Renal epithelial gene expression profile and bismuth-induced resistance against cisplatin nephrotoxicity

Nephrotoxicity is the most important dose-limiting factor in cisplatin based anti-neoplastic treatment. Pretreatment with bismuth salts, used as pharmaceuticals to treat gastric disorders, has been demonstrated to reduce cisplatin-induced renal cell death in clinical settings and during in vivo and in vitro animal experiments. To investigate the genomic basis of this renoprotective effect, we exposed NRK-52E cells, a cell line of rat proximal tubular epithelial origin, to 33 microM Bi3+ for 12 hours, which made them resistant to cisplatin-induced apoptosis. Differentially expressed genes in treated and untreated NRK-52E cells were detected by subtraction PCR and microarray techniques. Genes found to be down regulated (0.17-0.31-times) were cytochrome c oxidase subunit I, BAR (an apoptosis regulator), heat-shock protein 70-like protein, and three proteins belonging to the translation machinery (ribosomal proteins S7 and L17, and S1, a member of the elongation factor 1-alpha family). The only up-regulated gene was glutathione S-transferase subunit 3A (1.89-times). Guided by the expression levels of these genes, it may be possible to improve renoprotective treatments during anti-neoplastic therapies.     

Hydroxocobalamin uptake into the cerebrospinal fluid after nasal and intravenous delivery in rats and humans

The possibility of direct transport of hydroxocobalamin from the nasal cavity into the cerebrospinal fluid (CSF) after nasal administration in rats was investigated and the results were compared with a human study. Hydroxocobalamin was given to rats (n=8) both intranasally (214 microg/rat) and intravenously (49.5 microg/rat) into the jugular vein using a Vascular Access Port (VAP). Prior to and after drug administration, blood and CSF samples were taken and analysed by radioimmunoassay. The AUCCSF/AUCplasma ratio after nasal delivery does not differ from the ratio after intravenous infusion, indicating that hydroxocobalamin enters the CSF via the blood circulation across the blood-brain barrier (BBB). This same transport route is confirmed by the cumulative AUC-time profiles in CSF and plasma, demonstrating a 30 min delay between plasma absorption and CSF uptake of hydroxocobalamin in rats and in a comparative human study. The present results in rats show that there is no additional uptake of hydroxocobalamin in the CSF after nasal delivery compared to intravenous administration, which is in accordance with the results found in humans. This indicates a predictive value of the used rat model for the human situation when studying the nose to CSF transport of drugs.     

Guidelines for childhood obesity prevention programs: promoting healthy weight in children

These guidelines for obesity prevention programs encourage a health-centered, rather than weight-centered, approach that focuses on the whole child, physically, mentally, and socially. The emphasis is on living actively, eating in normal and healthful ways, and creating a nurturing environment that helps children recognize their own worth and respects cultural foodways and family traditions. It is recognized that obesity, eating disorders, hazardous weight loss, nutrient deficiencies, size discrimination, and body hatred are all interrelated and need to be addressed in comprehensive ways that do no harm.     

Photochemical internalization (PCI)--a novel technology for release of macromolecules from endocytic vesicles

The utilisation of macromolecules in therapy of cancer and other diseases is becoming increasingly relevant. Recent advances in molecular biology and biotechnology have made it possible to improve targeting and design of cytotoxic agents or DNA complexes for clinical applications. To achieve the expected biological effect of these macromolecules in many cases internalization to the cell cytosol is crucial. A number of different methods for internalization of membrane impermeable molecules has been established, including electroporation, liposome fusion, antibodies/targeting ligands as protein carriers and the utilisation of various types of vectors such as cationic polymers and viruses, for gene therapy. Although new delivery systems have improved the cellular uptake of macromolecules, tissue penetration, cellular uptake and efficient transfer of the molecules into the cytosol of the target cell are still fundamental obstacles. At an intracellular level, the most fundamental obstruction for cytosolic release of the therapeutic molecule is the membrane-barrier of the endocytic vesicles. Photochemical internalization (PCI) is a novel technology for release of endocytosed macromolecules into the cytosol. The technology is based on the use of photosensitizers located in endocytic vesicles that upon activation by light induce a release of macromolecules from their compartmentalization in endocytic vesicles. PCI has been shown to potentiate the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including proteins, peptides, and DNA delivered as a complex with cationic polymers or incorporated in adenovirus. The basis as well as the utilization of this technology will be briefly reviewed in this paper.     

Influence of educational level on determinants of folic acid use

In The Netherlands, periconceptional folic acid use to prevent neural tube defects was promoted through a national 'Folic Acid Campaign'. In two regions, a local campaign supplemented the national campaign to increase the chances of reaching women with low socio-economic status (SES). A framework of outcome criteria, defined as awareness knowledge, perceived safety, attitudes and subjective norms, was developed to evaluate the effectiveness of the two local campaigns. Data were gathered by means of two cross-sectional studies conducted just before and 1 year after the campaigns took place. Before the campaigns were conducted, there were already differences in all effect criteria and folic acid use between women of different educational levels, mostly in favour of women with a high level of education. Although both educational campaigns appeared to have a positive impact on all outcome criteria, they failed to reduce the existing differences in these outcome criteria between women of different educational levels. Folic acid use can be promoted effectively by mass media campaigns, certainly in a large group of women with no prior knowledge of the health benefits associated with periconceptional folic acid use. However, in order to achieve more equal health outcomes among women of low and high SES, it seems that more tailored interventions for women of low SES are needed.     

