ABSTRACT
Leishmaniasis is a zoonotic disease caused by Leishmania spp., impacts multiple systems and organs. While hematological and biochemical profiles aren't definitive for diagnosis, recent studies have identified the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) as predictors of morbidity and mortality in critically ill human and dog patients. This study examined 100 dogs diagnosed with leishmaniasis, categorized by the International Renal Interest Society (IRIS) stages 1-4. Additionally, the dogs were divided based on whether they survived less or more than one year (L1Y and G1Y). Control group consisted of 43 dogs. The NLR increased as the disease progressed (IRIS 1-4), presenting statistically significant differences (P<0.05) when compared to the control group (2,37±2,08) IRIS 3 and 4 (4,59±13,39 and 6,99±12,86, respectively), and G1Y and L1Y (3,60±4,02 and 4,87±5,82, respectively). Significant changes in SII were only evident in short-term survivors (L1Y 951,93±1402) and advanced renal disease cases (IRIS 4 stage 1073,68±1901,09). Conversely, PLR remained largely unchanged. In conclusion, these results suggest that the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) may serve as potential markers for assessing disease progression and prognosis in dogs diagnosed with leishmaniasis.
Subject(s)
Leishmaniasis , Neutrophils , Humans , Dogs , Animals , Clinical Relevance , Lymphocytes , Inflammation/veterinary , Leishmaniasis/diagnosis , Leishmaniasis/veterinary , Retrospective StudiesABSTRACT
Pineal melatonin is important not only for synchronization of biological rhythms, but also in the ageing process as a potential drug to relieve oxidative damage. During ageing, the nocturnal melatonin production decreases resulting in an increased incidence of disorders. Present in vivo experiments were performed to study the effects of exogenous melatonin chronically administered to old rats on the pineal biosynthesis of melatonin and the precursor serotonin (5-HT) mediated by tryptophan hydroxylase type 1 (TPH-1). Accumulation of 5-hydroxytryptophan (5-HTP) after decarboxylase inhibition was used as a measure of the TPH-1 activity. 5-HT and its metabolite 5-HIAA were also quantified by HPLC-ED. As expected, ageing resulted in worsening of different neurochemical parameters. However, chronic intake of melatonin (1mg/kg/day, diluted in drinking water, 4 weeks) increased TPH-1 activity and significantly improved the age-induced deficits in nocturnal melatonin content in the pineal gland. Results suggest that melatonin intake (or melatonin rich foods) may contribute to recover the pineal function preventing the nocturnal descent of 5-HT and melatonin biosynthesis that normally occur in pineal gland as a consequence of ageing.
Subject(s)
Aging/metabolism , Antioxidants/pharmacology , Melatonin/pharmacology , Pineal Gland/drug effects , Tryptophan Hydroxylase/drug effects , Aging/physiology , Animals , Antioxidants/administration & dosage , Antioxidants/metabolism , Circadian Rhythm/drug effects , Circadian Rhythm/physiology , Drug Administration Schedule , Drug Evaluation, Preclinical/methods , Male , Melatonin/administration & dosage , Melatonin/biosynthesis , Pineal Gland/metabolism , Pineal Gland/physiology , Rats , Rats, Sprague-Dawley , Serotonin/biosynthesis , Tryptophan Hydroxylase/metabolismABSTRACT
OBJECTIVE: To ascertain the incidence and prevalence of juvenile idiopathic arthritis (JIA) in Catalonia (autonomous region in northeast Spain), examined according to the currently established disease subtypes. METHODS: Before initiating the study, we conducted an educational programme on paediatric rheumatology, addressed to all general paediatricians in Catalonia. A 2-year (2004-2006), prospective, population-based study was then carried out to determine the incidence of JIA. Prospective and retrospective data retrieval was performed to calculate prevalence. The International League of Associations for Rheumatology (ILAR, Edmonton revision) classification criteria were applied. RESULTS: Over the study period, 145 new cases of JIA were diagnosed. The mean annual incidence was 6.9/105 children aged less than 16 years (range 5.8-8.1 years; 9.0 years for girls and 4.8 years for boys). On separate analysis of patients ≤ 6 and > 6 years, the distribution in younger children was found to be similar for both girls and boys, whereas in older children, most girls belonged to the oligoarthritis and polyarthritis subgroups, and boys to the enthesitis-related arthritis and undifferentiated subgroups. The calculated prevalence of JIA (31 October 2006) was 39.7 (36.1-43.7)/105 children younger than 16. The relative risk of girls having JIA was 2.1 [95% confidence interval (CI) 1.7-2.7, p < 0.001]. In 70% of patients, the diagnosis was established before the age of 7. Subgroup distribution of prevalent cases mirrored that of incident cases. CONCLUSION: This is the first population-based study on the epidemiology of JIA in Catalonia. Incidence and prevalence rates are lower than those reported for several areas in Nordic countries of Europe. Oligoarthritis was the most common subtype.
