Histopathological effects of long-term exposure to realistic concentrations of cadmium in the hepatopancreas of Sparus aurata juveniles.

In recent decades, cadmium has emerged as an environmental stressor in aquatic ecosystems due to its persistence and toxicity. It can enter water bodies from various natural and anthropogenic sources and, once introduced into aquatic systems, can accumulate in sediments and biota, leading to bioaccumulation and biomagnification in the food chain. For this reason, the effects of cadmium on aquatic life remain an area of ongoing research and concern. In this paper, a multidisciplinary approach was used to assess the effects of long-term exposure to an environmental concentration on the hepatopancreas of farmed juveniles of sea bream, Sparus aurata. After determining metal uptake, metallothionein production was assessed to gain insight into the organism's defence response. The effects were also assessed by histological and ultrastructural analyses. The results indicate that cadmium accumulates in the hepatopancreas at significant concentrations, inducing structural and functional damage. Despite the parallel increase in metallothioneins, fibrosis, alterations in carbohydrate distribution and endocrine disruption were also observed. These effects would decrease animal fitness although it did not translate into high mortality or reduced growth. This could depend on the fact that the animals were farmed, protected from the pressure deriving from having to search for food or escape from predators. Not to be underestimated is the return to humans, as this species is edible. Understanding the behaviour of cadmium in aquatic systems, its effects at different trophic levels and the potential risks to human health from the consumption of contaminated seafood would therefore be essential for informed environmental management and policy decisions.

From ancient leech to direct thrombin inhibitors and beyond: New from old.

Medicinal leeches have been used in health care since before written history, with widely varying popularity over the centuries. Nowadays, medicinal leech therapy is mainly used in plastic and reconstructive microsurgery, with new interesting potential therapeutic applications in many other diseases. The leech's best-known salivary product, hirudin - one of the most powerful natural anticoagulants - was the only remedy to prevent blood clotting until the discovery of heparin. Starting from hirudin, pharmacological research succeeded in developing new anticoagulants, which represent a cornerstone of prevention and treatment of thromboembolic disease. While we are perhaps on the threshold of a new era of anticoagulation, with the development of FXI and XII inhibitors and direct reversible covalent thrombin inhibitors, which promise to achieve effective anticoagulation without bleeding risk. This review retraces the intriguing journey of these drugs in cardiovascular disease, highlighting the fil rouge that links the ancient leech to the current and oncoming antithrombotic therapy. We think that knowledge of the past is key to understanding and appreciating the present and to seize future opportunities.

Patterns of coronary heart disease mortality in Italy from 1931 to 2015 and a focus on a region with highly industrialized areas.

BACKGROUND: Coronary Heart Disease (CHD) is associated with various risk factors, including environmental stressors. The aim of our paper is to study the mortality patterns in Italy with a focus on provinces of the Apulia Region from 1931 to 2015 to analyze the burden of the disease over time. METHODS: We conducted an ecological analysis of mortality from all causes and from CHD in main Italian geographical areas and in the Apulian provinces, from 1931 to 2015. Sex-specific mortality and population data were obtained from the Italian National Institute of Statistics since 1969. Direct standardized mortality rates (SDRs) per 10,000 inhabitants with 90% confidence intervals (90%CI) were calculated from 1969, using the European population as standard. The standardized mortality ratios (SMRs%) were calculated with 90%CI and the Italian population as reference. RESULTS: The SDRs indicate a decline in mortality from CHD in all geographical Italian areas and in the Apulian provinces for both sexes. However, this decline slowed over time, particularly in the South. The highest values of SMRs% were observed in the industrialized areas of Taranto and especially Brindisi, in both sexes. CONCLUSIONS: The historical reconstruction over about 80 years highlighted critical issues for CHD at the start of the industrial development in the provinces of Brindisi and Taranto. This might suggest environmental pollution as risk factor for cardiovascular diseases. Furthermore, it would be necessary to verify how much other risk factors (eg. diabetes and obesity) affect the slowdown in the CHD mortality decline over the last decade.

Eighty years of oral anticoagulation: Learning from history.

