RESUMEN
This study aimed to estimate the frequency of the SNPs (+45T>G and +276G>T) genotypes and investigate the association between the two SNPs and adiponectin concentration, metabolic parameters and risk of T2DM in the Bahraini population. We genotyped the two ADIPOQ SNPs in 140 unrelated T2DM patients and 66 nondiabetic controls using the polymerase chain reaction-restriction fragment length polymorphism assay. Lipid profile was measured by enzymatic methods. Total serum adiponectin levels were measured by immunoassay. T2DM patients had reduced adiponectin levels compared with controls. +45T>G was more prevalent in patients than controls. The rare G allele of +45T>G occurred more frequently than the common T allele in T2DM patients compared with controls, and was associated with lower serum adiponectin levels. There was no significant difference in allele and genotype frequencies of +276G>T between type T2DM patients and controls. There was no association between both SNPs and metabolic parameters.
Asunto(s)
Adiponectina/sangre , Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleótido Simple/genética , Adiponectina/genética , Bahrein , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Medición de RiesgoRESUMEN
Recent developments in colonic surgery generate exciting opportunities for surgeons and trainees. In the first instance, the anatomy of the entire mesenteric organ has been clarified and greatly simplified. No longer is it regarded as fragmented and complex. Rather it is continuous from duodenojejunal flexure to mesorectum, spanning the gastrointestinal tract between. Recent histologic findings have demonstrated that although apposed to the retroperitoneum, the mesenteric organ is separated from this via Toldt's fascia. These fundamentally important observations underpin the principles of complete mesocolic excision, where the mesocolic package is maintained intact, following extensive mesenterectomy. More importantly, they provide the first opportunity to apply a canonical approach to the development of nomenclature in resectional colonic surgery. In this review, we demonstrate how the resultant nomenclature is entirely anatomic based, and for illustrative purposes, we apply it to the procedure conventionally referred to as right hemicolectomy, or ileocolic resection.
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Colectomía/métodos , Colon/anatomía & histología , Colon/cirugía , Mesocolon/anatomía & histología , Mesocolon/cirugía , Terminología como Asunto , HumanosRESUMEN
The standardisation of the surgical management of rectal cancer has been facilitated by adoption of an anatomic surgical nomenclature. Thus, "total mesorectal excision" substituted "anterior resection" or "proctosigmoidectomy" and implies resection of both rectum and mesorectum. Similar trends towards standardisation of colonic surgery are ongoing, yet there remains a heterogeneity of terminology utilised (eg, "right hemicolectomy", "ileocolic resection", and "total mesocolic excision"). Recent descriptions of mesocolic anatomy provide an opportunity to standardise colonic resection according to a more precise and informative anatomic nomenclature. This article aims to firstly emphasise the central importance of the mesocolon and from this propose a related nomenclature for resectional colonic surgery. Introduction of a standardised nomenclature for colonic resection is a necessary step towards standardisation of colonic surgery in general.
Asunto(s)
Colectomía/clasificación , Mesocolon/anatomía & histología , Terminología como Asunto , Humanos , Mesocolon/cirugíaRESUMEN
AIM: The aim of this study was to characterize formally the mesocolic anatomy during and following total mesocolic excision. Total mesocolic excision may improve survival in patients with colon cancer. Although this requires a detailed knowledge of normal and variant mesocolic anatomy, the latter is poorly characterized. No studies have prospectively characterized the anatomy of the entire mesocolon. METHOD: Total mesocolic excision was performed in 109 patients undergoing total abdominal colectomy. The mesocolon was maintained intact thereby permitting a precise anatomical characterization from ileocaecal to mesorectal levels. Two- and three-dimensional schematic reconstructions were generated to illustrate in situ conformation. RESULTS: Several previously undocumented findings emerged, including: (i) the mesocolon was continuous from ileocaecal to rectosigmoid level; (ii) a mesenteric confluence occurred at the ileocaecal and rectosigmoid junction as well as at the hepatic and splenic flexures; (iii) each flexure (and ileocaecal junction) was a complex of peritoneal and omental attachments to the colon centred on a mesenteric confluence; (iv) the proximal rectum originated at the confluence of the mesorectum and mesosigmoid; and (v) a plane occupied by Toldt's fascia separated the entire apposed mesocolon from the retroperitoneum. CONCLUSION: When the mesocolon is fully mobilized during a total mesocolic excision of the colon, several anatomical findings that have not been previously documented emerge. These findings provide a rationalization of the surgical, embryological and anatomical approaches to the mesocolon. This has implications for all related sciences.
