ABSTRACT
Introducción: La relación entre la corteza entorrinal y el hipocampo ha sido estudiada por diferentes autores, que han destacado la importancia de las células de cuadrícula, las células de posicionamiento y la conexión trisináptica en los procesos que regulan: la persistencia de la memoria espacial, explícita y reciente, y su posible afección con el envejecimiento. Objetivo: Observar si existen diferencias en el tamaño y número de células de cuadrícula contenidas en la lámina iii de la corteza entorrinal y en la capa granular del giro dentado del hipocampo de pacientes mayores. Métodos: Realizamos estudios posmortem del cerebro de 6 sujetos de edades comprendidas entre los 56 y 87 años. Los cortes de cerebros que contenían el giro dentado del hipocampo y la corteza entorrinal adyacente se tiñeron con el método de Klüver-Barrera, después se midió, mediante el programa Image J, el área neuronal individual, el área neuronal total, así como el número de neuronas, contenidas en cuadrículas rectangulares a nivel de la lámina iii de la corteza entorrinal y la lámina ii del giro dentado y se llevó a cabo un análisis estadístico. Resultados: Se ha observado una reducción de la población celular de la capa piramidal externa de la corteza entorrinal, así como de las neuronas de la capa granular del giro dentado relacionada con el envejecimiento. Conclusión: Nuestros resultados indican que el envejecimiento produce una disminución en el tamaño y la densidad neuronal en las células de cuadrícula de la corteza entorrinal y de posicionamiento del giro dentado.(AU)
Introduction: The relationship between the entorhinal cortex and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. Objective: We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the entorhinal cortex and in the granular layer of the dentate gyrus of the hippocampus. Methods: We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the dentate gyrus and the adjacent entorhinal cortex were stained according to the Klüver-Barrera method, then the Image J software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the entorhinal cortex and layer II of the dentate gyrus. Statistical analysis was subsequently performed. Results: We observed an age-related reduction in the cell population of the external pyramidal layer of the entorhinal cortex, and in the number of neurons in the granular layer of the dentate gyrus. Conclusion: Our results indicate that ageing causes a decrease in the size and density of grid cells of the entorhinal cortex and place cells of the dentate gyrus.(AU)
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Entorhinal Cortex , Hippocampus , Spatial Memory , Neurology , Nervous System DiseasesABSTRACT
INTRODUCTION: The relationship between the entorhinal cortex (EC) and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. OBJECTIVE: We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the EC and in the granular layer of the dentate gyrus (DG) of the hippocampus. METHODS: We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the DG and the adjacent EC were stained according to the Klüver-Barrera method, then the ImageJ software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the EC and layer II of the DG. Statistical analysis was subsequently performed. RESULTS: We observed an age-related reduction in the cell population of the external pyramidal layer of the EC, and in the number of neurons in the granular layer of the DG. CONCLUSION: Our results indicate that ageing causes a decrease in the size and density of grid cells of the EC and place cells of the DG.
Subject(s)
Entorhinal Cortex , Place Cells , Humans , Entorhinal Cortex/physiology , Dentate Gyrus/physiology , Hippocampus , NeuronsABSTRACT
INTRODUCTION: The choroid plexuses, blood vessels, and brain barriers are closely related both in terms of morphology and function. Hypertension causes changes in cerebral blood flow and in small vessels and capillaries of the brain. This review studies the effects of high blood pressure (HBP) on the choroid plexuses and brain barriers. DEVELOPMENT: The choroid plexuses (ChP) are structures located in the cerebral ventricles, and are highly conserved both phylogenetically and ontogenetically. The ChPs develop during embryogenesis, forming a functional barrier during the first weeks of gestation. They are composed of highly vascularised epithelial tissue covered by microvilli, and their main function is cerebrospinal fluid (CSF) production. The central nervous system (CNS) is protected by the blood-brain barrier (BBB) and the blood-CSF barrier (BCSFB). While the BBB is formed by endothelial cells of the microvasculature of the CNS, the BCSFB is formed by epithelial cells of the choroid plexuses. Chronic hypertension induces vascular remodelling. This prevents hyperperfusion at HBPs, but increases the risk of ischaemia at low blood pressures. In normotensive individuals, in contrast, cerebral circulation is self-regulated, blood flow remains constant, and the integrity of the BBB is preserved. CONCLUSIONS: HBP induces changes in the choroid plexuses that affect the stroma, blood vessels, and CSF production. HBP also exacerbates age-related ChP dysfunction and causes alterations in the brain barriers, which are more marked in the BCSFB than in the BBB. Brain barrier damage may be determined by quantifying blood S-100ß and TTRm levels.
