Implementación de la reforma de la salud: percepción del profesional químico farmacéutico / Health sector reform implementation: the pharmacists’ perceptions

Objetivo: Analizar las percepciones de los profesionales Químicos Farmacéuticos respecto de la implementación de los cambios de la reforma de la salud en la gestión farmacéutica. Métodos: Se condujo un estudio de tipo cualitativo, descriptivo y exploratorio en base a entrevistas semi-estructuradas en profundidad a 13 profesionales Químicos Farmacéuticos de la red asistencial pública de la Región de los Ríos. El análisis de la información se realizó a través del análisis del contenido. Resultados: Para los entrevistados, la reforma de la salud ha introducido mejoras en la gestión farmacéutica a través de mejor calidad de los procesos y de centrar la atención en el usuario. Sin embargo, la ausencia de políticas y estrategias en recursos humanos ha sido destacada como uno de sus principales obstáculos para implementar los cambios tanto de la reforma como los específicos respecto de la gestión farmacéutica. Conclusiones: La reforma de la salud ha permitido mejorar la gestión farmacéutica. Sin embargo se hace necesario fortalecer la implementación de los cambios.

Aim: Analyze the perception of the Pharmacists in relation to the implementation of the changes in the pharmaceutical management. Methods: A qualitative, descriptive and exploratory study was conducted on the basis of semi-structured in depth interviews to 13 Pharmacists from the public health care network from the Region de los Ríos. The information was analyzed through content analysis. Results: For the interviewee, the health reform introduced improvements in the pharmaceutical management through better quality of the processes and by focusing the attention on the user. Nevertheless, the absence of policies and strategies in human resources has been highlighted as one of the main obstacles to implement the changes of the reform as well as the specific ones with respect to the pharmaceutical management. Conclusions: The health sector reform has improved pharmaceutical management. However it is necessary to strengthen the implementation.

A microarray screen for novel candidate genes in coeliac disease pathogenesis.

BACKGROUND AND AIMS: The causative molecular pathways underlying the pathogenesis of coeliac disease are poorly understood. To unravel novel aspects of disease pathogenesis, we used microarrays to determine changes in gene expression of duodenal biopsies. METHODS: cDNA microarrays representing 19 200 genes were used to compare gene expression profiles of duodenal biopsies from 15 coeliac disease patients with villous atrophy (Marsh III) and seven control individuals with normal biopsies (Marsh 0). In addition, the specific effect of gluten was studied by comparing the expression profiles of Marsh III lesions of seven patients exposed to gluten with four patients on a gluten free diet. RESULTS: Comparing Marsh III with Marsh 0 lesions identified 109 genes that differed significantly (p<0.001) in expression levels between patients and controls. A large number of these genes have functions in proliferation and differentiation pathways and might be important for correct development of crypt-villous units. Alterations in these pathways may lead to the characteristic hyperplasia and villous atrophy seen in coeliac disease. The analyses also revealed 120 differentially expressed genes (p<0.005) when comparing patients on a gluten free diet with those exposed to gluten. These genes further strengthen our observation of increased cell proliferation in the presence of gluten. CONCLUSIONS: Our study provides new candidate genes in the pathogenesis of coeliac disease. Based on our results, we hypothesise that villous atrophy in coeliac disease patients is due to failure in cell differentiation. These genes are involved in pathways not previously implicated in coeliac disease pathogenesis and they may provide new targets for therapy.

In vitro evidence for differential involvement of CTGF, TGFbeta, and PDGF-BB in mesangial response to injury.

BACKGROUND: Connective tissue growth factor (CTGF) is a profibrotic growth factor, which is upregulated in wound healing and renal fibrosis, including anti-Thy-1.1 nephritis. The kinetics of CTGF mRNA expression in anti-Thy-1.1 nephritis suggested that CTGF regulation might contribute to glomerular response to injury downstream of transforming growth factor-beta (TGFbeta). In anti-Thy-1.1 nephritis the initial damage is followed by mesangial repair and limited sclerosis, which involves mesangial cell (MC) activation (alpha-smooth-muscle actin (alphaSMA) expression), proliferation, migration, and extracellular matrix production. The present in vitro study addresses the possible role of CTGF in these different aspects of mesangial response to injury, and how CTGF activity might relate to effects of TGFbeta and platelet-derived growth factor-BB (PDGF-BB). METHODS AND RESULTS: Immunostaining and ELISA showed that alphaSMA expression and transformation of MC into myofibroblast-like cells was induced by TGFbeta, but not affected by PDGF-BB, CTGF, or neutralizing anti-CTGF antibodies. [(3)H]thymidine incorporation and Ki67 staining demonstrated that, unlike PDGF-BB, neither CTGF nor TGFbeta induced the proliferation of MC. In contrast, both CTGF and TGFbeta induced MC migration, as evidenced by approximation of wound edges in scrape-wounded, non-proliferating rat MC monolayers. In addition, fibronectin expression was upregulated by both CTGF and TGFbeta, as measured by dot-blot analysis. Anti-CTGF completely blocked the effect of added CTGF. Moreover, anti-CTGF significantly reduced TGFbeta-induced increase in fibronectin. CONCLUSION: It thus appears that CTGF is specifically involved in a subset of the adaptive changes of MC involved in mesangial repair and sclerosis, which makes it an interesting candidate target for future intervention strategies.

