RESUMEN
Obstetric complications, like maternal hypertension and neonatal hypoxia, disrupt brain development, leading to psychiatry disorders later in life, like schizophrenia. The exact mechanisms behind this risk are not yet well known. Spontaneously hypertensive rats (SHR) are a well-established model to study neurodevelopment of schizophrenia since they exhibit behavioral alterations mimicking schizophrenia that can be improved with antipsychotic drugs. SHR mothers are hypertensive, and the SHR offspring develop in preeclampsia-like conditions. Hypoxic conditions increase levels of adenosine, which play an important role in brain development. The enhanced levels of adenosine at birth could be related to the future development of schizophrenia. To investigate this hypothesis adenosine levels of brain neonatal Wistar rats and SHR were quantified. After that, caffeine, an antagonist of adenosinergic system, was administrated on PND (postnatal day) 7 (neurodevelopmental age similar to a human at delivery) and rats were observed at adolescent and adult ages. We also investigated the acute effects of caffeine at adolescent and adult ages. SHR control adolescent and adult groups presented behavioral deficits like hyperlocomotion, deficit in social interaction (SI), and contextual fear conditioning (CFC). In SHR, neonatal caffeine treatment on PND 7 normalized hyperlocomotion, improved SI, and CFC observed at adolescent period and adult ages, showing a beneficial effect on schizophrenia-like behaviors. Wistar rats neonatally treated with caffeine exhibited hyperlocomotion, deficit in SI and CFC when observed at adolescent and adult ages. Acutely caffeine treatment administrated at adolescent and adult ages increased locomotion and decreased SI time of Wistar rats and impair CFC in adult Wistars. No effects were observed in SHR. In conclusion, caffeine can be suggested as a useful drug to prevent behavioral deficits observed in this animal model of prenatal hypoxia-induced schizophrenia profile when specifically administered on PND 7.
Asunto(s)
Cafeína/farmacología , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/fisiopatología , Adenosina/análisis , Animales , Animales Recién Nacidos/metabolismo , Modelos Animales de Enfermedad , Locomoción/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Esquizofrenia/metabolismoRESUMEN
The adenosine A2b receptor is a G-protein coupled receptor. Its activation occurs with high extracellular adenosine concentration, for example in inflammation or hypoxia. These conditions are generated in the tumor environment. Studies show that A2b receptor is overexpressed in various tumor lines and biopsies from patients with different cancers. This suggests that A2b receptor can be used by tumor cells to promote progression. Thus A2b participates in different events, such as angiogenesis and metastasis, besides exerting immunomodulatory effects that protect tumor cells. Therefore, adenosine A2b receptor appears as an interesting therapeutic target for cancer treatment.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias/genética , Neoplasias/patología , Receptor de Adenosina A2B/genética , Regulación hacia Arriba , Adenosina/análisis , Adenosina/genética , Adenosina/inmunología , Antagonistas del Receptor de Adenosina A2/farmacología , Antagonistas del Receptor de Adenosina A2/uso terapéutico , Animales , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Terapia Molecular Dirigida/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Receptor de Adenosina A2B/análisis , Receptor de Adenosina A2B/inmunología , Microambiente Tumoral/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The pathogenesis of diabetic nephropathy (DN) has not been clearly established, making diagnosis and patient management difficult. Recent studies using experimental diabetic models have implicated adenosine signaling with renal cells dysfunction. Therefore, the study of the biochemical mechanisms that regulate extracellular adenosine availability during DN is of emerging interest. Using streptozotocin-induced diabetic rats we demonstrated that urinary levels of adenosine were early increased. Further analyses showed an increased expression of the ecto 5'-nucleotidase (CD73), which hydrolyzes AMP to adenosine, at the renal proximal tubules and a higher enzymatic activity in tubule extracts. These changes precede the signs of diabetic kidney injury recognized by significant proteinuria, morphological alterations and the presence of the renal fibrosis markers alpha smooth muscle actin and fibronectin, collagen deposits and thickening of the glomerular basement membrane. In the proximal tubule cell line HK2 we identified TGF-ß as a key modulator of CD73 activity. Importantly, the increased activity of CD73 could be screened in urinary sediments from diabetic rats. In conclusion, the increase of CD73 activity is a key component in the production of high levels of adenosine and emerges as a new tool for the early diagnosis of tubular injury in diabetic kidney disease.