In the year 2021 we celebrate the 80th anniversary of the first clinical use of vitamin K antagonists (VKAs), the mainstay of prevention and long-term treatment of thromboembolic disease. The discovery and development of oral anticoagulants is one of the most important chapters in the history of medicine, a goal pursued by physicians trying to combat the clinical manifestations of thrombosis since ancient times. Until the last decade, VKAs were the only oral anticoagulants available and used in clinical practice. Today, their clinical use has progressively shrunk, as the non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly replacing VKAs in various conditions after the successful completion of several large randomized controlled trials. Currently, new research is tackling upstream components of the intrinsic pathway - particularly factor XI and factor XII - for the development of new, even safer anticoagulants promising to reduce bleeding without compromising efficacy. This review highlights the evolution of oral anticoagulant therapy tracing the key stages of a long and fascinating history that has unfolded from the first part of the twentieth century until today, indeed an intriguing journey where serendipity is intertwined with the tenacious work of many researchers.

Reflections on Atherosclerosis: Lesson from the Past and Future Research Directions.

The clinical manifestations of atherosclerosis are nowadays the main cause of death in industrialized countries, but atherosclerotic disease was found in humans who lived thousands of years ago, before the spread of current risk factors. Atherosclerotic lesions were identified on a 5300-year-old mummy, as well as in Egyptian mummies and other ancient civilizations. For many decades of the twentieth century, atherosclerosis was considered a degenerative disease, mainly determined by a passive lipid storage, while the most recent theory of atherogenesis is based on endothelial dysfunction. The importance of inflammation and immunity in atherosclerosis's pathophysiology was realized around the turn of the millennium, when in 1999 the famous pathologist Russell Ross published in the New England Journal of Medicine an article entitled "Atherosclerosis - an inflammatory disease". In the following decades, inflammation has been a topic of intense basic research in atherosclerosis, albeit its importance has ancient scientific roots. In fact, in 1856 Rudolph Virchow was the first proponent of this hypothesis, but evidence of the key role of inflammation in atherogenesis occurred only in 2017. It seemed interesting to retrace the key steps of atherosclerosis in a historical context: from the teachings of the physicians of the Roman Empire to the response-to-injury hypothesis, up to the key role of inflammation and immunity at various stages of disease. Finally, we briefly discussed current knowledge and future trajectories of atherosclerosis research and its therapeutic implications.

The Mediterranean Diet And Cardioprotection: Historical Overview And Current Research.

Ancient Greece was the cradle of the Mediterranean food tradition, characterized by the Mediterranean "eternal trinity" wheat - olive oil - wine, the very essence of the country's traditional agricultural and dietary regime, enriched by a culture of sharing and commensality. This food model, subsequently adopted and spread by the Romans, was rediscovered at the end of the Second World War by two American researchers, Leland Allbaugh and Ancel Keys. With the famous Seven Countries Study, Keys demonstrated for the first time that populations practicing a Mediterranean diet - such as the Greeks and southern Italians - showed low mortality rates from ischemic heart disease compared to the peoples of Northern Europe and North America. Since then, numerous subsequent epidemiological studies and randomized clinical trials have confirmed the beneficial effects of the Mediterranean diet both in primary and secondary prevention of cardiovascular diseases. This review will focus on the origins of the Mediterranean diet from its roots and its relationship to cardiovascular disease, with a brief overview of the nutritional mechanisms that influence atherosclerosis.

The first 200 years of cardiac auscultation and future perspectives.

Cardiac auscultation - even with its limitations - is still a valid and economical technique for the diagnosis of cardiovascular diseases, and despite the growing demand for sophisticated imaging techniques, clinical use of the stethoscope in medical practice has not yet been abandoned. In 1816, René-Théophile-Hyacinthe Laënnec invented the stethoscope, while examining a young woman with suspected heart disease, giving rise to mediated auscultation. He described in detail several heart and lung sounds, correlating them with postmortem pathology. Even today, a correct interpretation of heart sounds, integrated with the clinical history and physical examination, allows to detect properly most of the structural heart abnormalities or to evaluate them in a differential diagnosis. However, the lack of organic teaching of auscultation and its inadequate practice have a negative impact on the clinical competence of physicians in training, also reflecting a diminished academic interest in physical semiotic. Medical simulation could be an effective instructional tool in teaching and deepening auscultation. Handheld ultrasound devices could be used for screening or for integrating and improving auscultatory abilities of physicians; the electronic stethoscope, with its new digital capabilities, will help to achieve a correct diagnosis. The availability of innovative representations of the sounds with phono- and spectrograms provides an important aid in diagnosis, in teaching practice and pedagogy. Technological innovations, despite their undoubted value, must complement and not supplant a complete physical examination; clinical auscultation remains an important and cost-effective screening method for the physicians in cardiorespiratory diagnosis. Cardiac auscultation has a future, and the stethoscope has not yet become a medical heirloom.