Subject(s)
Endothelial Cells , Hypertension , Aging , Brain , Choroid , HumansABSTRACT
Introducción: Los plexos coroideos, los vasos sanguíneos y las barreras cerebrales están íntimamente relacionados tanto morfológica como funcionalmente. Por otro lado, la hipertensión produce cambios en el flujo sanguíneo y en los pequeños vasos y capilares cerebrales. El propósito de la presente revisión es estudiar los efectos de la hipertensión arterial sobre los plexos coroideos y las barreras cerebrales. Desarrollo: Los plexos coroideos (PC) son una estructura del cerebro situada en los ventrículos cerebrales, altamente conservada filogenética y ontogénicamente. Los PC se desarrollan temprano durante la embriogénesis y constituyen una barrera funcional en las primeras semanas de gestación. Están compuestos por tejido epitelial altamente vascularizado, cubiertos por microvellosidades y su función principal es la producción del líquido cefalorraquídeo (LCR). El sistema nervioso central se encuentra aislado y protegido por la barrera hematoencefálica (BHE) y por la barrera sangre-LCR (BSLCR). Mientras que la BHE se localiza al nivel de las células endoteliales en la microvasculatura del encéfalo, la BSLCR está formada por las células epiteliales de los plexos coroideos. La hipertensión arterial crónica induce una remodelación vascular para adaptarse a los valores elevados de presión arterial, con lo que se evita el riesgo de hiperperfusión ante presiones elevadas, pero se incrementa el riesgo de isquemia a presiones bajas; en cambio, en las personas normotensas la circulación cerebral se autorregula y el flujo sanguíneo permanece constante y se mantiene la integridad de la BHE. [...] (AU)
Introduction: The choroid plexuses, blood vessels, and brain barriers are closely related both in terms of morphology and function. Hypertension causes changes in cerebral blood flow and in small vessels and capillaries of the brain. This review studies the effects of high blood pressure (HBP) on the choroid plexuses and brain barriers. Development: The choroid plexuses (ChP) are structures located in the cerebral ventricles, and are highly conserved both phylogenetically and ontogenetically. The ChPs develop during embryogenesis, forming a functional barrier during the first weeks of gestation. They are composed of highly vascularised epithelial tissue covered by microvilli, and their main function is cerebrospinal fluid (CSF) production. The central nervous system (CNS) is protected by the blood-brain barrier (BBB) and the bloodCSF barrier (BCSFB). While the BBB is formed by endothelial cells of the microvasculature of the CNS, the BCSFB is formed by epithelial cells of the choroid plexuses. Chronic hypertension induces vascular remodelling. This prevents hyperperfusion at HBPs, but increases the risk of ischaemia at low blood pressures. In normotensive individuals, in contrast, cerebral circulation is self-regulated, blood flow remains constant, and the integrity of the BBB is preserved. Conclusions: HBP induces changes in the choroid plexuses that affect the stroma, blood vessels, and CSF production. HBP also exacerbates age-related ChP dysfunction and causes alterations in the brain barriers, which are more marked in the BCSFB than in the BBB. Brain barrier damage may be determined by quantifying blood S-100β and TTRm levels. (AU)
Subject(s)
Humans , Aging , Endothelial Cells , Hypertension , Cerebrum , ChoroidABSTRACT
INTRODUCTION: The relationship between the entorhinal cortex and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. OBJECTIVE: We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the entorhinal cortex and in the granular layer of the dentate gyrus of the hippocampus. METHODS: We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the dentate gyrus and the adjacent entorhinal cortex were stained according to the Klüver-Barrera method, then the Image J software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the entorhinal cortex and layer II of the dentate gyrus. Statistical analysis was subsequently performed. RESULTS: We observed an age-related reduction in the cell population of the external pyramidal layer of the entorhinal cortex, and in the number of neurons in the granular layer of the dentate gyrus. CONCLUSION: Our results indicate that ageing causes a decrease in the size and density of grid cells of the entorhinal cortex and place cells of the dentate gyrus.