Subject(s)
Arthritis, Juvenile/epidemiology , Adolescent , Arthritis, Juvenile/diagnosis , Child , Child, Preschool , Female , HLA-B27 Antigen/analysis , Humans , Incidence , Infant , Male , Prevalence , Prospective Studies , Retrospective Studies , Sex Factors , Spain/epidemiologyABSTRACT
Secondary hyperparathyroidism (SHP) is still an early and frequent complication of chronic renal disease (CRD). Currently, CRD is an independent cardiovascular risk factor, and calcium-phosphorus metabolism is one of the modifiable related factors. In this first article, we summarize the recent SHP treatment paradigm shift in dialysis patients, derived from the better knowledge and understanding of vascular calcification. We analyze the most recent guidelines (K/DOQI), and describe the general implications of hyperphosphatemia, as well as our therapeutic approach with phosphorus-binders. Since sevelamer additionally presents some pleiotropic effects and it attenuates the progression of vascular calcification, we consider it in the first-line of treatment despite it is not yet demonstrated a survival benefit. We also minimize the use of elemental calcium to a maximum of 1000 to 1500 mg/day. Lanthanum carbonate may well be an important therapeutic agent in the near future, especially if security concerns related to metal accumulation are overcome. Ferric citrate, colestilan and nicotinamide may soon play a role. All these drugs, isolated or in combination, are important in the treatment of SHP since a great deal of its success and the avoidance of some dialysis-related complications depend on an efficient phosphorus control.
Subject(s)
Hyperparathyroidism, Secondary/therapy , Kidney Failure, Chronic/therapy , Renal Dialysis , Algorithms , Bile Acids and Salts/administration & dosage , Bile Acids and Salts/therapeutic use , Calcium/administration & dosage , Calcium/metabolism , Calcium/therapeutic use , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Disease Progression , Drug Therapy, Combination , Epoxy Compounds/administration & dosage , Epoxy Compounds/therapeutic use , Female , Ferric Compounds/administration & dosage , Ferric Compounds/therapeutic use , Humans , Hyperparathyroidism, Secondary/etiology , Kidney Failure, Chronic/complications , Lanthanum/administration & dosage , Lanthanum/therapeutic use , Male , Multivariate Analysis , Niacinamide/administration & dosage , Niacinamide/therapeutic use , Phosphate-Binding Proteins/therapeutic use , Phosphates/blood , Phosphates/metabolism , Phosphorus/metabolism , Polyamines , Polyethylenes/administration & dosage , Polyethylenes/therapeutic use , Practice Guidelines as Topic , Randomized Controlled Trials as Topic , Renal Dialysis/adverse effects , Risk Factors , Sevelamer , Time FactorsABSTRACT
Secondary hyperparathyroidism (SHP) is a frequent complication of dialysis patients. In this second article we will analyze the new vitamin D analogs, capable of decreasing parathyroid hormone (PTH) levels with a lower effect on intestinal calcium and phosphorus absorption. Among other advantages described in the experimental setting, paricalcitol shows a survival benefit in dialysis patients as compared to calcitriol, at least in retrospective studies, and thus it became our first-line vitamin D derivative. Calcimimetics are unique since they decrease PTH levels without increasing serum calcium and phosphorus. Actually, calcium and phosphorus decrease in a significant number of patients. These drugs will soon be authorized in Spain, and we describe the better achievement of K/DOQI guidelines as well as other beneficial effects observed in the experimental animal with them. Finally, we mention the potential benefit of mild metabolic acidosis, the use of bisphosphonates, the role of bone morphogenetic protein BMP-7, and the use of teriparatide. The future treatment of SHP will probably require the independent management of calcium, phosphorus, vitamin D and PTH. Thus, low-dose combined treatments with selective drugs may prove more effective than sequential therapies.