Asunto(s)
5'-Nucleotidasa/metabolismo , 5'-Nucleotidasa/orina , Adenosina/orina , Diabetes Mellitus Experimental/orina , Nefropatías Diabéticas/orina , Riñón/patología , 5'-Nucleotidasa/análisis , Adenosina/análisis , Adenosina/metabolismo , Adenosina Monofosfato/metabolismo , Animales , Línea Celular , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Humanos , Riñón/metabolismo , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
To investigate the effect of ischemic preconditioning (IPC) and adenosine as strategies to protect cardiac injury caused by intestinal IR in rats, based on increasing in adenosine bioavailability and improvement of cell energy state by IPC. Male Wistar rats were submitted to 60 minutes of intestinal ischemia and 120 minutes of reperfusion. Intravenous injections of saline or Adenosine (AD) was administered five minutes before ischemia, five minutes before reperfusion and after 55 minutes reperfusion. Cardiac samples were obtained, fixed in formalin solution, embedded in paraffin, and sections of 5 μm were stained by hematoxylin-eosin. Histological analysis of myocardium was performed according occurrence of necrosis signs: piknosis, band contraction, eosinophilic cytoplasm, karyorrhexis and vacuolization (score - zero to 5). The groups submitted to ischemia alone (I=4.0), and reperfusion (IR=4.5) showed highest level of lesion compared to the others (I+IPC=3.3, IR+IPC=3.6, I+AD=3.0, IR+AD=3.8). The most interesting result was association of IPC and AD in IR model (IR+IPC+AD=1.2, p=0.002), showing preservation of the heart tissue, with fibers showing typical cross-striations and nuclei characteristics. Rare and small areas of tissue necrosis was observed and suggestion of capillaries congestion. CONCLUSION: Intestinal ischemia reperfusion promotes cardiac tissue injury. Ischemic preconditioning in association with adenosine is an efficient strategy to protect the heart against ischemia and reperfusion injury.(AU)
Asunto(s)
Animales , Ratas , Isquemia/metabolismo , Adenosina/análisis , Lesiones Cardíacas/complicaciones , Inyecciones Intravenosas , Ratas/clasificaciónRESUMEN
Cordyceps is a fastidious pathogenic fungus infecting insects, and recent years have witnessed rapid progress in its medical properties. In this study, a wild isolate, C. cicadae MP12, was characterized through in vitro cultivation and its nuclear small-subunit (SSU) ribosomal DNA (rDNA) data. In vitro culture of C. cicadae MP12 was established by growing its fruiting bodies in a solid matrix. C. cicadae MP12 was inoculated into Cryptotympana atrata cicada pupae for in vivo culture, where the fungi developed its fruiting body as well. The contents of adenosine and cordycepin in dried fruiting bodies after culture were 1421.45µg/g and 1398.12 µg/g, respectively. Therefore, the established cultures from this study could be used for the production of various medically important metabolic substances.
Asunto(s)
Animales , Adenosina/análisis , Adenosina/aislamiento & purificación , Cordyceps/genética , Cordyceps/aislamiento & purificación , ADN Ribosómico/análisis , ADN Ribosómico/aislamiento & purificación , Hongos/patogenicidad , Técnicas In Vitro , Reacción en Cadena de la Polimerasa/métodos , Activación Enzimática , Métodos , VirulenciaRESUMEN
The studies on the purinergic system in the kidney clearly showed its role on the renal hemodynamics, glomerular filtration and tubular function. The effectsof purinergic agonists on the mechanisms of tubuloglomerular feedback, and tubular transport of water and solutes, are well defined. In addition, severalstudies have documented the role of adenosine and specific ATP receptors on the processes of renal diseases, with special interest on the ischemiareperfusioninjury, renal cystic disease, glomerular and tubulointerstitial diseases. Therefore, the purinergic system has become a growing field for researchin renal physiology and pathophysiology, leading to therapeutic possibilities of using specific agonists and antagonists.
