PubMed · 14818629
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O LINDAHL, S ORELL. 1951. Experiments with bone extracts.. https://pubmed.ncbi.nlm.nih.gov/14818629/
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Leprosy was a well-recognized and dreaded disease in Denmark in the Middle Ages (AD 1000-1536). A large fraction of the population was affected by leprosy in the 13th century. This paper analyzes the correlation between signs of leprosy and risk of dying in the small Danish village of Tirup (AD 1150-1350). Seven different dichotomous osteological lesions indicative of leprosy are analyzed, and it is possible to score at least one of these conditions on 135 skeletons of adult or adolescent people (aged 14 or more). Scores were transformed to a statistic, lambda, indicating the likelihood that the person to whom the skeleton belonged suffered from leprosy. The analyses indicate that the prevalence of leprosy among adult people in Tirup was 26% (95% confidence interval, 17-35%). The lambda statistic indicates that people who died with signs of leprosy did not differ in the distribution of age at death from those who did not have such signs. Skeletons showing dental enamel hypoplasia were less likely to come from skeletons with high lambda-values. The association between lambda and dental enamel hypoplasia indicates a relationship between stress in early childhood (ages 1-6 years) and subsequent development of signs of leprosy.
Published reports of palaeopathological analyses of skeletal collections from Central Asia are, to date, scarce. During the macroscopic examination of skeletal remains dating to the early first millennium AD from the Ustyurt Plateau, Uzbekistan, diagnostic features suggestive of leprosy were found on one individual from Devkesken 6. This adult female exhibited rhinomaxillary changes indicative of leprosy: resorption of the anterior nasal spine, rounding and widening of the nasal aperture, erosion of the alveolar margin, loss of a maxillary incisor, and inflammatory changes in the hard palate. While it is unclear whether the bones of the hands and the feet from this individual were absent as a result of collection strategy or poor preservation, lesions affecting the tibia and fibula were recorded, and the ways in which they may be related to a diagnosis of leprosy are discussed. This is the first skeletal evidence of leprosy from Central Asia and raises questions not only about the spread of the disease in the past, but also about the living conditions of what traditionally were thought of as nomadic peoples.
Hormone treatment with an estrogen plus a progestagen (EPT) increases the risk of breast cancer. Both hormone activities are also induced by tibolone. In order to assess the breast safety of tibolone, it was evaluated in several pre-clinical models. The effects were inconclusive in breast cancer cell lines but, in various in vivo models, it did not stimulate the breast. In the 17,12-dimethylbenz(a)anthracene (DMBA) model, tibolone clearly inhibited the growth of breast tumors and, when given prophylactally, far less tumors developed. Ovariectomized monkeys showed no increase in the expression of the proliferation marker Ki67. The effects of tibolone and its metabolites on the steroid metabolizing enzymes in breast tissues were investigated in order to unravel its mode of action in the breast. Tibolone and its metabolites did not inhibit aromatase, but sulfatase was profoundly inhibited. The sulfated 3alpha-OH tibolone metabolite even showed irreversible inhibition of sulfatase. In addition, 17ss-hydroxysteroid dehydrogenase activities were slightly inhibited and sulfotransferase activity was stimulated at low concentrations. The consequence of these effects is that, for both endogenous estrogens and estrogenic-metabolites of tibolone, the equilibrium is preferential for the sulfated forms. The intracellular hormonal milieu tibolone and its metabolites also influence cellular homeostasis. It inhibits cell proliferation of normal breast epithelial cells and stimulates apoptosis. In this respect, tibolone behaves differently from estrogens. Clinical studies have shown that tibolone users experience less breast tenderness and do not show an increase in mammographic density as found with continuous combined EPT. The data concerning tibolone and breast cancer risk are inconclusive and require further investigation.