Subject(s)
Hyperparathyroidism, Secondary/drug therapy , Kidney Failure, Chronic/therapy , Renal Dialysis , Animals , Bone Morphogenetic Protein 7 , Bone Morphogenetic Proteins/administration & dosage , Bone Morphogenetic Proteins/therapeutic use , Calcium/metabolism , Cinacalcet , Diphosphonates/therapeutic use , Drug Therapy, Combination , Ergocalciferols/administration & dosage , Ergocalciferols/therapeutic use , Humans , Hyperparathyroidism, Secondary/blood , Hyperparathyroidism, Secondary/metabolism , Naphthalenes/administration & dosage , Naphthalenes/therapeutic use , Parathyroid Hormone/blood , Phosphorus/metabolism , Practice Guidelines as Topic , Randomized Controlled Trials as Topic , Retrospective Studies , Teriparatide/therapeutic use , Transforming Growth Factor beta/administration & dosage , Transforming Growth Factor beta/therapeutic use , Vitamin D/analogs & derivativesABSTRACT
El hiperparatiroidismo secundario (HPS) es una complicación frecuente y precozde la enfermedad renal crónica (ERC). La ERC es hoy un factor de riesgo cardiovascularindependiente y las alteraciones del metabolismo calcio-fósforo sonuno de sus factores inherentes modificables. En este primer artículo resumimos loscambios conceptuales recientes en pacientes en diálisis, derivados del reconocimientoy fisiopatología de la calcificación vascular, analizando las guías más actuales(K/DOQI), definiendo las implicaciones generales de la hiperfosfatemia ydescribiendo nuestra actitud terapéutica en relación a los captores del fósforo.Dada la atenuación de la progresión de la calcificación vascular y sus efectospleiotrópicos, consideramos el sevelamer como el captor de elección aunque aúnno haya demostrado una mejoría en la supervivencia, limitando en cualquier casoel uso de captores de calcio a 1.000-1.500 mg/día de calcio elemento. El carbonatode lantano es una importante alternativa terapéutica de futuro, especialmentesi se aclaran los problemas de seguridad relacionados con la potencial acumulacióndel metal. Las sales de hierro y los más recientes colestilán y nicotinamidapueden también jugar próximamente un papel. Del eficiente control del fósforo,con una sola droga o varias en combinación, depende hoy no sólo el éxito deltratamiento del HPS sino también el control de complicaciones graves asociadasa la diálisis
Secondary hyperparathyroidism (SHP) is still an early and frequent complicationof chronic renal disease (CRD). Currently, CRD is an independent cardiovascularrisk factor, and calcium-phosphorus metabolism is one of the modifiable relatedfactors. In this first article, we summarize the recent SHP treatment paradigmshift in dialysis patients, derived from the better knowledge and understanding ofvascular calcification. We analyze the most recent guidelines (K/DOQI), and describethe general implications of hyperphosphatemia, as well as our therapeuticapproach with phosphorus-binders. Since sevelamer additionally presents somepleiotropic effects and it attenuates the progression of vascular calcification, weconsider it in the first-line of treatment despite it is not yet demonstrated a survivalbenefit. We also minimize the use of elemental calcium to a maximum of 1,000to 1,500 mg/day. Lanthanum carbonate may well be an important therapeuticagent in the near future, especially if security concerns related to metal accumulation are overcome. Ferric citrate, colestilan and nicotinamide may soon play arole. All these drugs, isolated or in combination, are important in the treatment ofSHP since a great deal of its success and the avoidance of some dialysis-relatedcomplications depend on an efficient phosphorus controlSecondary hyperparathyroidism (SHP) is a frequent complication of dialysis patients.In this second article we will analyze the new vitamin D analogs, capableof decreasing parathyroid hormone (PTH) levels with a lower effect on intestinalcalcium and phosphorus absorption. Among other advantages described in the experimentalsetting, paricalcitol shows a survival benefit in dialysis patients as comparedto calcitriol, at least in retrospective studies, and thus it became our firstlinevitamin D derivative. Calcimimetics are unique since they decrease PTH levelswithout increasing serum calcium and phosphorus. Actually, calcium and phosphorusdecrease in a significant number of patients. These drugs will soon be authorizedin Spain, and we describe the better achievement of K/DOQI guidelinesas well as other beneficial effects observed in the experimental animal with them.Finally, we mention the potential benefit of mild metabolic acidosis, the use of albisphosphonates,the role of bone morphogenetic protein BMP-7, and the use ofteriparatide. The future treatment of SHP will probably require the independentmanagement of calcium, phosphorus, vitamin D and PTH. Thus, low-dose combinedtreatments with selective drugs may prove more effective than sequential therapies
