antagonistas & inhibidores , Excitación Neurológica/efectos de los fármacos , Convulsiones/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Dexametasona/farmacología , Mediadores de Inflamación/metabolismo , Excitación Neurológica/metabolismo , Masculino , Ratas , Ratas Wistar , Convulsiones/metabolismo , Resultado del Tratamiento

RESUMEN

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease characterized by progressive inflammatory demyelization in the brain, adrenal insufficiency, and an abnormal accumulation of very long chain fatty acids (VLCFA) in tissue and body fluids. Considering that inflammation might be involved in pathophysiology of X-ALD, we aimed to investigate pro- and anti-inflammatory cytokines in plasma from three different male phenotypes (CCER, AMN, and asymptomatic individuals). Our results showed that asymptomatic patients presented increased levels of pro-inflammatory cytokines IL-1ß, IL-2, IL-8, and TNF-α and the last one was also higher in AMN phenotype. Besides, asymptomatic patients presented higher levels of anti-inflammatory cytokines IL-4 and IL-10. AMN patients presented higher levels of IL-2, IL-5, and IL-4. We might hypothesize that inflammation in X-ALD is related to plasmatic VLCFA concentration, since there were positive correlations between C26:0 plasmatic levels and pro-inflammatory cytokines in asymptomatic and AMN patients and negative correlation between anti-inflammatory cytokine and C24:0/C22:0 ratio in AMN patients. The present work yields experimental evidence that there is an inflammatory imbalance associated Th1, (IL-2, IL-6, and IFN-γ), Th2 (IL-4 and IL-10), and macrophages response (TNF-α and IL-1ß) in the periphery of asymptomatic and AMN patients, and there is correlation between VLCFA plasmatic levels and inflammatory mediators in X-ALD. Furthermore, we might also speculate that the increase of plasmatic cytokines in asymptomatic patients could be considered an early biomarker of brain damage and maybe also a predictor of disease progression.

Asunto(s)

Adrenoleucodistrofia/inmunología , Citocinas/sangre , Macrófagos/inmunología , Células TH1/inmunología , Adolescente , Adrenoleucodistrofia/sangre , Adulto , Niño , Preescolar , Ácidos Grasos/sangre , Humanos , Lactante , Interleucina-10/sangre , Interleucina-1beta/sangre , Interleucina-2/sangre , Interleucina-4/sangre , Interleucina-5/sangre , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/sangre , Adulto Joven

RESUMEN

PURPOSE: To evaluate the relationship between salivary secretory immunoglobulin A (sIgA) concentration and dental caries in children with Down syndrome (DS) and compare it with findings in non-DS children. METHODS: The sample comprised 61 DS children and 52 non-DS children, aged 6 to 14 years. Caries experience, plaque index (PI), and gingival bleeding index (GBI) were recorded. Saliva samples were collected from all children. Total salivary sIgA concentrations were determined using an enzymatic assay method. RESULTS: Caries experience in primary and permanent dentitions were similar in DS and non-DS children. However, PI and GBI values were significantly lower in DS compared to non-DS children. DS children had higher salivary sIgA concentrations compared to non-DS children. No difference in sIgA concentration was observed between children with and without caries experience in either group. CONCLUSIONS: DS children have higher salivary sIgA concentrations than non-DS children. However, this finding did not correlate with caries experience in the study population.

Asunto(s)

Caries Dental/epidemiología , Síndrome de Down , Inmunoglobulina A Secretora/análisis , Saliva/química , Adolescente , Estudios de Casos y Controles , Niño , Atención Dental para Niños , Atención Dental para la Persona con Discapacidad , Femenino , Humanos , Masculino

RESUMEN

Epilepsy is a disorder that affects 1-2% of the population and a significant percentage of these patients do not respond to anticonvulsant drugs available in the market suggesting the need to investigate new pharmacological treatments. Several studies have shown that inflammation occurs during epileptogenesis and may contribute to the development and progression of epilepsy, demonstrating increased levels of pro-inflammatory interleukins in animal models and human patients. The objective of this study was to evaluate the effect of non-steroidal anti-inflammatory diclofenac sodium on the severity of seizures and levels of pro-inflammatory interleukins in animals with kindling model induced by PTZ. The kindling model was induced by injections of subconvulsant doses of PTZ (20mg/kg) in alternated days for 15days of treatment. The animals were divided into four groups: control group given saline, group treated with diazepam (2mg/kg) and groups treated with diclofenac sodium (5 and 10mg/kg). After treatment the open field tests was conducted. The severity of seizures was evaluated by the Racine scale. We evaluated the levels of IL-1ß, IL-6 and TNF-α in the blood, hippocampus and cortex of animals. The treatment with diclofenac sodium, in the PTZ induced kindling model, decreased severity of seizures and interleukin-6 and TNF-α levels in the hippocampus of animals treated with doses of 5 and 10mg/kg. New studies are needed to investigate a new therapeutic approach in the treatment of epilepsy with this anti-inflammatory non-steroidal drug.

