RESUMO
Monogenic autoinflammatory syndromes (MAISs), are caused by pathogenic genetic variants in the innate immune system, leading to dysregulation and aberrant inflammasome activation spontaneously or with minimal triggering. The diagnosis and treatment of MAISs can be intricate, relying on an increased recognition of potential differential diagnoses. This review examines the clinical features of MAIS, with a special focus on uveitis. It also evaluates treatment options and assesses the effects of activating molecular and cytokine pathways.
Assuntos
Doenças Hereditárias Autoinflamatórias , Uveíte , Criança , Humanos , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Citocinas , Uveíte/diagnóstico , Uveíte/genética , Inflamassomos/genética , Inflamação/diagnósticoRESUMO
Gonadotrophins play key roles in follicular development; however, the underlying molecular mechanisms are not fully understood. Follicle stimulating hormone (FSH) regulation of aromatase and subsequent estradiol (E2) production relies on ß-catenin, a key effector of WNT signaling. We previously demonstrated that treatment with the canonical WNT inhibitor, IWR-1, reduced FSH induced bovine granulosa cell E2 production in vitro. Here we demonstrated that intrafollicular injection in vivo with IWR-1 alters steroidogenesis and triggers a significant decrease in estrogen to progesterone ratio in the IWR-1 treated follicles compared to diluent injected control follicles. We next examined markers of canonical and noncanonical WNT signaling in dominant and subordinate follicles collected at different stages of follicular development and showed that protein for both CTNNB1 (canonical pathway) and phosphorylated (p)-LEF1 (noncanonical pathway) was significantly elevated in dominant compared to subordinate follicles at the early dominance stage of development. Therefore, we hypothesized that canonical and/or noncanonical WNT ligands modulate FSH stimulated E2 production. Hence, we examined the effects of specific WNT ligands on FSH stimulated E2 production in the absence of endogenous WNT production in vitro. Universal WNT signaling inhibitor, LGK-974 was able to inhibit FSH stimulation of E2 and reduce the abundance of proteins linked to canonical and noncanonical WNT pathway activation. Supplementation with the canonical ligand WNT2b did not affect the inhibitory effects of LGK-974 on FSH stimulated E2 production but rescued the LGK-974 mediated inhibition of CTNNB1 (canonical pathway) but not p-LEF1, p-JNK or p-P38 abundance (noncanonical pathway) abundance. In contrast, WNT5a treatment rescued FSH stimulated estradiol production and indices of activation of both the canonical (CTNNB1) and noncanonical (p-LEF1, p-JNK and p-P38) WNT signaling pathways in LGK-974 treated granulosa cells. Taken together, these results suggest that both canonical and noncanonical WNT pathways activation is linked to FSH stimulation of E2 production by bovine granulosa cells.
Assuntos
Células da Granulosa , Via de Sinalização Wnt , Animais , Bovinos , Células Cultivadas , Estradiol/farmacologia , Feminino , Hormônio Foliculoestimulante , Progesterona/metabolismoRESUMO
PURPOSE: To identify the socioeconomic and psychosocial impacts of clinical treatment decisions for advanced unilateral intraocular retinoblastoma. DESIGN: Retrospective observational case series. SETTING: institutional study at Alexandria Main University Hospital. STUDY POPULATION: records of 66 unilateral retinoblastoma cases treated from May 2005 to May 2013 were retrospectively reviewed. Sixty cases were eligible (International Intraocular Retinoblastoma Classification [IIRC] group C, D or E). PROCEDURES: two treatment groups were compared: enucleation vs. salvage treatment. Salvage treatment eyes were further subdivided based on IIRC group. Six socioeconomic parameters (financial burden, financial impact, psychological, social, medical and tumor impacts) were scored. Parameter scores ranged from 0 to 3, for overall score range 0 (no adverse impact) to 18 (severe adverse impact). MAIN OUTCOME MEASURES: derived Socioeconomic scores were correlated with treatment and outcomes. RESULTS: The enucleation group (28 eyes) had a median overall Socioeconomic score of 4/18, significantly lower than the salvage treatment group (32 eyes), median score 11/18 (P<0.01). Socioeconomic score varied with IIRC group. Attempted eye salvage failed in 25 children, due to uncontrolled tumor (44%) and socioeconomic impact of cumulative therapies (56%). Treatment duration and Socioeconomic score were higher for the 5 children in the salvage treatment group who developed metastatic disease compared to those without metastasis (P<0.01). CONCLUSIONS: The socioeconomic and psychosocial impacts of attempted ocular salvage for unilateral intraocular retinoblastoma are severe, in comparison to primary enucleation. Primary enucleation is a good treatment for unilateral retinoblastoma.
