Detection of the antiviral activity of epicatechin isolated from Salacia crassifolia (Celastraceae) against Mayaro virus based on protein C homology modelling and virtual screening.

Mayaro fever, caused by Mayaro virus (MAYV) is a sub-lethal disease with symptoms that are easily confused with those of dengue fever, except for polyarthralgia, which may culminate in physical incapacitation. Recently, outbreaks of MAYV have been documented in metropolitan areas, and to date, there is no therapy or vaccine available. Moreover, there is no information regarding the three-dimensional structure of the viral proteins of MAYV, which is important in the search for antivirals. In this work, we constructed a three-dimensional model of protein C of MAYV by homology modelling, and this was employed in a manner similar to that of receptors in virtual screening studies to evaluate 590 molecules as prospective antiviral agents. In vitro bioassays were utilized to confirm the potential antiviral activity of the flavonoid epicatechin isolated from Salacia crassifolia (Celastraceae). The virtual screening showed that six flavonoids were promising ligands for protein C. The bioassays showed potent antiviral action of epicatechin, which protected the cells from almost all of the effects of viral infection. An effective concentration (EC50) of 0.247 µmol/mL was observed with a selectivity index (SI) of 7. The cytotoxicity assay showed that epicatechin has low toxicity, with a 50% cytotoxic concentration (CC50) greater than 1.723 µmol/mL. Epicatechin was found to be twice as potent as the reference antiviral ribavirin. Furthermore, a replication kinetics assay showed a strong inhibitory effect of epicatechin on MAYV growth, with a reduction of at least four logs in virus production. Our results indicate that epicatechin is a promising candidate for further testing as an antiviral agent against Mayaro virus and other alphaviruses.

A critical view on antimalarial endoperoxide QSAR studies.

Malaria is one of the most dangerous diseases in developing countries. The chemotherapy of malaria has been based on drugs developed more than half a century ago. These drugs are continuously losing their efficacy, mainly due to multi-drug resistance developed by the malaria-causing parasite. In the last three decades, artemisinin and artemisinin-like compounds have proven to be efficient alternatives to the chemotherapeutic control of malaria. These facts have led to an increasing interest in the development of Quantitative Structure Activity Relantioship (QSAR) models for these compounds. This work presents a critical view on some QSAR models, and shows that, due to lack of a rigorous selection of the descriptors entering the models, most of them are unable to accurately indicate the molecular cause of biological activity. Some reasons for the weakness of the published models are discussed.

HPV in exhaled breath condensate of lung cancer patients.

BACKGROUND: A recent intriguing carcinogenetic hypothesis for lung cancer foresees its viral aetiology. The human papilloma virus (HPV) is the main virus actually recognised in the pathogenesis of lung cancer. The aim of this study was to investigate, for the first time to our knowledge, the presence of HPV in the exhaled breath condensate (EBC) of lung cancer patients. MATERIALS AND METHOD: We enrolled 89 patients affected by lung cancer and 68 controls. HPV infections were investigated in their EBC, paired bronchial brushing and neoplastic lung tissue through genotyping. RESULTS: We were able to detect HPV in the EBC, bronchial brushing and neoplastic lung tissue. We described the presence of an HPV infection in 16.4% of the subjects affected by non-small cell lung cancer, but in none of the controls. HPV 16 and 31 turned out to be the most widespread genotypes. The HPV positivity in airways as well as in the smoking habit was seen to independently increase the individual's susceptibility to developing lung cancer. CONCLUSION: When summing up, we demonstrated the possibility to identify an HPV infection in the EBC of lung cancer patients; further, we supported the notion that the EBC is a suitable tool to study airway colonisation. That being said, although further studies are needed to confirm our results, we retain the study of HPV in EBC to be very interesting in terms of future programmes involving lung-cancer screening.

[HPV infection: comparison between morphological studies and molecular biology]. / L'infezione da HPV: confronto diagnostico tra indagini morfologiche e biologia molecolare.

