Sodium azide and 2-deoxy-D-glucose-induced cellular stress affects phosphorylation-dependent AbetaPP processing

Production of the amyloid beta (Abeta) peptide via altered metabolism of the amyloid beta-Protein Precursor (AbetaPP) appears to be a key event in the pathology of Alzheimer Disease (AD). Accordingly, altered processing of AbetaPP was observed under conditions of abnormal cellular stress induced by sodium azide in the presence of 2-deoxy-D-glucose (2DG). As previously reported, the production of sAbetaPP (the secreted fragment of AbetaPP) was inhibited. However, our data further suggests that 2DG alone can account for most of the observed effects on AbetaPP processing in COS-1 cells and PC12 cells. It appears that 2DG interferes with the normal glycosylation of AbetaPP and its maturation process, having direct consequences on sAbetaPP production. Interestingly, PMA (phorbol 12-myristate 13-acetate)-induced sAbetaPP production was maintained under the stress conditions used, suggesting that potential non-amyloidogenic AbetaPP processing can still be favoured. This is of potential therapeutic interest, since it indicates that even under adverse stress conditions drugs such as PMA can affect AbetaPP processing, leading to increased sAbetaPP production and a concomitant reduction in Abeta production. However, the induction of sAbetaPP production was not identical when the phosphatase inhibitor OA (okadaic acid) was used. In fact, the typical OA-induced increase in sAbetaPP production could be abolished under specific conditions. This constitutes an interesting precedent for the possible dissociation of the PMA and OA responses in terms of sAbetaPP production. The involvement of protein phosphatases, which are inhibited by OA, inbetaPP processing, was reinforced by the increased co-localization of AbetaPP and PP1alpha (protein phosphatase 1alpha) at the cell surface upon exposure to OA and PMA. Overall, our results support the notion that signal transduction processes may be of particular relevance for our understanding of the molecular basis of AD, and for the design of rational signal transduction therapeutics.     

Neonatal immunoglobulin secretion and lymphocyte phenotype in rat small intestine lamina propria

We characterized the lymphocyte phenotype and the ability to produce Ig by lamina propria (LP) cells from rat ileum throughout the suckling period. In the first week after birth, <10% of LP lymphocytes were B cells, but at weaning, this figure rose to >30% as found in the adult. These B cells did not bear surface IgA (sIgA-). However, the number of sIgA+, which may correspond to B blast cells because they were outside lymphocyte cytometer gate, increased. In LP, IgM-secreting cells (SC) appeared during the second week of life, and IgA-SC were detected later but at a lower number. Regarding LP T cells, CD8+ cells were more abundant than CD4+ cells along the first 2 postnatal weeks, and CD3+CD8alphaalpha+TCRalphabeta+CD5-CD25- was their predominating phenotype. In this 2-wk period, between 8 and 20% of LP were natural killer cells. LP CD4+ lymphocytes in neonatal rats showed increasing co-expression of TCRalphabeta, whereas the co-expression of CD90 decreased and the CD4+CD25+ cell percentage did not achieve adult values. In conclusion, in the first 2 wk of the rat life, the gut LP immune system shows abundant CD8alphaalpha+ cells, including NK cells. Thereafter, LP B cells increase dramatically and Ig-SC appear, with IgM-SC being more abundant than IgA-SC. CD4+ LP lymphocytes acquire a mature phenotype and adult proportions later after weaning.     