ABSTRACT
INTRODUCTION: The choroid plexuses, blood vessels, and brain barriers are closely related both in terms of morphology and function. Hypertension causes changes in cerebral blood flow and in small vessels and capillaries of the brain. This review studies the effects of high blood pressure (HBP) on the choroid plexuses and brain barriers. DEVELOPMENT: The choroid plexuses (ChP) are structures located in the cerebral ventricles, and are highly conserved both phylogenetically and ontogenetically. The ChPs develop during embryogenesis, forming a functional barrier during the first weeks of gestation. They are composed of highly vascularised epithelial tissue covered by microvilli, and their main function is cerebrospinal fluid (CSF) production. The central nervous system (CNS) is protected by the blood-brain barrier (BBB) and the blood-CSF barrier (BCSFB). While the BBB is formed by endothelial cells of the microvasculature of the CNS, the BCSFB is formed by epithelial cells of the choroid plexuses. Chronic hypertension induces vascular remodelling. This prevents hyperperfusion at HBPs, but increases the risk of ischaemia at low blood pressures. In normotensive individuals, in contrast, cerebral circulation is self-regulated, blood flow remains constant, and the integrity of the BBB is preserved. CONCLUSIONS: HBP induces changes in the choroid plexuses that affect the stroma, blood vessels, and CSF production. HBP also exacerbates age-related ChP dysfunction and causes alterations in the brain barriers, which are more marked in the BCSFB than in the BBB. Brain barrier damage may be determined by quantifying blood S-100ß and TTRm levels.
ABSTRACT
The p73 proteins are present in different kinds of cells of the central nervous system, such as the choroid plexus, circumventricular structures and neuroepithelium. It has been reported that spontaneously hypertensive rats show ventricular dilation, changes in cerebrospinal fluid proteins and variations in the circumventricular structures such as the organum vasculosum of the lamina terminalis and the choroid plexus, which are altered in ventricular dilation. The aim of the present work is to study p73 expression in the organum vasculosum of the lamina terminalis and the choroid plexus and its variations in high blood pressure. Brains from control Wistar-Kyoto rats and spontaneously hypertensive rats were used. The organum vasculosum of the lamina terminalis and the choroid plexus were processed by immunohistochemistry and western blot with anti-TAp73. We found weaker markings in the organum vasculosum of the lamina terminalis and stronger markings in the choroid plexus of the hypertensive than the control rats. Therefore, hypertension in the spontaneously hypertensive rats produces alterations in choroid plexus protein p73 expression that is similar to that described for other circumventricular organs, but it is different in the organum vasculosum of the lamina terminalis. We can conclude that the functional balance between p73, organum vasculosum of the lamina terminalis and choroid plexus, which is probably necessary to maintain the normal functioning of these structures, is altered by the hypertension found in these rats.
Subject(s)
Choroid Plexus/metabolism , DNA-Binding Proteins/metabolism , Gene Expression Regulation , Hypothalamus/metabolism , Nuclear Proteins/metabolism , Tumor Suppressor Proteins/metabolism , Animals , Gene Expression Profiling , Hypertension/metabolism , Immunoblotting , Immunohistochemistry , Male , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Tumor Protein p73ABSTRACT