Assuntos
Adaptação Psicológica , Neoplasias da Retina/psicologia , Neoplasias da Retina/terapia , Retinoblastoma/psicologia , Retinoblastoma/terapia , Ajustamento Social , Criança , Pré-Escolar , Terapia Combinada/psicologia , Efeitos Psicossociais da Doença , Progressão da Doença , Egito , Enucleação Ocular/psicologia , Feminino , Hospitais Universitários , Humanos , Lactente , Masculino , Estadiamento de Neoplasias , Preservação de Órgãos/psicologia , Neoplasias da Retina/mortalidade , Neoplasias da Retina/patologia , Retinoblastoma/mortalidade , Retinoblastoma/patologia , Estudos Retrospectivos , Terapia de Salvação/psicologia , Fatores Socioeconômicos , Taxa de SobrevidaRESUMO
Embryo transfer remains a viable approach to increase propagation of offspring from high genetic merit females. Although it is now over 60 years since the report of the birth of the first calf from embryo transfer, utilisation of embryo transfer technology worldwide is not widespread. Limitations of conventional procedures for superovulation and embryo transfer are not limited to but include variability in response to superovulation, the labour intensive nature of superovulation procedures, time required between collections and cost of technology. Recently, harvest of ova and transfer of in vitro produced embryos has received more attention as a potential alternative to conventional superovulation and subsequent embryo transfer. Aspiration of follicular ova and in vitro embryo production offers potential advantages in reducing loss of female germplasm occurring through the natural process of ovarian follicular atresia, can increase yield of embryos from elite donor cows beyond that possible with superovulation, and provides a means of salvaging genetic material from valuable animals at slaughter or those culled for disease control or other reasons. Recent evidence indicates poor ovum quality is a major factor limiting in vitro embryo production and discovery of a role for intrinsic factors such as ovum follistatin and cumulus cell cathepsins in control of ovum quality has led to ongoing research on new technologies to increase yield of transferable embryos.
RESUMO
Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal dystrophies, characterised by rod photoreceptor cell degeneration with autosomal recessive RP (arRP) as the commonest form worldwide. To date, a total of 26 loci have been reported for arRP, each having a prevalence of 1-5%, except for the RP25 locus which was identified as the genetic cause of 14% of arRP cases in Spain. In order to validate the original linkage of RP25, we undertook a total genome scan using the 10K GeneChip mapping array on three of the previously linked families. The data obtained supported the initial findings of linkage. Additionally, linkage analysis in 18 newly ascertained arRP families was performed using microsatellite markers spanning the chromosome 6p12.1-q15 interval. Five out of the 18 families showed suggestive evidence of linkage to RP25, hence supporting the high prevalence of this locus in the Spanish population. Furthermore, the finding of a crossover in one of these families is likely to have refined the disease interval from the original 16 cM to only a 2.67 cM region between D6S257 and D6S1557.
