Possible role of tocopherols in the modulation of host microRNA with potential antiviral activity in patients with hepatitis B virus-related persistent infection: a systematic review.

Hepatitis B virus (HBV) infection represents a serious global health problem and persistent HBV infection is associated with an increased risk of cirrhosis, hepatocellular carcinoma and liver failure. Recently, the study of the role of microRNA (miRNA) in the pathogenesis of HBV has gained considerable interest as well as new treatments against this pathogen have been approved. A few studies have investigated the antiviral activity of vitamin E (VE) in chronic HBV carriers. Herein, we review the possible role of tocopherols in the modulation of host miRNA with potential anti-HBV activity. A systematic research of the scientific literature was performed by searching the MEDLINE, Cochrane Library and EMBASE databases. The keywords used were 'HBV therapy', 'HBV treatment', 'VE antiviral effects', 'tocopherol antiviral activity', 'miRNA antiviral activity' and 'VE microRNA'. Reports describing the role of miRNA in the regulation of HBV life cycle, in vitro and in vivo available studies reporting the effects of VE on miRNA expression profiles and epigenetic networks, and clinical trials reporting the use of VE in patients with HBV-related chronic hepatitis were identified and examined. Based on the clinical results obtained in VE-treated chronic HBV carriers, we provide a reliable hypothesis for the possible role of this vitamin in the modulation of host miRNA profiles perturbed by this viral pathogen and in the regulation of some cellular miRNA with a suggested potential anti-HBV activity. This approach may contribute to the improvement of our understanding of pathogenetic mechanisms involved in HBV infection and increase the possibility of its management and treatment.

Long-term stabilized immunological-virological parameters of HIV infection in an AIDS presenter followed for 20 years, with irregular or no antiretroviral therapy.

We report the case of an HIV-infected patient who has been followed for 20 years, and despite presenting with AIDS (due to three episodes of cryptococcosis plus one of Pneumocystis jirovecii pneumonia) who during subsequent years missed, refused or took with limited compliance all recommended medications, including combination antiretroviral therapy, and primary and secondary antimicrobial chemoprophylaxis against opportunistic infections. The unexpected clinical and laboratory stabilization of our patient paralleled a progressive increase in his peripheral CD4+ T-lymphocyte count (range 410-825 cells/mL) and a relatively controlled HIV viraemia (5970-44,000 HIV-RNA copies/mL). Such a recovery of sufficient immune competency after experiencing four episodes of severe AIDS-associated opportunistic infections, without reliable antiretroviral and antimicrobial support raises several questions.

Outpatient parenteral antibiotic therapy in the elderly: an Italian observational multicenter study.

Bacterial infections are the most frequent cause of hospitalization in elderly patients. In the early eighties, the advantages of Outpatient parenteral Antibiotic therapy (OPAT) were identified in the United States, and suitable therapeutic programs were established. In order to understand the different ways of managing OPAT, a National OPAT Registry was set up in 2003 in Italy. This study analyzes data concerning bacterial infections in 176 elderly patients including demographics, therapeutic management, clinical response, and side-effects. Bone and joint infections (48.9%) and skin and soft tissue infections (27.8%) were the most common infections treated with OPAT. Teicoplanin (28.9%) and ceftriaxone (22.1%) were the top two antibiotics chosen. OPAT was mainly performed at a hospital infusion center (52.8%). The clinical success rate was high and side-effects were low (12.6% of cases). Management of bacterial infections in the elderly with an outpatient program is effective and safe.

[Contribution of palaeopathology to defining the pathocoenosis of infectious diseases (Part two)]. / Apporti della paleopatologia alla definizione della patocenosi delle malattieinfettive (II parte).