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Mesocolon/anatomía & histología , Adolescente , Adulto , Anciano , Colectomía/métodos , Colon/anatomía & histología , Colon/cirugía , Fascia/anatomía & histología , Fasciotomía , Femenino , Humanos , Masculino , Mesocolon/cirugía , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Light plays a key role in the development and physiology of plants. One of the most profound effects of light on plant development is the derepression of expression of an array of light-responsive genes, including the genes encoding the chlorophyll a/b binding proteins (CAB) of photosystem II. To understand the mechanism by which light signals nuclear gene expression, we developed a genetic selection to identify mutants with reduced CAB transcription. Here, we describe a new Arabidopsis locus, CUE1 (for CAB underexpressed). Mutations at this locus result in defects in expression of several light-regulated genes, specifically in mesophyll but not in bundle-associated or epidermis cells. Reduced accumulation of CAB and other photosynthesis-related mRNAs in the mesophyll was correlated with defects in chloroplast development in these cells, resulting in a reticulate pattern with veins greener than the interveinal regions of leaves. Moreover, chalcone synthase mRNA, although known to be regulated by both phytochrome and a blue light receptor, accumulated normally in the leaf epidermis. Dark basal levels of CAB expression were unaffected in etiolated cue1 seedlings; however, induction of CAB transcription by pulses of red and blue light was reduced, suggesting that CUE1 acts downstream from both phytochrome and blue light photoreceptors. CUE1 appears to play a role in the primary derepression of mesophyll-specific gene expression in response to light, because cue1 mutants are severely deficient at establishing photoautotrophic growth. Based on this characterization, we propose that CUE1 is a cell-specific positive regulator linking light and intrinsic developmental programs in Arabidopsis leaf mesophyll cells.
RESUMEN
Most eubacteria, and all eukaryotes examined thus far, encode homologs of the DNA mismatch repair protein MutS. Although eubacteria encode only one or two MutS-like proteins, eukaryotes encode at least six distinct MutS homolog (MSH) proteins, corresponding to conserved (orthologous) gene families. This suggests evolution of individual gene family lines of descent by several duplication/specialization events. Using quantitative phylogenetic analyses (RASA, or relative apparent synapomorphy analysis), we demonstrate that comparison of complete MutS protein sequences, rather than highly conserved C-terminal domains only, maximizes information about evolutionary relationships. We identify a novel, highly conserved middle domain, as well as clearly delineate an N-terminal domain, previously implicated in mismatch recognition, that shows family-specific patterns of aromatic and charged amino acids. Our final analysis, in contrast to previous analyses of MutS-like sequences, yields a stable phylogenetic tree consistent with the known biochemical functions of MutS/MSH proteins, that now assigns all known eukaryotic MSH proteins to a monophyletic group, whose branches correspond to the respective specialized gene families. The rooted phylogenetic tree suggests their derivation from a mitochondrial MSH1-like protein, itself the descendent of the MutS of a symbiont in a primitive eukaryotic precursor.
