Historical account of clinical observations on leprosy and related manifestations in the Comacchio area, Italy, in the XIX century.

Known before Christ and in ancient Egypt, leprosy was believed to be a mysterious disease of supernatural origin. It covered the body with lumps and sores, dulled the senses, produced altered facial features and mutilation of the limbs. By the 6th century AD, the disease had certainly made its appearance in Western Europe and continued to occur in the following centuries. It was also thought to be attributable to poverty and poor sanitation. Leprosy was not considered an infectious disease until 1873, when physician G. H. A. Hansen first identified Mycobacterium leprae, calling it Hansen's bacillus, and the disease was named Hansen's disease. This paper analyses clinical reports on leprosy observed in Northern Italy, in the Comacchio area near Ferrara (Po Delta), in the 19th century, taking into consideration documents and manuscripts of the time. The scholars who made the greatest contribution to the description of the disease in and around Comacchio area were Antonio Campana, Andrea Verga, Alessandro Colla, Clodoveo Biagi, Ottone Schrön, Giacomo Sangalli, Raffaele Cavalieri, and local physicians Cristoforo Belloli, and Francesco Ballotta. Observations on the manifestations of the disease and attempts to cure it, including milk diet, are reported. In particular, this morbid form, which was not found in neighboring territories, was called "Mal di formica" because of its benignity at onset, its slowness and its slow progress. Tubercular Leprosy or Mal di fegato, a form of incurable leprosy was nothing more than the leprosy or elephantiasis described by the Greeks and Hebrews. The people most affected were women, who accounted for two-thirds of the sick. According to some authors, the causes of leprosy could be attributed to overuse of certain rotten or salted fish. Campana was the first to think that a lazaret should be erected for the sick.

A novel conjugated agent between dopamine and an A2A adenosine receptor antagonist as a potential anti-Parkinson multitarget approach.

We propose a potential antiparkinsonian prodrug DP-L-A(2A)ANT (2) obtained by amidic conjugation of dopamine (1) via a succinic spacer to a new triazolo-triazine A(2A) adenosine receptor (AR) antagonist A(2A)ANT (3). The affinity of 2 and its hydrolysis products-1, 3, dopamine-linker DP-L (4) and A(2A)ANT-linker L-A(2A)ANT (5)-was evaluated for hA(1), hA(2A), hA(2B) and hA(3) ARs and rat striatum A(2A)ARs or D(2) receptors. The hydrolysis patterns of 2, 4 and 5 and the stabilities of 1 and 3 were evaluated by HPLC analysis in human whole blood and rat brain homogenates. High hA(2A) affinity was shown by compounds 2 (K(i) = 7.32 ± 0.65 nM), 3 (K(i) = 35 ± 3 nM) and 5 (K(i) = 72 ± 5 nM), whose affinity values were similar in rat striatum. These compounds were not able to change dopamine affinity for D(2) receptors but counteracted the CGS 21680-induced reduction of dopamine affinity. DP-L (4) was inactive on adenosine and dopaminergic receptors. As for stability studies, compounds 4 and 5 were not degraded in incubation media. In human blood, the prodrug 2 was hydrolyzed (half-life = 2.73 ± 0.23 h) mainly on the amidic bound coupling the A(2A)ANT (3), whereas in rat brain homogenates the prodrug 2 was hydrolyzed (half-life > eight hours) exclusively on the amidic bound coupling dopamine, allowing its controlled release and increasing its poor stability as characterized by half-life = 22.5 ± 1.5 min.

Synthesis, antioxidant and antimicrobial activity of a new phloridzin derivative for dermo-cosmetic applications.