Brain tumor classification by proton MR spectroscopy: comparison of diagnostic accuracy at short and long TE

BACKGROUND AND PURPOSE: Different TE can be used for obtaining MR spectra of brain tumors. The purpose of this study was to determine the influence of the TE used in brain tumor classification by comparing the performance of spectra obtained at two different TE (30 ms and 136 ms). METHODS: One hundred fifty-one studies of patients with brain tumors (37 meningiomas, 12 low grade astrocytomas, 16 anaplastic astrocytomas, 54 glioblastomas, and 32 metastases) were retrospectively selected from a series of 378 consecutive examinations of brain masses. Single voxel proton MR spectroscopy at TE 30 ms and 136 ms was performed with point-resolved spectroscopy in all cases. Fitted areas of nine resonances of interest were normalized to water. Tumors were classified into four groups (meningioma, low grade astrocytoma, anaplastic astrocytoma, and glioblastoma-metastases) by means of linear discriminant analysis. The performance of linear discriminant analysis at each TE was assessed by using the leave-one-out method. RESULTS: Tumor classification was slightly better at short TE (123 [81%] of 151 cases correctly classified) than at long TE (118 [78%] of 151 cases correctly classified). Meningioma was the only group that showed higher sensitivity and specificity at long TE. Improved results were obtained when both TE were considered simultaneously: the suggested diagnosis was correct in 105 (94%) of 112 cases when both TE agreed, whereas the correct diagnosis was suggested by at least one TE in 136 (90%) of 151 cases. CONCLUSION: Short TE provides slightly better tumor classification, and results improve when both TE are considered simultaneously. Meningioma was the only tumor group in which long TE performed better than short TE.     

Visceral fat accumulation as a risk factor for prostate cancer

OBJECTIVE: No clear association between obesity or body fat distribution and prostate cancer has been shown. We investigated the relation between visceral fat accumulation as measured by computed tomography (CT) and the occurrence of prostate cancer. RESEARCH METHODS AND PROCEDURES: We compared body fat distribution assessed by a direct method (CT) in 63 prostate cancer cases with 63 age-matched healthy community controls. A CT scan at the level of the fourth lumbar vertebra was performed in all participants. RESULTS: Patients presented a significantly higher mean total abdominal fat area (509.2 +/- 226.1 vs. 334.3 +/- 132.9 cm2, p < 0.001), mostly because of a higher mean visceral fat area (VF; 324.7 +/- 145.6 vs. 177.4 +/- 88.4 cm2, p < 0.001) and a significantly higher mean ratio between visceral and subcutaneous fat areas (V/S ratio; 1.8 +/- 0.4 vs. 1.2 +/- 0.4, p < 0.001). A significantly higher risk of prostate cancer was found for participants with higher VF (odds ratio = 4.6; 95% confidence interval = 2.6 to 8.2 per SD increase) and V/S ratio (odds ratio = 6.0; 95% confidence interval = 2.3 to 11.0 per SD increase). DISCUSSION: These results suggest a role for visceral obesity, quantified by CT, as a risk factor for prostate cancer. The action of the adipocytokines secreted by visceral fat cells, steroid hormone disturbances, and increased levels of insulin or other hormones noted in visceral obesity may explain this association.     

Detection of Anaplasma phagocytophilum DNA in Ixodes ticks (Acari: Ixodidae) from Madeira Island and Setubal District, mainland Portugal

A total of 278 Ixodes ticks, collected from Madeira Island and Setubal District, mainland Portugal, were examined by polymerase chain reaction (PCR) for the presence of Anaplasma phagocytophilum. Six (4%) of 142 Ixodes ricinus nymphs collected in Madeira Island and 1 nymph and 1 male (2%) of 93 I. ventalloi collected in Setubal District tested positive for A. phagocytophilum msp2 genes or rrs. Infection was not detected among 43 I. ricinus on mainland Portugal. All PCR products were confirmed by nucleotide sequencing to be identical or to be most closely related to A. phagocytophilum. To our knowledge, this is the first evidence of A. phagocytophilum in ticks from Setubal District, mainland Portugal, and the first documentation of Anaplasma infection in I. ventalloi. Moreover, these findings confirm the persistence of A. phagocytophilum in Madeira Island's I. ricinus.     