Asunto(s)

Antiinflamatorios no Esteroideos/farmacología , Anticonvulsivantes/farmacología , Diclofenaco/farmacología , Convulsiones/tratamiento farmacológico , Convulsiones/inmunología , Animales , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/inmunología , Diazepam/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Epilepsia/tratamiento farmacológico , Epilepsia/inmunología , Hipocampo/efectos de los fármacos , Hipocampo/inmunología , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Excitación Neurológica , Masculino , Actividad Motora/efectos de los fármacos , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Introduction: Polyomaviruses (BKV and JCV) cause infection mainly in immunocompromised adults. A sensitive and specific diagnosis tool is fundamental to demonstrate the BKV and JCV infections. Nowadays many laboratories are using a PCR technique for detecting polyomaviruses genome in clinical samples. In this context, the purpose of this study is to determine the threshold of detection of the nested-PCR for polyomaviruses JC and BK. Methods: Serial dilutions of the samples of BKV and JCV of known concentration (100 copies/mL, 50 copies/mL, 25 copies/mL, 10 copies/mL, 5 copies/mL, and 1 copy/ml) were subjected to the technique of nested-PCR. All dilutions were tested 11 times to determine the minimum detection limit. Results: The minimum detection limit of the nested-PCR for JC and BK viruses was 25 copies/mL. This dilution (25 copies/mL) showed 100% PCR positive reaction. Furthermore, we found that weak positive results were obtained at dilutions of 1,5 and 10 copies/mL in some repetitions. Dilutions of 25, 50, and 100 copies/mL always had very positive results. Conclusions: These values are similar to those reported in other studies, contributing to the indication of this PCR for potential diagnostic purposes.

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Introdução: Os poliomavírus (JCV e BKV) causam infecções principalmente em adultos imunocomprometidos. Um diagnóstico sensível e específico é de fundamental importância para os pacientes portadores de JCV e BKV. Atualmente alguns laboratórios têm utilizado a técnica de PCR para a detecção do material genético destes vírus em amostras clínicas. Assim, o objetivo deste estudo é determinar o limite mínimo de detecção da técnica de nested-PCR para os poliomavírus JC e BK. Métodos: Diluições seriadas (100 cópias/mL; 50 cópias/mL; 25 cópias/mL; 10 cópias/mL; 5 cópias/mL e 1 cópia/mL) de controles positivos comerciais de JCV e BKV com concentrações conhecidas foram submetidas à técnica de nested-PCR semi-duplex. Todas as diluições foram testadas 11 vezes para determinação do limite mínimo de detecção. Resultados: O limite mínimo de detecção da reação de nested-PCR para os vírus JC e BK foi de 25 cópias/mL para ambos, com 100% de positividade das diluições testadas na reação de PCR. Ainda, pudemos observar que resultados positivos fracos foram obtidos nas diluições de 1, 5 e 10 cópias/mL em algumas das repetições realizadas. As diluições de 25, 50 e 100 cópias/mL sempre obtiveram resultado rancamente positivo. Conclusões: Estes valores são semelhantes aos relatados em outros estudos, contribuindo para a indicação desta reação de PCR para potenciais fins diagnósticos.

Asunto(s)

Humanos , Virus BK , Infecciones por Polyomavirus/diagnóstico , Virus JC , Límite de Detección , Reacción en Cadena de la Polimerasa , Terapia de Inmunosupresión , Manejo de Especímenes/normas

RESUMEN

The phenomenon of transfusion-related immunomodulation (TRIM) has been studied since the observation of a higher kidney allograft survival in patients who had received a higher number of transfusions. Conversely, it has been suggested as one of the possible causes related to the development of infections in patients with multiple blood transfusions and/or after a major surgery, and has been also associated with a decreased function of natural killer cells (NK) and antigen-presenting cells (APCs), reduced cell-mediated immunity, and increased regulatory T cells (Tregs). This review aimed to conceptualize TRIM and discuss some aspects related to its mechanisms and the prevention of immunomodulatory events.

