RESUMEN
OBJECTIVES: PNS is involved in Systemic Sclerosis (SSc) since the earliest phases. Our aim is to perform an ultrastructural study on skin PNS fibers in SSc. METHODS: Skin biopsies were taken from forearms of 8 patients affected by limited SSc (lSSc) and 3 controls and processed for transmission electron microscopy (TEM). The semithin sections (2 mm) were observed at light microscope and optical fields were chosen for ultrathin sections (1 mm) preparation and TEM examination. RESULTS: In lSSc skin, in the semithin sections, damaged areas are close to apparently spared areas. At TEM, in early lSSc patients, signs of inflammation and damaged microvessels are visible in derma. PNS fibers are no damaged. In advanced lSSc, fibrosis prevails on inflammation, and slight ultrastructural alterations of PNS fibers are evident in papillar derma. CONCLUSIONS: PNS lesions are different in severity in lSSc according to the disease duration, resulting more severe in advanced than in early phase.
Asunto(s)
Fibras Nerviosas/ultraestructura , Sistema Nervioso Periférico/fisiopatología , Esclerodermia Limitada/fisiopatología , Piel/inervación , Biopsia , Distribución de Chi-Cuadrado , Interpretación Estadística de Datos , Femenino , Fibrosis , Técnicas de Preparación Histocitológica , Humanos , Masculino , Microcirculación , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Esclerodermia Limitada/patología , Piel/patología , Factores de TiempoRESUMEN
We recently conducted detailed cardiovascular and blood pressure-related phenotypic studies of mice lacking the bradykinin-B(2) receptor and were unable to identify a phenotype despite insensitivity to infused bradykinin. We therefore used oligonucleotide microarray analysis of some 12 000 genes and expressed sequence tags to identify molecular mechanisms that might be involved in compensating for the lack of a functional B(2) receptor in the kidneys of the mice. We identified 2 gene families that may have an impact on cardiovascular regulation and the bradykinin pathway. A water transport channel in the kidney, AQP4, was downregulated in the mice, whereas other members of the gene family did not show differences in expression levels. In addition, a number of serine proteases were upregulated in B(2) receptor-deficient mice. These genes are all located within a gene cluster on mouse chromosome 7. The findings were verified by an independent method. We suggest that microarray analysis has usefulness in elucidating otherwise unappreciated compensatory signaling pathways.
Asunto(s)
Receptores de Bradiquinina/metabolismo , Animales , Acuaporina 4 , Acuaporinas/genética , Acuaporinas/metabolismo , Bradiquinina/metabolismo , Mapeo Cromosómico , Regulación hacia Abajo , Perfilación de la Expresión Génica , Masculino , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Receptor de Bradiquinina B2 , Receptores de Bradiquinina/deficiencia , Receptores de Bradiquinina/genética , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Transducción de Señal , Regulación hacia ArribaRESUMEN
The involvement of kinins, calcitonin gene-related peptide (CGRP), and tachykinins during mesenteric post-ischemic reperfusion was studied in anesthetized rats by using antagonists for bradykinin (BK) B1, BK B2, CGRP1, or tachykinin NK1 receptor, or by capsaicin-induced desensitization. B1, B2, or CGRP1 receptor antagonists or desensitization attenuated the transient hypotension and plasma protein and leukocyte infiltration of intestinal wall observed during post-ischemic reperfusion. These effects were abolished by the combination of B2 and CGRP1 blockade as well as by B2 antagonism in capsaicinized rats, while NK1 blockade was ineffective. Our results suggest that kinins and CGRP contribute to systemic vasodilatation and microvascular leakage during mesenteric reperfusion. Pharmacological blockade of these systems could help preventing hypotension and intestinal injury consequent to reperfusion.