Restoration and preservation of the anatomical specimens of the Museum of Pathological Anatomy at the University of Pisa

The recent establishment of the University Museum System, whose aim is to promote and enhance the University collections, encouraged the rearrangement of the Museum of Pathological Anatomy, currently not operating, because its precious pieces are stored in a warehouse. The economic support of the “Fondazione Pisa” permitted, in the last year, to begin the recovery and restoration of a part of the specimens. The collection consists in 1500 human and animal pathological specimens of great scientific relevance, some of which dated back to the Granducal period. The remains consist in pathological changes and congenital anomalies detected on human and animal bodies and organs, preserved in formaldehyde or dry. In particular, the Museum includes: a collection of 50 human bladder stones dating back to the first half of the 19th century; a collection of malformed human newborns documenting 25 rare congenital malformations, dating back to the end of 19th and the beginning of 20th century; a collection of animal teratology; a collection of helminthic parasitology. In the last 30 years, the Museum was then enriched with a collection of pieces from pathological autopsies, such as lung, cardio-vascular, renal, and brain diseases. The recovery was initially addressed to restore the wet preparations preserved in formaldehyde that required an urgent emergency. In fact, in many cases the evaporation of the liquid has determined the deterioration of the specimens; moreover, formalin was replaced with alcohol because it has been declared toxic and the new Museum dispositions require impose the substitution with not dangerous preserving liquids. In the GiPaleo Meeting a selection from over 100 artifacts restored will be exhibited

Early Recovery of Aphasia through Thrombolysis: The Significance of Spontaneous Speech

Aphasia in one of the most devastating stroke-related consequences for social interaction and daily activities. Aphasia recovery in acute stroke depends on the degree of reperfusion after thrombolysis or thrombectomy. As aphasia assessment tests are often time-consuming for patients with acute troke, physicians have been developing rapid and simple tests. The aim of our study is to evaluate the improvement of language functions in the earliest stage in patients treated with thrombolysis and in nontreated patients using our rapid screening tes

A human MMTV-like betaretrovirus linked to breast cancer has been present in humans at least since the copper age

The betaretrovirus Mouse Mammary Tumor Virus (MMTV) is the well characterized etiological agent of mammary tumors in mice. In contrast, the etiology of sporadic human breast cancer (BC) is unknown, but accumulating data indicate a possible viral origin also for these malignancies. The presence of MMTVenv-like sequences (MMTVels) in the human salivary glands and saliva supports the latter as possible route of interhuman dissemination. In the absence of the demonstration of a mouse-man transmission of MMTV, we considered the possibility that a cross-species transmission could have occurred in ancient times. Therefore, we investigated MMTVels in the ancient dental calculus, which originates from saliva and is an excellent material for paleovirology. The calculus was collected from 36 ancient human skulls, excluding any possible mouse contamination. MMTV-like sequences were identified in the calculus of 6 individuals dated from the Copper Age to the 17th century. The MMTV-like sequences were compared with known human endogenous betaretroviruses and with animal exogenous betaretroviruses, confirming their exogenous origin and relation to MMTV. These data reveal that a human exogenous betaretrovirus similar to MMTV has existed at least since 4,500 years ago and indirectly support the hypothesis that it could play a role in human breast cancer

3-Aroyl-1,4-diarylpyrroles inhibit chronic myeloid leukemia cell growth through an interaction with tubulin

We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different substituents at the 1- or 4-phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation. Compound 10 minimally affected the proliferation of normal blood cells, indicating that it may be a promising agent to overcome broad tyrosine kinase inhibitor resistance in relapsed/refractory CML patients. Compound 10 significantly decreased CML proliferation by inducing G2/M phase arrest and apoptosis via a mitochondria-dependent pathway. ARDAP 10 augmented the cytotoxic effects of IM in human CML cells. Compound 10 represents a robust lead compound to develop tubulin inhibitors with potential as novel treatments for CML

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

New tubulin and NHERF1 targeting anticancer agents

The thesis focused on the discovery of novel chemical entities with therapeutic activity. The results presented in this manuscript are divided into three parts and were conducted in Sapienza University – Rome (Part 1-2) and Cardiff University – UK (part 3). The first part contains a set of results on the synthesis and biological evaluation of novel indole and pyrrole derivatives as tubulin polymerization inhibitors. The second part discusses the synthesis of new NHERF1 antagonists in the treatment of colorectal cancer. In the last part, are briefly described the synthesis and biological evaluation of novel inhibitors of Norovirus RNA-dependent RNA polymerase

The rector of the hospital and his wife: two artificial mummies of the late 15th century from Siena (central Italy)

Two artificial mummies found in the hospital church of S. Maria della Scala in Siena (Tuscany, central Italy) and dated bock to the end of the 15th century, were examined. The mummies, in good state of preservation and still wearing their renaissance clothes, were identified as the rector of the hospital, named Salimbene Capacci, and his wife, Margherita Sozzini. Imaging studies, X-rays and CAT were performed. Autopsy made it possible to ascertain that the bodies had been eviscerated by a longitudinal cut from the neck to the pubis and that the thoracic and abdominal cavities had been filled with vegetable material. The pelvis was not eviscerated and the pelvic organs were conserved. The skull showed no traces of craniotomy or excerebration

3-Aroyl-1,4-diarylpyrroles inhibit chronic myeloid leukemia cell growth through an interaction with tubulin

Microtubules are an attractive target for the development of effective anti-leukemia agents.[1] Evidence has accumulated correlating inhibition of tubulin polymerization and leukemic cell proliferation.[2] The activity of colchicine site agents in chronic myeloid leukemia (CML) has not been adequately explored. Recently, starting from previously reported aroylindoles (ARI, 1)[3] we developed a class of 3-aroyl-1-arylpyrroles (ARAPs, 2) via benzocracking approach by shifting the indole benzene moiety to position 1 of the pyrrole ring.[4] ARAPs proved to be potent inhibitors of both tubulin assembly and cancer cells growth, by binding the colchicine binding site. Pursuing our studied on tubulin targeting agents, we designed 3-aroyl-1,4-diarylpyrroles (ARDAPs, 3-16) as potential anticancer agents bearing different substituents at the 1- or 4-phenyl ring (Chart 1). ARDAPs exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin and cancer cell growth. (4-(4-Aminophenyl)-1-phenyl-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from CML patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation. The same compound minimally affected the proliferation of normal blood cells, indicating that it may be a promising agent to overcome broad tyrosine kinase inhibitor resistance in relapsed/refractory CML patients. New ARDAP significantly decreased CML proliferation by inducing G2/M phase arrest and apoptosis via a mitochondria-dependent pathway and increased the cytotoxic effects of IM in human CML cells. References. [1] de Bruin, E. C.; Medema, J. P. Cancer Treat. Rev. 2008, 34, 737-749. [2] Bates, D.; Feris, E. J.; Danilov, A. V. et al. Cancer Biol. Ther. 2016, 17, 291-299. [3] La Regina, G.; Sarkar, T.; Bai, R. et al. J. Med. Chem. 2009, 52, 7512-7527. [4] La Regina, G.; Bai, R.; Coluccia, A. et al. J. Med. Chem. 2014, 57, 6531-6552