Asunto(s)

Antígenos HLA/efectos adversos , Antígenos de Grupos Sanguíneos/efectos adversos , Antígenos de Grupos Sanguíneos/inmunología , Conservación de la Sangre , Inmunomodulación , Terapia de Inmunosupresión , Procedimientos de Reducción del Leucocitos , Tolerancia al Trasplante , Transfusión Sanguínea/efectos adversos , Infecciones Oportunistas/sangre

RESUMEN

Oxidative damages in hepatocytes may be caused by epilepsy and/or anticonvulsant drugs. Epilepsy is one of the most common neurological disorders, characterized by recurrent seizures, which may increase the content of reactive oxygen species. Organic and conventional grape juices are rich in polyphenols, compounds with important antioxidant activity. It is hypothesized that organic and conventional purple grape juices may have protective effect against oxidative damage induced by pentylenetetrazole (PTZ) (a standard convulsant drug) in the liver and serum of Wistar rats. Animals (n = 16 in each group) received, by gavage, saline, organic grape juice or conventional grape juice (10 µL/g of body weight) for 17 days. Subsequently, half of the rats in each group received PTZ (60 mg/kg). After 30 minutes, the animals were euthanized by decapitation. Liver and blood samples were isolated to evaluate oxidative parameters (lipid and protein oxidation, nitric oxide metabolite content, antioxidant defenses, and protein sulfhydryl content). The results of this study showed that although organic juice contains higher polyphenol content than conventional juice, both juices conferred protection against lipid and protein oxidative damage and limited the increase in PTZ-induced nitric oxide metabolite content in the liver and serum. In addition, both juices inhibited the PTZ-induced reduction in enzymatic antioxidant defenses (superoxide dismutase and catalase activities) and sulfhydryl protein content in the liver and serum. In summary, both organic and conventional grape juices were able to reduce oxidative damage induced by PTZ in the liver and serum of Wistar rats.

Asunto(s)

Proteínas Sanguíneas/metabolismo , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Pentilenotetrazol/efectos adversos , Preparaciones de Plantas/farmacología , Polifenoles/farmacología , Vitis/química , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Bebidas , Catalasa/metabolismo , Convulsivantes/efectos adversos , Alimentos Orgánicos , Frutas/química , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Masculino , Óxido Nítrico/metabolismo , Preparaciones de Plantas/química , Polifenoles/análisis , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Compuestos de Sulfhidrilo , Superóxido Dismutasa/metabolismo

RESUMEN

Organic and conventional yerba mate (Ilex paraguariensis) is widely used in South America to prepare nonalcoholic drinks rich in polyphenols. These compounds are able to prevent the generation of reactive species, thus minimizing the incidence of several diseases. In this perspective, we hypothesized that yerba mate may have protective effects against pentylenetetrazol (PTZ)-induced oxidative damage in liver and serum of rats. Animals (n = 42) received distilled water (control) or yerba mate (organic or conventional) for fifteen days. Then, half of the rats of each group received 60 mg/kg PTZ intraperitoneally or saline solution. After 30 min the animals were euthanized and the liver and blood were collected. The results showed that organic and conventional yerba mate avoided PTZ-induced oxidative damage and nitric oxide production in the liver and serum of the rats. Moreover, both kinds of yerba mate prevented the decrease in enzymatic (superoxide dismutase and catalase) and non-enzymatic (sulfhydryl protein content) defenses in the liver and serum. In addition, histopathologic analysis of the liver showed that yerba mate reduced PTZ-induced cell damage. These findings indicate that yerba mate provides hepatoprotection and improves antioxidant status in the serum, which may contribute to the development of new therapeutic strategies using nutraceuticals drinks.

RESUMEN

Epilepsy, which is one of the most common neurological disorders, involves the occurrence of spontaneous and recurrent seizures that alter the performance of the brain and affect several sensory and behavioral functions. Oxidative damage has been associated with post-seizure neuronal injury, thereby increasing an individual's susceptibility to the occurrence of neurodegenerative disorders. The present study investigated the possible anticonvulsive and neuroprotective effects of organic and conventional yerba mate (Ilex paraguariensis), a plant rich in polyphenols, on pentylenetetrazol (PTZ)-induced seizures in Wistar rats. The behavioral and polyphenolic profiles of the yerba mate samples were also evaluated. Infusions of yerba mate (50mg/kg) or distilled water were given to rats for fifteen days by oral gavage. On the 15th day the animals were subjected to open field test, and exploratory behavior was assessed. Subsequently, 60mg/kg PTZ (i.p.) was administered, and animals were observed for the appearance of convulsions for 30min. Latency for the first seizure, tonic-clonic and generalized seizures time, frequency of seizures and mortality induced by PTZ were recorded. The animals were then sacrificed, and the cerebellum, cerebral cortex and hippocampus were quickly removed and frozen to study the neuroprotective effects of yerba mate. The oxidative damage in lipids and proteins, nitric oxide levels, the activities of the antioxidant enzymes superoxide dismutase (Sod) and catalase (Cat) and non-enzymatic cellular defense (sulfhydryl protein) were quantified in all the tissues. The results showed that organic and conventional yerba mate infusions were able to reduce the frequency of seizures when compared to the PTZ group. Besides, organic yerba mate infusion decreases the tonic-clonic seizures time in relation to the PTZ group. It was also shown that organic and conventional yerba mate infusions reduced the oxidative damage in lipids and proteins and nitric oxide levels and prevented the decrease in Sod and Cat activities and sulfhydryl protein content when compared to the PTZ group in all the CNS tissues assayed. Organic and conventional yerba mate commercial samples did not change the behavior (locomotion, exploration or anxiety) of the treated animals. In both organic and conventional infusions, the presence of the polyphenols rutin, chlorogenic acid and their acyl derivatives were detected, which could be associated with the biological effects observed. These data indicate that yerba mate may provide new perspectives for the development of therapeutic approaches with natural compounds in the pharmaceutical area, both to reduce the convulsions' frequency and to minimize the neuronal damage associated with recurrent seizures.