Inter-observer reproducibility of measurements of range of motion in patients with shoulder pain using a digital inclinometer

Background  

Reproducible measurements of the range of motion are an important prerequisite for the interpretation of study results. The digital inclinometer is considered to be a useful instrument because it is inexpensive and easy to use. No previous study assessed inter-observer reproducibility of range of motion measurements with a digital inclinometer by physical therapists in a large sample of patients.     

Dietary plasma protein affects the immune response of weaned rats challenged with S. aureus Superantigen B

The aim of this study was to determine the potential modulatory effects of diets supplemented with spray-dried animal plasma (SDAP) or immunoglobulin concentrates (IC) on the immune response of rats challenged with Staphylococcus aureus enterotoxin B (SEB). Lewis rats were fed diets containing 80 g of SDAP/kg diet, 22.7 g of IC/kg diet, or milk proteins (Control diet) from postnatal d 21 (weaning) for 14 d. On d 30 and 33, rats were given SEB (0.5 mg/kg body weight; i.p.). Organized gut-associated lymphoid tissue (GALT) populations, intestinal secretion, mucosal and serum immunoglobulin concentrations, and neutrophil infiltration were studied. On d 35, blood was collected under anesthesia and samples of intestinal mucosa, Peyer's patches, mesenteric lymph nodes (MLN), and spleen were taken. SEB increased the water content of feces, which was prevented by diets containing either SDAP (P < 0.002) or IC (P < 0.001), indicating that plasma protein-supplemented diets can reverse the SEB-induced secretory response. In Peyer's patches, the diet containing SDAP partially prevented the SEB-induced increase in T lymphocytes (P < 0.1) and reduced the percentage of activated T helper cells (P < 0.05). In MLN, activated T lymphocytes were increased by SEB but they were not affected by diet. No effects of SEB or dietary supplementation on mucosal IgA and serum IgA and IgG were observed. The effects of SDAP supplementation on the lymphocyte populations of GALT in rats challenged with SEB support the view that SDAP can modulate the immune response and suggest that plasma protein supplementation can prevent GALT from possible activation by luminal bacterial superantigens.     

Celiac disease in a group of children and adolescents with type 1 diabetes mellitus

To know the prevalence of celiac disease (CD) in a group of children and adolescents with type I diabetes mellitus. A cross sectional study was conducted at the Instituto Materno Infantil de Pernambuco (IMIP) in March 2000. The sample consisted of 19 children and adolescents with type I diabetes mellitus that had the human anti-tissue transglutaminase antibodies assessed using kits from the Eurospital Laboratory. In case of positive results it was realized small intestine biopsy to confirm the diagnosis. For the calculation of the prevalence of CD it was considered the number of patients with serum positive histological alterations of the mucous membrane of the small intestine compatible with CD. Four patients presented serum positivity for human anti-tissue transglutaminase antibodies with a serum prevalence of 21% (4/19). Out of these four subjects, three who accomplished small intestine biopsy presented histological alterations compatible with CD. The prevalence of CD in this group was 15.8% (3/19). The prevalence of CD in this study group was high, suggesting that those with type I diabetes mellitus should be led as a group of high risk to develop this disease.     

Health and immigration: new situations and challenges

The new social and demographic framework in Spain that has appeared since the arrival of new migrant populations, raises the need to improve the knowledge of their health status and to identify preventive measures and priorities in heath services.A bibliographic review of the available information on migration and health in Spain is performed, together with an analysis of their contents from a Public Health point of view. The high proportion of new borns from foreign mothers, the mental needs, deficits in oral and dental health, and the increase of tuberculosis in migrants, together with limited vaccine coverage in children, define the main health needs of these populations. The analysis of health services, reveals a high use of pediatric, obstetric and gynecologic resources by migrant populations. Conclusions; although no particular health needs have been identified for migrants, special attention for tuberculosis, mother and child health and health promotion and prevention, have to be funded for specific migrant populations. Health resources and services have to be reinforced with health agents, human resources, and specialized education for health professionals.