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Objective To investigate the expression of vascular cell adhesion molecule-1 (VC.AM-1) in oxidative stress induced hypertrophic chondrocytes,in Kaschin-Beck disease (KBD) patients and in rat fed with T-2 toxin under selenium deficient conditions in order to analyze the relationship between VCAM-1 biological function and the dysregulation of chondrocyte differentiation in KBD.Methods The ATDC5 was cultured in 1％ ITS solution (10 mg/L insulin,5.5 mg/L transferrin,and 6.7 μg/L sodium selenite) for 21 days,and stimulated with 3-morpholino-sydnonimine (SIN-1,a nitric oxide [NO] donor) to obtain the oxidative stress induced hypertrophic chondrocytes.Real-time PCR was used to detect VCAM-1 mRNA in hypertrophic chondrocytes induced by different concentrations of SIN-1.The expressions of VCAM-I in articular cartilage of child and adult KBD patients and KBD animal model were determined via the immunohistochemical method,and KBD cartilage samples were obtained in KBD areas from KBD child who had died or from adults who had had surgery.Results After treatment of hypertrophic chondrocytes (ATCD5 cells) with SIN-1 (0,1,3,5 mmol/L),VCAM-1 mRNA levels (1.00 + 0.00,1.22 ± 0.20,0.71 ± 0.22,0.37 ± 0.16) were decreased in a dose-dependent manner when compared with the control group (F =27.788,P ＜ 0.05).The densities of VCAM-1 positive cells in superficial and middle zones of the articular cartilage of children KBD patients [(16.08 ± 5.20)％,(19.20 ± 9.71)％] were higher than those of control group [(0.00 ± 0.00)％,(0.00 ± 0.00)％],while that in the deep zone [(7.00 ± 4.40)％] in children KBD patients was significantly lower than that of control [(51.60 ± 20.58)％,tS/M/D=-10.972,-6.249,6.564,P ＜ 0.05].The positive cell density of VCAM-1 in the adult patients was significantly increased in the superficial zone [(7.92 ± 4.29)％ vs (3.12 ± 1.12)％] but significantly decreased in the middle zone [(17.54 ± 8.27)％ vs (31.75 ± 13.30)％] of articular cartilage when compared with that of control group (tS/D =-3.824,3.037,P ＜ 0.05).In articular cartilage of the four groups of KBD rats,the density of VCAM-1 positive cells in the superficial zone was significantly higher in low selenium diet group,T-2 toxin diet group and selenium deficient plus T-2 toxin diet group [(4.11 ± 1.90)％,(5.00 ±2.02)％,(2.78 ± 1.48)％ vs (1.89 ± 1.76)％,P ＜ 0.05].But the density of VCAM-1 positive cells in the deep zone was significantly lower in rat feed with selenium diet and selenium deficient plus T-2 toxin diet [(13.67 ± 2.45)％,(20.56 ± 7.42)％] than that of control group [(33.00 ± 12.57)％,P ＜ 0.05] in the epiphyseal cartilage of KBD rats.Conclusions The level of VCAM-1 is decreased both in the SIN-1 induced hypertrophic chondrocytes and in the deep zone of articular cartilage in KBD patients and in rat fed with T-2 toxin and selenium-deficient diets.VCAM-1 may be associated with the death of deep zone chondrocytes and differentiation disorder in cartilage.
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INTRODUCCIÓN: La Hiperplasia suprarrenal congénita (HSC) es una enfermedad autosómica recesiva cuya principal causa es la deficiencia de 21-hidroxilasa, quien participa en la síntesis del cortisol y aldosterona. Se describen dos formas de HSC, una clásica y otra no clásica, siendo la primera el objetivo de análisis a lo largo del caso clínico. Sus manifestaciones clínicas varían en gravedad, dependiendo del nivel de deficiencia hormonal. Dentro de la clásica se describe la forma perdedora de sal, cuyas consecuencias son el exceso de andrógenos e insuficiencia de cortisol y mineral o corticoides. Así esta se puede manifestar como un trastorno de la diferenciación sexual (virilización de los genitales externos si el feto es femenino) e insuficiencia suprarrenal. Para su diagnóstico se consideran los antecedentes familiares, manifestaciones clínicas, medición de los niveles de 17-hidroxiprogesterona y la detección de la alteración genética. PRESENTACIÓN DEL CASO: Paciente con antecedentes familiares de hermano con HSC, nace con un trastorno de la diferenciación sexual y es dado de alta con sexo legal masculino. Después de 3 meses desarrolla una insuficiencia suprarrenal, diagnosticándose HSC forma clásica perdedora de sal y por cariotipo se determina sexo femenino. DISCUSIÓN: Los pilares del manejo de la HSC son el consejo genético en las familias con riesgo, el tratamiento antenatal con dexametasona, terapia postnatal con glucocorticoides y el tratamiento quirúrgico de las alteraciones de los genitales externos, junto con las nuevas investigaciones en base a terapia genética y el uso de células madre, requiriendo de este modo la HSC una vista integral.
INTRODUCTION: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease whose main cause is the deficiency of 21-hydroxylase, an enzyme involved in the synthesis of cortisol and aldosterone. There are two forms of CAH, a classical and nonclassical form, being the first objective of analysis in the clinical case. Its clinical manifestations vary in severity, depending on the level of hormone deficiency. Within the classic is described the salt-wasting form, whose consequences are androgen excess and insufficiency of cortisol and mineral o corticoids. So this may manifest as a sex differentiation disorder (virilization of the external genitalia if the fetus is female) and adrenal insufficiency. For diagnosis are considered the family history, clinical manifestations, measuring 17-hydroxyprogesterone levels and detection of genetic alteration. CASE REPORT: Patient with a family history of a brother with HSC brother, born with a disorder of sexual differentiation and is discharged with legal male sex. After three months develops adrenal insufficiency and was diagnosed with classical HSC salt-wasting form and determined female karyotype. DISCUSSION: The Pillars of the HSC are handling genetic counseling in families at risk, prenatal treatment with dexamethasone, postnatal glucocorticoid therapy and surgical treatment of disorders of the external genitalia, along with new research based therapy gene and the use of stem cells, requiring this way an integral view of HSC.