Mutation in the beta 2m gene is not a frequent event in head and neck squamous cell carcinomas.

In cryostat sections of 84 head and neck squamous cell carcinomas (HNSCC) HLA class I and beta 2m expression was analysed using monomorphic and locus specific monoclonal antibodies. Loss of expression was heterogeneous and none of the tumours tested showed a total loss of HLA class I and/or beta 2m when analysed with W6/32, which recognises HLA class I determinants and anti-beta 2m MoAbs. Weak HLA class I and beta 2m expression was found in 9 tumours (11%) and heterogeneous expression was found in 2 tumours (2%). When analysed with locus-specific antibodies (HCA2 and HC10, anti-HLA-A and anti-HLA-B/C, respectively) 37 tumours (44%) showed a loss, weak or heterogeneous expression of one or both loci. Tumours showing a down-regulated HLA class I expression were analysed for mutations in either allele of the beta 2m gene by sequencing based mutation analysis (SBMA). Exon 1 and exons 2 and 3 were amplified separately by PCR using M13-tailed intron-specific primers. PCR products were sequenced in two directions. In none of the tumours mutations in the beta 2m gene were detected. In 59% of the tumours with down-regulated HLA class I expression, lost or down-regulated TAP 1 expression was found when analysed with anti-TAP 1 antibodies. This indicates an important role for TAP in down-regulation of HLA class I expression in HNSCC.

Deletion of the H19 differentially methylated domain results in loss of imprinted expression of H19 and Igf2.

Differentially methylated sequences associated with imprinted genes are proposed to control genomic imprinting. A 2-kb region located 5' to the imprinted mouse H19 gene is hypermethylated on the inactive paternal allele throughout development. To determine whether this differentially methylated domain (DMD) is required for imprinted expression at the endogenous locus, we have generated mice harboring a 1.6-kb targeted deletion of the DMD and assayed for allelic expression of H19 and the linked, oppositely imprinted Igf2 gene. H19 is activated and Igf2 expression is reduced when the DMD deletion is paternally inherited; conversely, upon maternal transmission of the mutation, H19 expression is reduced and Igf2 is activated. Consistent with the DMD's hypothesized role of setting up the methylation imprint, the mutation also perturbs allele-specific methylation of the remaining H19 sequences. In conclusion, these experiments show that the H19 hypermethylated 5' flanking sequences are required to silence paternally derived H19. Additionally, these experiments demonstrate a novel role for the DMD on the maternal chromosome where it is required for the maximal expression of H19 and the silencing of Igf2. Thus, the H19 differentially methylated sequences are required for both H19 and Igf2 imprinting.

A 5' 2-kilobase-pair region of the imprinted mouse H19 gene exhibits exclusive paternal methylation throughout development.

The imprinted mouse H19 gene is hypermethylated on the inactive paternal allele in somatic tissues and sperm. Previous observations from a limited analysis have suggested that methylation of a few CpG dinucleotides in the region upstream from the start of transcription may be the mark that confers parental identity to the H19 alleles. Here we exploit bisulfite mutagenesis coupled with genomic sequencing to derive the methylation status of 68 CpGs that reside in a 4-kb region 5' to the start of transcription. This method reveals a 2-kb region positioned between 2 and 4 kb upstream from the start of transcription that is strikingly differentially methylated in midgestation embryos. At least 12 of the cytosine residues in this region are exclusively methylated on the paternal allele in blastocysts. In contrast, a 350-bp promoter-proximal region is less differentially methylated in midgestation embryos and, like most of the genome, is largely devoid of methylation on both alleles in blastocysts. We also demonstrate exclusive expression of the maternal H19 allele in the embryos that exhibit paternal methylation of the upstream 2-kb region. These data suggest that the 2-kb differentially methylated region acts as a key regulatory domain for imprinted H19 expression.

[The population debates of Cairo from an Islamic viewpoint]. / Die Bevolkerungsdebatte von Kairo aus muslimischer Sicht.

PIP: This paper focuses on Islamic attitudes toward the population issues discussed at the International Conference on Population and Development, held in Cairo in September 1994.^ieng