Subject(s)
Humans , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/therapy , Hyperparathyroidism, Secondary/etiology , Hyperparathyroidism, Secondary/therapy , Lanthanum , Niacinamide , Phosphate-Binding Proteins/therapeutic use , Algorithms , Calcium , Cardiovascular Diseases , Disease Progression , Drug Therapy, Combination , Epoxy Compounds , Ferric Compounds , Phosphates , Polyethylenes , Bile Acids and SaltsABSTRACT
El hiperparatiroidismo secundario (HPS) sigue siendo una complicación frecuentedel paciente renal. En este segundo artículo se analizarán los análogos dela vitamina D capaces de disminuir la hormona paratiroidea (PTH) pero con menorefecto sobre la absorción de calcio y fósforo intestinal. Aparte de otras ventajasobservadas en el animal experimental, el paricalcitol ha demostrado una mejoríade la supervivencia en relación al calcitriol, al menos en estudios retrospectivos,por lo que lo consideramos el derivado de elección. Los calcimiméticos serán losúnicos fármacos capaces de disminuir la PTH sin inducir aumentos de calcio y/ofósforo séricos. De hecho en un porcentaje notable de estos pacientes, calcio yfósforo disminuyen. Pendientes de su incorporación al mercado español, se describela mejoría de cumplimiento de los objetivos de las guías y sus otros efectosbeneficiosos en el animal experimental. Finalmente se hace mención al potencialbeneficio de la acidosis metabólica leve, el uso de bisfosfonatos, el papel de laproteína morfogenética del hueso BMP-7 y la utilización de teriparatide. El futurode la terapia del HPS probablemente pasa por el manejo independiente de calcio,fósforo (P), vitamina D y PTH, de modo que los tratamientos combinados adosis bajas con drogas selectivas parecen más adecuados que las monoterapiassecuenciales
Secondary hyperparathyroidism (SHP) is still an early and frequent complicationof chronic renal disease (CRD). Currently, CRD is an independent cardiovascularrisk factor, and calcium-phosphorus metabolism is one of the modifiable relatedfactors. In this first article, we summarize the recent SHP treatment paradigmshift in dialysis patients, derived from the better knowledge and understanding ofvascular calcification. We analyze the most recent guidelines (K/DOQI), and describethe general implications of hyperphosphatemia, as well as our therapeuticapproach with phosphorus-binders. Since sevelamer additionally presents somepleiotropic effects and it attenuates the progression of vascular calcification, weconsider it in the first-line of treatment despite it is not yet demonstrated a survivalbenefit. We also minimize the use of elemental calcium to a maximum of 1,000to 1,500 mg/day. Lanthanum carbonate may well be an important therapeuticagent in the near future, especially if security concerns related to metal accumulation are overcome. Ferric citrate, colestilan and nicotinamide may soon play arole. All these drugs, isolated or in combination, are important in the treatment ofSHP since a great deal of its success and the avoidance of some dialysis-relatedcomplications depend on an efficient phosphorus controlSecondary hyperparathyroidism (SHP) is a frequent complication of dialysis patients.In this second article we will analyze the new vitamin D analogs, capableof decreasing parathyroid hormone (PTH) levels with a lower effect on intestinalcalcium and phosphorus absorption. Among other advantages described in the experimentalsetting, paricalcitol shows a survival benefit in dialysis patients as comparedto calcitriol, at least in retrospective studies, and thus it became our firstlinevitamin D derivative. Calcimimetics are unique since they decrease PTH levelswithout increasing serum calcium and phosphorus. Actually, calcium and phosphorusdecrease in a significant number of patients. These drugs will soon be authorizedin Spain, and we describe the better achievement of K/DOQI guidelinesas well as other beneficial effects observed in the experimental animal with them.Finally, we mention the potential benefit of mild metabolic acidosis, the use of albisphosphonates,the role of bone morphogenetic protein BMP-7, and the use ofteriparatide. The future treatment of SHP will probably require the independentmanagement of calcium, phosphorus, vitamin D and PTH. Thus, low-dose combinedtreatments with selective drugs may prove more effective than sequential therapies
