Search

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.

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 14 th 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 15 th 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.

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.

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., Competing Interests: Conflict of interest None., (Copyright © 2016 - 2021 InfezMed.)

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.

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., (© 2020 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

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.

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.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

Purpose: The aim of the present study was to compare two therapeutic protocols of dexamethasone for the prevention of postoperative swelling, pain, and other complications after the extraction of impacted third molars, in a prospective, randomized, crossover, double-blinded clinical trial., Methods: Fifty patients with symmetrical impaction of third molars were randomly assigned to two different protocols of dexamethasone for each side. Patients underwent two sessions performed at a 21-day interval. In group 1, patients took 8 mg of dexamethasone orally 1 h before the procedure, and in group 2, 4 mg dexamethasone orally 1 h before and 24 h after the procedure. Surgery duration, volume of local anesthetics, surgical technique, and rescue medication were standardized. Postoperative pain was evaluated using a visual analog scale (VAS) at predefined times: before operation; immediately after; 1, 2, 4, and 12 h; and 1, 2, 3, and 7 days after operation. The patients were also instructed to take notes of the number of rescue medication tablets taken. Edema and mouth opening were clinically evaluated before surgery and in the postoperative period (second and seventh postoperative days)., Results: There were no significant differences between groups for VAS scales (p = 0.5048), but the use of rescue medication was significantly lower in group 1 (p = 0.006). None statistically significant differences (p > 0.05) were observed between groups in any of the time points for all measurements of edema. However, the mouth opening limitation (DIINC) was bigger (p = 0.0069) for group 1 at 2 days., Conclusion: Pre-emptive use of different dexamethasone regimens had a beneficial effect against pain, edema, and mouth opening limitation, especially when administered at an 8 mg concentration, which suggests that this protocol may also be efficient for more invasive surgery.

Louse infestation is one of the oldest contagious pestilential diseases of humankind, which has recently re-emerged in several developing countries as well as in homeless individuals and migrants. The present work provides the first phase of an historical excursus of louse remedies based on the classics of pharmaceutical literature, codes, pharmacopoeia and treatises. The second phase involves a literature search, based on the principal medical databases (SciFinder, Pubmed, Google Scholar, ISI-Web of Science and Scopus), to match ancient raw materials and active principles for the treatment of pediculosis and their possible applications, with other current infectious pathologies transmitted by different carriers. In this regard, Rhododendron tomentosum has revealed repellent insect activity, particularly against Aedes aegypti, responsible for Dengue fever, Chikungunya, Zika fever, Mayaro, yellow fever and other infectious diseases. Petroselinum crispum is an insecticide employed for resistant strains of A. aegypti. In the case of Delphinium staphisagria, the phytochemical profile was further investigated with the identification of further molecules in addition to delphinine. The latter shows interesting activities against Trypanosoma cruzi and Leishmania. Anthemis pyrethrum, now renamed as Anacyclus pyrethrum, although not containing pyrethrins present in several plants of the genus Chrysanthemum, revealed pediculicidal activity but did not produce satisfactory results in antiprotozoal activity.

A comprehensive study on essential oil samples of Foeniculum vulgare Miller from Tarquinia (Italy) is reported. A 24-h systematic steam distillation was performed on different harvested samples applying different extraction times. The GC-MS analysis of the residue outcome showed o-cymene, α-phellandrene, α-pinene and estragole as the major constituents. The predominance and continued presence of o-cymene makes this fennel oil a rather unique chemotype. An evident correlation between the antifungal activity and phenological stage is demonstrated. The most active fractions were particularly rich in estragole, as well as a significant amount of fenchone that possibly exerts some additive effect in the expression of overall antifungal potency. Pre-fruiting material produced oil particularly rich in o-cymene. With reference to the duration of the extraction, the maximum amount of oil was released within the first 3 h, whereas the reproductive phase material needed at least 6 h for the extraction.

