RESUMEN
The hypothalamic paraventricular nucleus (PVN) plays a central role in regulating cardiovascular activity and blood pressure (BP). We administered hydroxylamine hydrochloride (HA), a cystathionine-ß-synthase (CBS) inhibitor, into the PVN to suppress endogenous hydrogen sulfide (H2S) and investigate its effects on the mitogen-activated protein kinase (MAPK) pathway in high salt-induced hypertension. We randomly divided 40 male Dahl salt-sensitive rats into 4 groups: the NS+PVN vehicle group, the NS+PVN HA group, the HS+PVN vehicle group, and the HS+PVN HA group, with 10 rats in each group. The rats in the NS (normal salt) groups were fed a normal-salt diet containing 0.3% NaCl, while the HS (high salt) groups were fed a high-salt diet containing 8% NaCl. The mean arterial pressure (MAP) was calculated after noninvasive measurement using an automatic sphygmomanometer to occlude the tail cuff once a week. HA or vehicle was infused into the bilateral PVN using Alzet osmotic mini-pumps for 6 weeks after the hypertension model was successfully established. We measured the levels of H2S in the PVN and plasma norepinephrine (NE) using ELISA. Additionally, we assessed the parameters of the MAPK pathway, inflammation, and oxidative stress through western blotting, immunohistochemical analysis, or real-time PCR. In the current study, we discovered that decreased levels of endogenous hydrogen sulfide in the PVN contributed to the onset of high salt-induced hypertension. This was linked to the activation of the MAPK signaling pathway, proinflammatory cytokines, and oxidative stress in the PVN, as well as the activation of the sympathetic nervous system.
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In this paper we have adapted a delayed dengue model to Zika. By assuming that the epidemic starts by a single infected individual entering a disease-free population at some initial time t0 we have used the least squares parameter estimation technique in R to estimate the initial time t0 using observed Zika data from Brazil as well as the transmission probabilities of Zika in Brazil between humans and mosquitoes and vice-versa. Different values of Aedes aegypti (A. aegypti) biting rate are used throughout the paper. We have estimated the value of the basic reproduction number for Zika in Brazil and calculated the expected number of cases of microcephaly in newborns as a result of women infected with Zika during pregnancy. We started off with a non-age-structured model then introduced age-structure into the model. However in reality seasonality, in particular temperature and rainfall, have a great impact on the population size of A. aegypti. Hence we repeat both the non-age-structured and age-structured analyses introducing seasonality into the A. aegypti birth function to model the effect of these environmental factors.
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Microcefalia/epidemiología , Microcefalia/virología , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/transmisión , Aedes , Algoritmos , Animales , Brasil/epidemiología , Control de Enfermedades Transmisibles , Dengue/epidemiología , Ambiente , Epidemias , Femenino , Humanos , Recién Nacido , Análisis de los Mínimos Cuadrados , Modelos Teóricos , Embarazo , Virus ZikaRESUMEN
BACKGROUND: Previous studies have reported that spore powder of Ganoderma lucidum (SPGL) may be effective for the treatment of Alzheimer's disease (AD). However, its efficacy is still inconclusive. Thus, this systematic review will aim to assess its efficacy and safety for AD. METHODS: We will search the electronic databases of Cochrane Central Register of Controlled Trials, EMBASE, MEDILINE, the Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database to assess the efficacy and safety of SPGL for patients with AD from their inceptions to the present. All case-control studies and randomized controlled trials will be considered for inclusion in this study. Two review authors will independently perform the study selection, data extraction, and risk of bias evaluation. RESULTS: The primary outcome includes the cognitive status for patients. The secondary outcomes consist of the quality of life, AD symptoms, and adverse events. CONCLUSIONS: This systematic review will present the existing evidence for the efficacy and safety of SPGL for treating patients with AD. DISSEMINATION AND ETHICS: The results of this systematic review will be disseminated by through peer-reviewed journals. It does not needs ethic approval, because it does not involve individual patient data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019119426.