Introducción y objetivos. La esclerosis múltiple (EM) es la enfermedad neurológica crónica más frecuente y discapacitante en adultos jóvenes. El objetivo de este trabajo fue partiendo de la relación que existe entre la escala ampliada del estado de discapacidad de Kurtzke (con las siglas en inglés EDSS [Expanded Disability Status Scale of Kurtzke])y el porcentaje de minusvalía en pacientes con EM, obtener un predictor del porcentaje de minusvalía, que permita a los clínicos, orientar al paciente acerca de las ayudas y beneficios fiscales a los que tendrían derecho. Material y métodos. Estudio transversal en 67 pacientes con EM que tenían asignado un índice de discapacidad utilizando la escala EDSS en base a su última exploración neurológica. Valoramos en estos pacientes su grado de minusvalía, empleando el baremo para la calificación del grado de minusvalía (RD 1971/1999, de 23 de diciembre). Se realizó el análisis estadístico de los datos obtenidos mediante el paquete estadístico de última generación: R Development Core Team (R). Resultados. La representación gráfica de los EDSS y sus respectivos porcentajes de minusvalía nos permitió estimar un modelo de regresión lineal simple: P.Mi=probabilidad de minusvalía para un valor del EDSS alpha=-14.23 Beta=12.49 ei=variabilidad biológica. A partir de este modelo, calculamos los porcentajes de minusvalía para cada valor del EDSS con un intervalo de confianza del 95%. Conclusión. El modelo estadístico obtenido nos permite utilizar el índice de discapacidad de Kurtzke como un predictor de la minusvalía de los pacientes con EM (AU)
Introduction and objectives. Multiple sclerosis (MS) is most frequent and disabling chronic neurological disease in young adults. This study has aimed to, based on the relation between EDSS (Expanded Disability Status Scale of Kurtzke) and the grade of handicap of MS patients, obtain a predictor of the handicap grade that would allow the clinicians to orient the patient on the social aid program and tax benefits that they are entitled to. Material and methods. A cross-sectional study was performed on 67 MS-diagnosed patients who had been previously assigned a EDSS grade of disability during their respective neurological evaluations. After, we evaluated the individual handicap grade in these patients, using the scale for the The Grade of handicap (RD 1971/1999, of 23 december). The statistical study of the data was performed using the last generation statistical program of R Development Core Team (R). Results. The graphical representation of the EDSS and the respective handicap grades allowed us to develop a statistical model of simple linear regression, which is as follows: P.Mi=handicap degree (EDSS value dependent). alpha=-14.23 Beta=12.49 ei=biological variability Using this model, we calculated the percentages of handicap for each value of the EDSS with a 95% confidence interval. Conclusions. The statistical model allows us to use the Kurtzke Expanded Disability Status Scale as a predictor of the handicap grade of MS patients (AU)
Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Health of the Disabled , Multiple Sclerosis/epidemiology , Multiple Sclerosis/rehabilitation , Cross-Sectional Studies/methods , Cross-Sectional Studies , 28599 , Linear ModelsABSTRACT
Reissner's fibre (RF) is formed by the polymerization of the glycoprotein secreted by the subcommissural organ (SCO). The SCO also secretes soluble glycoprotein into the cerebrospinal fluid (CSF); variations in RF and SCO have been reported in hydrocephalus. On the other hand, hydrocephalus and other brain alterations have been described in p73 mutant mice. The p73 belongs to the tumour suppressor p53 protein family and has two isoforms: the TAp73 with apoptotic activity and DeltaNp73 with anti-apoptotic function. Moreover, the TAp73 isoform is glycosylated and secreted into the CSF. In the present work, we analysed the variations in RF and p73 proteins in the CSF and SCO of spontaneously hydrocephalic rats. Brains from control rats and spontaneously hydrocephalic rats of 12 months of age were used. The SCO sections were immunohistochemically processed with anti-TAp73 and anti-Reissner fibre (AFRU). The spontaneous hydrocephalus presents a decrease in the AFRU immunoreactive material in the SCO and an absence of RF. The anti-TAp73 was also present, slightly decreased, in the hydrocephalic SCO. AFRU and p73 bands were also detected in the CSF by western blot and six AFRU and p73 protein bands of a similar molecular weight were found in the CSF of the control rats. The number of AFRU and p73 bands was lower in the hydrocephalic rats than in the control rats. In conclusion, hydrocephalus produces a decrease in the secretions of the SCO and an absence of RF and a decrease in p73 and RF proteins in the CSF.