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Adenosina Trifosfatasas , Proteínas Bacterianas/genética , Disparidad de Par Base , Reparación del ADN/genética , Proteínas de Unión al ADN , Proteínas de Escherichia coli , Evolución Molecular , Secuencia de Aminoácidos , Animales , Proteínas Bacterianas/química , Duplicación de Gen , Humanos , Datos de Secuencia Molecular , Proteína MutS de Unión a los Apareamientos Incorrectos del ADN , Filogenia , Homología de Secuencia de AminoácidoRESUMEN
Ca(2+)-handling proteins are important regulators of the excitation-contraction-relaxation cycle in skeletal muscle fibres. Although domain binding studies suggest protein coupling between various Ca(2+)-regulatory elements of triad junctions, no direct biochemical evidence exists demonstrating high-molecular-mass complex formation in native microsomal membranes. Calsequestrin represents the protein backbone of the luminal Ca(2+) reservoir and thereby occupies a central position in Ca(2+) homeostasis; we therefore used calsequestrin blot overlay assays in order to determine complex formation between sarcoplasmic reticulum components. Peroxidase-conjugated calsequestrin clearly labelled four major protein bands in one-dimensional (1D) and 2D electrophoretically separated membrane preparations from adult skeletal muscle. Immunoblotting identified the calsequestrin-binding proteins of approximately 26, 63, 94 and 560 kDa as junctin, calsequestrin itself, triadin and the ryanodine receptor, respectively. Protein-protein coupling could be modified by ionic detergents, non-ionic detergents, changes in Ca(2+) concentration, as well as antibody and purified calsequestrin binding. Importantly, complex formation as determined by blot overlay assays was confirmed by differential co-immunoprecipitation experiments and chemical crosslinking analysis. Hence, the key Ca(2+)-regulatory membrane components of skeletal muscle form a supramolecular membrane assembly. The formation of this tightly associated junctional sarcoplasmic reticulum complex seems to underlie the physiological regulation of skeletal muscle contraction and relaxation, which supports the biochemical concept that Ca(2+) homeostasis is regulated by direct protein-protein interactions.
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Señalización del Calcio , Proteínas de Unión al Calcio , Calsecuestrina/metabolismo , Proteínas Portadoras/metabolismo , Proteínas de la Membrana , Oxigenasas de Función Mixta , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Retículo Sarcoplasmático/metabolismo , Animales , Calsecuestrina/química , Calsecuestrina/aislamiento & purificación , Membrana Celular/metabolismo , Reactivos de Enlaces Cruzados , Electroforesis en Gel Bidimensional , Electroforesis en Gel de Poliacrilamida , Immunoblotting , Masculino , Contracción Muscular , Pruebas de Precipitina , Unión Proteica , ConejosAsunto(s)
Prescripciones de Medicamentos/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Atención Primaria de Salud/estadística & datos numéricos , Adulto , Antibacterianos/uso terapéutico , Bahrein , Distribución de Chi-Cuadrado , Centros Comunitarios de Salud/estadística & datos numéricos , Utilización de Medicamentos/estadística & datos numéricos , Medicamentos Genéricos/uso terapéutico , Femenino , Encuestas de Atención de la Salud , Necesidades y Demandas de Servicios de Salud , Humanos , Inyecciones/estadística & datos numéricos , Masculino , Programas Nacionales de Salud , Polifarmacia , Indicadores de Calidad de la Atención de Salud , Estudios Retrospectivos , Vitaminas/uso terapéuticoRESUMEN
BACKGROUND: Aside from muscle, brain is also a major expression site for dystrophin, the protein whose abnormal expression is responsible for Duchenne muscular dystrophy. Cognitive impairments are frequently associated with this genetic disease, we therefore studied the fate of brain and skeletal muscle dystrophins and dystroglycans in dystrophic animal models. RESULTS: All dystrophin-associated glycoproteins investigated were reduced in dystrophic muscle fibres. In Dp427-deficient mdx brain and Dp71-deficient mdx-3cv brain, the expression of alpha-dystroglycan and laminin was reduced, utrophin isoforms were up-regulated and beta-dystroglycan was not affected. Immunofluorescence localization of beta-dystroglycan in comparison with glial, endothelial and neuronal cell markers revealed co-localization of von Willebrand factor with beta-dystroglycan. Its expression at the endothelial-glial interface was preserved in dystrophin isoform-deficient brain from mdx and mdx-3cv mice. In addition, chemical crosslinking revealed that the Dp71 isoform exists in mdx brain predominantly as a monomer. CONCLUSIONS: This suggests an association of beta-dystroglycan with membranes at the vascular-glial interface in the forebrain. In contrast to dystrophic skeletal muscle fibres, dystrophin deficiency does not trigger a reduction of all dystroglycans in the brain, and utrophins may partially compensate for the lack of brain dystrophins. Abnormal oligomerization of the dystrophin isoform Dp71 might be involved in the pathophysiological mechanisms underlying abnormal brain functions.