The phenolic compound phloridzin (phloretin 2′-O-glucoside, variously named phlorizin, phlorrhizin, phlorhizin or phlorizoside) is a prominent member of the chemical class of dihydrochalcones, which are phenylpropanoids. Phloridzin is specifically found in apple and apple juice and known for its biological properties. In particular we were attracted by potential dermo-cosmetic applications. Here we report the synthesis, stability studies and antimicrobial activity of compound F2, a new semi-synthetic derivative of phloridzin. The new derivative was also included in finished formulations to evaluate its stability with a view to a potential topical use. Stability studies were performed by HPLC; PCL assay and ORAC tests were used to determine the antioxidant activity. F2 presented an antioxidant activity very close to that of the parent phloridzin, but, unlike the latter, was more stable in formulations. To further explore potential health claims, antifungal activity of phloridzin and its derivative F2 were determined; the results, however, were rather low; the highest value was 31,6% of inhibition reached by F2 on Microsporum canis at the highest dose.

The treatment of scrofula in Ferrara (Italy) in the 19th century.

The therapeutic approaches used against scrofula in the 19th Century in Ferrara are discussed. In the manuscripts and treatises of the time treasured in the town's libraries, hygienic and dietetic rules and treatment of this illness were described. In particular, baths and mineral water spas (sulphurous, ferruginous and other mineral waters, such as a bromo-iodine-salt water) and the sea-bathing establishment were recommended. The remedies reported in Campana's Pharmacopoeia ferrarese and the efficacious treatments employed in St Anna Hospital are discussed. The Committee and its President, Marquis Giovanni Manfredini, decided to cure the scrofulous in bathing establishments.

The Italian lazarets of the Adriatic Sea: from their institution to the fight against the economic and demographic collapse caused by epidemics.

Since antiquity, with the growth of the human population and the expansion of nuclei of people (aggregations), infectious diseases have been a constant presence which decisively changed the course of history. The word "lazaret", meaning hospital for the hospitalization and treatment of plague victims and later, also leprosy, is Venetian. It was coined in the 14th century, and was exported to the world; it is still in use although it has slightly modified its meaning: "hospital in general, and shelter for infectious diseases". Lazarets perhaps arose from the overlapping and crossing of the name Nazareth associated with Lazarus, protector of leprosy patients and from other contagious diseases in general. The island of "Lazzaretto Vecchio", overlooking the Lido di Venezia, was named Isola di Santa Maria di Nazareth before the 15th century. However, the first city to take an official step in this direction was the Republic of Ragusa (Croatia), a city-state and flourishing Maritime Republic which was a trading pivot between the Ottoman Empire and the West. In 1377, for the first time in history, the city established a thirty-day quarantine on the three uninhabited islands of Mrkan, Bobara and Supetar for people arriving from infected places. The Republic of San Marco (Venezia) devised one of the oldest and most far-sighted sanitary solutions to contain the spread of the plague: a lazaret, or sanitary model of isolation and treatment that spread, with the name radiating from Venice, around the world. Venetian lazarets were the site of the Republic's innovative strategy to prevent and combat the plague, not only by isolating people for quarantine and goods from infected countries, but also by implementing complex procedures of 'contumacy and purgation' that required a constant investment of economic resources and slowed down traffic. Venice's governors quickly realized that spending money to prevent and fight the plague in lazarets was the only way to counter the economic and demographic collapse caused by epidemics. In the wake of the Venetian and Ragusian lazarets, Trieste also established its first lazaretto in 1717. This was because ships laden with goods from the Near East began to arrive in the city, and this new situation necessitated the adoption of a regulation of contumacy and the construction of a lazaret. This study aims to bring light to the main lazarets over the centuries, particularly those in the Ferrara district and those located in the upper Adriatic Sea, such as Trieste and other neighbouring cities built to fights pandemics.

Antidermatophytic activity of pyrazolo[3,4-c]isothiazoles: a preliminary approach on 4-chlorophenyl derivative for evaluation of mutagenic and clastogenic effects on bacteria and human chromosomes in vitro.