In this work, we evaluated the antidermatophytic activities of three resorcinol derivatives that have a history of use in dermo-cosmetic applications to discover molecules with multiple dermatological activities (i.e., multi-target drugs), thereby reducing the cost and time necessary for new drug development. The antidermatophytic activities of the three skin lighteners were evaluated relative to the known antifungal drug fluconazole on nine dermatophytes responsible for the most common dermatomycoses: Microsporum gypseum , Microsporum canis , Trichophyton violaceum , Arthroderma cajetani , Trichophyton mentagrophytes , Epidermophyton floccosum , Nannizzia gypsea , Trichophyton rubrum and Trichophyton tonsurans . Among the three tested resorcinols, only two showed promising properties, with the ability to inhibit the growth of all tested dermatophytes; additionally, the IC 50 values of these two resorcinols against the nine dermatophytes confirmed their good antifungal activity, particularly for phenylethyl resorcinol against M. gypseum . Ultrastructural alterations exhibited by the fungus were observed using scanning electron microscopy and transmission electron microscopy and reflected a dose-dependent response to treatment with the activation of defence and self-preservation strategies.

The retrospective analysis undertaken by our working group in the sphere of infectious diseases, with particular emphasis on nineteenth-century epidemics, regards influenza, which according to the scholar W.I. Beveridge, was defined as "one of the greatest enemies of man". The work is divided into three parts: influenza, its historical names and the characteristics of the recurrent epidemics from the sixteenth to the nineteenth century among the world's population. This part is followed by treatment and remedial action in the nineteenth century. The third, deals with death attributed to influenza and its complications observed in the city of Ferrara in the years when outbreaks occurred, affecting the majority of the populations: 1830-1833, 1836-1837, 1847-1848, 1857-1858, 1873-1875, 1889-1892, the latter known as the great pandemic.

Multi-target strategies are directed toward targets that are unrelated (or distantly related) and can create opportunities to address different pathologies. The antidermatophytic activities of nine natural skin lighteners: α-bisabolol, kojic acid, β-arbutin, azelaic acid, hydroquinone, nicotinamide, glycine, glutathione and ascorbyl tetraisopalmitate, were evaluated, in comparison with the known antifungal drug fluconazole, on nine dermatophytes responsible for the most common dermatomycoses: Microsporum gypseum, Microsporum canis, Trichophyton violaceum, Nannizzia cajetani, Trichophyton mentagrophytes, Epidermophyton floccosum, Arthroderma gypseum, Trichophyton rubrum and Trichophyton tonsurans. α-Bisabolol showed the best antifungal activity against all fungi and in particular; against M. gypseum. Further investigations were conducted on this fungus to evaluate the inhibition of spore germination and morphological changes induced by α-bisabolol by TEM.

Some areas of Northern Italy, especially Ferrara during the nineteenth century, represent privileged observatories regard to malaria, a disease that affected the poor, but did not spare the rich and powerful people. The so called Delta of the River Po, as well as the Maremma and other lowland areas in Italy, was particularly noted for its marshland environment (mosquito breeding grounds). Spared from Malaria because of the better hygienic conditions of the city that restricted the proliferation of anopheles, Ferrara represented an important study centre due to the presence of renowned physicians and scientists who exchanged knowledge and findings in the medical academies. Among these, Antonio Campana was very attentive to the latest scientific findings, and wrote about antimalarial remedies in his famous Ferrarese Pharmacopoeia. This paper analyses the main remedies listed in the various editions of Campana Pharmacopoeia since 1798 and particularly that of 1841, in the reports from the Accademia Medico Chirurgica di Ferrara and of Argenta physicians of the mid nineteenth century and in the Reports (1871 and 1876) from Alessandro Bennati, director of Arcispedale Santa Anna and concerned with hospital practice. Other printed documents referring to the town of Argenta are discussed.

Health interventions against smallpox during the two epidemics in the second half of the 19th century are outlined. The 1871 hospital health report and the medical report on smallpox patients treated at the hospital and poorhouse of Ferrara between January 1891 and January 1892, drawn up by Alessandro Bennati, provide both interesting data and insights into the treatments and remedies of the time. The treatment of this illness was - and indeed could be - nothing other than symptomatic, there being no real means to halt the spread of the disease. Rather, other remedies were found by alleviating pain and regaining energy during the various stages of the disease. A close relationship between vaccination and the incidence and gravity of the illness is underlined. When the practice of vaccination started to be widely employed at the end of the century, there were almost no cases of death due to smallpox. The pharmacopoeias of the time, Antonio Campana's Farmacopea ferrarese in particular, proved an essential guide in the analysis of each document.