Assuntos
Cromossomos Humanos Par 6/genética , Ligação Genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Retinose Pigmentar/genética , Família , Feminino , Genoma Humano , Genótipo , Humanos , Escore Lod , Masculino , Repetições de Microssatélites , Linhagem , EspanhaRESUMO
A large scale bioinformatics and molecular analysis of a 34 Mb interval on chromosome 6q12 was undertaken as part of our ongoing study to identify the gene responsible for an autosomal recessive retinitis pigmentosa (arRP) locus, RP25. Extensive bioinformatics analysis indicated in excess of 110 genes within the region and we also noted unfinished sequence on chromosome 6q in the Human Genome Database, between 58 and 61.2 Mb. Forty three genes within the RP25 interval were considered as good candidates for mutation screening. Direct sequence analysis of the selected genes in 7 Spanish families with arRP revealed a total of 244 sequence variants, of which 67 were novel but none were pathogenic. This, together with previous reports, excludes 60 genes within the interval ( approximately 55%) as disease causing for RP. To investigate if copy number variation (CNV) exists within RP25, a comparative genomic hybridization (CGH) analysis was performed on a consanguineous family. A clone from the tiling path array, chr6tp-19C7, spanning approximately 100-Kb was found to be deleted in all affected members of the family, leading to a major refinement of the interval. This will eventually have a significant impact on cloning of the RP25 gene.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 6/genética , Retinose Pigmentar/genética , Biologia Computacional , Análise Mutacional de DNA , Deleção de Genes , Ligação Genética , Genoma Humano , Humanos , Dados de Sequência Molecular , Mutação , Hibridização de Ácido Nucleico , LinhagemRESUMO
Retinitis pigmentosa (RP) is a group of retinal dystrophies characterised primarily by rod photoreceptor cell degeneration. Exhibiting great clinical and genetic heterogeneity, RP be inherited as an autosomal dominant (ad) and recessive (ar), X-linked (xl) and digenic disorder. RP25, a locus for arRP, was mapped to chromosome 6p12.1-q14.1 where several retinal dystrophy loci are located. A gene expressed in the retina, FAM46A, mapped within the RP25 locus, and computational data revealed its involvement in retinal signalling pathways. Therefore, we chose to perform molecular evaluation of this gene as a good candidate in arRP families linked to the RP25 interval. A comprehensive bioinformatic and retinal tissue expression characterisation of FAM46A was performed, together with mutation screening of seven RP25 families. Herein we present 4 novel sequence variants, of which one is a novel deletion within a low complexity region close to the initiation codon of FAM46A. Furthermore, we have characterised for the first time a coding tandem variation in the Caucasian population. This study reports on bioinformatic and moleculardata for the FAM46A gene that may give a wider insight into the putative function of this gene and its pathologic relevance to RP25 and other retinal diseases mapping within the 6q chromosomal interval.
Assuntos
Família , Genes Recessivos , Repetições Minissatélites/genética , Retinose Pigmentar/genética , Alelos , Sequência de Bases , Estudos de Casos e Controles , Mapeamento Cromossômico , Cromossomos Humanos Par 6 , Biologia Computacional/métodos , Análise Mutacional de DNA , Frequência do Gene , Humanos , Íntrons , Linhagem , Polimorfismo de Nucleotídeo Único , Retinose Pigmentar/patologia , Deleção de Sequência , EspanhaRESUMO
Autosomal recessive retinitis pigmentosa (arRP) is the commonest form of RP worldwide. To date 22 loci have been implicated in the pathogenesis of this disease; however none of these loci independently account for a significant proportion of recessive RP. Linkage studies of arRP in consanguineous families have been mainly based on homozygosity mapping, but this strategy cannot be applied in the case of non-consanguineous families. Therefore, we implemented a systematic approach for identifying the disease locus in three non-consanguineous Chinese families with arRP. Initially, linkage analysis using SNPs/microsatellite markers or mutation screening of known arRP genes excluded all loci/genes except RP25 on chromosome 6. Subsequently a whole genome scan for the three families using the 10K GeneChip Mapping Array was performed, in order to identify the possible disease locus. To the best of our knowledge this is the first report on the utilisation of the 10K GeneChip to study linkage in non-consanguineous Chinese arRP. This analysis indicates that the studied families are probably linked to the RP25 locus, a well defined arRP locus in other populations. The identification of another ethnic group linked to RP25 is highly suggestive that this represents a major locus for arRP.