In the second part of their review the authors focus on palaeopathological studies, performed in mummified tissues, with reference to infectious diseases. The analysis of samples obtained from both natural and artificial mummies may provide, in some favourable events, a more complete knowledge of these findings in comparison to information obtained from only comprehensive examination of the skeleton. The acquired data enable us to understand not only the diseases which afflicted mankind, but also dietary and hygiene conditions of ancient populations. We report knowledge acquired regarding some palaeopathological conditions, including schistosomiasis, smallpox, cisticercosis, trichinosis, ascaridiasis, echinococcosis, filariasis, hepatitis E virus, condylomatosis, pulmonary tubercolosis, pediculosis, visceral leishmaniasis as well as Diphyllobotrium sp., Dicrocoelium dendriticum and Fasciola hepatica infestations. In addition some interesting findings concerning the relationship between dietary and food intake colonized by streptomyces are described. This review reports the discovery of human remains from different geographic areas: while most of these studies describe findings in two Mediterranean countries (Italy and Egypt), some refer to Britain and German-speaking countries (Austria and Germany) as well as the area in Africa known as Nubia, along the Nile. Both histological and biomolecular diagnosis are useful not only to identify a specific disease in a subject from the remote past, but also to achieve information concerning its frequency and evolution. Such knowledge may thus allow us to understand the intensity of cultural exchanges and links among different populations and the role of these relationships in transmitting and spreading infectious diseases in a certain geographic area.

[The Antonine Plague and the decline of the Roman Empire]. / La peste antonina e il declino dell'Impero Romano. Ruolo della guerra partica e della guerra marcomannica tra il 164 e il 182 d.c. nella diffusione del contagio.

The Antonine Plague, which flared up during the reign of Marcus Aurelius from 165 AD and continued under the rule of his son Commodus, played such a major role that the pathocenosis in the Ancient World was changed. The spread of the epidemic was favoured by the occurrence of two military episodes in which Marcus Aurelius himself took part: the Parthian War in Mesopotamia and the wars against the Marcomanni in northeastern Italy, in Noricum and in Pannonia. Accounts of the clinical features of the epidemic are scant and disjointed, with the main source being Galen, who witnessed the plague. Unfortunately, the great physician provides us with only a brief presentation of the disease, his aim being to supply therapeutic approaches, thus passing over the accurate description of the disease symptoms. Although the reports of some clinical cases treated by Galen lead us to think that the Antonine plague was caused by smallpox, palaeopathological confirmation is lacking. Some archaeological evidence (such as terracotta finds) from Italy might reinforce this opinion. In these finds, some details can be observed, suggesting the artist's purpose to represent the classic smallpox pustules, typical signs of the disease. The extent of the epidemic has been extensively debated: the majority of authors agree that the impact of the plague was severe, influencing military conscription, the agricultural and urban economy, and depleting the coffers of the State. The Antonine plague affected ancient Roman traditions, also leaving a mark on artistic expression; a renewal of spirituality and religiousness was recorded. These events created the conditions for the spread of monotheistic religions, such as Mithraism and Christianity. This period, characterized by health, social and economic crises, paved the way for the entry into the Empire of neighbouring barbarian tribes and the recruitment of barbarian troops into the Roman army; these events particularly favoured the cultural and political growth of these populations. The Antonine Plague may well have created the conditions for the decline of the Roman Empire and, afterwards, for its fall in the West in the fifth century AD.

A very particular case of long-term non-progressor: nineteen consecutive years of follow-up in the absence of any detectable HIV-1 viraemia.

A case of extremely prolonged non-progression of HIV-1 infection, characterized by 19 consecutive years of persistently undetectable viraemia (or no laboratory markers of HIV replication) is presented and discussed based on recent literature issues regarding virological and immunological outcome of the natural history of HIV-1 infection.

[Syphilis, brothels, unwanted children and wet nurses. Italy and syphilis infection in the 19th century]. / La sifilide e le case di tolleranza, i bambini esposti e le balie. L' Italia e il contagio luetico nell'ottocento.

In 1861 in Italy a repressive law was passed against prostitution to reduce syphilis transmission. After the constitution of the Kingdom of Italy there began a debate on this law which was harsh on prostitutes and failed to resolve the health problem in question. In 1880, in Italy, studies were promoted under the aegis of a royal commission to understand the social situation of prostitution and the epidemic spread of syphilis. In 1888 Crispi issued new regulations concerning prostitution, prevention and therapy of infectious diseases: three years later a new regulation was established which partly restored the 1861 law. In this paper we present not only the question of prostitution in Italy in relation to syphilis, but also the serious problem of infection transmission to unweaned babies and to wet nurses in orphanages.