Human Papilloma Virus plays an essential role in the development of cervical cancer. We investigated the global prevalence of Human Papilloma Virus infection in a population of 699 women recruited at the Ospedali Riuniti in Foggia for gynaecological controls from September 2005 to March 2007, and compared with a group of 90 women, selected on clinical aspects for Human Papilloma Virus features. The observed prevalence was 27.4%, which is higher that that reported in the literature. In the study group, the most frequent viral type was 16, while type 18 was considerably less frequent compared with other emergent viral types (39, 52, 56, 58, 59). The high prevalence of Human Papilloma Virus-DNA in women with negative cytology or inflammatory changes raises doubts about the utility of the Human Papilloma Virus-DNA method as a primary screening test because of the low cost/benefit ratio. The absence of uniform and standardised reports does not allow objective comparison between different methods of analysis (cytology, colposcopy and molecular biology), pointing out the need for a unique centre for collection and data analysis.

Ovarian vascular pedicle sign in ovarian metastasis arising from gall bladder carcinoma.

A case of a large mass in the pelvis confirmed to be a rare ovarian metastasis arising from a primary adenocarcinoma of the gall bladder is presented. The value of the recently described ovarian pedicle sign in confirming the organ of origin of the pelvic mass is emphasized.

Osteoporosis and anorexia nervosa: relative role of endocrine alterations and malnutrition.

BACKGROUND AND AIM: Anorexia nervosa (AN) is a psychiatric disorder characterised by self-induced starvation or a very reduced caloric intake, and frequently by severe life-threatening protein calory malnutrition. Its physiological consequences include amenorrhea, estrogen deficiency and osteoporosis. Osteoporosis may develop as a consequence of a lack of estrogens, low calcium or vitamin D intake, hypercortisolemia or the duration of the illness. The aim of this study was to identify the best endocrinological and nutritional indicators of bone density. SUBJECTS AND METHODS: The study involved 49 young females with AN and malnutrition and 24 age-matched normal controls in whom AN had been excluded on the basis of a clinical evaluation using DSM IV criteria. We studied bone density in early osteopenia, a condition in which the potential risk of fractures is certainly high and traditionally related to a variety of endocrinological and nutritional factors. RESULTS: Bone density was significantly lower in the AN than the control group in all of the examined bone districts: bone mineral density (BMD) spine 0.89 +/- 0.19 vs 1.27 +/- 0.2 (p<0.0001), BMD neck 0.75 +/- 0.14 vs 1.08 +/- 0.17 (p<0.001), BMD Ward 0.74 +/- 0.17 vs 1.12 +/- 0.11 (p<0.0001). Non-significant differences were found in the patients who had undergone previous estrogen medication. Body mass index (BMI) correlated with bone density, but caloric and calcium intake were not significant predictors. IGF-1, a known nutritionally dependent trophic bone factor, was significantly reduced in our patients but did not correlate with BMD. Like other authors, we found a close correlation between lean body mass and BMD in neck and spine. Physical exercise, urinary free cortisol osteocalcin and type I collagen-telopeptide (NTX) did not significantly correlate with the degree of osteopenia. CONCLUSIONS: Our data suggest the importance of nutritional factors (particularly lean body mass and BMI) in determining bone mass, and the relatively limited importance of endocrinological factors with the exception of the duration of amenorrhea as an indirect indicator of endocrinological status.

Tricuspid regurgitation and acute myocardial infarction.

A 71-year-old man had a right ventricular infarct complicated with hypotension and transient complete atrioventricular block. The patient was found to have tricuspid regurgitation, which was corrected with a prosthetic tricuspid valve. After correction, there was dramatic improvement in his clinical status, with correction of persistent hypotension and weakness and early discharge home to full activity. Tricuspid regurgitation is a mechanical defect of acute myocardial infarction that benefits greatly from surgical correction. This therapy should be considered in any individual in whom tricuspid regurgitation complicates acute right ventricular infarction.