Subject(s)
Animals , Humans , Hyperparathyroidism, Secondary/blood , Hyperparathyroidism, Secondary/drug therapy , Hyperparathyroidism, Secondary/metabolism , Renal Insufficiency, Chronic/therapy , Renal Dialysis , Bone Morphogenetic Proteins , Calcium , Diphosphonates/therapeutic use , Drug Therapy, Combination , Ergocalciferols , Naphthalenes , Vitamin D , Teriparatide , Transforming Growth Factor betaABSTRACT
La National Kidney Foundation americana ha definido recientemente criterios que definen un nuevo concepto denominado enfermedad renal crónica. Más o menos discutibles, suponen un importante método de estandarización de rápida aceptación internacional. En este artículo se revisa la nueva definición y estadios, los métodos de diagnóstico y evaluación, sus complicaciones y asociaciones, así como sus factores de progresión a estadios terminales con necesidad de tratamiento sustitutivo. Asimismo se establece el importante nuevo vínculo de la enfermedad renal crónica como factor de riesgo cardiovascular (AU)
The American National Kidney Foundation has recently defined new criteria to define the concept of chronic Kidney disease (CKD). Althougt they are partially under discussion, they have become a very helpful way of standarization and widely internationally accepted. In this article, we review the new definition and stages, the diagnostic and evaluation methods, complications and associations, as well as progression factors to end stage renal disease. It is also underlined the important newly recognized link between chronic kidney disease and cardiovascular risk (AU)
Subject(s)
Humans , Renal Insufficiency, Chronic/physiopathology , Renal Replacement Therapy , Disease Progression , Risk Factors , Cardiovascular Diseases/epidemiology , Kidney Function Tests , Glomerular Filtration RateABSTRACT
No disponible
Subject(s)
Humans , Female , Pregnancy , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Pregnancy Complications, Neoplastic/pathology , Eclampsia/epidemiologyABSTRACT
El síndrome antifosfolipídico (SAFL) se caracteriza por la presencia de autoanticuerpos antifosfolípidicos (aFL) o de autoanticuerpos dirigidos contra proteínas de las membranas celulares. Sus manifestaciones clínicas consisten en trombosis arteriales o venosas y abortos de repetición. Puede manifestarse de forma aislada o asociada a enfermedades autoinmunes como el lupus eritematoso sistémico. A nivel renal, se observa trombosis de grandes vasos o de los capilares glomerulares (microangiopatía trombólica). En caso de afectación de 3 o más órganos, sistemas o tejidos se produce un SAFL catastrófico. El tratamiento consiste en una anticoagulación agresiva con heparina seguida de antivitamina K (AU)
The association of thrombotic events and/or pregnacy complications with circulating antiphospholipid antibodies defines antiphospholipid syndrome (APS). It can occur in patients without any disease. Beta 2 glycoprotein I-dependent anticardiolipin and lupus anticoagulant are the diagnostic tools. Renal involvement consists mainly of Thrombotic vascular complications involving large vessels or intrarenal small-sized vessels (thrombotic microangiopathy). A minority of patients may develop an acute catastrophic or devastating syndrome with multiple vascular occlusions. Treatment is based on IV beparin followed by warfarin (AU)
Subject(s)
Humans , Female , Pregnancy , Antiphospholipid Syndrome/diagnosis , Antibodies, Antiphospholipid/isolation & purification , Thrombosis/epidemiology , Autoantibodies/isolation & purification , Anticoagulants/therapeutic use , Heparin/therapeutic use , Autoimmune Diseases/complications , Pregnancy Complications, Hematologic , Lupus Erythematosus, Systemic/epidemiology , Thrombotic Microangiopathies/epidemiologyABSTRACT