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Encéfalo/metabolismo , Proteínas del Citoesqueleto/biosíntesis , Proteínas del Citoesqueleto/metabolismo , Distrofina/análogos & derivados , Distrofina/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de la Membrana/biosíntesis , Distrofia Muscular Animal/metabolismo , Animales , Proteínas del Citoesqueleto/análisis , Proteínas del Citoesqueleto/inmunología , Distroglicanos , Distrofina/análisis , Técnica del Anticuerpo Fluorescente , Cinética , Sustancias Macromoleculares , Glicoproteínas de Membrana/análisis , Glicoproteínas de Membrana/inmunología , Ratones , Ratones Endogámicos mdx , Modelos Biológicos , Fibras Musculares Esqueléticas/química , Músculo Esquelético/metabolismo , Regulación hacia Arriba , Utrofina , Factor de von Willebrand/análisisRESUMEN
The membrane cytoskeletal component dystrophin and its associated glycoproteins play a central role in the molecular pathogenesis of several muscular dystrophies, i.e. Duchenne/Becker muscular dystrophy, congenital muscular dystrophy and various forms of limb-girdle muscular dystrophy. Although the most frequent of these disorders, Duchenne muscular dystrophy, is mainly recognized as a disease of skeletal muscle fibers, pathophysiological changes also involve the heart and diaphragm, as well as the peripheral and central nervous system. Thus current research efforts into the elucidation of the molecular mechanisms underlying these genetic diseases are not only directed towards studying skeletal muscle necrosis but also investigate abnormalities of heart and brain dystrophin-glycoprotein complexes in cardiomyopathy and brain deficiencies associated with muscular dystrophy. Furthermore, many isoforms of dystrophin and dystrophin-associated components have been identified in various non-muscle tissues and their function(s) are mostly unknown. With respect to skeletal muscle fibers, the characterization of new dystrophin-associated proteins, such as dystrobrevin, sarcospan and the syntrophins, led to a modified model of the spatial configuration of the dystrophin-glycoprotein complex. However, it is generally accepted now that beta-dystroglycan forms the plasmalemma-spanning linkage between dystrophin and the laminin-binding protein alpha-dystroglycan and that this complex is associated with the sarcoglycan subcomplex of sarcolemmal glycoproteins.
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Encéfalo/anomalías , Proteínas Asociadas a la Distrofina , Distrofina/fisiología , Cardiopatías Congénitas/metabolismo , Proteínas de la Membrana/metabolismo , Distrofias Musculares/metabolismo , Proteínas de Neoplasias , Proteínas Portadoras/metabolismo , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Distroglicanos , Humanos , Glicoproteínas de Membrana/metabolismo , Proteínas de la Membrana/genética , Proteínas Musculares/metabolismo , Distrofias Musculares/complicaciones , Distrofias Musculares/fisiopatología , UtrofinaRESUMEN
This study aimed to estimate the frequency of the SNPs [+45T>G and +276G>T] genotypes and investigate the association between the two SNPs and adiponectin concentration, metabolic parameters and risk of T2DM in the Bahraini population. We genotyped the two ADIPOQ SNPs in 140 unrelated T2DM patients and 66 nondiabetic controls using the polymerase chain reaction-restriction fragment length polymorphism assay. Lipid profile was measured by enzymatic methods. Total serum adiponectin levels were measured by immunoassay. T2DM patients had reduced adiponectin levels compared with controls. +45T>G was more prevalent in patients than controls. The rare G allele of +45T>G occurred more frequently than the common T allele in T2DM patients compared with controls, and was associated with lower serum adiponectin levels. There was no significant difference in allele and genotype frequencies of +276G>T between type T2DM patients and controls. There was no association between both SNPs and metabolic parameters