Asunto(s)

Anticonvulsivantes/uso terapéutico , Ilex paraguariensis , Fitoterapia/métodos , Extractos Vegetales/uso terapéutico , Convulsiones/tratamiento farmacológico , Convulsiones/fisiopatología , Análisis de Varianza , Animales , Anticonvulsivantes/química , Catalasa/metabolismo , Cromatografía Líquida de Alta Presión , Convulsivantes/toxicidad , Modelos Animales de Enfermedad , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Óxido Nítrico/metabolismo , Pentilenotetrazol/toxicidad , Extractos Vegetales/química , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo

RESUMEN

Seizure disorder is a chronic condition in the brain that affects approximately 50 million people worldwide. Oxidative stress plays a crucial role in the pathophysiology of this disorder and can cause neuronal injury. Approximately one in three treated patients suffers from seizures regardless of pharmacological intervention, which results in oxidative damage. The present study aims to investigate the possible protective effect of antioxidant-rich Vitis labrusca extract on pentylenetetrazol-induced oxidative damage in Wistar rats. Possible behavioral alterations, genotoxic and mutagenic effects of the extract were also evaluated. The results showed that V. labrusca extract provides a significant protective effect against oxidative damage to lipids and proteins induced by pentylenetetrazol in the cerebral cortex, cerebellum, hippocampus and liver of rats. Also, the extract did not alter locomotor behavior. Moreover, it was non-genotoxic and non-mutagenic. Our results suggest the possibility of using V. labrusca extract as a therapeutic agent to minimize neuronal damage associated with seizures.

Asunto(s)

Antioxidantes/farmacología , Flavonas/farmacología , Pentilenotetrazol , Animales , Antioxidantes/toxicidad , Cerebelo/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Ensayo Cometa , Flavonas/toxicidad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Linfocitos/citología , Linfocitos/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , Mutación , Oxidación-Reducción , Extractos Vegetales/farmacología , Extractos Vegetales/toxicidad , Ratas , Ratas Wistar , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética , Semillas , Vitis

RESUMEN

Epilepsy is the most common neurological disorder worldwide. Studies have shown that recurrent seizures may increase the concentration of reactive oxygen species, which can lead to oxidative stress and neuronal damage. These seizures result in substantial deleterious effects on an individual's health. Organic and conventional grape juices are rich in polyphenols, compounds with important antioxidant activity. However, these juices could have differences in their polyphenol content. The aim of this study was to investigate the neuroprotective and anticonvulsant effects of organic and conventional grape juice treatments in Wistar rats against pentylenetetrazole (a convulsant drug)-induced damage. In addition, we evaluated potential behavioral changes in rats treated with the juices and the polyphenolic profile of those samples. Animals (n=16 in each group) received treatment with saline, organic or conventional grape juice for 17 days. On the eighteenth day, behavioral changes were evaluated by an open field test. Afterwards, half of the rats from each group received pentylenetetrazole and were observed for 30 min to evaluate possible seizure characteristics. The animals were subsequently killed by decapitation and their hippocampus, cerebellum and cerebral cortex tissues were isolated. The results of this study showed that neither organic nor conventional grape juice altered the behavior parameters, and no statistical differences were observed in the seizure characteristics of the groups. Nevertheless, both juice types were able to protect from lipid and protein oxidative damage, decrease nitric oxide content and increase enzymatic (superoxide dismutase and catalase) and non-enzymatic (sulfhydryl protein) antioxidant defenses in brain tissues following pentylenetetrazole-induced seizures. In general, organic juice showed superior results in each test, probably due to its higher polyphenol content relative to conventional juice. These results indicate that grape juices can provide further insight into natural neuroprotective compounds and may lead to the development of new therapeutic strategies for epileptic patients.

Asunto(s)

Pentilenotetrazol/toxicidad , Extractos Vegetales/uso terapéutico , Convulsiones/tratamiento farmacológico , Vitis/química , Animales , Masculino , Ratas , Ratas Wistar , Convulsiones/inducido químicamente