Assuntos
Retinose Pigmentar/genética , Povo Asiático/genética , Sequência de Bases , China , Mapeamento Cromossômico , Cromossomos Humanos Par 6/genética , Biologia Computacional , Primers do DNA/genética , Éxons , Feminino , Genes Recessivos , Ligação Genética , Haplótipos , Humanos , Escore Lod , Masculino , Repetições de Microssatélites , Análise de Sequência com Séries de Oligonucleotídeos , Linhagem , Polimorfismo de Nucleotídeo ÚnicoRESUMO
AIMS: To report a Bangladeshi family displaying intrafamilial phenotypic heterogeneity of lattice corneal dystrophy type I (LCDI) and to identify the causative mutation. METHODS: Molecular genetic analysis was performed on DNA extracted from all members of the family. Exons of BIGH3 gene were amplified by polymerase chain reaction. Gene mutation and polymorphisms were identified by heteroduplex and sequence analyses. Segregation of the mutation in the family was confirmed by restriction digestion of amplified gene fragments. RESULTS: A heterozygous C --> T transition at the first nucleotide position of codon 124 of the BIGH3 gene was detected in the three affected members and not in the unaffected members of the family. CONCLUSIONS: This is the first report of BIGH3 gene mutation in a Bangladeshi family with phenotypic heterogeneity. This study confirms that BIGH3 gene screening should be undertaken for proper classification of corneal dystrophy, especially in the absence of histopathological examination.
Assuntos
Distrofias Hereditárias da Córnea/genética , Proteínas da Matriz Extracelular/genética , Mutação , Fator de Crescimento Transformador beta/genética , Adulto , Criança , Feminino , Análise Heteroduplex/métodos , Humanos , Masculino , Linhagem , FenótipoRESUMO
AIMS: To establish a clinical, histopathological, and genetic diagnosis in two unrelated British families with Avellino corneal dystrophy (ACD). METHODS: Genomic DNA was extracted from peripheral blood leucocytes of all members participating in the study. Exons 4 and 12 of the human transforming growth factor beta induced (BIGH3) gene were amplified by polymerase chain reaction. The mutation and polymorphism were identified by direct sequencing and restriction digest analysis. A review of the patients' clinical symptoms and signs was undertaken and a histopathological study on corneal specimen obtained from the proband of one family after keratoplasty was performed. RESULTS: A heterozygous G to A transition at the second nucleotide position of codon 124 of BIGH3 gene was detected in all affected members of both families. This mutation changes an arginine residue to a histidine. The clinical diagnosis for ACD was more evident with advancing age. Histopathological study revealed granular deposits in the anterior stroma and occasional positive Congo red areas of amyloid deposition in the mid to deep stroma typical of ACD. CONCLUSIONS: This is the first report of ACD families in the United Kingdom and, furthermore, of BIGH3 gene mutation in British patients with this rare type of corneal dystrophy. The results indicate that BIGH3 gene screening along with clinical and histopathological examinations is essential for the diagnosis and clinical management of corneal dystrophies.
