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.

[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.

[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.

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.

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.

[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.

[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.

Unusual malignant tumours in 49 patients with HIV infection.

Between December 1986 and December 1988, the Italian Cooperative Group on AIDS-Related Tumours documented 49 HIV-related tumours other than malignant lymphomas (ML) and Kaposi's sarcomas (KS), predominantly among HIV-infected intravenous drug abusers (IVDA). Of 12 germinal testicular tumours collected, six were seminomas, two of which were pure embryonal and the other four embryonal mixed. Cervical carcinoma was observed in nine IVDAs (intraepithelial in eight and advanced, with rapid progression, in one). Lung cancer associated with HIV infection was reported in eight patients, of whom four had an adenocarcinoma, two a small cell carcinoma, one an epidermoid carcinoma and one a mesothelioma. All patients with non-small-cell-lung cancer (SCLC) were at stage III, while those with SCLC and mesothelioma had limited disease. Five out of eight presented with limited disease at onset. The median age was low; lung cancer occurred predominantly in young adults, of whom all but one were smokers. Three patients could not be treated; four died while on treatment because of progression of the neoplasia and one died of an overdose. Acute lymphoblastic leukaemia (ALL) was diagnosed in five patients. The immunophenotype was always Burkitt-like (L3), and acute myeloblastic leukaemia (M2) was diagnosed in one. Of the central nervous system (CNS) tumours, two cases of glioblastoma and one of medulloblastoma were described. Two cases of young adults with multiple myeloma and two cases of colorectal carcinoma were also reported. One case of chronic lymphocytic leukaemia, one anorectal carcinoma, one oral carcinoma, one pancreatic carcinoma, one thymoma, one kidney carcinoma, one malignant melanoma and thyroid carcinoma were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

HIV-1-specific immunity in persistently seronegative individuals at high risk for HIV infection.

A growing number of reports indicates that certain groups of individuals who almost certainly have been exposed to human immunodeficiency virus (HIV), yet continue to exhibit no signs or symptoms of infection, often have subtle evidence of specific immunity. We studied such a high-risk (HR) cohort of persistently seronegative individuals with histories of long-term sexual exposure to an HIV-infected partner to look for evidence of both humoral and cellular immunity that might have been induced by exposure to the virus. Twenty-three heterosexual and four homosexual monogamous couples with discordant HIV status were included in the study. Twelve of the HR partners were studied for in vitro stimulation of peripheral blood mononuclear cells (PBMC) by HIV envelope-derived peptides. All 12 responded overwhelmingly to a peptide containing the fifth conserved region of gp120. By generating and cloning T cell lines specific for this peptide, we concluded that in these individuals the T cell response to the envelope is mainly focused on the carboxy-terminus region of gp120 and is characterized by an oligoclonal expansion of CD4+ T cells expressing the same TCR Eighteen HR partners and 37 HIV-1 seropositive subjects were tested for the presence of anti-CD4 antibodies (anti-CD4 Abs) using a recombinant CD4-based enzyme-linked immunosorbent assay (ELISA). Anti-CD4 Abs were detected in eight of the HR partners (six confirmed by Western blot) and in nine of the HIV-1 seropositive subjects (eight confirmed by Western blot). Results from binding competition assays with a panel of monoclonal anti-CD4 Abs suggested that the anti-CD4 Abs detected in the HR partners are directed toward epitopes that are induced by gp120 binding. Twenty-seven of the HR partners were tested for the presence of antibodies that cross-react with HLA class I and gp120 (anti-HLA Abs). Anti-HLA Abs were detected in 16 of the HR partner sera and in 4/94 sera from a control population of normal healthy blood donors. Taken together, the results suggest that in some individuals with a history of long-term exposure to HIV, specific immunity may develop in the absence of overt infection. The common trigger for these responses is gp120.

Tissue polypeptide antigen (TPA) modifications in hepatic cirrhosis, aggressive chronic hepatitis, persistent chronic hepatitis, and in minimal pathology.