The antifungal activity of eight pyrazolo[3,4-c]isothiazole derivatives was evaluated on five dermatophytes: three were of an anthropophilic species (i.e., Epidermophyton floccosum, Trichophyton rubrum, and Trichophyton tonsurans) and two were of a geophilic species (i.e., Microsporum gypseum and Nannizzia cajetani). The new compounds proved to be unlikely effective in inhibiting the growth of the different strains. In general, the fungi parasitic on man were more sensitive than the geophilic species. This fact can be positive for a possible practical-therapeutic utilization of this class of compounds. To verify their possible use against fungi of medical interest, the most interesting substance at low doses, 6-(4-chlorophenyl)-4-methyl-6H-pyrazolo[3,4-c]isothiazol-3-amine, was chosen to perform in vitro genotoxicity tests using the following: Salmonella/microsome test (SAL), sister chromatid excange test (SCE), cytokinesis-blocked micronucleus test (CBMN), and its improvement (Ara-C/CBMN). The compound showed no mutagenic activity at low doses, whereas at the highest dose (100 µg/mL), it caused a generalized cytotoxic effect. The high growth inhibition exerted on fungi at the lowest dose and the concomitant lack of genotoxicity, at least until the dose of 50 µg/mL, might suggest the compound as a safe candidate as an antidermatophytic substance.

Pyrazolo[3,4-c]isothiazole and isothiazolo[4,3-d]isoxazole derivatives as antifungal agents.

CONTEXT: The diseases of plants and humans due to pathogenic fungi are increasing. Among the substances used to combat fungi, the azoles are of primary interest, both in agricultural field both in health. To avoid fungal resistance phenomena, the synthesis and tests of new derivatives are necessary. OBJECTIVE: This article discusses the synthesis and the antifungal activity of pyrazolo[3,4-c]isothiazole and isothiazolo[4,3-d]isoxazole derivatives against three fungi that are pathogenic only for plants and two fungi that are opportunistic in humans and plants. MATERIALS AND METHODS: The compounds were prepared starting from 2-cyano-3-ethoxy-2-butenethioamide. The antifungal activity of the compounds was determined by measuring the inhibition of growth of the fungi tested at 20, 50, and 100 µg/mL in comparison with the controls. RESULTS: Results demonstrated that several compounds were able to control the mycelial growth of the tested fungi, even if they showed different sensitivity to the different azole-derivatives. In general Magnaporthe grisea (T.T. Hebert) Yaegashi & Udagawa was the most sensitive fungus, being blocked almost entirely by 4-chloro derivative even at 20 µg/mL, a concentration at which the reference commercial compound tricyclazole was nearly ineffective. DISCUSSION AND CONCLUSION: These findings demonstrate that the pyrazolo[3,4-c]isothiazole derivatives have a wide spectrum of activity on phytopathogenic and opportunistic fungi. In particular the 4-chloro derivative seems to have a great potential as new product to combat M. grisea in the agricultural field.

Epidemiological and clinical features of Spanish flu in the city of Ferrara and in Italy. Containment rules and health measures adopted in the past to fight the pandemic.

The "Spanish" flu has often been described as the "Greatest Medical Holocaust in History" and most victims were young and healthy. In Italy, as elsewhere, this pandemic influenza struck in three successive and close waves with incredible speed in a very short time. The virus first arrived in a few Italian regions and gripped the country in an epidemic clamp. When the flu hit Ferrara, the health authorities began to claim that it was no more or less like the same disease that Ferrara had also experienced in the 19th century, although the population was not very willing to believe them. Moreover, the control measures were considered by all to be extremely mild, varying only the opening hours of cinemas and pharmacies and forbidding spitting on the ground; there was no disinfection of stores and streets and the dead were left at home for three days, unlike in larger cities. In 1918-19, Ferrara did much to contain the devastating effects of the war, especially in terms of saving lives. The largest Red Cross unit in Italy, later called Ospedale Nuovo, was built. Moreover, since Ferrara was the first hospital evacuation zone, it was necessary to build other hospitals in the city's schools in addition to the already existing ones, including the famous Ospedale Militare Neurologico di Villa Seminario, which was the first Italian neurological hospital of the Great War for veterans of the front line, intended for the specialised treatment of nervous disorders and psychosis caused by the war or by bombs. We have extracted the cases of death from the Register of Deaths of the Municipality of Ferrara. During the period January 1918 - June 1919, in addition to the number of deaths due to influenza, grippe or Spanish flu we also considered influenza-related complications affecting mortality and identified seven main groups of diseases by grouping them according to morbid forms and anatomical location. According to these criteria, 1,059 deaths were attributable to influenza or related causes during January-December 1918. This partly reflects the excess of deaths in the year 1918 of 1,279 over the average for the years 1916-1919, and 1920. The largest number of deaths was attributable to bronchopneumonia and pneumonia. However, an increase in mortality from other infectious diseases such as typhoid ileus, tuberculosis, malaria and smallpox was observed during the same period until January 2019, making up the shortfall in the total number of deaths recorded.