[Contribution of paleopathology to defining the pathocoenosis of infectious diseases (Part one)]. / Apporti della paleopatologia alla definizione della patocenosi delle malattie infettive (prima parte).

Studying the remains of mummies obtained by archaeological research may provide key information concerning historical pathocoenosis. Paleopathology makes it possible to recognise, characterise and connect different features involved in human pathocoenosis, such as epidemiology, in a historical perspective, and cultural development, via the introduction of new livestock farming techniques and agriculture in general. Several distinct pathologies may produce direct and indirect changes in the skeleton of affected individuals. Therefore bone remains represent very important sources of information to study such diseases. Changes related to trauma and nutrition deficiency as well as secondary signs, induced by tuberculosis, brucellosis, leprosy, syphilis, malaria, periostitis and aspecific osteomyelitis, persist in bones. In addition, other diseases may cause indirect alterations and subsequent secondary bone in the skeleton via different mechanisms. A secondary bone dimorphism may be induced by poliomyelitis. Aspecific lesions may arise in a skeletal bone and then cause secondary alterations in near-bone segments. Reviewing studies of paleopathologic research found in the literature, we emphasize the relationship between the appearance of major infectious diseases and the development of human activities; whereas it is clear that the introduction of livestock farming had a key role in the pathocoenosis of distinct infections such as tuberculosis, brucellosis and leprosy, some doubts and uncertainty remain in relation to the origin of others with epidemiologically important pathologies, such as syphilis.

[The Spanish influenza pandemic]. / La pandemia influenzale "spagnola".

The influenza pandemic of 1918-1919, so-called Spanish influenza, spread to almost all nations worldwide. This outbreak is thought to have killed 25 million people, although some have claimed that the epidemic resulted in as many as 40 million deaths. This pandemic was a particularly dramatic event, because it occurred at the end of World War I, when both armies and the civilian population, in nations involved in the war, were exhausted. In Italy 600,000 people are estimated to have died of Spanish influenza. Together with the death of 650,000 soldiers during the war, this had a major demographic impact. We describe the course of the epidemic in Italy as a whole and in Bologna in particular. In Bologna and in its province we analysed the lists drawn up at the end of the World War I by the Central Records Office in Bologna, which coordinated research into causes of death of soldiers engaged in the conflict. We also examined the trend of burials at Certosa in Bologna in the first decades of the last century in order to establish, during the two-year period 1918-1919, the impact of the epidemic upon annual mortality. In Bologna the impact of the epidemic, albeit important in comparison to other situations, was not particularly dramatic. No special preventive measures were adopted, with the exception of isolating seriously ill patients in a former school converted by the military authorities into a hospital. Family doctors worked together actively with the city's medical authorities when the epidemiological survey was carried out.

Outpatient parenteral antibiotic therapy for bone and joint infections: an italian multicenter study.

In the early eighties, the advantages of outpatient parenteral antibiotic therapy (OPAT) (reduced costs, no hospitalization trauma in children, no immobilization syndrome in elderly, reduction in nosocomial infections by multiresistant organisms) were identified in the United States, and suitable therapeutic programs were established. Currently, more than 250,000 patients per year are treated according to an OPAT program. In order to understand the different ways of managing OPAT and its results, a National OPAT Registry was set up in 2003 in Italy. Analysis of data concerning osteomyelitis, septic arthritis, prosthetic joint infection and spondylodiskitis, allowed information to be acquired about 239 cases of bone and joint infections, with particular concern to demographics, therapeutic management, clinical response, and possible side effects. Combination therapy was the first-line choice in 66.9% of cases and frequently intravenous antibiotics were combined with oral ones. Teicoplanin (38%) and ceftriaxone (14.7%), whose pharmacokinetic/pharmacodynamic properties permit once-a-day administration, were the two top antibiotics chosen; fluoroquinolones (ciprofloxacin and levofloxacin) were the most frequently utilized oral drugs. Clinical success, as well as patients' and doctors' satisfaction with the OPAT regimen was high. Side-effects were mild and occurred in 11% of cases. These data confirm that the management of bone and joint infections in an outpatient setting is suitable, effective and safe.

