The immune system in atherosclerosis and in acute myocardial infarction

Acute myocardial infarction (AMI) occurs when the atheromatous process prevents total blood flow through the coronary artery. It was previously thought that progressive luminal narrowing from the continued growth of smooth muscle cells (SMCs) in the plaque was the main cause of infarction, however, angiographic studies, have identified culprit lesions that do not cause marked stenosis. Is now evident that plaque activation, rather than stenosis, precipitates ischemia and infarction. Coronary spasm could be involved to some extent, but most cases of AMI are due to the formation of an occluding thrombus on the surface of the plaque; the two major causes of coronary thrombosis are plaque rupture and endothelial erosion. Plaque rupture is detectable in 60- 70% of cases and preferentially occurs when the fibrous cap is thin and partly destroyed. One of the major challenges in modern cardiology is the knowledge of the factors that induce a silent atherosclerotic plaque shifting from a stable to a vulnerable form

Interleukin-21 receptor (IL-21R) is up-regulated by CD40 triggering and mediates proapoptotic signals in chronic lymphocytic leukemia B cells

Interleukin-21 (IL-21) is a member of the IL-2 cytokine family, which mediates proliferation or growth arrest and apoptosis of normal B cells, depending on their activation state. Here we demonstrate that surface IL-21 receptor (R) is expressed at variable levels by chronic lymphocytic leukemia (CLL) B cells freshly isolated from 33 different patients. IL-21R expression was up-regulated following cell stimulation via surface CD40. Therefore, IL-21 effects were more evident in CD40-activated CLL B cells. IL-21 induced an early signaling cascade in CLL B cells, which included JAK-1 and JAK-3 autophosphorylation and tyrosine phosphorylation of STAT-1, STAT-3, and STAT-5. IL-21 signaling failed to stimulate CLL B-cell proliferation, but induced their apoptosis. In addition, IL-21 counteracted the proliferative and antiapoptotic signals delivered by IL-15 to CLL B cells. IL-21-mediated apoptosis involved activation of caspase-8 and caspase-3, cleavage of Bid to its active form t-Bid, and cleavage of PARP and of p27Kip-1. Recent data indicate that CLL B cells require interaction with the microenvironment for their survival and expansion. The present findings thus provide a set of new mechanisms involved in the balance between cell-survival and apoptotic signals in CLL B cells

Résistance aux estrogènes et déficit en aromatase chez l’Homme

Le rôle fondamental des estrogènes dans les fonctions de reproduction chez la femelle est bien connu. Récemment la production de souris transgéniques déficientes en récepteurs aux estrogènes (ERKO) ou en aromatase (ArKO), et la découverte chez l’homme de mutations inactivatrices portant sur le gène de l’aromatase et le récepteur aux estrogènes (ER) ont apporté des précisions quant au rôle des estrogènes dans les processus métaboliques tant chez la femelle que chez le mâle. A ce jour 8 cas bien documentés (5 femmes et 3 hommes) de déficiences congénitales en estrogènes ont été rapportés dans la littérature. La description des souris déficientes en ERa antérieure à ces cas cliniques a définitivement prouvé que l’absence d’estrogènes est compatible avec la vie et donc rejeté le « concept de létalité » attaché à l’absence d’estrogènes vu leur rôle pressenti dans l’implantation et la maintenance de la gestation. Les souris ERKO sont phénotypiquement normales mais stériles avec une densité osseuse inférieure (20-25 %) à celle des souris contrôles. De même, les hommes dépourvus d’aromatase ou de ER présentent une croissance continue, une ostéoporose, mais aussi (et non systématiquement) des altérations de la fonction testiculaire. Dans quelle mesure des fonctions aussi capitales que le développement osseux, le contrôle de la sécrétion des gonadotropines et le métabolisme lipidique, sont elles dépendantes des estrogènes? Ces questions élégamment élucidées suite aux traitements par la testostérone et par l’estradiol chez un homme déficient en aromatase font l’objet de cette synthèse

Resistance aux estrogenes et deficit en aromatase chez l’homme

The primordial role of estrogens in female reproductive function is well known. The recent production of transgenic mice deficient in estrogen receptors (ERKO) or in aromatase (ArKO) and the discovery in man of inactivating mutations of the corresponding genes (ER) have contributed to the understanding of the role of estrogens in metabolic processes in female as well as male. To date 8 well documented cases (5 women and 3 men) of congenital deficiencies in estrogens have been reported. As mice deficient in ERa had been previously described, these cases definitely proved that estrogen absence was compatible with survival and disproved the "lethality concept" previously held because the role of estrogens in implantation and gestation maintenance. ERKO mice are phenotypically normal though sterile, but their bone density is lower (20-25%) than that of controls. Similarly, men with no aromatase or no ER display continuous growth, osteoporosis and also (but not necessarily) alterations in testicular functions. How much do primordial functions such as bone development, control of gonadotrophin secretion and lipid metabolism depend on estrogens? These interrogations, elegantly clarified following testosterone and estradiol treatment in an aromatase deficient man are considered in this present synthesis

Sex Steroids in ageing male

Estrogens and testosterone declines with aging and serum estradiol remains higher in older men than in wome

Terapia sostitutiva e maturazione ossea

This abstract summarize the role of sex steroids (in particular estrogens) played for the achievement of peak bone mass both in men and women

Estrogeni e riproduzione maschile.

The effects of estrogen excess and estrogen deprivation on male reproductive function is reviewed and summarized

Calcified uterine leiomyoma: A rare association with inguinal hernia in a dog

A 10-year-old intact female Pug dog was presented with a 3-month history of left inguinal distension. A tentative diagnosis of cystic endometrial hyperplasia and uterine mineralisation with inguinal herniation was made together with palpation, abdominal radiographic and ultrasonographic examination. Ovariohysterectomy and hernioplasty were simultaneously performed. The left uterine horn was herniated through the inguinal ring. On histopathology, multinodular calcified uterine leiomyoma associated with a diffuse endometrial cystic hyperplasia was diagnosed. Uterine herniation should be considered in the differential diagnosis of inguinal mass in an intact bitch, and uterine neoplasia may be found as an underlying diseas

Oestrog\ue8nes et reproduction masculine [Estrogens and male reproduction]

Abstract The role of estrogen on male reproductive function has become clearer in the last decade. During these years the study of the effect of testosterone, estrogen or an aromatase inhibitor in hypogonadal men provided a first evidence of the effects of estrogens in the regulation of gonadotropin secretion. At the same time, the development of a line of transgenic male mice lacking estrogen receptor \u3b1, estrogen receptor \u3b2 or aromatase gene provided further evidence about the role of estrogens not only in the regulation of gonadotropin secretion, but also on the effects of estrogens on testicular function and development. A confirmation of these actions of estrogens came from the observation of naturally occurring mutations of the estrogen receptor and of the aromatase gene in human males. Based on these data it has been demonstrated that estrogens are major regulators of gonadotropin secretion acting both at pituitary and hypotalamic level. The presence in the human reproductive structures of estrogen receptor \u3b1, estrogen receptor \u3b2 and the aromatase enzyme indicates the existence of receptor \u3b1, estrogen receptor \u3b2 or aromatase estrogen actions at this level. Anyway, the precise role of estrogens in testicular development and function and on the regulation of human spermatogenesis has not yet been precisely clarified

Aromatase deficiency in the male: intriguing effects of testosterone, alendronate and estradiol treatment

Description of the fourth case of an adult man with aromatase deficiency, in particulare the effect of different treatment strategies on bone metabolism