La présente étude avait pour objectif de mesurer la fréquence des polymorphismes mononucléotidiques [+45T>G et +276G>T] des génotypes et d'évaluer l'association entre ces deux polymorphismes et la concentration d'adiponectine, les paramètres métaboliques et le risque de diabète non insulino-dépendant [DNID] dans la population bahreinienne. Nous avons génotypé les deux polymorphismes mononucléotidiques du gène ADIPOQ chez 140 patients atteints de DNID sans lien de parenté et 66 témoins non diabétiques en recourant à l'analyse du polymorphisme de longueur des fragments de restriction par réaction en chaîne de polymérase. Le profil lipidique a été mesuré au moyen de méthodes enzymatiques. Les concentrations d'adiponectine totale sérique ont été mesurées par immunodosage. Les patients atteints de DNDI affichaient des concentrations d'adiponectine réduites par rapport aux témoins. Le polymorphisme +45T>G avait une prévalence plus élevée chez les patients que chez les témoins. L'allèle rare G du polymorphisme +45T>G apparaissait plus fréquemment que l'allèle commun T chez les patients atteints de DNID que chez les témoins, et était associé à des concentrations d'adiponectine sérique plus faibles. Il n'existait pas de différence significative entre les fréquences des allèles et des génotypes du polymorphisme +276G>T entre les patients atteints de DNID et les témoins. Aucune association entre les deux polymorphismes et les paramètres métaboliques n'a été notée
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Enfermedades no Transmisibles , Diabetes Mellitus Tipo 2 , Polimorfismo de Nucleótido Simple , Adiponectina , Reacción en Cadena de la Polimerasa , Alelos , Genotipo , Riesgo , Encuestas y Cuestionarios , BahreinRESUMEN
Sets of degenerate oligomers corresponding to highly conserved domains of MutS-homolog (MSH) mismatch-repair proteins primed polymerase chain reaction amplification of two Arabidopsis thaliana DNA fragments that are homologous to eukaryotic MSH-like genes. Phylogenetic analysis places one complete gene, designated atMSH2, in the evolutionarily distinct MSH2 subfamily.
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Adenosina Trifosfatasas , Proteínas de Arabidopsis , Arabidopsis/genética , Proteínas Bacterianas/genética , Reparación del ADN/genética , Proteínas de Unión al ADN , Proteínas de Escherichia coli , Genes de Plantas , Proteínas de Plantas/genética , Secuencia de Aminoácidos , Proteínas Bacterianas/clasificación , Secuencia Conservada , ADN Complementario/genética , Datos de Secuencia Molecular , Proteína MutS de Unión a los Apareamientos Incorrectos del ADN , Proteína 2 Homóloga a MutS , Filogenia , Proteínas de Plantas/clasificación , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
Arabidopsis mismatch repair genes predict MutS-like proteins remarkably similar to eukaryotic MutS homologs-MSH2, MSH3, and MSH6. A novel feature in Arabidopsis is the presence of two MSH6-like proteins, designated AtMSH6 and AtMSH7. Combinations of Arabidopsis AtMSH2 with AtMSH3, AtMSH6, or AtMSH7 proteins-products of in vitro transcription and translation-were analyzed for interactions by analytical gel filtration chromatography. The AtMSH2 protein formed heterodimers with AtMSH3, AtMSH6, and AtMSH7, but no single proteins formed homodimers. The abilities of the various heterodimers to bind to mismatched 51-mer duplexes were measured by electrophoretic mobility-shift assays. Similar to the behavior of the corresponding human proteins, AtMSH2*AtMSH3 heterodimers bound "insertion-deletion" DNA with three nucleotides (+AAG) or one nucleotide (+T) looped out much better than they bound DNA with a base/base mispair (T/G), whereas AtMSH2*AtMSH6 bound the (+T) substrate strongly, (T/G) well, and (+AAG) no better than it did a (T/A) homoduplex. However, AtMSH2*AtMSH7 showed a different specificity: moderate affinity for a (T/G) substrate and weak binding of (+T). Thus, AtMSH2*AtMSH7 may be specialized for lesions/base mispairs not tested or for (T/G) mispairs in special contexts.