[Syphilis in sixteenth-century in Bologna. Health care and social assistance (part two)]. / Il contagio luetico a Bologna nel Cinquecento. L'assistenza sanitaria e sociale.

Syphilis arrived in Bologna in the summer of 1495, after Fornovo's battle on the Taro where Charles VIII's army, following the invasion of Naples, fought against the anti-French league who faced up to the invaders as they withdrew. It was the battle-weary Bolognesi, prisoners, deserters and probably some prostitutes following the French and mercenary army who introduced the infection into the city. At the beginning of the syphilis epidemic, the disease was very aggressive with particularly visible symptoms and many resulting deaths. Subsequently, contemporaries mention an abatement of this aggressivity in time spans that varied, but in no cases exceeded 60 years. In 1507 Bologna lost its political autonomy, becoming dependent on Rome. This was symptomatic of the upheavals throughout Italy in the sixteenth century. In this situation of economic and institutional crisis the Bolognesi were able to react with decision to the epidemic, re-converting the municipal hospital dedicated to S. Maria dei Guarini during the sixteenth century. This hospital, specializing in treating syphilis, was called "Ospedale di San Giobbe". It was closed in 1798, after the entry of the French army into Bologna. In 1560 the Bolognesi, realising that the most important causes of the spread of syphilis were social degradation, prostitution and poverty, founded another institution for the poor and for the prevention of prostitution. This institution was developed by the Opera dei Mendicanti and provided hospitality during the 1590 famine, in a city of 55,000 inhabitants, for as many as 1400 poor and sick. We also present the cure (guaiac and mercury) that they used at the time against syphilis. In such a difficult historical period beset with political and economic problems, the Bolognesi established two important institutions and showed that social solidarity is a value for the whole population.

[Syphilis in sixteenth-century in Bologna. Health care and social assistance (Part one)]. / Il contagio luetico a Bologna nel Cinquecento. L'assistenza sanitaria e sociale.

Syphilis arrived in Bologna in the summer of 1495, after Fornovo's battle on the Taro where Charles VIII's army, following the invasion of Naples, fought against the anti-French league who faced up to the invaders as they withdrew. It was the battle-weary Bolognesi, prisoners, deserters and probably some prostitutes following the French and mercenary army who introduced the infection into the city. At the beginning of the syphilis epidemic, the disease was very aggressive with particularly visible symptoms and many resulting deaths. Subsequently, contemporaries mention an abatement of this aggressivity in time spans that varied, but in no cases exceeded 60 years. In 1507 Bologna lost its political autonomy, becoming dependent on Rome. This was symptomatic of the upheavals throughout Italy in the sixteenth century. In this situation of economic and institutional crisis the Bolognesi were able to react with decision to the epidemic, re-converting the municipal hospital dedicated to S. Maria dei Guarini during the sixteenth century. This hospital, specializing in treating syphilis, was called "Ospedale di San Giobbe". It was closed in 1798, after the entry of the French army into Bologna. In 1560 the Bolognesi, realising that the most important causes of the spread of syphilis were social degradation, prostitution and poverty, founded another institution for the poor and for the prevention of prostitution. This institution was developed by the Opera dei Mendicanti and provided hospitality during the 1590 famine, in a city of 55,000 inhabitants, for as many as 1400 poor and sick. We also present the cure (guaiac and mercury) that they used at the time against syphilis. In such a difficult historical period beset with political and economic problems, the Bolognesi established two important institutions and showed that social solidarity is a value for the whole population.

Bartonellosis: light and shadows in diagnostic and therapeutic issues.