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Enfermedad de Alzheimer/terapia , Reishi , Esporas Fúngicas , Humanos , PolvosRESUMEN
Carbon monoxide (CO) presents anti-inflammatory and antioxidant activities as a new gaseous neuromessenger produced by heme oxygenase-1 (HO-1) in the body. High salt-induced hypertension is relevant to the levels of pro-inflammatory cytokines (PICs) and oxidative stress in the hypothalamic paraventricular nucleus (PVN). We explored whether CO in PVN can attenuate high salt-induced hypertension by regulating PICs or oxidative stress. Male Dahl Salt-Sensitive rats were fed high-salt (8% NaCl) or normal-salt (0.3% NaCl) diet for 4 weeks. CORM-2, ZnPP IX, or vehicle was microinjected into bilateral PVN for 6 weeks. High-salt diet increased the levels of MAP, plasma norepinephrine (NE), reactive oxygen species (ROS), and the expressions of COX2, IL-1ß, IL-6, NOX2, and NOX4 significantly in PVN (p < 0.05), but decreased the expressions of HO-1 and Cu/Zn-SOD in PVN (p < 0.05). Salt increased sympathetic activity as measured by circulating norepinephrine, and increased the ratio of basal RSNA to max RSNA, in part by decreasing max RSNA. PVN microinjection of CORM-2 decreased the levels of MAP, NE, RSNA, ROS and the expressions of COX2, IL-1ß, IL-6, NOX2, NOX4 significantly in PVN of hypertensive rat (p < 0.05), but increased the expressions of HO-1 and Cu/Zn-SOD significantly (p < 0.05), which were all opposite to the effects of ZnPP IX microinjected in PVN (p < 0.05). We concluded that exogenous or endogenous CO attenuates high salt-induced hypertension by regulating PICs and oxidative stress in PVN.
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Antiinflamatorios/farmacología , Antihipertensivos/farmacología , Antioxidantes/farmacología , Presión Arterial/efectos de los fármacos , Monóxido de Carbono/farmacología , Citocinas/metabolismo , Hipertensión/prevención & control , Mediadores de Inflamación/metabolismo , Compuestos Organometálicos/farmacología , Estrés Oxidativo/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Animales , Antiinflamatorios/metabolismo , Antihipertensivos/metabolismo , Antioxidantes/metabolismo , Monóxido de Carbono/metabolismo , Ciclooxigenasa 2/metabolismo , Modelos Animales de Enfermedad , Hemo Oxigenasa (Desciclizante)/metabolismo , Hipertensión/metabolismo , Hipertensión/fisiopatología , Masculino , Compuestos Organometálicos/metabolismo , Núcleo Hipotalámico Paraventricular/metabolismo , Núcleo Hipotalámico Paraventricular/fisiopatología , Ratas Endogámicas Dahl , Cloruro de Sodio DietéticoRESUMEN
OBJECTIVE: To investigate the changes of xanthine oxidase (XOD), myeloperoxidase (MPO) and mitochondrial succinate dehydrogenase (SDH) in the testis and the protective effect of ganoderma lucidum spores on the testicular tissue of rats with non-insu- lin-dependent diabetes mellitus (NIDDM). METHODS: Fifty male Wistar rats were divided randomly into a model, a ganoderma and a normal control group, the first two groups injected with 2% STZ (25 mg/kg) through the peritoneum, and the last one with half-and-half sodium citrate/citrate buffer solution. Two weeks after normal diet, glucose tolerance tests were performed and the rats with abnormal glucose tolerance in the model and ganoderma groups received high-fat and high-carbohydrate food, the latter given ganoderma lycium spores (250 mg/kg x d) in addition, both for 10 weeks and all rats fed alone. Glucose tolerance tests were repeated 1 day before the end of the experiment and the testes of the rats were harvested for the determination of XOD, MPO and SDH. RESULTS: SDH was significantly lower (P < 0.05) while XOD and MPO significantly higher in the model group than in the ganoderma and control groups (P < 0.05). The model rats exhibited abnormal convoluted seminiferous tubules, indistinct parietal layers, decreased or abolished gonepoiesis, luminal peripheral fibrous tissue (interstitial substance) accrementition, basal lamina thickening, and vessel wall fibrous tissue accrementition and sclerosis. CONCLUSION: Ganoderma lucidum spores can protect the testis of diabetic rats by reducing free radical-induced damage to the testicular tissue and enhancing the activity of SDH.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Reishi , Testículo/metabolismo , Animales , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Esporas Fúngicas , Succinato Deshidrogenasa/metabolismo , Xantina Oxidasa/metabolismoRESUMEN
Hydrogen sulfide (H2S) is an important gaseous signaling molecule in neuro-modulation, anti-inflammatory, anti-oxidant and anti-hypertensive effects. The paraventricular nucleus (PVN) is a major integrative nucleus in regulating BP and SNA. The aim of this study is to explore whether endogenous or exogenous H2S changed by hydroxylamine hydrochloride (HA) or GYY4137 infused in the PVN affects RSNA and MAP by regulating oxidative stress or the balance between pro-inflammatory cytokines (PICs) and anti-inflammatory cytokines in high salt-induced hypertensive rats. Male Dahl rats were fed by high-salt or normal-salt diet. At the end of the 4th week, GYY4137, HA or vehicle was microinjected into bilateral PVN for 6 weeks. The levels of MAP, HR, plasma norepinephrine (NE), reactive oxygen species (ROS), NOX2, NOX4 and IL-1ß were increased significantly in high salt-induced hypertensive rats. Higher levels of these parameters were detected in the group treated by HA, but lower levels in the GYY4137 group. The trends of H2S, CBS, IL-10 and Cu/Zn SOD were opposite to the parameters described above. These findings suggest that endogenous or exogenous H2S in the PVN attenuates sympathetic activity and hypertensive response, which are partly due to decrease of ROS and PICs within the PVN in high salt-induced hypertension.
