HIV-1 Tat enhances Kaposi sarcoma-associated herpesvirus (KSHV) infectivity

The high frequency of Kaposi sarcoma (KS) in immunodeficiency states, particularly in patients with AIDS, has been attributed to increased replication of KS-associated herpesvirus (KSHV), a necessary cofactor for KS development. However, experimental KSHV infection of endothelial lineage cells that compose KS lesions has been difficult even in the absence of immune cells. Here we show that HIV-1 Tat protein can directly promote KSHV transmission. Full-length HIV-1 Tat and a 13-amino-acid peptide corresponding to the basic region of Tat specifically enhances the entry of KSHV into endothelial and other cells, presenting evidence for an active role of HIV-1 in the development of KSHV-associated diseases. These results can explain why AIDS-KS is more frequent and clinically more aggressive than KS in other immunodeficiency states.     

A comparative drug utilisation study of the treatment of diabetes in Malaysia and Australia

Background

Once a disease of developed countries, type 2 diabetes mellitus (T2DM) has become widespread worldwide. For people with T2DM, achievement of therapeutic outcomes demands the rational and quality use of medicine.

Aims

The primary aim of this study was to examine the prevalence of diabetes and prescribing patterns of anti-diabetic medications in Australia and Malaysia.

Methods

The most recent, publicly available, statistical reports (2004–2008) on the use of medicines published in Australia and in Malaysia were evaluated. Defined daily doses (DDDs/1,000 population/day) were derived from the reports and used to rank and compare individual drug use.

Results

There was an increasing trend in the prevalence of diabetes in Australia, although there is a greater predicted increase in prevalence for Malaysia. While drugs used for the treatment of diabetes were not the most highly used drugs in Australia, their use increased during the study period, from 42.64 to 48.61 DDD/1,000/day. Anti-diabetic drugs were the most frequently dispensed class of drugs in Malaysia. Although the total consumption of anti-diabetic drugs in Malaysia decreased between 2006 and 2007 (from 40.30 to 39.72), this was followed by a marked increase to 46.69 in 2008. There was a marked reduction in the dispensing of insulin in Malaysia from 2004 to 2007 (7.77 to 3.23).

Conclusion

The use of drugs to treat diabetes does not reflect the usage patterns found in Australia. Effective drug use reviews are required to ensure impartial access in middle- and low-income countries.     

Assessment of EtQxBox complexation in solution by steady-state and time-resolved fluorescence spectroscopy

Reliable chemical sensors with high selectivity and sensitivity toward specific target molecules require rational synthesis of receptors, in-depth characterization of their complexation abilities and highly efficient transduction of the molecular recognition event. Here we report a steady-state and time-resolved fluorescence investigation of EtQxBox, a fluorescent conformationally blocked quinoxaline-based cavitand, aimed at assessing its selectivity toward aromatic versus non-aromatic analytes in solution. Fluorescence quenching of the EtQxBox in acetone is observed at increasing concentration of both aromatic (i.e. benzonitrile) and aliphatic (i.e. acetonitrile) compounds. The combination with fluorescence lifetime measurements permits to discriminate the predominantly static quenching of the aromatic analyte, due to non-fluorescent host–guest complex formation, from the mostly dynamic quenching of the non-aromatic compound, resulting from aspecific diffusive collisions between the fluorophore and the quencher. The equilibrium association constants for both the complexes have been estimated using Stern–Volmer model.

We investigate the role of combined static and dynamic quenching in fluorescence transduction of benzonitrile and acetonitrile complexation by a rigid quinoxaline-based cavitand.     

Juvenile patients with the homozygous MTHFR C677T genotype develop ischemic stroke 5 years earlier than wild type

Journal of Thrombosis and Thrombolysis - To compare age at 1st ischaemic stroke (IS) in a cohort of juvenile (<?46 years of age) IS patients evaluated for the rs1801133...     

Latest culture techniques: cracking the secrets of bone marrow to mass-produce erythrocytes and platelets ex vivo

Since the dawn of medicine, scientists have carefully observed, modeled and interpreted the human body to improve healthcare. At the beginning there were drawings and paintings, now there is three-dimensional modeling. Moving from two-dimensional cultures and towards complex and relevant biomaterials, tissue-engineering approaches have been developed in order to create three-dimensional functional mimics of native organs. The bone marrow represents a challenging organ to reproduce because of its structure and composition that confer it unique biochemical and mechanical features to control hematopoiesis. Reproducing the human bone marrow niche is instrumental to answer the growing demand for human erythrocytes and platelets for fundamental studies and clinical applications in transfusion medicine. In this review, we discuss the latest culture techniques and technological approaches to obtain functional platelets and erythrocytes ex vivo. This is a rapidly evolving field that will define the future of targeted therapies for thrombocytopenia and anemia, but also a long-term promise for new approaches to the understanding and cure of hematologic diseases.     

Hepatocellular carcinoma,hepatitis C virus infection and miRNA involvement: Perspectives for new therapeutic approaches

Chronic hepatitis C virus (HCV) infection is the principal etiology of cirrhosis and, ultimately, hepatocellular carcinoma (HCC). At present, approximately 71 million people are chronically infected with HCV, and 10%–20% of these are expected to develop severe liver complications throughout their lifetime. Scientific evidence has clearly shown the causal association between miRNAs, HCV infection and HCC. Although it is not completely clear whether miRNA dysregulation in HCC is the cause or the consequence of its development, variations in miRNA patterns have been described in different liver diseases, including HCC. Many studies have analyzed the importance of circulating miRNAs and their effect on cell proliferation and apoptosis. In this Review, we aim to summarize current knowledge on the association between miRNA, HCV and HCC from a diagnostic point of view, and also the potential implications for therapeutic approaches.     

Factors affecting long-term changes of liver stiffness in direct-acting anti-hepatitis C virus therapy: A multicentre prospective study

The long-term changes of liver stiffness (LS) in patients who achieve viral clearance after direct-acting anti-HCV therapy remain undefined. We conducted a multicentre prospective study to investigate this aspect. Patients with HCV infection treated with DAAs were enrolled from six Italian centres; they underwent clinical, biochemical, ultrasound and transient elastography evaluations before treatment (T0), 12 weeks (SVR12) and 24 months (T24) after the end of therapy. Among the 516 consecutive patients enrolled, 301 had cirrhosis. LS significantly decreased from T0 to SVR (14.3 vs 11.1 kPa, p = .002), with a progressive reduction until T24 (8.7 kPa, p < .001). However, only patients with steatosis and those who developed HCC did not experience a late improvement in LS. Multivariate analysis of baseline and follow-up variables identified steatosis as the only independent predictor of failure of LS improvement (OR 1.802, p = .013). ROC curve analysis of the association of LS with the risk of developing HCC showed that SVR12 ≥14.0 kPa had the highest accuracy (sensitivity 82%, specificity 99%; AUC: 0.774). Multivariate analysis revealed that LS was the only variable independently associated with an increased risk of developing HCC (OR 6.470, p = .035). Achieving an SVR was associated with a progressive, long-term decline of LS, suggesting a late improvement in liver fibrosis, besides the resolution of inflammation. Fatty liver and the development of HCC interfered with late reduction of LS. Patients with an LS ≥14 kPa at 12 weeks after the end of treatment were at higher risk for developing HCC.     

Subcutaneous implantable cardioverter defibrillator in children and adolescents: results from the S-ICD “Monaldi care” registry

Journal of Interventional Cardiac Electrophysiology - Implantable cardioverter defibrillators (ICD) are widely accepted therapy in children and adolescents who are survivors of cardiac arrest or...