Cat-scratch disease involves a prolonged and/or complicated course, and lymph node drainage is usually required. Culture and molecular techniques often yield negative results, but immunofluorescence assays may give early information, and elevated antibodies may persist for months. Cat-scratch disease should be suspected in patients with prominent swelling of lymph nodes draining from the upper limbs, limited systemic involvement, and typical epidemiological-clinical features. The temporal antibody response during the sub-acute course remains unknown. Although biomolecular assays are available, the time between onset and investigation is an obstacle to positive results. The role of surgical debridement and the unpredictable activity of antimicrobial agents warrant further investigation.

[Attempts to fight paludism and malaria in the middle ages. Role of Benedictine and Cistercian monks in the rise of monastic medicine and in land reclamation during the Middle Ages]. / Tentativi di lotta al paludismo e alla malaria nel Medio Evo. Ruolo dei Monaci Benedettini e Cistercensi nella nascita della Medicina Monastica e nelle bonifiche ambientali nel Medio E.

The loss of low-lying farm-land to marshes and swamps was a striking phenomenon in Italy and other regions of Europe after the fall of the Roman Empire. Throughout the Middle Ages extensive fertile agricultural lands were abandoned due to increased marshiness and the risk of the spread of malaria diffusion. In economic and social terms, this was a further source of decline. In this scenario of progressive abandonment which supported the spread of disease, Benedictine and Cistercian monks performed extensive land reclamation (relying on channels, dams and embankments), leading to a progressive control of seasonal flooding by rivers and basins. Inside the abbeys monastic medicine flourished, which in some regions often represented the main reference point for health care for all residents (whether the common people, nobles or clergy), in the "Dark Ages". Many monks paid with their own lives: malaria and malnutrition were the most frequent causes of morbidity and mortality. Benedictine and Cistercian monks, who had embraced the Benedictine rule, today deserve high consideration, as the major supporters of Europe's recovery, which took place on the continent from the 13th century onward. Their motto, "Pray and work" (Ora et labora) and "That God may be glorified in all things" (Ut in omnibus glorificatur Deus) supported their daily life and action. For centuries inside abbeys and fortified farmsteads known as grancie monks added prayers to work, in their attempt to reclaim land. Nature often treated them badly, at despite such difficulties, the monks never shrank from danger.

Voriconazole proves effective in long-term treatment of a cerebral cryptococcoma in a chronic nephropathic HIV-negative patient, after fluconazole failure.

Although being a rare occurrence, brain cryptococcoma may represent an emerging issue, because of its relationship with a broadening range of risk factors, including malignancies, neutropenia, end-organ failure, bone marrow and solid-organ transplantation, and multiple underlying causes of primary-secondary immunodeficiency. A cerebral cryptococcoma in a chronic nephropathic HIV-negative subject with homocystinuria, completely cured with neurosurgery and voriconazole after fluconazole failure, is described.

Capnocytophaga spp. brain abscess in an immunocompetent host: problems in antimicrobial chemotherapy and literature review.

The fourth case report of a brain abscess due to the fastidious Gram-negative organism Capnocytophaga spp. is described and discussed on the grounds of clinical, microbiological, and therapeutic evidence. A probable origin from a cat bite and/or an underlying severe mandibulary granuloma is suspected. Due to lack of clinical and neuroradiological response to neurosurgery and a combination of imipenem-amikacin-clindamycin-fluconazole, second-line empiric llnezolid treatment proved rapidly successful, in the absence of further microbial isolations. In vitro antimicrobial susceptibility testing is often unpredictable for Capnocytophaga spp., and agents usually active on Gram-positive organisms may also be effective, both in vitro and in vivo. Due to its favorable brain penetration and its dual mode of administration, linezolid may be an alternative option for patients with multiple risk factors, brain abscess of suspected polymicrobial origin, and lack of response to empiric or culture-driven therapeutic attempts.

[First attempts at smallpox engrafting (variolation) in the18th-century in Bologna]. / I primi tentativi di innesto del vaiolo a Bologna nel XVIII secolo.