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Presión Sanguínea/efectos de los fármacos , Sulfuro de Hidrógeno/farmacología , Hipertensión/sangre , Estrés Oxidativo/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Cloruro de Sodio Dietético/efectos adversos , Animales , Antiinflamatorios/farmacología , Cistationina betasintasa/antagonistas & inhibidores , Cistationina betasintasa/genética , Cistationina betasintasa/metabolismo , Regulación hacia Abajo , Frecuencia Cardíaca/efectos de los fármacos , Hidroxilamina/farmacología , Hipertensión/inducido químicamente , Hipertensión/tratamiento farmacológico , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Morfolinas/farmacología , NADPH Oxidasa 2 , NADPH Oxidasa 4 , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Norepinefrina/sangre , Compuestos Organotiofosforados/farmacología , Núcleo Hipotalámico Paraventricular/metabolismo , Ratas , Ratas Endogámicas Dahl , Especies Reactivas de Oxígeno/metabolismo , Cloruro de Sodio Dietético/administración & dosificación , Cloruro de Sodio Dietético/sangre , Superóxido Dismutasa/sangreRESUMEN
PURPOSE: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II α expression in a model of epileptic neurons were investigated. METHOD: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg(2+) free medium for 3 hours; 3) Model group II: neurons were incubated with Mg(2+) free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg(2+) free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg(2+) free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II α protein expression was assessed by Western-blot. Ca(2+) turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca(2+) turnover was observed under a laser scanning confocal microscope. RESULTS: The CaMK II α expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca(2+) fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. CONCLUSION: GLP may inhibit calcium overload and promote CaMK II α expression to protect epileptic neurons.
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Anticonvulsivantes/uso terapéutico , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Calcio/metabolismo , Epilepsia/tratamiento farmacológico , Hipocampo/patología , Neuronas/enzimología , Polisacáridos/uso terapéutico , Reishi/química , Animales , Animales Recién Nacidos , Anticonvulsivantes/farmacología , Modelos Animales de Enfermedad , Epilepsia/enzimología , Epilepsia/patología , Fluorescencia , Espacio Intracelular/metabolismo , Neuronas/efectos de los fármacos , Neuronas/patología , Fitoterapia , Polisacáridos/farmacología , Ratas WistarRESUMEN
Epilepsy can cause cerebral transient dysfunctions. Ganoderma lucidum spores (GLS), a traditional Chinese medicinal herb, has shown some antiepileptic effects in our previous studies. This was the first study of the effects of GLS on cultured primary hippocampal neurons, treated with Mg(2+) free medium. This in vitro model of epileptiform discharge hippocampal neurons allowed us to investigate the anti-epileptic effects and mechanism of GLS activity. Primary hippocampal neurons from <1 day old rats were cultured and their morphologies observed under fluorescence microscope. Neurons were confirmed by immunofluorescent staining of neuron specific enolase (NSE). Sterile method for GLS generation was investigated and serial dilutions of GLS were used to test the maximum non-toxic concentration of GLS on hippocampal neurons. The optimized concentration of GLS of 0.122 mg/ml was identified and used for subsequent analysis. Using the in vitro model, hippocampal neurons were divided into 4 groups for subsequent treatment i) control, ii) model (incubated with Mg(2+) free medium for 3 hours), iii) GLS group I (incubated with Mg(2+) free medium containing GLS for 3 hours and replaced with normal medium and incubated for 6 hours) and iv) GLS group II (neurons incubated with Mg(2+) free medium for 3 hours then replaced with a normal medium containing GLS for 6 hours). Neurotrophin-4 and N-Cadherin protein expression were detected using Western blot. The results showed that the number of normal hippocampal neurons increased and the morphologies of hippocampal neurons were well preserved after GLS treatment. Furthermore, the expression of neurotrophin-4 was significantly increased while the expression of N-Cadherin was decreased in the GLS treated group compared with the model group. This data indicates that GLS may protect hippocampal neurons by promoting neurotrophin-4 expression and inhibiting N-Cadherin expression.