Os estudos sobre o sistema purinérgico no rim evidenciaram ao longo dos anos a sua participação na hemodinâmica renal, filtração glomerular e funçãotubular. É bem conhecida a participação de efetores purinérgicos no mecanismo de feedback túbulo-glomerular e transporte tubular de água e solutos.Além disso, vários trabalhos têm mostrado a participação da adenosina e de receptores específicos de ATP em processos de doença renal, com umespecial interesse na lesão da isquemia-reperfusão, doença cística renal, doenças glomerulares e túbulo-intersticiais. Portanto, o sistema purinérgico temse tornado alvo crescente de pesquisa em fisiologia e fisiopatologia renal, voltando-se para as possibilidades terapêuticas no uso de agentes agonistas eantagonistas específicos.
Asunto(s)
Humanos , Adenosina/análisis , Enfermedades Renales/terapia , Receptores Purinérgicos , Receptores Purinérgicos/uso terapéutico , Adenosina Trifosfato/análisisRESUMEN
An RP-HPLC method for the analysis of adenosine (ADO) has been developed and validated. In the present study, we report an RP-HPLC-based method with modifications of mobile phase and shorter retention time that substantially improved the efficiency of ADO analysis. The HPLC separation of the ADO was achieved on a C18 column, using a mobile phase consisting of water, containing 7% v/v ACN, at a flow rate of 0.8 mL/min. The column effluent was monitored by UV detection at 260 nm. A linear response was achieved over the concentration range of 0.25-100.00 micromol/L. The analytical method inter- and intra-run accuracy and precision were better than +/- 15%. The LOQ was 0.25 micromol/L, with ADO detection in the range of 6.25 pmol per sample. The method has been applied to the study of adenosine kinase (AK) kinetics.
Asunto(s)
Adenosina Quinasa/metabolismo , Adenosina/análisis , Técnicas de Química Analítica/métodos , Cromatografía Líquida de Alta Presión/métodos , Agua/química , Animales , Cromatografía/métodos , Cinética , Ratones , Control de Calidad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrofotometría Ultravioleta , Factores de TiempoRESUMEN
Com o objetivo de avaliar o papel da determinacao da atividade da enzima adenosina deaminase (ADA) no diagnostico da peritonite tuberculosa, foram estudados 44 pacientes. De acordo com os resultados das determinacoes bioquimicas, citologicas, histopatologicas e microbiologicas, os pacientes foram divididos em dois grupos: G1 - ascite tuberculosa (n=8); G2 - neoplasica (n=13); G3 - peritonite baracteriana espontanea (n=6); G4 - ascite pancreatica (n=2); G5 - miscelania (n=15). A concentracao de ADA no grupo de pacientes com peritonite tuberculosa foi de 133.50+-24.74 U/l, significantemente mais elevada que nos outros grupos (G2=41.85+-52.07; G3=10.63+-5.87; G4=18.00+-7.07; G5=11.23+-7.66). Com um limite de corte de 31 U/l, a sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo para diagnostico de tuberculose foram, respectivamente 100, 92, 72 e 100 por cento...
Asunto(s)
Humanos , Ascitis/diagnóstico , Tuberculosis/diagnóstico , Adenosina/análisis , Ascitis/enzimología , Diagnóstico DiferencialRESUMEN
Se estudiaron los efectos de la adenosina (ADO) sobre el automatismo y las oscilaciones post-potencial de fibras de Purkinje de corazones de perro. Se emplearon concentraciones de ADO desde 10-8 hasta 10-5 M. Se obtuvieron registros de la actividad eléctrica celular mediante microelectrodos. La ADO en concentraciones mayores de 10-8 M produce durante los dos primeros minutos un incremento súbito de la longitud del ciclo básico (LCB), de alrededor del 50 por ciento de su valor control, lo que después progresa hacia un estado estable. La curva dosis-respuesta en la fase estable es sigmoidal típica y semeja a las curvas de ocupación de receptores. Las pendientes del potencial de marcadores tienden a disminuir junto con la depresión de la LCB. Las oscilaciones post-potencial inducidas por tener de estimulación muestran que la pendiente de despolarización de la oscilación post-potencial disminuye con ADO 10-8 M pero no con concentraciones mayores. Los resultados encontrados sugieren que la ADO provoca un incremento en la corriente de potasio tiempo independiente. Este efecto parece depender de la estimulación de receptores específicos. El que la adenosina tenga un curso temporal bifásico sugiere la existencia de receptores purinérgicos con afinidades y constantes de disociación distinta pero con efectos similares y que podrían ser subtipos de receptores A1