In Bologna in the mid 18th century some brilliant doctors were among the first in Italy to carry out smallpox engrafting (variolation), obtaining interesting results. Academics and Scientific Establishment censured the activities of these experimenters, such that one of them had to continue his work in Padova, where he went to teach and continued the practice of variolation. However, Bologna's Curia pronounced a positive theological judgement on such experiments. Forty years later, in 1801, Bologna's Senate called upon Luigi Sacco to organize campaigns to vaccinate and thereby smallpox infection. Bologna had been scourged by a new epidemic that year. What happened in Bologna during the 18th century regarding scientific research reflected the demographic, economic and political situation that the city was experiencing. This trend was to come to an end only with the unification of Italy.

[A case of cerebral coenurosis]. / Su di un caso di cenurosi cerebrale.

In this article the authors describe a case of cerebral coenurosis, a rare infection caused by the larval stage of the tapeworm Taenia multiceps, encountered during their professional practice. The specific epidemiological elements, linked to the parasitic lifecycle in dogs, will also be covered. The authors consider the diagnostic, pathologic and clinical elements that allow differential diagnosis with respect to neurocysticercosis, a parasitic infection caused by the larval form of other Cestoda, discussing possible medical therapeutic approaches (albendazole or praziquantel) and neurosurgical intervention. They emphasize the need to obtain a correct hystopathological diagnosis in order to achieve a differential diagnosis versus the other larval parasitosis. According to current public health regulations this diagnosis must be reported to the Health Official to allow the necessary epidemiological interventions to be planned.

A Comparison of the Therapeutic Plan Costs in the Treatment of HIV-Positive Patients.

OBJECTIVE: To determine the cost of each therapeutic protocol (TP) used for HIV-positive patients and to identify the most frequently adopted one by relating it to the cost and by identifying the drug (drugs) that is more competitive in relation to expense. SETTING: Infectious Disease Department and Hospital Pharmacy, Ospedale Maggiore, Bologna, Italy. The department treats approximately 600 outpatients with HIV infection each year. PATIENTS AND METHODS: 464 patients with HIV infection were examined every 3 months and clinicians judged whether the treatment (usually consisting of three drugs) was to be continued or changed according to its effectiveness, availability and possible new treatment options. The study also ascertained the cost of antiretroviral drugs within the period 1 January 2001-30 April 2002, and identified the most commonly used therapeutic protocols, the relevant daily cost and the frequency of use in all patients. The cost of the various protocols (most TPs were grouped in the most frequently used 15 regimens) was considered only at the end of the study, in order to define the percentage differences in cost. Importantly, from the beginning, this aspect was not a primary factor in drug choice. RESULTS: The antiretroviral drug cost was 4 448 186 Euro (euro) in 2001 and euro1 536 984 in the first 4 months of 2002, with an increase of 3.5% compared with the same period in 2001. In the 16 months under consideration, 55.21% of the cost was associated with nucleoside reverse transcriptase inhibitors (NRTI), 25.97% with protease inhibitors (PI) and 18.83% with non-nucleoside reverse transcriptase inhibitors (NNRTI). Among the 464 TPs considered, 331 (71.33%) were distributed among 15 prevalent TPs. The least expensive TP (euro9.95/day; time of costing 1 January 2001-30 April 2002) comprised two drugs (stavudine and lamivudine) and showed a cost differential of +euro16.74 (+62.70%) compared with the most expensive one (zidovudine, lamivudine, lopinavir and ritonavir). The most used TP (zidovudine, lamivudine and nevirapine) covered 61 cases (13.1%) with a daily cost of euro19.61 (time of costing 1 January 2001-30 April 2002). CONCLUSIONS: This study demonstrated that, starting with decisions that take into account the efficacy of the therapy and the compliance of the patients, and choosing ethical protocols agreed upon with the patients, it is possible to reduce the costs of the TPs. Of the 464 TPs examined, NNRTIs were used in 46.7% of the cases and a PI in 39.6% (16.1% of the latter drug group was boosted with ritonavir). Only 7% of TPs used two drugs (NRTIs). The two less expensive TPs comprised two drugs only (NRTIs). Among the three-drug TPs with a lower cost, the drug pattern was two NRTIs and one NNRTI. The remaining TPs included a PI as a third drug and demonstrated a cost increase greater than 50% with respect to the less expensive treatment.