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Adenosina Trifosfatasas , Proteínas de Arabidopsis , Arabidopsis/genética , Proteínas de Unión al ADN , Proteínas de Escherichia coli , Proteínas de Plantas/genética , Secuencia de Aminoácidos , Arabidopsis/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Disparidad de Par Base , Cromatografía en Gel , ADN de Plantas/metabolismo , Dimerización , Electroforesis en Gel de Poliacrilamida , Datos de Secuencia Molecular , Proteína MutS de Unión a los Apareamientos Incorrectos del ADN , Proteína 2 Homóloga a MutS , Proteína 3 Homóloga de MutS , Ácidos Nucleicos Heterodúplex/metabolismo , Filogenia , Proteínas de Plantas/metabolismo , Homología de Secuencia de AminoácidoRESUMEN
Abnormalities in the muscle dystrophin-glycoprotein complex are implicated in the molecular pathogenesis of various neuromuscular disorders. Weakening of the trans-sarcolemmal linkage between the actin membrane-cytoskeleton and the extracellular matrix appears to trigger destabilization of the muscle cell periphery. In addition to muscular weakness, one-third of patients suffering from Duchenne muscular dystrophy exhibit mental retardation. Since little is known about the pathophysiology of brain abnormalities in these patients, we investigated the fate of the most abundant dystrophin-associated protein, beta-dystroglycan, in the central nervous system. It was found to be present throughout all normal brain regions studied. In contrast, this glycoprotein was greatly reduced in brain microsomes derived from Duchenne specimens, while it is of normal abundance in the brain from the dystrophic animal model mdx. Deficiency in brain beta-dystroglycan might render nervous tissue more susceptible to cellular disturbances and this may result in cognitive impairment in some Duchenne patients.
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Encéfalo/metabolismo , Proteínas del Citoesqueleto/biosíntesis , Glicoproteínas de Membrana/biosíntesis , Distrofias Musculares/metabolismo , Animales , Distroglicanos , Ratones , Ratones Endogámicos mdx , ConejosRESUMEN
Altered mechanisms of Ca2+ transport may underlie the contractile dysfunctions that have been frequently reported to occur in diabetic cardiac and skeletal muscle tissues. Calsequestrin, a high-capacity Ca2+-binding protein, is involved in the regulation of the excitation-contraction-relaxation cycle of both skeletal and cardiac muscle fibres. We have investigated the expression of calsequestrin and Ca2+ binding in cardiac and skeletal muscle from streptozotocin-induced diabetic rat. Immunoblotting of microsomal membranes from normal and streptozotocin-induced diabetic muscle revealed no significant changes in heart, but an increase in the relative abundance of calsequestrin and calsequestrin-like proteins in skeletal muscle. In analogy, the overall Ca2+-binding capacity of sarcoplasmic reticulum vesicles from diabetic skeletal muscle was drastically increased. The expression of fast muscle marker proteins was not affected, indicating that no relevant fibre transformation occurred in streptozotocin-treated rat muscles. The up-regulation of the high-capacity Ca2+-binding element calsequestrin might represent a compensatory mechanism of diabetic skeletal muscle. An increased Ca2+-buffering capacity of the sarcoplasmic reticulum lumen might counteract elevated cytosolic Ca2+ levels in diabetes thereby preventing Ca2+-dependent myo-necrosis.
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Calcio/metabolismo , Calsecuestrina/biosíntesis , Diabetes Mellitus Experimental/metabolismo , Músculo Esquelético/metabolismo , Miocardio/metabolismo , Animales , Western Blotting , Señalización del Calcio/fisiología , Electroforesis en Gel de Poliacrilamida , Masculino , Microsomas/metabolismo , Fibras Musculares de Contracción Rápida/metabolismo , Proteínas Musculares/metabolismo , Ratas , Ratas WistarRESUMEN
The aim of this study was to analyse drug prescribing practices in primary health care centres in Bahrain. We retrospectively evaluated 600 prescriptions selected randomly from all primary health care centres in Bahrain [n = 20] in 2004. Analysis followed WHO recommended prescribing core indicators. The mean number of drugs prescribed at each encounter was 3.3 [SD 0.7]. A single drug was prescribed on 6.3% of prescriptions and drugs were prescribed by generic name on 10.2%. The percentage of total prescriptions for antibiotics was 45.8%, for injections was 9.3% and for vitamins was 12.5%. The prescribing pattern in primary health care centres in Bahrain is associated with polypharmacy, over-prescribing of antibiotics and an under-prescribing of drugs by generic names