Cancer rehabilitation indicators for Europe

Little is known of cancer rehabilitation needs in Europe. EUROCHIP-3 organised a group of experts to propose a list of population-based indicators used for describing cancer rehabilitation across Europe. The aim of this study is to present and discuss these indicators. A EUROCHIP-3 expert panel reached agreement on two types of indicators. (a) Cancer prevalence indicators. These were proposed as a means of characterising the burden of cancer rehabilitation needs by time from diagnosis and patient health status. These indicators can be estimated from cancer registry data or by collecting data on follow-up and treatments for samples of cases archived in cancer registries. (b) Indicators of rehabilitation success. These include: return to work, quality of life, and satisfaction of specific rehabilitation needs. Studies can be performed to estimate these indicators in individual countries, but to obtain comparable data across European countries it will be necessary to administer a questionnaire to randomly selected samples of patients from population-based cancer registry databases. However, three factors complicate questionnaire studies: patients may not be aware that they have cancer; incomplete participation in surveys could lead to bias; and national confidentiality laws in some cases prohibit cancer registries from approaching patients. Although these studies are expensive and difficult to perform, but as the number of cancer survivors increases, it is important to document their needs in order to provide information on cancer control.     

Absence of genotypic drug resistance and presence of several naturally occurring polymorphisms of human immunodeficiency virus‐1 CRF06_cpx in treatment‐naive patients in Estonia

All non‐B HIV‐1 subtypes and circulating recombinant forms (CRFs) are characterized by several polymorphisms in protease (PR) region. In addition, in recent years the increasing use of antiretroviral treatment (ART) has rapidly raised the spread of transmitted drug resistance. We aimed to determine the presence of naturally occurring polymorphisms and transmitted drug resistance mutations (DRMs) in ART naïve HIV‐1‐positive subjects in Estonia. A total of 115 drug‐naive HIV‐1‐infected subjects (mean age 27 years; 70% male; 65% infected via intravenous drug use and 34% by heterosexual contact) were enrolled. Viral genomic RNA from plasma was directly sequenced in PR, revertase (RT), and envelope (env) regions. Phylogenetic analysis of RT and env regions revealed that 89% and 3% of sequenced viruses belonged to CRF06_cpx and subtype A1, respectively, and 6% were described as unique recombinants (signed A1‐06) between CRF06_cpx and subtype A1 viruses. No primary DRMs were found in PR or RT regions indicating the absence of transmitted drug resistance. The most common polymorphisms in the PR region were K14R, M36I, H69K, and L89M seen in 96%, 100%, 99%, and 100%, respectively. The clinical relevance of these polymorphisms in terms of success of ART has to be monitored in future clinical studies. J. Med. Virol. 81:953–958, 2009. © 2009 Wiley‐Liss, Inc.     

Mitochondria permeability transition-dependent tert-butyl hydroperoxide-induced apoptosis in hepatoma HepG2 cells

Tert-butyl hydroperoxide (t-BHP) has been demonstrated to induce apoptosis in hepatoma cell line HepG2, but poor data were available on the signaling pathway initiated by t-BHP. In this work, we studied in details the apoptotic pathways induced in HepG2 cells by t-BHP. DNA fragmentation, activation of caspases and cytochrome c release were demonstrated. Permeability transition pore inhibitors prevented the DNA fragmentation and caspase activation induced by t-BHP. In addition, changes in the mitochondrial membrane potential were detected: hyperpolarization preceded loss of membrane potential. It also preceded caspase activation which occurred before the induction of DNA fragmentation. Taken together, these results emphasize the central role played by mitochondria in the initiation of apoptosis in HepG2 cells exposed to oxidant agents.     

Tetracyclines, doxycycline and calcified tissues.

The use of radioactive isotope techniques has led to a thorough re-assessment of our knowledge of bone histology. It is known that tetracyclines faithfully follow the pattern of calcium metabolism in the body. Fluorescence microscopy, after double labeling with tetracyclines and alizarin red S, is very useful for collection of qualitative and quantitative data on compact and spongy bone remodeling. Two illustrations are presented which demonstrate how oxytetracycline and doxycycline administered in therapeutic doses to growing dogs, become deposited in the dentine. The significance of these findings is discussed.     