Dutch Institute for Health Care Improvement's standard code of practice entitled, "Donation of fetal tissue"

The Dutch Law on Foetal Tissue (Wet Foetaal Weefsel) sets out conditions and regulations concerning the donation, storage and permissibility of use of foetal tissue. Each institution where foetal tissue becomes available has to formulate an in-house code of conduct describing how the law will be applied within that institution. A committee, including abortion physicians and gynaecologists, has formulated a number of rules of conduct within the standard code of conduct under the auspices of the Kwaliteitsinstituut voor de Gezondheidszorg CBO [Dutch Institute for Healthcare Improvement]. Complying with this standard code ensures that the law is upheld. In clinical practice, one may deviate from this standard code in case of solid reasons only. Generally, all women can be asked to donate foetal tissue. A basic prerequisite for the inclusion of non-Dutch women is that oral and written communication is possible. The committee considers the age of 16 as a minimum threshold and mental incompetence as an exclusion criterion. Much attention should be paid to providing the women with information and to requesting permission. The basic principle is that the decision to terminate a pregnancy should be strictly separated from the decision to donate foetal tissue. As a general rule, foetal tissue should be stored anonymously. Adjustment of the abortion method in view of the intended scientific research is not permitted.     

Diagnostic image (145). A girl with striae. Irreversible striae due to longterm use of corticosteroids

A 9-year-old girl presented with irreversible striae, due to prolonged local corticosteroid use.     

Nutrition and health--vitamins and vitamin supplements

A balanced diet based on the Guidelines of the Netherlands Nutrition Centre provides a suitable basis for the maintenance of good health. However, there are a number of situations where supplementation with vitamins is clearly indicated. These include infants (vitamin A, D and K), young children, and pregnant and lactating women (vitamin D), future expectant mothers (folic acid) and the elderly (vitamin D). If doubts exist about a sufficient vitamin intake via the regular diet, a daily supplement supplying all vitamins at the level of the recommended daily allowance (RDA) is considered to be a responsible and safe choice. Epidemiological research indicates that the incidence of certain diseases is lower if the intake of vitamins is significantly higher than the RDA. However to date, targeted intervention studies have provided little unequivocal evidence to support this argument. For certain vitamins (A, D, folic acid, B6, nicotinic acid and beta-carotene) excessive intakes are associated with a health risk or clear toxicity. In the case of vitamin B6, nicotinic acid, folic acid and beta-carotene this risk is mainly limited to the use of high-dose supplements.     

A Turkish man with Behçet disease and recurrent acute abdomen

Following a total hip prosthesis, a 52-year-old Turkish man with Beh?et's disease developed persistent ileus due to intestinal perforations. Resection of the intestine was followed by new perforations, resulting in resection of another portion of the intestine and the start of immunosuppressive medication. Following the 5th resection for a perforated ulcer in the space of two weeks, an ileostomy was performed. One year later the stoma could be eliminated and the patient remained symptom-free. Beh?et's disease is relatively rare in the Netherlands. However, the gastrointestinal complications may be life-threatening. Surgical intervention is then often necessary. Complications and recurrences are frequent.     

Less ethnic knowledge in the Dutch College of General Practitioner's practice guidelines on type 2 diabetes mellitus, hypertension and asthma in adults than in the supporting literature

OBJECTIVE: To assess whether ethnic differences present in the scientific literature used as the basis for the Dutch College of General Practitioner's (NHG) practice guidelines were reflected in the ethnic-specific information the guidelines contained. DESIGN: Analysis of published information. METHOD: The scientific literature used as the basis for the guidelines about type 2 diabetes mellitus, hypertension and asthma in adults was collected and carefully screened. Relevant ethnic-specific information was compared to the content of the guidelines. RESULTS: Several relevant ethnic differences were stated in the scientific literature used as the basis for the guidelines. Differences in prevalence and clinical progress were stated for type 2 diabetes mellitus, differences in lung-volume were stated for asthma and differences in prevalence, onset, complications, response to pharmacological treatment and dietary salt restriction were stated for hypertension. The type 2 diabetes mellitus guideline stated a higher prevalence of diabetes in Hindustani people and recommended earlier screening in this group. The asthma guideline stated that the lung volume is dependent of ethnicity. The hypertension guideline did not state any ethnic-specific information. CONCLUSION: The guidelines on type 2 diabetes mellitus, hypertension and asthma in adults only adopted a limited number of the ethnic differences contained in the scientific literature on which they were based. Possible explanations are that information was only included if there was a clear scientific basis, and that ethnic distinctions were found to be politically and socially undesirable. However, this lack of information might lead to ineffective or sub-optimal care for ethnic minorities.