Gene-environment interactions in the pre-Industrial Era: the cancer of King Ferrante I of Aragon (1431-1494).

King Ferrante I of Aragon, leading figure of the Italian Renaissance, died in 1494. The autopsy of his mummy revealed a tumor infiltrating the small pelvis. We examined the histologic and molecular features of this ancient tumor to investigate its primary origin. Hematoxylin-eosin, Van Gieson, and Alcian Blue staining showed neoplastic cells infiltrating muscular fibers and forming pseudo-glandular lumina disseminated in fibrous stroma with scarce mucus. A strong immunoreactivity of the neoplastic cells was shown for pancytokeratins and proliferating cell nuclear antigen. Molecular fingerprints were investigated by examining K-ras, BRAF, and microsatellite instability in ancient tumor DNA. Sequencing analysis showed G-to-A transition in codon 12 of K-ras. BRAF mutations and microsatellite instability were not observed. Because the presence of K-ras codon 12 mutation could be associated with exposure to chemical carcinogens, possibly present in some food items, paleodietary reconstruction of the King Ferrante I was carried out by carbon (δ(13)C ) and nitrogen (δ(15)N) stable isotopes analysis. δ(13)C and δ(15)N values found in bone collagen of the King were consistent with a massive intake of animal proteins. Overall, our data show that the tumor of Ferrante I was a mucinous adenocarcinoma with molecular fingerprints characteristic of colorectal carcinogenesis linked to K-ras pathway. Paleodietary reconstruction and historical chronicles indicate a strong consumption of meat by the King. The possible abundance of dietary carcinogens, related to meat consumption, could explain the K-ras mutation causing the colorectal tumor that killed Ferrante I more than 5 centuries ago.

[Pre-judices versus rational observations in infectious diseases]. / Pre-giudizi versus osservazione razionale nelle malattie trasmissibili-infettive: l'errore in agguato.

The article deals with the history of the concepts of epidemic diseases and contagion. The idea that illnesses could be transmitted from animals to humans and from humans to humans is totally absent in ancient medical theories, but present in the works of historicians, veterinaries, architects. Which is the idea that brings ancient medicine to the refusal of the idea of contagion? And can a supposed 'medical authority' still be a real obstacle toward the comprehension of the ethiology of infectious diseases?

Neuroanatomy and cadaver dissection in Italy: History, medicolegal issues, and neurosurgical perspectives.

Despite the significant Italian tradition of important anatomical studies, an outdated law historically influenced by the Catholic church restricts the use of cadavers for teaching and scientific purposes. The object of the present paper was to trace the historical evolution of the Italian anatomical tradition, particularly neuroanatomical studies, in relation to the juridical regulations on the use of cadavers today. Special attention was paid to the opportunities offered to neurosurgery by using cadavers and to the scientific and social issues in neurosurgical training in the twenty-first century. Considering the new Common European Constitution, the authors advocate a political solution from the European community to improve the quality of training in the disciplines with a social impact such as neurosurgery.

[Molecular paleopathology: a novel perspective for biomedical history]. / La paleopatologia moleceolare: il futuro per indagare il passato.

Molecular paleopathology is an emerging field that is devoted to the detection, indentification and characterization of the molecular signatures in past diseases. When studied with modern molecular techniques, ancient human remains may yield direct informations on the diseases of ancient populations as well as the history of human diseases. Data concerning specific diseases of infectious, neoplastic and genetic origin can be obtained by molecular investigations of skeletal and mummified human remains. In particular, ancient DNA extracted from bone tissue, teeth and mummified soft tissue can be deeply analyzed by using PCR-based molecular techniques. Additionally, DNA of ancient pathogens, including bacteria, viruses and parasites, can be isolated from human remains and molecular diagnosis of infectious diseases can be made. Thus, molecular data, complemented by morphological and biochemical analyses, could help to reconstruct the epidemiology of past diseases and epidemics.

[Blood as a clinical sign in the corpus hippocraticum]. / Il sangue come segno clinico nel corpus hippocraticum.

Blood as a clinical sign has a key role throughout the Corpus Hippocraticum: as the most prominent and visible of the four fluids which make up the humoral system, it recurs quite often as a crucial cue for prognosis. This paper collects and classifies some of the most important loci in the Corpus which are devoted to describe and interpret the different qualities of human blood and the ways it can be altered and corrupted; this recollection clearly shows the systematic character of the Hippocratic treatment of blood and its function within the whole theoretical building of CH. The status of blood within the evolution of medical theories in the Antiquity is also scrutinized, especially as far as the polemics on encephalocentrism vs haemocentrism is concerned. The nature of observations about the manifestation of pure and altered blood sheds light on the epistemological status of clinical observation within the clinical methods of the Hippocratic school.

Possible human sacrifice at the origins of Rome: novel skeletal evidences.

Recent archaeological excavations at the Carcer/Tullianum, in the Roman Forum, allowed the unexpected recovery of human burials associated with the very early foundations of the monument, at the beginning of the iron age. The study of these burials resulted in interesting paleopathological discoveries, concerning the skeleton of a strongly-built male, radiocarbon-dated between 830 and 780 BC. The telltale posture of the skeleton and the presence of a massive perimortal blunt force trauma of the skull shed light on the mode and circumstances of the death of this subject, and are suggestive of ritual sacrifice. The archaeological, mythological and historical backgrounds, combined with the paleopathological evidence, help us to get a glimpse of life and death at the origins of Rome.

[Clinical epigraphies and apology in theurgical medicine]. / Incrizioni cliniche ed apologia nella medicine teurgico-templare.

Greek and Roman theurgical medicine well testify the existence of healing rational practices in Asclepius' temples, accordingly with contemporary and later testimonies of hippocratic medicine. Spatial disposition of theurgical epigraphic material in the healing temples suggest the possible link with the publicization of law.