The authors carried out an observational study for the years 1867-1874 on the morbidity of children from Ferrara suffering from scrofula, sent to marine hospices for sea bathing treatment. A total of 490 cases (250 F, 240 M) were studied in relation to the following variables: age, sex, forms of scrofula, years and outcome. In particular, the present work describes the preliminary organizational steps planned to allow the seaside stay, the clinical features and the outcomes. Dissemination of information to the public and to benefactors had the specific aim to strengthen these benefits for those children affected by the sad and serious consequences of scrofula.

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 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.

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.

Our first study of tuberculosis in Ferrara during the nineteenth century, whose results have been recently published, focused on disease treatment. Here we present the descriptive analysis of mortality, with the following results being attained: two behavioural patterns are detected with regard to the onset of disease, before and after 1850; TB is a specific disease that affects all parts of the body in all age groups: childhood, and active and passive populations; there are no significant differences with regard to gender; as regards the occupations performed by the deceased, those related to industry and agriculture and to various other activities and services are those with the highest mortality; tuberculosis has a seasonal pattern; summer and autumn are the periods of greatest prevalence (hot weather and humidity are factors that affect the respiratory system); among the forms of tuberculosis it can be observed that up to the year 1850 people died in Ferrara either of pulmonary tuberculosis or TB localised in other areas; from 1851 onward there appears to have been a dramatic change, with a decrease in unspecific diagnosis but the appearance of disease manifestations in its various clinical forms.

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.

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.

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 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.

The present study was carried out to investigate the antifungal activity of pyrazole/isoxazole-3-carboxamido-4-carboxylic acids, 4-oxo-5-substituted pyrazolo[3,4-d]pyrimidine-6-thiones, and N-alkyl/aryl-N'-(4-carbethoxy-3-pyrazolyl)thioureas against Pythium ultimum, Botrytis cinerea, and Magnaporthe grisea. The results on growth inhibition showed differences in the sensitivity of the three fungi to the tested substances, and in general P. ultimum was shown to be the most sensitive. On all phytopathogens the best results within the pyrazole/isoxazolecarboxamide series are given by the compounds with the carboxamide and carboxylic groups in positions 3 and 4; the presence of these groups seems to be critical for biological activity in this series of compounds. Among the pyrazolopyrimidines the derivative supplied with the benzylic group was the most active on the three fungi and in particular against P. ultimum. Several compounds belonging to the thiourea series are able to inhibit selectively M. grisea at 50 and 10 microg mL(-1), doses at which the reference commercial compound tricyclazole had low or no effect.

Derivatives of pyrazolo[1,5-a][1, 3, 5]triazine-2,4-dione,pyrazolo[1,5-c][1, 3, 5]thiadiazine-2-one, pyrazolo[3,4-d][1, 3]thiazine-4-one, and pyrazolo[3,4-d][1, 3]thiazine-4-thione were screened for antifungal activity against the causal agent of rice blast disease, Magnaporthe grisea. The compounds were tested at doses ranging from 10 to 200mugml(-1), using the commercial fungicide tricyclazole as reference compound. All triazine derivatives inhibited the growth and pigmentation of the mycelia less effectively than tricyclazole. The thiadiazine derivatives proved to be more effective than their triazine counterparts, but only 4-(butylimino)-7-methylpyrazolo[1,5-c][1,3,5]thiadiazine-2-one (2h) and 4-(cyclohexylimino)-7-methylpyrazolo[1,5-c][1,3,5]thiadiazine-2-one (2j) were more effective than tricyclazole. Pyrazolo[3,4-d][1,3]thiazine-4-one derivatives were active only at the highest doses, whereas members of the pyrazolo[3,4-d][1,3]thiazine-4-thione series inhibited fungal growth at the lowest concentrations used, at which tricyclazole had no effect. A dose-dependent mechanism might be responsible for this effect, with lipophilicity as the governing factor. Within a given set, the presence of a cyclohexyl or an n-butyl group generally increased antifungal activity, with respect to both growth inhibition and cell de-pigmentation of the mycelium, suggesting that a higher lipophilicity might improve transport inside the cells. SEM and TEM of M. grisea hyphae showed that treatment with the most active substance (2h) caused significant ultrastructural effects, particularly on the endomembrane system, suggesting a mechanism of action similar to that of most azole fungicides. Dissimilarities were also observed, with no alterations of the cell wall evident. In conclusion, several compounds showed greater inhibition than tricyclazole, and therefore provide useful new chemistry for control of M. grisea infections.