A total of 104 patients with various liver diseases were studied. Hepatic biopsy was performed and the AST, ALT and TPA in serum were measured. Higher levels of TPA, AST and ALT were found in CAH and LC, lower in CPH and MHP. High serum TPA values, usually suggesting the possibility of neoplasm, should be considered with attention. A follow-up with periodic TPA assays (in addition to AST and ALT) is suggested in patients with acute hepatitis, in order to predict further possible complications such as CAH and LC.

Serum thymidine kinase (TK) evaluation in HIV infection.

Serum thymidine kinase (TK), measured using Prolifigen TK-REA, from AB Sangtec Medical, was investigated in 24 HIV seropositive patients without immunological alterations, 26 seropositives with immunological alterations, 125 LAS, 25 ARC, and 20 AIDS. Subjects with serological markers of prior EBV, HBV, and CMV infection were included but none with acute infectious mononucleosis or acute viral hepatitis. Serum TK was elevated from the beginning of the HIV infection, the seropositive stage, and more markedly afterwards during the course of the infection, with a close correlation with the stage. TK also increased during AZT treatment, due to bone-marrow toxicity. On lowering the dosage or discontinuing the drug TK returned to basal levels. Although the rise in serum may well not be correlated only with the HIV infection, it does add to the picture given by other clinical and/or laboratory methods. Serum TK can be a helpful laboratory test in the follow-up of patients with HIV infection, especially when serum levels are disproportionate to the stage, opportunistic infections, lymphoproliferative malignancies. In such cases bone-marrow toxicity due to treatment can be suspected.

67Ga citrate scanning, X-ray computed tomography and chest X-ray in the study of interstitial pneumonia in patients with AIDS.

Problems in the investigation of pulmonary interstitial pneumocystis carinii in AIDS patients in the early phase with 67Ga, high-resolution CT scan and chest X-ray are discussed, and a clinical study of 12 individuals is presented. The combination of the three examinations is useful in reducing false negative cases. The use of 67Ga scanning, chest X-ray and high-resolution CT is also proposed in the follow-up of AIDS patients during remission of their lung pathology.

Use of TPA in hepatology of infectious nature. Initial observations.

The tissue polypeptide antigen, TPA, is a tumour-associated antigen which is synthesized during the S phase of cellular division and released later by the tissues when rapid growth takes place. For this reason, the TPA is considered to be a specific phase tumour-associated antigen. Since Björklund detected the antigen in 1957 much less has been written about research into the presence of the TPA in high concentration in the blood of subjects with tumours in different sites. The TPA can, however, be measured in moderate quantities in healthy individuals and in those with hepatic pathology (hepatitis and cirrhosis) and pathology of a viral nature. In hepatic parenchymal pathology, repeated measurements of this marker show normalization with the benign course of the disease. The aim of this work is to evaluate if the use of the TPA can be useful in hepatology of an infectious nature as an index of cytoreproduction, a phenomenon which often affects the hepatocytic cytolysis which is found in acute viral hepatitis.

Combination of tissue polypeptide antigen (TPA) and carcino embryonic antigen (CEA) in different types of cancer.

Tissue polypeptide antigen (TPA) and carcino embryonic antigen (CEA) were measured in 55 patients with cancer in different locations (21 lung cancer, 133 breast cancer, 9 stomach cancer, 5 colorectal cancer, 7 cancer of unknown origin). TPA gives elevated values in all types of cancer. The statistical analysis shows that TPA is about equally sensitive for all cancer types, while CEA has a particularly high sensitivity for colorectal carcinoma. The TPA values in the group of cancer patients is significantly different from those in a group of healthy controls. TPA gives higher sensitivity than CEA in all tumour locations. By the use of combined determination of TPA and CEA the sensitivity can be further increased, to 64% for the whole patient population and 89% for the gastric tumour patients, even when the cut-off values are chosen so high that no false positives are obtained in either reference group (150 Ul-1 for TPA, 10 ng ml-1 for CEA). A limited correlation exists between the markers in tumour patients.

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.