The first 3500 years of aspirin history from its roots - A concise summary.

Aspirin is currently the most widely used drug worldwide, and has been clearly one of the most important pharmacological achievements of the twentieth century. Historians of medicine have traced its birth in 1897, but the fascinating history of aspirin actually dates back >3500 years, when willow bark was used as a painkiller and antipyretic by Sumerians and Egyptians, and then by great physicians from ancient Greece and Rome. The modern history of aspirin precursors, salicylates, began in 1763 with Reverend Stone - who first described their antipyretic effects - and continued in the 19th century with many researchers involved in their extraction and chemical synthesis. Bayer chemist Felix Hoffmann synthesized aspirin in 1897, and 70 years later the pharmacologist John Vane elucidated its mechanism of action in inhibiting prostaglandin production. Originally used as an antipyretic and anti-inflammatory drug, aspirin then became, for its antiplatelet properties, a milestone in preventing cardiovascular and cerebrovascular diseases. The aspirin story continues today with the growing evidence of its chemopreventive effect against colorectal and other types of cancer, now awaiting the results of ongoing primary prevention trials in this setting. This concise review revisits the history of aspirin with a focus on its most remote origins.

[Tobacco cultivationin Salento (Apulia Region, Southern Italy) from 1929 to 1993: possible health implications]. / La tabacchicoltura nel Salento dal 1929 al 1993: possibili implicazioni sanitarie.

The Province of Lecce (Apulia Region, Southern Italy) is one of the Italian areas where the prevalence of respiratory disease and cancer of the respitartory tract is very high. Through a descriptive analysis of the historical series of tobacco culture indicators, a historical reconstruction of the development of tobacco cultivation in Salento (the area where the Province of Lecce is located) is here presented, in order to provide an additional element of knowledge on potential risk factors for respiratory diseases and cancers. Data regarding extensions in hectares and crop productions in the province of Lecce, in Apulia, and in Italy are from the Chamber of commerce of Lecce province and from the Italian National Institute of Statistics (Istat). From 1929 to 1993, the province of Lecce provided between 75% and 94% of the tobacco cultivated in Apulia Region and 25% of the national tobacco until 1945. Since the late Sixties, a growing increase in annual average production was observed, reaching 21.5 quintals per hectare in 1991 in Salento. This large tobacco production, associated with intensive use of pesticides, could be an element to be observed in analytical studies as a determining potential for the high prevalence of respiratory diseases and pulmonary cancers in the male population of the province of Lecce.

History of Music Therapy and Its Contemporary Applications in Cardiovascular Diseases.

Contrary to what is commonly believed, music therapy is an old cure, the use of which is lost in the mists of time. Music always has been perceived to have particular healing powers, and the entire history of civilization contains aspects that link music to physical and mental healing. It seems that the adoption of music for therapeutic purposes harks back to a distant past, probably since the Paleolithic period: it was believed that listening to music could affect the behavior of human beings. In later centuries, the concept of "musical organ-tropism" was born and developed, because according to the type of music, one may affect the cardiovascular, respiratory, and neuroendocrine systems. Studies have shown that music can powerfully evoke and modulate emotions and moods, along with changes in heart activity, blood pressure, and breathing. Indeed, the following findings arise from the literature: heart and respiratory rates are higher in response to exciting music than in the case of tranquilizing music. In addition, music produces activity changes in brain structures (amygdala, hypothalamus, insular and orbitofrontal cortex) known to modulate heart function. This article provides a careful overview of music therapy history from prehistory to the present and a review of the latest applications of music therapy in cardiovascular diseases.