A Historical Collection of Termites in Ferrara: Recovery, Cataloguing and Geographical Analyses.

Termites are an insect group relevant for recycling of organic matter, but they are also biodeteriogenic and may cause serious damages to wooden structures (including historical buildings and ancient libraries) in anthropogenic environments. The collection of Italian and foreign termites gathered over the years by Antonio Springhetti, Professor of Zoology at the University of Ferrara (Ferrara, Italy) and internationally renowned entomologist, contains over 44,000 specimens, collected by Springhetti during his field campaigns or donated by other entomologists from all over the world. The collection is currently preserved at the Department of Life Sciences and Biotechnology of the University of Ferrara. Unfortunately, all documents, publications and notes concerning the Springhetti Collection were lost; thus, in 2020, the collection was completely re-catalogued within the University Museum System and analyzed in detail. The collection contains specimens dating back to 1878 and represents not only a valuable scientific tool for studies on these ecologically relevant insects that may cause damages to historical buildings, ancient books and artworks but also an important cultural asset for the University Museum System.

Analysis of Insect Pests in an 18th-Century Historical Pharmacy: A Case Study in Ferrara.

Historical pharmacies are valuable artistic, cultural, and scientific assets. In Italy, 482 historical pharmacies have been catalogued thus far, among which is the Navarra-Bragliani Pharmacy in Ferrara, whose wood furniture dates back to the 18th century. A study on insects causing biodeterioration was carried out for the first time on this valuable asset in order to monitor and preserve it. Insect samples were collected during surveys and examined by stereomicroscopy and scanning electron microscopy, using taxonomical keys for identification. The results revealed the presence of three species of Coleoptera-the first one specialised to attack wood materials, the second one polyphagous, and the third one feeding on materials of animal origin. The data obtained in this investigation may be useful for the preservation of the precious furnishing of the historical Navarra-Bragliani Pharmacy for performing similar studies on other ancient pharmacies aimed to protect these valuable cultural and scientific assets.

Cutaneous myiasis in cats and dogs: Cases, predisposing conditions and risk factors.

Two cases of cutaneous myiasis diagnosed in 2018 in Emilia-Romagna region (northern Italy) were reported. The first one, described in a domestic cat Felis silvestris catus L. (Carnivora: Felidae) and caused by Calliphora vicina Robineau-Desvoidy (Diptera: Calliphoridae), was the first one of this type ever reported in Italy in cats. The second one was described in a domestic dog Canis lupus familiaris L. (Carnivora: Canidae) and caused by Lucilia sericata (Meigen) (Diptera: Calliphoridae) and was unusual because it occurred in absence of lesions. An extensive literature search on cutaneous myiasis in these two domestic animal species was performed in order to draw attention to predisposing conditions and risk factors.

The treatment of tuberculosis in Ferrara (Italy) in the 19th century.

