How Ethnicity

Correspondence

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Estrogen receptor alpha to beta ratio: A counterpart also in adrenal cortical neoplasia? Dear Editor, Estrogen receptors (ER) alpha and beta are wellestablished counterparts of neoplasia in estrogen-responsive tissues, such as the breast or the endometrium. In this context, the ER-alpha to ER-beta balance (ratio) has been described as an important predictor [1]. Interestingly however, ERs have emerged as significant factors in neoplasms of other tissues, such as the pancreas, the stomach and the liver. Although the adrenal cortex is a major endocrine organ, the studies that have been published till now on its estrogen-mediated regulation have focused on the actions of ERs in the central nervous system (reviewed in [2]). Actions in the CNS subsequently and indirectly modulate the adrenal secretion. Regarding direct in vivo modulation, only one study in the human fetus has documented the expression of ER-beta [3]. Apart from the scarcity of data concerning normal regulation, the physiological implication of ERs in adrenal cortical adenomas and carcinomas has not been systematically studied. To our knowledge, adenoma remains an uninvestigated domain and regarding carcinoma data come from two case reports. One of them supports that ERs are undetectable in pregnancy-associated adrenal cortical carcinoma [4], and the other one suggests that the expression is present, but at the same levels as in the adjacent normal tissue [5]. The main point of the hypothesis is that ER-beta, ER-alpha and the ER-beta/ER-alpha ratio may be important predictors also in adrenal neoplasia, irrespectively of pregnancy. Given the expression in of ER-beta in the fetus, ER-beta may become

particularly important during adrenal cortical tumorigenesis and may indeed exhibit a regulatory role, as the cells return to a dedifferentiated, ‘‘fetal-like’’ status. At any case, this Letter points to the need of ER-alpha and beta quantitative evaluation in large series of adrenal cortical carcinomas, which is to date absent in the literature.

References [1] Shaaban AM, O’Neill PA, Davies MP, et al. Declining estrogen receptor-beta expression defines malignant progression of human breast neoplasia. Am J Surg Pathol 2003;27: 1502–12. [2] Bodo C, Rissman EF. New roles for estrogen receptor beta in behavior and neuroendocrinology. Front Neuroendocrin 2006;27:217–32. [3] Takeyama J, Suzuki T, Inoue S, et al. Expression and cellular localization of estrogen receptors alpha and beta in the human fetus. J Clin Endocrinol Metab 2001;86:2258–62. [4] Fallo F, Pezzi V, Sonino N, Altavilla G, Barzon L. Adrenal incidentaloma in pregnancy: clinical, molecular and immunohistochemical findings. J Endocrinol Invest 2005;28:459–63. [5] Sanfilippo JS, Wittliff JL. Steroid hormone receptors in adrenal cortical carcinoma. Am J Obstet Gynecol 1984;150: 326–7.

Despina Georgiadou* Theodoros N. Sergentanis George Papastratis 3rd Surgical Clinic, ‘‘George Gennimatas’’ General Hospital, 154, Mesogeion Avenue, Athens 156 69, Greece * Tel.: +30 2106546496; fax: +30 2107706915; mobile: +30 6976435861 E-mail address: [email protected] (D. Georgiadou)

doi:10.1016/j.mehy.2007.12.006

How ethnicity affects risk of primary open-angle glaucoma? Dear Editor, We read the paper by Weale [1] carefully in a recent issue of Medical Hypotheses. First, some established epidemiologic data do not support the current hypothesis:

1. There are many evidences, which show that peoples of the same place (same temperature), have different risks for primary open angle glaucoma (POAG). The first example is the prevalence of POAG between age-adjusted men and women of the same place [2]. Second example

1226 is arising from the difference in the prevalence of POAG between black and white adults in the United States [3]. The third example is that at regions with cold climates, older individuals have lived in the cold weather for a longer time. According to the hypothesis, they seem to have more constricted superficial capillaries with narrower lumens and lower predisposition to glaucoma. Nevertheless, the risk for POAG increases with age there [2]. 2. Some investigators have compared the prevalence of glaucoma between African persons in Africa and African-derived persons in the United States [4]. They found remarkably similar prevalence of POAG between those two groups. In other words, when African persons migrate from Africa (warm climate) to United States (more temperate climate); the prevalence of POAG does not change remarkably. 3. Based on the hypothesis, at regions with more temperate climates, superficial capillaries will be constricted. Hence, the aqueous outflow channels might dilate, and reduce a predisposition for POAG. In Europe (especially northern places such as Norway, Sweden that are near the North Pole) and the north of Canada, the common pattern of glaucoma is POAG [4,2]. As we understand from the article’s title, the author tries to explain ethnical differences in the prevalence of glaucoma by different environmental temperatures. We believe that 3-D configuration of the eyeball which varies between different ethnic groups and is related to genetic factors, lead to different magnitudes of the eye’s wall mechanical stress and consequently different risks for glaucoma [5].

Correspondence

Acknowledgement The authors thank Doctor Robert A. Weale (Eye Department, University College London Hospital, Euston Road, London WC1, United Kingdom) because of his permission to discuss about his published article and for his honesty to respond some of our questions and ambiguities about the article by e-mail.

References [1] Weale RA. Ethnicity and glaucoma: higher environmental temperatures may accelerate the onset, and increase the prevalence, of primary open-angle glaucoma. Med Hypotheses 2007;69:432–7. [2] Coleman A. Epidemiology of glaucoma. In: Morrison J, Pollack I, editors. Glaucoma: science and practice. New York: Thieme; 2003. p. 3–7. [3] Friedman DS, Wolfs RC, O’Colmain BJ, Klein BE, Taylor HR, West S. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol 2004;122:532–8. [4] Buhrmann RR, Quigley HA, Barron Y, West SK, Oliva MS, Mmbaga BBO. Prevalence of glaucoma in a rural east African population. Invest Ophthalmol Vis Sci 2000;41: 40–8. [5] Mehdizadeh AR, Hoseinzadeh A, Fazelzadeh A. What is the real cause of glaucoma? Med Hypotheses 2007;69: 459–60.

Alireza Mehdizadeh Amin Hoseinzadeh* Afsoon Fazelzadeh Mashad University of Medical Sciences (MUMS), School of Medicine, Mashad, Iran * Tel.: +98 9177075754; fax: +98 5118517505 E-mail address: [email protected] (A. Hoseinzadeh)

doi:10.1016/j.mehy.2007.12.005

Exosomes: The Trojan horses of neurodegeneration Exosomes are part of the family of ‘‘bioactive vesicles’’. Their role in bloodstream, where the distal communication between cells is crucial, has been extensively described in particular related to the immune system activation. Exosomes secretion can be used by cells – including neurons and astrocytes [1] – to eject molecules destined for lysosomal degradation. In addition, secreted exosomes are biologically active entities which are important for the intercellular communication.

Exosomes from prion-infected neuronal cells have been demonstrated to be efficient initiators of prion propagation in uninfected recipient cells and, more importantly, to produce prion disease when inoculated into mice [2]. In Alzheimer disease (AD), b-amyloid peptides, that are intracellularly generated, were shown to be released to the extracellular space in association with exosomes [3]. AD is characterized by a continuous loss of neurons that are not replaced: why neurons die