Sodium lauryl sulfate, a microbicide effective against enveloped and nonenveloped viruses

The number of individuals infected with human immunodeficiency virus (HIV) and other pathogens causing sexually transmitted diseases (STDs) is growing dramatically worldwide. Globally, heterosexual transmission may account for as much as 85-90% of new cases of HIV infection. Latex condoms represent an effective barrier against sexually transmitted pathogens, but unfortunately, their use is not generalized. Therefore, there is an urgent need to develop safe and potent topical microbicides under the control of women to efficiently reduce the spread of sexually transmitted infections. Sodium lauryl sulfate (SLS), an anionic surfactant with protein denaturing potency, is a potent inhibitor of the infectivity of several enveloped (Herpes simplex viruses, HIV-1, Semliki Forest virus) and nonenveloped (papillomaviruses, reovirus, rotavirus and poliovirus) viruses. The mechanism of action of SLS involves the solubilization of the viral envelope and/or the denaturation of envelope and/or capsid proteins. Studies have shown that SLS is not toxic for cultured cell lines of different origins at concentrations that inactivate HIV-1, herpes and human papillomavirus in vitro. In addition, intravaginal pretreatment of mice with a gel formulation containing SLS, completely protected animals against Herpes simplex virus type-2 infection. The gel formulation containing SLS was also well-tolerated following repeated intravaginal administrations to rabbits. Taken together, these data suggest that SLS represents a potential candidate for the use as a topical microbicide to prevent the sexual transmission of HIV-1, herpes, human papillomavirus and possibly other sexually transmitted pathogens. The impact of such a preventive tool on public health can be enormous.     

Radionuclide absolute left ventricular volumes during upright exercise: validation in normal subjects by simultaneous hemodynamic measurements

A nongeometric radionuclide technique for the determination of absolute left ventricular volumes was validated during exercise in nine normal subjects. Simultaneous reference stroke volume and cardiac output measurements were obtained by the Fick method. The reference left ventricular volumes were calculated by combining the Fick stroke volume and the isotopic ejection fraction. Data were collected at rest in the supine and upright positions and during 60° upright exercise, at three levels of increasing severity. At rest, from supine to upright position, the reference end-diastolic volume decreased significantly from 182±24 ml to 154±21 ml (mean±SD, P<0.005); during upright exercise of low intensity, end-diastolic volume increased to 176±24 ml (P<0.05); at maximal exercise, end-diastolic volume was not different from the resting value in upright position. The end-systolic volume gradually decreased at rest from 67±11 ml in the supine position to 54±8 ml in the upright position (P<0.05) and to 32±7 ml at maximal exercise (P<0.005). Compared with these reference data, the scintigraphic measurements were significantly lower on average by 23% for stroke volume, 21% for cardiac output, 22% for end-diastolic volume, and 23% for end-systolic volume. The overall changes in stroke volume (P<0.05) and end-systolic volume (P<0.001) occurring at rest and during exercise were correctly detected by the scintigraphic method but the smaller changes in end-diastolic volume (less than 15%) were not (P<0.15) because they were within the range of the precision of the technique. If subtle changes in left ventricular volume are to be quantitated, attempts should be made to reduce the random variability of the scintigraphic method.Supported in part by grants from the Fonds de la Recherche Scientifique Médicale, nr 3.4554.79 and 3.4536.83 and from the Services de Programmation de la Politique Scientifique nr 83/8851With the technical assistance of Roland J. Vanbutsele and Tony Berckmans     

<Emphasis Type="Italic">N-acetyltransferase 8</Emphasis>, a positional candidate for blood pressure and renal regulation: resequencing,association and <Emphasis Type="Italic">in silico</Emphasis> study

Background  

Kidneys have an important function in blood pressure (BP) regulation and elevated BP may lead to kidney failure. Chr2p12-p13 region linked to BP traits in multiple studies harbours a potential candidate for BP and renal function, N-acetyltransferase 8 (NAT8) expressed in embryonic and adult kidney and associated with nephrotoxicity response.