Four series of new pyrazoles, namely, 5 4-carboxypyrazolo-3-tert-butylcarboxamide and 6 4-carboxypyrazolo-3-cyclopropylcarboxamide derivatives and 10 pyrazolo[3,4-d][1,3]thiazine-4-one and 9 pyrazolo[3,4-d][1,3]thiazine-4-thione derivatives, were synthesized and screened as potential inhibitors of photosynthetic electron transport. The structures were confirmed by 1H NMR, elemental, and IR analyses. Their biological activity was evaluated in vitro as the ability to interfere with the light-driven reduction of ferricyanide by isolated spinach chloroplasts. Only a few compounds exhibited excellent inhibitory properties in the micromolar range, comparable to those of commercial herbicides sharing the same target, such as diuron, lenacil, and hexazinone. Nevertheless, most of the remaining molecules exerted a remarkable inhibition in the millimolar range. Combined with previous results on 6 pyrazolo[1,5-a][1,3,5]triazine-2,4-dione and 4 pyrazolo[1,5-c][1,3,5]thiadiazine-2-one derivatives, these data allowed a comprehensive analysis of structure-activity relationship. Molecular modeling studies were undertaken to rationalize the structural determinants of activity in terms of shape, size, and molecular fields. Results suggested that the inhibitory potential of these compounds is associated mainly with their electrostatic properties.

The essential oil extracted by steam distillation from the capitula of Indian Tagetes patula, Asteraceae, was evaluated for its antifungal properties and analyzed by gas chromatography and gas chromatography-mass spectrometry. Thirty compounds were identified, representing 89.1% of the total detected. The main components were piperitone (24.74%), piperitenone (22.93%), terpinolene (7.8%), dihydro tagetone (4.91%), cis-tagetone (4.62%), limonene (4.52%), and allo-ocimene (3.66%). The oil exerted a good antifungal activity against two phytopathogenic fungi, Botrytis cinerea and Penicillium digitatum, providing complete growth inhibition at 10 microl/ml and 1.25 microl/ml, respectively. The contribution of the two main compounds, piperitone and piperitenone, to the antifungal efficacy was also evaluated and ultrastructural modifications in mycelia were observed via electron microscopy, evidencing large alterations in hyphal morphology and a multisite mechanism of action.

Two series of new pyrazoles, namely six pyrazolo[1,5-a][1,3,5]triazine-2,4-dione and four pyrazolo[1,5-c][1,3,5]thiadiazine-2-one derivatives, were synthesized as potential inhibitors of the photosynthetic electron transport chain at the photosystem II level. The compounds were confirmed by 1H NMR, elemental, and IR analyses. Their biological activity was evaluated in vivo upon both the growth of blue-green algae and the photosynthetic oxygen evolution by eukaryotic algae and in vitro as the ability to interfere with light-driven reduction of ferricyanide by isolated spinach chloroplasts. Some compounds exhibited remarkable inhibitory properties, comparable to those of the reference commercial herbicides lenacil, diuron, and hexazinone. Results suggest that the substitution of triazine with thiadiazine ring may act as amplifier for herbicidal activity.

Melanins are very important pigments for the survival and longevity of fungi, so their biosynthesis inhibition is a new biochemical target aiming at the discovery of selective fungicides. In this work is described the synthesis of new pyrazolo-thiazolo-triazole compounds, analogues of tricyclazole (a commercial antifungal product that acts by inhibiting melanin synthesis), and their biological activity was studied on some dermatophytes and phytopathogens. The compounds poorly inhibited the growth and pigmentation of fungi tested and were less efficient than tricyclazole. Electron microscopy on Botrytis cinerea showed that treatment with the most active compound caused abnormally thickened and stratified walls in fungi, whose ultrastructure was, in contrast, generally normal. The fungus treated with tricyclazole, on the other hand, appeared to be drastically altered, so as to become completely disorganized. These results suggest that the new azole compounds employ an action mechanism similar to that of other azoles, but dissimilar to that of tricyclazole.