La glomerulopatía membranosa (GNM) es una de las causas más frecuentes de síndrome nefrótico en el adulto. Dos tercios de los sujetos afectos desarrollan una insuficiencia renal o mantienen una proteinuria de rango nefrótico durante los 10 primeros años después de la biopsia renal, el otro tercio remite espontáneamente. Es difícil individualizar en el momento del diagnóstico los pacientes que van a evolucionar hacia la insuficiencia renal terminal. Sólo algunos datos bioquímicos son claros factores de pronóstico: una proteinuria inferior a 3g/24h durante más de 6 meses se asocia a un buen pronóstico, una insuficiencia renal en el momento de la BR o aparecida durante el seguimiento es factor de mal pronóstico. Un modelo matemático que utiliza el factor tiempo y la proteinuria permite calcular el riesgo de evolución de un paciente hacia la insuficiencia renal. Frente a estos datos, los nefrólogos han propuesto alternativas terapéuticas opuestas adoptar una actitud conservadora intentando evitar a pacientes que hubieran presentado una remisión espontánea los riesgos de un tratamiento agresivo o administrar corticoides e inmmunosupresores para evitar a dos tercios de los pacientes la evolución hacia una insuficiencia renal o las complicaciones de un síndrome nefrótico persistente (AU)
Idiopathic membranous nephropathy is a common cause of nephrotic syndrome in adults and is characterized by great variability of the evolution. Studies on its natural history show that up to 40% of the untreated patients progress to end stage renal disease, up to 30% experience spontaneous remission and another one third of patients have a slow progression and remain proteinuric. Its treatment is a controversial issue. Some nephrologist recommend and immunosupresive therapy and others prone toward a more conservative approach. The first group have proposed several protocols: steroids and chlorambucil for six months, oral or intravenous cyclophosphamide and steroids for one to two years, low-dose oral azathioprine plus steroids for very prolonged periods. Several risk factors that do predict a worse outcome (sex, age, massive proteinuria, elevation of serum creatinine, histologic changes such as tubular intersticial damage and glomeruloesclerosis) have been proposed to select individuals worth treating. Cattran et al. have suggested that time must be added to the pronostic factors to improve prediction. Their algorithm, which uses only the presenting creatinine level, the quantity of proteinuria and change in renal function over the initial 6 month of observation improve the ability to separate patients with poor from those with good prognosis (AU)
Subject(s)
Humans , Glomerulonephritis, Membranous/therapy , Proteinuria/epidemiology , Nephrotic Syndrome/prevention & control , Kidney Failure, Chronic/prevention & control , Adrenal Cortex Hormones/therapeutic use , Kidney Function Tests , Dyslipidemias/epidemiologyABSTRACT
No disponible
No disponible
Subject(s)
Humans , Male , Adult , Ketosis/diagnosis , Hypokalemia/diagnosis , Diarrhea/etiology , Acid-Base Imbalance/physiopathologyABSTRACT
OBJECTIVE: To investigate whether the corticotrophin-releasing hormone (CRH) genomic region confers genetic susceptibility to rheumatoid arthritis (RA) in the Spanish population. METHODS: DNA was obtained from 121 simplex RA families and 101 healthy controls, all from Spanish origin. Two microsatellites, CRHRA1 and CRHRA2, located 25 and 20 kb downstream respectively from the CRH gene were examined using a new multiplex design. Linkage disequilibrium (LD) between the markers was assessed and association studies were carried out using the transmission disequilibrium test (TDT) implemented in TRANSMIT. RESULTS: Both markers are in Hardy-Weinberg equilibrium and there is significant LD between them in the Spanish population. Neither the polymorphic alleles of CRHRA1 and CRHRA2 markers nor their resulting haplotypes were significantly associated to RA. The associated haplotype in the UK population (CRHRA1*10; CRHRA2*14) was undertransmitted in RA patients (12 obs vs 17.43 exp), although the difference is not statistically significant (P > 0.05). CONCLUSIONS: This is the first follow-up study of the association between the CRH genomic region and RA and suggests that the CRH gene may not be involved in the pathogenesis of RA in the Spanish population. Further studies in other populations will help untangle the real contribution of this genomic region to the susceptibility to RA.