The wounded maternity in the fine arts.

The historian Fielding Garrison wrote that the history of medicine is the history of mankind, as it encompasses all of human life. This means that the history of medicine encourages us to critically reflect not only on the information (the what, the world of facts) but also invites us to move towards understanding (the who, the world of stories). Next to the historical change, there is the anthropological duration with its baggage of immutable values that art brings to light. The merit of art is to focus not only on the biological aspects, but also on the social and emotional ones that define the mother/child relationship. The paintings that we have analyzed "speak" of care and caregiving, grief and suffering where maternity is experienced in solitude, in misery, in sickness. And it is to this latter aspect that we have drawn our attention. Most of the works are autobiographical or relate to events actually experienced by the artist. The theme of the wounded maternity has many facets, but all are united by the absence and loss of something precious: a son, a husband, health, affection.

Long term exposure to cadmium: Pathological effects on kidney tubules cells in Sparus aurata juveniles.

The effects of an exposure to cadmium chloride 0.47µM for 150days were studied in kidneys of juveniles Sparus aurata by a multidisciplinary approach so to correlate uptake and detoxification potential to changes in brush border and glycocalyx sugar composition. Results demonstrated that cadmium concentration in kidney significantly increased from day 30 reaching a plateau on day 120 while metallothioneins reached a peak on day 90 and by day 120 were already decreasing to control values. Cytological damage was extensive on day 90, clearly detectable at both structural and ultrastructural levels, in tubular cells and brush-border. Staining with a panel of four lectins revealed a significant increase in N-Ac-Gal and a decrease in mannose in the glycocalyx and the tubular basal membranes. From day 120, when cadmium concentration was high and metallothionein concentration decreasing, a clear recovery was observed in tubular cells morphology and sugar composition. Possible significance of these apparently contrasting data are discussed.

[Mortality from respiratory diseases in the provinces of Apulia Region (Southern Italy) from 1933 to 2010]. / La mortalità per patologie respiratorie nelle province pugliesi dal 1933 al 2010.

OBIETTIVI: valutare l'andamento temporale della mortalità per patologie respiratorie nelle province pugliesi utilizzando dati omogenei per fonte e metodologia di calcolo. DISEGNO: analisi ecologica storica degli andamenti temporali di mortalità per tumori e patologie dell'apparato respiratorio nelle province pugliesi, in Puglia e nelle ripartizioni geografiche italiane dal 1933 al 2010. SETTING E PARTECIPANTI: i dati di mortalità e le popolazioni residenti sono di fonte Istat. Sono state esaminate tutte le cause di decesso, il tumore della laringe, il tumore del polmone, l'insieme dei tumori respiratori, la bronchite, la polmonite e la broncopolmonite considerate congiuntamente, e l'insieme delle patologie respiratorie. Le analisi sono disaggregate per sesso dal 1969. PRINCIPALI MISURE DI OUTCOME: rapporti standardizzati di mortalità (SMR%) in riferimento all'Italia, con intervalli di confidenza al 95%, e tassi di mortalità standardizzati col metodo diretto (TSD ) in riferimento alla popolazione standard europea. RISULTATI: dal 1933 al 2010, i TSD per tumori respiratori e per bronchiti diminuiscono in tutte le aree analizzate. Tuttavia, nelle province di Taranto, Brindisi e Lecce, l'SMR% per tumori respiratori, inferiore al riferimento nazionale fino agli anni Sessanta, si allinea (a Brindisi) e supera (a Lecce e Taranto) il riferimento negli anni successivi. Nelle province di Foggia e Bari il numero dei decessi per tumore del polmone è costantemente inferiore all'atteso. CONCLUSIONI: la ricostruzione storica e l'analisi dei trend temporali di mortalità dal 1933 al 2010 mostrano alcune criticità sanitarie in periodi specifici. L'elaborazione dei dati di mortalità per un arco temporale di circa 80 anni ha messo in evidenza la maggiore rilevanza di queste criticità con l'avvio dello sviluppo industriale.