Subject(s)
Cell Adhesion Molecules, Neuronal/cerebrospinal fluid , DNA-Binding Proteins/cerebrospinal fluid , Hydrocephalus/veterinary , Nuclear Proteins/cerebrospinal fluid , Rats, Inbred WKY , Rodent Diseases/cerebrospinal fluid , Subcommissural Organ/metabolism , Tumor Suppressor Proteins/cerebrospinal fluid , Animals , Blotting, Western/veterinary , Case-Control Studies , Cell Adhesion Molecules, Neuronal/analysis , DNA-Binding Proteins/analysis , Hydrocephalus/cerebrospinal fluid , Hydrocephalus/metabolism , Immunohistochemistry/veterinary , Nuclear Proteins/analysis , Rats , Rodent Diseases/metabolism , Subcommissural Organ/chemistry , Tumor Protein p73 , Tumor Suppressor Proteins/analysisABSTRACT
The objective of this study was to analyze the proteins in the cerebrospinal fluid of spontaneously hypertensive rats and to study their possible role in the relationship between hydrocephalus, arterial hypertension and variations in the subfornical organ. Brains and cerebrospinal fluid from control Wistar-Kyoto rats and spontaneously hypertensive rats sacrificed with chloral hydrate were used. Cerebrospinal fluid and extract of subfornical organ were processed by protein electrophoresis. Antisera against protein bands of 141, 117 and 48 kDa and Concanavalin A were used for immunohistochemical and western blot study of the subfornical organ, adjacent circumventricular structures and cerebrospinal fluid. Ventricular dilation in the spontaneously hypertensive rats and the presence of quite a lot of protein bands in the cerebrospinal fluid of the hypertensive rats, which were either not observed or scarcely present in the cerebrospinal fluid of the Wistar-Kyoto rats, were confirmed. The subfornical organ, third ventricle ependyma and choroideus plexus showed immunoreactive material for antibodies against 141kDa, 117 and 48 kDa proteins band (anti-B1, anti-B2 and anti-B3). The larger amount of the immunoreactive material was found in the subfornical organ of the spontaneously hypertensive rat. Our results and the alterations observed by other authors in the subfornical organ in hydrocephalic and hypertensive rats support the possibility that this circumventricular organ, some proteins of the cerebrospinal fluid and ventricular dilation could be connected with the physiopathology of this type of hypertension.
Subject(s)
Cerebrospinal Fluid/metabolism , Gene Expression Regulation , Immunohistochemistry/methods , Subfornical Organ/metabolism , Animals , Brain/metabolism , Brain/pathology , Disease Models, Animal , Gene Expression , Hypertension/pathology , Male , Rats , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
Alloreactive T cells recognize donor antigens by two routes: direct and indirect pathways of allorecognition. Although the direct pathway is reported to be dominant in allograft rejection, indirect allorecognition also plays an important role. Indirect alloreactivity is also observed in renal transplant patients irrespective of rejection. Previously we showed a predominance of interleukin (IL)-10 induced by indirect allorecognition of donor human leucocyte antigen (HLA)-DR peptides, suggesting the existence of indirect alloreactive T cells displaying regulatory activity. In the present work, our objective was to characterize these regulatory T cells. We detected indirect alloproliferation of peripheral blood mononuclear cells (PBMC) from renal transplant patients, induced by donor HLA-DR peptides, dependent on IL-4 or IL-10, suggesting regulatory activity as part of the alloreactive T-cell repertoire. PBMC-derived indirect alloreactive T-cell lines were established and produced both inflammatory and regulatory cytokines. We showed that two of these T-cell lines which were able to inhibit both direct and indirect alloproliferation of another T-cell line from the same patient presented a CD4(+)CD25(+)Foxp3(+) T-cell population. These data support the idea that indirect alloreactive T cells may also have regulatory activity and may contribute to the maintenance of the human renal allograft.
Subject(s)
Antigen Presentation/immunology , Forkhead Transcription Factors/biosynthesis , Kidney Transplantation/immunology , Signal Transduction/immunology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Adolescent , Adult , Aged , Cell Proliferation , Child , Humans , Middle Aged , Self Tolerance/immunologyABSTRACT
Alloreactive T cells recognize donor antigens by two routes: direct and indirect pathways of allorecognition. Although the direct pathway is reported to be dominant in allograft rejection, indirect allorecognition also plays an important role. Indirect alloreactivity is also observed in renal transplant patients irrespective of rejection. Previously we showed a predominance of interleukin (IL)-10 induced by indirect allorecognition of donor human leucocyte antigen (HLA)-DR peptides, suggesting the existence of indirect alloreactive T cells displaying regulatory activity. In the present work, our objective was to characterize these regulatory T cells. We detected indirect alloproliferation of peripheral blood mononuclear cells (PBMC) from renal transplant patients, induced by donor HLA-DR peptides, dependent on IL-4 or IL-10, suggesting regulatory activity as part of the alloreactive T-cell repertoire. PBMC-derived indirect alloreactive T-cell lines were established and produced both inflammatory and regulatory cytokines. We showed that two of these T-cell lines which were able to inhibit both direct and indirect alloproliferation of another T-cell line from the same patient presented a CD4+CD25 +Foxp3+ T-cell population. These data support the idea that indirect alloreactive T cells may also have regulatory activity and may contribute to the maintenance of the human renal allograft.
