Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells.

Glioblastoma multiforme (GBM) is the most common subtype of primary malignant brain tumor. Although serotype 5 adenoviral vectors (Ads) have been used successfully in clinical trials for GBM, the capacity of Ads to infect human glioma cells and the expression of adenoviral receptors in GBM cells have been challenged. In this report, we studied the expression of three molecules that have been shown to mediate adenoviral entry into cells, i.e., coxsackie and adenovirus receptor (CAR), integrin alphavbeta3 (INT), and major histocompatibility complex class I (MHCI), in rodent glioma cell lines and low-passage primary cultures and cell lines from human GBM. We correlated levels of expression of CAR, INT, and MHCI with transduction efficiency elicited by several high-capacity helper-dependent adenoviral vectors (HC-Ads). Expression levels of adenoviral receptors were variable among the different GBM cells studied. HC-Ad-mediated therapeutic gene expression was efficient, ranging between 20 and 80% of the total target cells expressing the encoded transgenes. Our results show no correlation between the levels of CAR, INT, or MHCI molecules and the levels of transgene expression or the number of GBM cells transduced. We conclude that expression levels of adenoviral receptors do not predict their transduction efficiency or biological function.     

Gene therapy for pituitary tumors

Pituitary tumors are the most common primary intracranial neoplasms. Although most pituitary tumors are considered typically benign, others can cause severe and progressive disease. The principal aims of pituitary tumor treatment are the elimination or reduction of the tumor mass, normalization of hormone secretion and preservation of remaining pituitary function. In spite of major advances in the therapy of pituitary tumors, for some of the most difficult tumors, current therapies that include medical, surgical and radiotherapeutic methods are often unsatisfactory and there is a need to develop new treatment strategies. Gene therapy, which uses nucleic acids as drugs, has emerged as an attractive therapeutic option for the treatment of pituitary tumors that do not respond to classical treatment strategies if the patients become intolerant to the therapy. The development of animal models for pituitary tumors and hormone hypersecretion has proven to be critical for the implementation of novel treatment strategies and gene therapy approaches. Preclinical trials using several gene therapy approaches for the treatment of anterior pituitary diseases have been successfully implemented. Several issues need to be addressed before clinical implementation becomes a reality, including the development of more effective and safer viral vectors, uncovering novel therapeutic targets and development of targeted expression of therapeutic transgenes. With the development of efficient gene delivery vectors allowing long-term transgene expression with minimal toxicity, gene therapy will become one of the most promising approaches for treating pituitary adenomas.     

Mathematical and Pharmacokinetic Approaches for the Design of New 3D Printing Inks Using Ricobendazole

Pharmaceutical Research - 3D printing (3DP) makes it possible to obtain systems that are not achievable with current conventional methods, one of them, sustained release floating systems. Floating...     

Household burden of malaria in South Africa and Mozambique: is there a catastrophic impact?

Objectives  To evaluate treatment-seeking behaviour, financial impact and time lost due to malaria events, in southern Mozambique and eastern South Africa.
Methods  In-depth household surveys (828 in Mozambique and 827 in South Africa) were analysed. An asset index was calculated using principal component analysis to allow comparison across socio-economic groups. Direct costs of seeking care and the time lost due to malaria were determined. The extent of catastrophic payments was assessed using as thresholds the traditional 10% of household income and 40% of non-food income, as recently recommended by WHO.
Results  Poverty was highly prevalent: 70% of the South African and 95% of Mozambican households studied lived on less than $1 per capita per day. Around 97% of those with recent malaria sought healthcare, mainly in public facilities. Out-of-pocket household expenditure per malaria episode averaged $2.30 in South Africa and $6.50 in Mozambique. Analysis at the individual household level found that 32–34% of households in Mozambique, compared with 9–13% of households in South Africa, incurred catastrophic payments for malaria episodes. Results based on mean values underestimated the prevalence of catastrophic payments. Days off work/school were higher in Mozambique.
Conclusions  The high rate of health seeking in public health facilities seems unusual in the African context, which bodes well for high coverage with artemisinin-based combinations, even if only deployed within the public sector. However, despite no or modest charges for public sector primary healthcare, households frequently incur catastrophic expenditure on a single malaria episode.     

Drug-resistant and immune-escape hepatitis B virus mutants, occult hepatitis B infection and coinfections in public hospital patients from Argentina

Virus Genes - Argentina exhibits low serological prevalence for Hepatitis B virus (HBV); however, occult hepatitis B infection (OBI) has been reported in blood donors, Amerindians and individuals...     

Perceptions of elder abuse among Australian older adults and general practitioners

Objectives: To examine the perceptions of elder abuse among older Australian adults and general practitioners, a topic that has not been explored to the same extent as elsewhere. Methods: Forty‐eight general practitioners, 40 independent older adults, 38 older adult caregivers and 36 older care‐receivers completed a modified version of Moon and Williams’ (1993) questionnaire, which describes 10 potential elder abuse scenarios. Results: Split‐plot analysis of variance showed significant differences in the perceptions of severity of elder abuse scenarios across groups and gender. General practitioners tended to view the scenarios as less severe than the older‐aged groups. Within the older adult groups, caregivers generally perceived the scenarios as less abusive. Females generally perceived sexual abuse scenarios as more severe compared to males. Conclusions: With such differences in views evident, the development of effective assessment strategies will require more targeted efforts to increase the awareness of elder abuse in the community.     

Advances of the investigation of "Ambulatory Care Sensitive Conditions" in primary care in Spain

Hospitalization due to ambulatory care sensitive conditions (ACSC) is an indicator of hospital activity that has demonstrated its usefulness as an indirect measurement of primary care effectiveness. Since this indicator was recently introduced in Spain, a collaborative effort between the different research groups could facilitate and promote its development and progress. The objective of this paper is to propose a working agenda that, starting from the most recent information, enhances the advance in this research field. The agenda includes the following sections: 1) To draw up specific ACSC lists for adult and pediatric population, as well as to look in greater depth into the concepts of, and differences in avoidable hospitalization and ACSC. 2) To complete the indicator validation process by assessing the external validity. 3) To propose, for future studies, the municipality as the unit of analysis, as well as to individualize the analysis of health conditions allowing for the differences between acute and chronic ones. 4) To adjust the indicators of hospital activity by hospital use index, when data from some hospitals are lacking and comparisons are wanted 5) To include a new variable, provider of primary health care services, in the Minimum Basic Data Set of Hospital Discharges. 6) To use this indicator as a measure of both the distribution of functions between levels of care and the coordination among them.