[The mortality rate for homicide among women in Italy: a historical and geographical analysis as a contribution to the study of femicide]. / La mortalità per omicidio tra le donne in Italia: un'analisi storico-geografica come contributo allo studio del femminicidio.

As 70% of the killings of women takes place in the context of relational dynamics and in 80% of the cases the perpetrator is a man, we can presume that femicide constitutes much of the homicide mortality among women. Epidemiological surveillance of the killings of women can, therefore, provide indicators on the trends and geographical distribution of femicide and, indirectly, of the more general phenomenon of harassment and violence against women. The analysis of 40 years of mortality shows only a slight decrease of the murders of women nationwide. This suggests that the factors that underline this phenomenon are deeply rooted in the relationship between men and women. The decrease has taken place mainly in the South and Islands and the percentage SMRs point to a reversal of the relationship between geographic areas: thus, at the end of the observation period the North-West assumes a greater weight than the South and Islands. So we cannot exclude that part of the decrease in murders of women can be attributed to the overall decrease in homicides related to criminal activity, most pronounced in the South and Islands.

Endothelial safety of radiological contrast media: why being concerned.

Iodinated radiocontrast media have been the most widely used pharmaceuticals for intravascular administration in diagnostic and interventional angiographic procedures. Although they are regarded as relatively safe drugs and vascular biocompatibility of contrast media has been progressively improved, severe adverse reactions may occur, among which acute nephropathy is one of the most clinically significant complications after intravascular administration of contrast media and a powerful predictor of poor early and long-term outcomes. Since radiocontrast media are given through the arterial or the venous circulation in vascular procedures, morphological and functional changes of the microvascular and macrovascular endothelial cells substantially contribute to the pathogenesis of organ-specific and systemic adverse reactions of contrast media. Endothelial toxicity of contrast media seems to be the result of both direct proapoptotic effects and morphological derangements, as well as endothelial dysfunction and induction of inflammation, oxidative stress, thrombosis, and altered vasomotor balance, with predominant vasoconstrictive response in atherosclerotic coronary arteries and kidney microcirculation. Further understanding of pathogenetic mechanisms underlying contrast media-induced adverse reactions in cellular targets, including endothelial cells, will hopefully lead to the development of novel preventive strategies appropriately curbing the pathogenesis of contrast media vasotoxicity.

[Historical epidemiology of leukaemia mortality in Salento (Italy) from 1902 to 2002]. / Analisi storico-epidemiologica sulla mortalità per leucemia nel Salento dal 1902 al 2002.

The aim of this study is to investigate leukaemia mortality in Salento. Leukaemia mortality in Salento's population is compared to data for Apulia and Italy, for 1902 to 2002. With particular reference to the period from 1969 to 2002, the paper looks at leukaemia mortality in male and female populations. Data on all eligible leukaemia deaths was obtained from the National Institute of Statistics (ISTAT). An increase of leukaemia mortality was observed both in male and female populations. Leukaemia mortality in Salento's female population was greater than amongst males.

Omega-3 fatty acids, inflammation and angiogenesis: nutrigenomic effects as an explanation for anti-atherogenic and anti-inflammatory effects of fish and fish oils.

Atherosclerosis is a dynamic process with inflammatory aspects playing a considerable pathogenetic role. In this process, the vascular endothelium is the key regulator of vascular function, promoting the maintenance of vascular homeostasis or the progression towards vascular disease. In the past 30 years, the dietary intake of omega-3 (n-3) polyunsaturated fatty acids - mainly derived from fish - has emerged as an important way to modify cardiovascular risk through beneficial effects on all stages of atherosclerosis. This review specifically focuses on the modulating effects of n-3 fatty acids on molecular events involved in early and late atherogenesis, including effects on endothelial expression of adhesion molecules, as well as pro-inflammatory and pro-angiogenic enzymes. By accumulating in endothelial membrane phospholipids, omega-3 fatty acids have been shown to decrease the transcriptional activation of several genes through a decreased activation of the nuclear factor-kappaB system of transcription factors. This occurs secondary to decreased generation of intracellular reactive oxygen species. This series of investigations configures a clear example of nutrigenomics, i.e. how nutrients may affect gene expression, ultimately affecting a wide spectrum of human diseases.