Subject(s)
Male , Female , Humans , Child , Adolescent , Adult , /cytology , /immunologyABSTRACT
The aim of this work was to analyze the proteins in the cerebrospinal fluid (CSF) of spontaneously hypertensive rats, to study their possible role in the relationship between hydrocephalus, arterial hypertension and alterations in the subcommissural organ. Brains from control Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) sacrificed with chloral hydrate were used. Antiserums against some cerebrospinal fluid protein bands and Reissner's fiber (RF) were used for immunohistochemical study of the SCO. Ventricular dilation was observed in the lateral and third ventricle of the SHR. Third ventricle ependyma showed immunoreactive material (IRM) for antibody against 141 kDa protein band anti-B1 and 117 protein band anti-B2 and the SCO of the SHR showed a decrease of the IRM when compared with WKY rats. An alteration in the expression of anti-RF was found to compare the SCO of the WKY and SHR groups. Our results demonstrate that hydrocephalus and hypertension are interconnected in this kind of rat which produce alterations in SCO secretions and some proteins of the CSF.
Subject(s)
Cerebrospinal Fluid Proteins/analysis , Hydrocephalus/cerebrospinal fluid , Hypertension/cerebrospinal fluid , Subcommissural Organ/metabolism , Animals , Cell Adhesion Molecules, Neuronal/analysis , Electrophoresis, Polyacrylamide Gel , Hydrocephalus/pathology , Hydrocephalus/physiopathology , Hypertension/pathology , Hypertension/physiopathology , Immunohistochemistry , Male , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Subcommissural Organ/chemistry , Subcommissural Organ/physiologyABSTRACT
Subcommissural organ (SCO) secretory activity of the goat (variations of Capra hircus, that live in arid conditions) was examined during the postnatal development, using specific antibodies against the Reissner's fibre (AFRU) and angiotensin II (AAGII). The SCO was strongly stained with the anti-glycoproteins that form the Reissner's fibre and lightly marked with the anti-angiotensin II. The AFRU-immunoreactivity (ir) was found in the ependymal and hypendymal cells and in the ventricular and peripheral secretory routes of the goat SCO. The amount AFRU increases at 6 months and decreases at adult age. In contrast, the anti-angiotensin II-ir was mainly found in the adult age, not being practically observed at one postnatal month. The AAGII-ir was mainly found in ependymal cells in which AFRU-ir was downregulated. In addition, we detected the presence of double immunostained for AFRU and AAGII in ependymocytes of the pre-commissural and subcommissural parts. In conclusion the present results may suggest a functional interrelation between AAGII and the secretory activity of the SCO of this kind of goat.
Subject(s)
Angiotensin II/analysis , Nerve Fibers/immunology , Subcommissural Organ/cytology , Subcommissural Organ/metabolism , Aging/physiology , Angiotensin II/immunology , Animals , Glycoproteins/immunology , Goats , Immunohistochemistry/veterinary , Subcommissural Organ/growth & developmentABSTRACT
We studied the effects of spontaneous high blood pressure and the captopril treatment on the subfornical organ (SFO) of rats. The brains of control Wistar-Kyoto rats (WKY), WKY rats treated with captopril (WKY-T), spontaneously hypertensive rats (SHR) and SHR rats treated with captopril (SHR-T) were processed immunohistochemically using anti-angiotensin II as primary antibody. Immunorective material (IRM) for angiotensin II was observed in a group of neurons and some cells of the ependymal layer of the SFO in WKY rats. The angiotensin II immunoreactive (AGII-ir) in the SHR rats was decreased, showing positive reaction only in a few neurons, while captopril treatment induced an increase in immunoreactive material in hypertensive rats, but contrarily, the expression of AGII-ir in the WKY-T group was scarce. The variations of the angiotensin II observed in the SFO could be owing to an interaction between the hypertension and its captopril treatment.