Assuntos
Distrofias Hereditárias da Córnea/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Córnea/patologia , Distrofias Hereditárias da Córnea/patologia , Éxons/genética , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Linhagem , Análise de Sequência , Reino UnidoRESUMO
PURPOSE: Mutations in keratocan (KERA), a small leucine-rich proteoglycan, have recently been shown to be responsible for cases of autosomal recessive cornea plana (CNA2). A consanguineous pedigree in which cornea plana cosegregated with microphthalmia was investigated by linkage analysis and direct sequencing. METHODS: Linkage was sought to polymorphic microsatellite markers distributed around the CNA2 and microphthalmia loci (arCMIC, adCMIC, NNO1, and CHX10) using PCR and nondenaturing polyacrylamide gel electrophoresis before KERA was directly sequenced for mutations. RESULTS: Positive lod scores were obtained with markers encompassing the CNA2 locus, the maximum two-point lod scores of 2.18 at recombination fraction theta = 0 was obtained with markers D12S95 and D12S327. Mutation screening of KERA revealed a novel single-nucleotide substitution at codon 215, which results in the substitution of lysine for threonine at the start of a highly conserved leucine-rich repeat motif. Structural modeling predicts that the motifs are stacked into an arched beta-sheet array and that the effect of the mutation is to alter the length and position of one of these motifs. CONCLUSIONS: This report describes a novel mutation in KERA that alters a highly conserved motif and is predicted to affect the tertiary structure of the molecule. Normal corneal function is dependent on the regular spacing of collagen fibrils, and the predicted alteration of the tertiary structure of KERA is the probable mechanism of the cornea plana phenotype.
Assuntos
Doenças da Córnea/genética , Doenças da Córnea/patologia , Topografia da Córnea , Genes Recessivos , Mutação/fisiologia , Proteoglicanas/genética , Criança , Pré-Escolar , Sequência Conservada/genética , Feminino , Ligação Genética , Humanos , Masculino , Repetições de Microssatélites , Modelos Genéticos , Linhagem , Estrutura Terciária de Proteína/genéticaRESUMO
Coronary artery aneurysms are usually diagnosed by contrast coronary angiography, which portrays the silhouette of the lumen but cannot distinguish true and false aneurysms. To differentiate true and false aneurysms and to study the morphologic changes of the vessel wall, intravascular ultrasound (IVUS) was performed in patients with angiographic signs of coronary artery aneurysms. We used a 4.8F or 3.5F, 20 MHz IVUS catheter for ultrasound examination. Fourteen patients (12 men and two women ranging in age from 43 to 73 years) with angiographic signs of coronary aneurysm were enrolled. IVUS imaging was optimally obtained in all patients. The vessel area, lumen area, and plaque area of the aneurysm segment and of the proximal and distal segments were determined. IVUS showed that both the proximal and distal reference segments were severely affected by atherosclerotic lesions in all the patients and by calcium deposits in six patients. The percent stenoses were 63.0% +/- 13.7% and 60.9% +/- 17.8% in the proximal and distal reference segments, respectively. In nine patients the walls of the aneurysms showed signs of atherosclerosis. Three angiographically indicated aneurysms were found to be plaque ruptures. Although the lumen and the vessel areas of the aneurysm segments were larger than those of the proximal and distal segments (p < 0.01 and (p < 0.001), no significant differences in plaque area and plaque composition were found between the aneurysm segment and adjacent vessel segments (p > 0.05). In conclusion, IVUS allows detailed characterization of coronary aneurysms. Atherosclerosis seems to play an important role in the formation of acquired coronary aneurysms.