The present work is a review of the remedies in use in Ferrara against tuberculosis in the 1800s. The work started from the discovery of accounts describing methods and remedies. These remedies were also in use world wide. Of particular interest is the work by Antonio Campana, a famous professor of Pharmaceutical Chemistry and Botany in Ferrara, who wrote a pharmacopoeia which had several editions between 1797 and 1841. The Farmacopea Ferrarese was addressed to the apothecaries of Ferrara. Nevertheless, due to its great reputation it had an international distribution. It provided us with an exhaustive view about the medical field in Ferrara in the early 1800s. The remedies adopted in the city in the second half of the century were in line with those present abroad. The work was also supported by the discovery of statistical accounts of the Sant'Anna hospital from 1871. The manuscript written by Alessandro Bennati enabled elucidation of the methods used to treat tuberculosis in the second half of the century. Bennati's work is an historical document completed by the work of the physician Cesare Minerbi.

The treatment of syphilis in Ferrara (Italy) in the 19th century: the example of the Ferrarese pharmacopoeia.

The authors have taken the Italian city of Ferrara as an example of the remedies against syphilis, commonly used worldwide in the 1800s. After having identified the terminologies used to diagnose syphilis, they evidence the legislative behaviours of the government authorities in 19th century in Italy and, in particular, the social and sanitary measures taken in Ferrara to limit the spread of the syphilis epidemic. Historical sources permitted description of the remedies employed in Ferrara from the beginning to the end of that century, not only to treat conditions linked directly to the malady itself, but also its complications and secondary pathologies. The pharmacopoeia written for the apothecaries of Ferrara by Antonio Campana, a famous Professor of Pharmaceutical Chemistry and Botany, won a great reputation and distribution in the international medical world not only of the first half of the 1800s. His authoritative work was much appreciated in Italy and abroad.

Control measures of a 400-year-old plague epidemic: an example of past efficiency at controlling disease and similarities with current epidemics.

The plague caused by the bacterium Yersinia pestis, provides one of the best historical examples of pandemic infection. It can therefore be considered the first "globalized" disease, thanks also to the crowds that favoured the rebalancing of infectious agents between Europe and the Middle East. In this paper we analyse all the official documents of the time, highlighting the most effective prevention measures implemented in the city of Ferrara during the Italian plague. Historical mortality data for the 1630 Italian plague in northern Italy are first analysed. In contrast to the high rates recorded throughout the area from Milan to Florence, the mortality rate in Ferrara remained normal over the period. From the city's documents it emerged that the authorities, from the 16th century onwards, had already understood that the spread of the contagion could also occur through domestic animals, although rats are never mentioned. The strength of Ferrara's response to the "plague emergency" stems from an efficient and emergency-ready health control system, financed and supported by the "permanent surveillance team of the city and the Pontifical Legation of Ferrara - Azienda Sanitaria Pubblica" even in times of great economic difficulty for the State. Among the various measures that the city of Ferrara adopted to deal with the plague the following should be mentioned: guards at the city gates, lazarettos, safety of doctors, self-isolation and treatment of every suspicious case as if it were a real case of plague, measures to support the poorer classes of the population, veterinary and hygiene standards for the city and for housing, management of Catholic religious functions and the precepts of the Legation of Ferrara, which was under papal control, closure of churches to avoid mass gatherings, and limitations of all kinds of social and economic relations within and outside the population. The broad regimen, laid down in the 16th century, contains extremely modern health rules which are very much in line with those recommended by the WHO and the health authorities of each individual state in the current COVID-19 pandemic, even starting with hand-washing. The fight against epidemics of the past, especially the history of the plague in the 17th century, anticipates very important and valid concepts, and represents a wake-up call for the recent epidemics of emerging pathogens.

Empirical "integrated disease management" in Ferrara during the Italian plague (1629-1631).