Subject(s)
Angiotensin II/metabolism , Antihypertensive Agents/pharmacology , Captopril/pharmacology , Subfornical Organ/drug effects , Animals , Cytoplasm/drug effects , Cytoplasm/metabolism , Immunohistochemistry , Male , Neurons/drug effects , Neurons/metabolism , Rats , Rats, Inbred SHR , Subfornical Organ/metabolismABSTRACT
The structure of the human subcommissuralorgan during its ontogenic development in 24human embryos and foetuses ranging from 6 to40 weeks of gestation (WG), and three adulthuman brains from 27-, 65- and 70-year old subjectswas investigated using both qualitative andquantitative methods. Concurrently, the appearanceof the subcommissural organ, pineal glandand mesocoelic recess was determined by studyingtheir structure, length and volume. Thehuman SCO appears at the beginning of 8th WG,which confirms previous results; the completematuration of the SCO occurs at the 15th WG andthe following three parts can be distinguished:the precommissural part, located in the rostralzone of the posterior commissure (PC) andextending to the pineal recess; the subcommissuralpart, located under the PC, and the retrocommissuralpart, located in the caudal zone ofthe PC, in the mesocoelic recess and at thebeginning of the Sylvian aqueduct. The reductionin size of the SCO begins after the 17th WGand this decrease in size begins in the precommissural,continues in the subcommissural, andfinishes in the retrocommissural part. The regressionand atrophies of the SCO begin after birth,and the SCO disappears completely after the ageof 30. The mesocoelic recess starts to form at thebeginning of the 10th WG, and is completely formedby the 14th WG and this is where the retrocommissuralpart of the SCO is located. In the 40th WG the regression of the mesocoelic recessbegins and this takes place at the same time asthe regression of the SCO. A parallel developmentbetween the SCO and the pineal wasfound. Thus, we observed the first appearance ofthe pineal recess in the 7-8th WG; during the 10thWG a compact mass of cells appeared in the rostralpart of pineal recess and by the 15th WG thepineal gland (PG) had acquired an almost definitiveaspect
No disponible
Subject(s)
Male , Female , Humans , Pineal Gland/anatomy & histology , Pineal Gland/growth & development , Immunohistochemistry/methods , Embryonic Structures/anatomy & histology , Embryonic Structures/physiopathology , Analysis of Variance , Subcommissural Organ/anatomy & histology , Subcommissural Organ/physiopathology , Subcommissural Organ/transplantation , Pineal Gland/transplantation , Immunohistochemistry/trends , Subcommissural Organ/growth & developmentABSTRACT
We have previously shown that TAP1-/- mice reject heart and skin grafts lacking an H-2 disparity. TAP1-/- mice, which are deficient for MHC-I molecules, probably have a T-cell repertoire with distinct reactivity to these molecules. We speculated that this rejection could be mediated by CD4+ T cells reactive to H-2(b) class I molecules, or to class I-derived peptides presented by self-APC. This hypothesis was tested in the present work. Presensitization of TAP1-/- mice with H-2K(b) peptides accelerated the rejection of C57BL/6 (H-2(b)) skin grafts (MST 13 days, P <.0057), indicating that these peptides were able to mobilize effector T cells that participate in rejection. In addition, CD4 T-cell depletion before transplantation induced a significant delay in rejection (P <.0011), showing that CD4 T cells have a major role in the rejection process, though other cells may also contribute. In conclusion, these results support our hypothesis that H-2(b) molecules may be targeted in graft rejection without an H-2 disparity. The low expression of MHC-I molecules on TAP1-/- mice may determine the selection of a T-cell repertoire that is reactive to self-MHC-I molecules, a phenomenon that is probably beyond the control of peripheral regulatory mechanisms.