Assuntos
Aneurisma Coronário/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Ultrassonografia de Intervenção , Adulto , Idoso , Angioplastia Coronária com Balão , Aneurisma Coronário/etiologia , Aneurisma Coronário/terapia , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Quality management within the catheterization laboratory includes the quality control, the heart catheterization technique and the policy. Quality management is critical in the heart catheterization laboratory. Dedication of all members of the lab and computer personnel ensures high patient satisfaction. A continued quality improvement program is patient-orientated and requires good planning. One of the main emphasis in the catheterization lab is standardization which includes the patient preparation, the procedure itself, and the management. It is supported by teamwork including the economic aspect of prompt delivery of material and avoidance of complications. A continuous circle of treatment planes, performance, and check is regarded as the Deming cycle and leads to continuous improvement of quality. Important are both the avoidance and detection of complications. The reasons for any such have to be evaluated. It is recommended to follow the zero mistake hypothesis of Crosby, which means quality control by the lab supervisor, a quality consciousness, a quality measurement and quality improvement, as well as using a day to day quality improvement and to teach quality control. In Germany a quality control questionnaire was administered in an analysis of the current structure, function, and results of catheterization labs. Most important was the analysis of complications. The data were based on diagnostic catheterization in 1992, which included 140668 catheterizations in 83 laboratories. Thus, a mean of 1030 heart catheterizations was performed in each lab. In the mean, 200 catheterizations were performed by each doctor. In 19% of the labs digital imaging was exclusively performed. Major complications occurred with ventricular fibrillation in 0.36% (range 0.75%), resuscitation 0.18% (0.43%), persistent cerebrovascular accident 0.08% (0.24%), myocardial infarcts 0.19% (0.59%), aortic dissection 0.05% (0.22%). Mortality was 0.03% (0.08%). In heart catheterization laboratories quality management is one of the major goals for the future work. Only the continued improvement of quality and very good quality management ensure patient safety. Quality is the sum of technique and consciousness.
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Cateterismo Cardíaco/normas , Equipe de Assistência ao Paciente/normas , Garantia da Qualidade dos Cuidados de Saúde , Cateterismo Cardíaco/mortalidade , Cardiologia/educação , Causas de Morte , Currículo , Alemanha , Humanos , Planejamento de Assistência ao Paciente/normas , Controle de Qualidade , Proteção Radiológica/normas , Fatores de RiscoRESUMO
In an experiment, 12 female and 8 male buffalo calves aged 3 to 4 weeks with an average of 65.2 kg live body weight were divided into 4 equal groups. Group 1 received dried skim milk plus non-milk fat. In groups 2, 3, and 4, 50% of the milk protein were replaced by American soybean flour, Egyptian soya meal, or corn glutine. Scouring occurred in all groups during the first three weeks. Death losses occurred in group 2 (2 calves) and 4 (1 calf). During the first three experimental weeks the calves consumed on average 828, 868, 847, 696 g dry matter (DM) as liquids. The average daily gain (ADG) was 229, 215, 252, 48 g/d, respectively. The energy consumption reached 4.1, 4.6, 3.8, 16.6 TDN/kg ADG. During the second period, the calves consumed 1.57, 1.45, 1.55, 1.65 kg DM as liquid and solid feedstuff. Up to a live body weight of 90 kg they had a daily increase of 695, 611, 593, 600 g. The energy used amounted to 1.98, 2.08, 2.28, 2.40 TDN/kg ADG. The apparent digestibility of the crude protein was 95, 92, 91, 92% during the first period and 81, 77, 76, 73% during the second period.
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Ração Animal , Búfalos/crescimento & desenvolvimento , Proteínas Alimentares , Proteínas do Leite , Proteínas de Plantas , Animais , Peso Corporal , Búfalos/metabolismo , Digestão , Ingestão de Alimentos , Metabolismo Energético , Feminino , Masculino , Nitrogênio/metabolismo , Proteínas de Vegetais Comestíveis , Proteínas de Soja , Desmame , Zea maysRESUMO
In an experiment, 9 female and 6 male buffalo calves at the age of 3 to 4 weeks were divided into 3 groups. The animals were given milk replacers in which 75% of the dried skim milk protein had been replaced by American soybean flour (ASP), Egyptian soya meal (ESP), or corn glutine (GP). Scouring occurred in all groups during the first 3 weeks of the experiment, continuing up to the fourth week in groups ESP and GP. In groups ESP and GP one calf each died. During the first 3 weeks of the experiment, the calves consumed on average 747, 631, 787 g dry matter (DM) as liquids. They achieved live weight gains of 314, 83, -286 g/d, with significant differences between the groups. The digestibility of the crude protein was 73, 74, 70%. During the second period--up to 70 or 62.5 kg live body weight--only groups ASP and ESP were investigated. The calves consumed 1.64 or 1.66 kg DM/d as liquid and dry feedstuff. The average daily weight gain was 3.87 or 3.50 TDN/kg ADG. During this period, the crude protein was digested by 76 or 73%.