Plague, a highly infective disease caused by Yersinia pestis (Proteobacteria: Enterobacteriales), ravaged Europe from 1347 over the course of more than 450 years. During the Italian Plague (1629-1631), the disease was rampaging in the entire Northern Italy down to Tuscany, but the city of Ferrara was relatively spared, in spite that the economic activities were maintained with highly affected cities, such as Milan, through the relevant salt commerce. The aim of the study is to evaluate the hygiene rules that were effective in preventing the spread of the plague in Ferrara in 1630, by examining historical documents and reports. According to these documents, a kind of empirical "integrated disease management" was carried out, using remedies including compounds with bactericidal, anti-parasite and repellent activity, and by technical strategies including avoidance of possible plague carriers. The anti-plague remedies and technical strategies used in ancient Ferrara are critically analysed using a multidisciplinary approach (pharmaceutic, medical, epidemiologic and entomological) and compared to current prevention protocols.

Comparative Study of SPA Mud from "Bacino Idrominerario Omogeneo dei Colli Euganei (B.I.O.C.E.)-Italy" and Industrially Optimized Mud for Skin Applications.

The term "Salus per aquam (SPA) therapies" refers to therapeutic pathways that includes mud therapy. The therapeutic efficacy of a peloid depends on its chemical and mineralogical composition, as well as its technological properties. Considering the increasing use of clay-based products, it becomes essential to characterize peloids from a qualitative and quantitative point of view. Therefore, this research project aimed to develop a protocol that allows characterization of the chemical-physical composition of sludges collected from different areas of the Homogeneous Euganean Hills Hydromineral Basin (B.I.O.C.E.). The study established a comparative study both between different matrices and between the same matrices at different maturation times, including also a comparison with an industrialized product, that can be used at home, which maintains the characteristics of a natural mud. This research was developed studying the pH, grain size distribution, and chemical and mineralogical composition. Peloids are characterized by a neutral/basic pH and are divided into two categories from a granulometric point of view: The chemical composition allowed observation of numerous correlations between oxides present in the samples and to quantify the presence of heavy metals. Mineralogical analysis made it possible to identify and compare the composition of each sample, also according to the maturation time. Thanks to the methods adopted, important correlations were achieved.

Gonorrhea, a current disease with ancient roots: from the remedies of the past to future perspectives.

Gonorrhea can be traced back to the earliest records of the human race even if Albert Neisser first described gonococcus in 1879. The Romans, Jews and Arabs all have documents referring to gonorrhea and each society had their own description of symptoms and treatment. The Roman physician Galen in 130 AD described the disease as an "involuntary escape of semen". The word itself derives from the Greek, meaning "the flow of seed". Gonorrhea is currently the second most commonly notifiable sexually transmitted infection (STI) reported to Centers for Disease Control and Prevention (CDC), second only to chlamydial infection. Gonorrhea notifications have been on the rise all over the world and in several European countries since the early 2000s, particularly in populations with higher frequency of spread of STIs, such as men who have sex with men and young heterosexual individuals of both sexes. Having been recognized at least 3500 years ago, the fight against the disease began infinitely before the antibiotic era, using healing compounds. In the absence of an ideal vaccine, the most important challenge today is the emergence of the multidrug-resistant gonorrhea, which is currently the main reason for public concern responsible for the evolution of N. gonorrheae into a superbug. N. gonorrheae strains resistant to extended spectrum cephalosporin (ESC) form a threat to effective control of gonorrhea for which there are currently ongoing clinical trials to evaluate the efficacy and safety profile of old and new antimicrobial molecules for monotherapy and as dual therapy of gonorrhea. In this paper we investigated the remedies and treatments employed against gonorrhea during the 19th century in Ferrara, referring to Campana's Pharmacopoeia and unpublished manuscripts concerning the treatment of this disease in medical practice. The remedies for gonorrhea adopted in the city were in line with those utilized in other countries. Among these, copaiba oleoresins have been demonstrated to have been efficacious in the past against gonococcal disease in popular medical use and, recently, against a large number of bacteria, fungi and protozoa, which will call for more in vitro and clinical studies to evaluate their real effectiveness on the N. gonorrheae bacterium.