Subject(s)
ATP-Binding Cassette Transporters/physiology , CD4-Positive T-Lymphocytes/immunology , Graft Rejection/immunology , Lymphocyte Depletion/methods , Skin Transplantation/immunology , ATP Binding Cassette Transporter, Subfamily B, Member 2 , ATP-Binding Cassette Transporters/genetics , Animals , Disease Models, Animal , Graft Survival/immunology , H-2 Antigens/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Time FactorsABSTRACT
We investigated the effects of bovine GH (bGH) on Ca(2+) handling, phospholipase C (PLC) activation and inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] formation in hepatocytes. bGH generates oscillations in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in single male rat hepatocytes microinjected with the photoprotein aequorin. In the absence of extracellular Ca(2+) these transients persisted for more than 10 min indicating a requirement for intracellular Ca(2+). Treatment of the hepatocyte with the phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitor U-73122 removed the oscillations. These results suggest bGH-induced oscillations are due to PLC activation and generation of Ins(1,4,5)P(3). We measured the mass of Ins(1,4,5)P(3) in freshly isolated hepatocyte suspensions in response to bGH, and vasopressin as a control. Both agonists rapidly increased the levels of Ins(1,4,5)P(3). This is the first study to indicate that early events in the signal transduction pathways mediated by GH in hepatocytes involve intracellular Ca(2+) mobilization via activation of a PI-PLC and subsequent Ins(1,4,5)P(3) production.
Subject(s)
Calcium/metabolism , Growth Hormone/metabolism , Hepatocytes/metabolism , Inositol 1,4,5-Trisphosphate/physiology , Type C Phospholipases/physiology , Animals , Cattle , Cytosol/metabolism , Enzyme Inhibitors/pharmacology , Estrenes/pharmacology , Male , Oscillometry , Pyrrolidinones/pharmacology , Rats , Rats, Sprague-Dawley , Signal Transduction , Time Factors , Type C Phospholipases/metabolismABSTRACT
The aim of this study was to perform an immunohistochemical study of the, angiotensinergic pathway from the arcuate nucleus (AN) to the posterior lobe of the hypophysis (PLH) of 10-week-old matched normotensive Wistar Kyoto rats (WKY), using our own policlonal antibody raised in mice against Angiotensin II (mouseantiangiotensin II, MAAII). Cells and fibers in the rostroventral and dorsocaudal parts of the AN, the internal zone of the median eminence and PLH showed immunoreactive material for antiangiotensin II. Angiontensin II fibers originating in the anteroventral part of the AN, crossing median eminence (ME) and infundibular stem and arriving at the PLH were also observed (AU)
No disponible
Subject(s)
Animals , Rats , Arcuate Nucleus of Hypothalamus/anatomy & histology , Arcuate Nucleus of Hypothalamus/immunology , Pituitary Gland, Posterior/anatomy & histology , Pituitary Gland, Posterior/immunology , Angiotensin II/immunology , Immunohistochemistry/instrumentation , Immunohistochemistry , Hypothalamus/anatomy & histologyABSTRACT
Ibuprofen is a peripherally acting nonsteroidal anti-inflammatory drug indicated fo ranalgesia, antipyresis, and various arthritic conditions. A solubilized 200 mg liquigel formulation of ibuprofen has been shown to have a more rapid rate of absorption compared with ibuprofen 200 mg tablets. Ibuprofen liquigels have a kinetic profile similar to ibuprofen suspension, with both a higher Cmax and an earlier tmax than any solid tablet. The objective of this single-dose, double-blind, triple-dummy, parallel-group study was to assess the time to onset of relief and overall analgesic efficacy of liquigel ibuprofen 400 mg, ketoprofen 25 mg compared with acetaminophen 1000 mg, and placebo in 239 patients with moderate or severe pain following third molar extractions. Treatments were compared over 6 hours using standard scales for pain intensity and relief and stopwatch onset of meaningful relief. All active treatments provided meaningful relief significantly faster compared with placebo. Ibuprofen provided significantly faster relief compared with acetaminophen and ketoprofen. By the end of the study (6 h), onset of meaningful relief was achieved by 36%, 99%, 96%, and 88% of the patients in the placebo, ketoprofen, ibuprofen, and acetaminophen groups, respectively. The median times to onset of relief were > 6 hours for placebo, 25.5 minutes for ketoprofen, 24.2 minutes for ibuprofen, and 29.9 minutes for acetaminophen. In addition, both ibuprofen and ketoprofen showed statistical superiority over acetaminophen at earlier time points on the time-effect curves for pain relief and pain intensity difference. Consistent results were seen with respect to the 6-hour summary efficacy variables: the three active treatments were significantly better than placebo, and ibuprofen was significantly better than both acetaminophen and ketoprofen. Liquigel ibuprofen 400 mg was shown to provide faster relief and superior overall efficacy compared with ketoprofen 25 mg, acetaminophen 1000 mg, and placebo. No serious adverse effects were reported in this single-dose study.