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Ração Animal , Búfalos/crescimento & desenvolvimento , Proteínas Alimentares/metabolismo , Proteínas de Vegetais Comestíveis/metabolismo , Proteínas de Plantas/metabolismo , Animais , Feminino , Masculino , Proteínas de Soja , Glycine max , Aumento de Peso , Zea maysRESUMO
10 Ossimi lamb carcasses were used to determine the specific gravity values of different joint cuts. The correlation coefficients were established between the specific gravities of these joints and the percentages of fat and muscle in the rib saddle joint. It was found that the gravity of different carcass sections was significantly related to the muscle and fat percentages in the rib saddle joint. The results indicate that the specific gravity values of carcass sections can be utilized for a practical estimate and assessment of carcass components.
Assuntos
Articulações/anatomia & histologia , Ovinos/anatomia & histologia , Tecido Adiposo/anatomia & histologia , Animais , Osso e Ossos/anatomia & histologia , Músculos/anatomia & histologia , Gravidade EspecíficaRESUMO
In order to determine the effect of hyperlipoproteinemia on the in vivo formation of circulating platelet aggregates (CPA) in patients with coronary artery disease, CPA ratios, lipoprotein pattern, serum cholesterol and triglycerides were determinated in 80 male patients with stable coronary artery disease and hyperlipoproteinemia. Similar studies were performed in 30 male age-matched patients with stable coronary artery disease without hyperlipoproteinemia and 60 male age-matched healthy volunteers; the latter group served as controls. CPA ratios were significantly lowered; i.e. an increase was observed in circulating platelet aggregates in 24 patients without hyperlipoproteinemia as compared with the values in the control group. All the cardiac patients with hyperlipoproteinemia had a significantly lower CPA ratio than the patients without hyperlipoproteinemia. Moreover, the lowering in CPA ratio was more marked among patients with type II a hyperlipoproteinemia than in those with type IV. We think that this in vivo test for platelet function may throw more light on the effect of hyperlipoproteinemia on the in vivo aggregation of circulating platelets in patients with coronary artery disease.
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Doença das Coronárias/sangue , Hiperlipoproteinemias/sangue , Lipoproteínas/sangue , Agregação Plaquetária , Colesterol/sangue , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo IV/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
The disposition and metabolism of a single oral 10 mg/kg (LD50) of uniformly phenyl-labeled [14C]EPN (O-ethyl O-4-nitrophenyl [14C]phenylphosphonothioate) were studied in adult hens. The birds were protected from acute toxicity with atropine sulfate. Three treated hens were killed at each time interval (days): 0.5, 2, 4, 8, 12. Radioactivity was adsorbed from the gastrointestinal tract and distributed in all tissues. Most of the dose was excreted in the combined urinary-fecal excreta (74%). Only traces of the radioactivity (0.2%) were detected in expired CO2. Most of the excreted radioactive materials were identified as phenylphosphonic acid (PPA), O-ethyl phenylphosphonic acid (EPPA), and O-ethyl phenylphosphonothioc acid (EPPTA). Radioactivity in tissues reached a peak of 11.8% in 12 days. The highest concentration of radioactivity was present in the liver followed by bile, kidney, adipose tissue, and muscle. EPN was the major compound identified in brain, spinal cord, sciatic nerve, kidney, and plasma. Most of the radioactivity in the liver was identified as EPPA followed by EPPTA and PPA. Kinetic studies showed that EPN disappeared exponentially from tissues. The half-life of the elimination of EPN from plasma was 16.5 days corresponding to a constant rate value of 0.04 day-1. Relative residence (RR) of EPN relative to plasma was shortest in liver and longest in adipose tissue followed by sciatic nerve and spinal cord.