Subject(s)
Arthritis, Rheumatoid/genetics , Chromosomes, Human, Pair 8/genetics , Corticotropin-Releasing Hormone/genetics , Genetic Predisposition to Disease , Gene Frequency , Genotype , Haplotypes , Humans , Microsatellite Repeats/genetics , Pedigree , Polymerase Chain Reaction/methods , SpainABSTRACT
As an approach to isolate novel cereal promoters, promoterless uidA constructs and particle bombardment were used to transform tritordeum. Five of eight transgenic lines containing uidA sequences showed evidence of promoter tagging. Expression of uidA was detected in four lines as: constitutive expression, expression in short cells of the epidermis of the spikelets, expression in pollen grains and in cells of the epidermis of the spikelet, and expression in anther primordia and pollen grains. In the fifth line, the uidA was shown by RT-PCR to be transcribed, but no GUS activity was detected. The different patterns of uidA expression indicate that different regulatory sequences were tagged in each of these lines. Analysis of the progeny resulting from self-fertilisation of the primary tagged plants, indicate that the transgenes integrated at one or two loci and the patterns of expression were stably inherited. To our knowledge, this is the first report of promoter tagging in cereals by direct gene transfer.
ABSTRACT
Seven transgenic lines of wheat have been evaluated under field conditions during 2 agonomic years. Four lines contained the transgenes for beta-glucuronidase ( uidA), herbicide resistance ( bar) and for one high-molecular-weight (HMW) subunit, and three lines contained only one transgene for one HMW glutenin subunit and no marker genes. Agronomic traits and yield components were studied in transgenic lines and compared with the non-transgenic parent and null segregant lines. Although phenotypic differences for many traits have been found, only heading date and the number of spikelets per spike showed clear genotypic differences for both field trials. All transgenic lines had a longer heading date than parent lines whereas the number of spikelets per spike in transgenic lines was around that for L88-31 and higher for L88-6 than the corresponding parent lines. No differences were found between lines constitutively expressing the uidA and bar genes from those which only expressed the HMW genes. We conclude that differences between transgenic lines and their parents are small, and could be eliminated by backcrossing transgenic lines with their parents and selecting for the wanted genotype.
ABSTRACT
A chimaeric gene was constructed comprising a wheat high molecular weight glutenin subunit gene promoter, a 304-bp sucrose non-fermenting-1-related (SnRK1) protein kinase sequence in the antisense orientation, and the cauliflower mosaic virus 35S RNA gene terminator. Transgenic barley plants containing the antisense SnRK1 chimaeric gene were produced by particle bombardment of barley immature embryos with the aim of obtaining plants expressing the antisense SnRK1 sequence in the seeds. Despite the fact that the promoter was expected to be active only in seeds, two independent transgenic lines were found to fail to transmit the transgene to the T1 generation. These T0 plants had matured and died before this was discovered, but subsequently four other independent transgenic lines were found to be affected in the same way. Cytological analysis of the pollen grains in these lines showed that about 50% were normal but the rest had arrested at the binucleate stage of development, were small, pear-shaped, contained little or no starch and were non-functional. The presence of antisense SnRK1 transcripts was detected in the anthers of the four lines analyzed and a ubiquitin promoter/UidA (Gus) gene, one of the marker genes codelivered with the antisense gene, was found to be expressed only in the abnormal pollen. Expression analyses confirmed that SnRK1 is expressed in barley anthers and that expression of one class of SnRK1 transcripts (SnRK1b) was reduced in the abnormal lines. All of the abnormal lines showed approximately 50% seed set, and none of the transgenes were detected in the T1 generation.
Subject(s)
Hordeum/growth & development , Protein Serine-Threonine Kinases/genetics , RNA, Antisense/biosynthesis , Cell Differentiation , Hordeum/cytology , Hordeum/genetics , Plants, Genetically Modified , Pollen/cytology , Pollen/growth & development , ReproductionABSTRACT
Ten current European wheat varieties were transformed at efficiencies ranging from 1-17% (mean 4% across varieties) following modifications in particle bombardment and tissue culture procedures. All plants surviving phosphinothricin selection were screened for uidA and bar gene activity, and for the presence of marker gene sequences by PCR analysis. A minimum of 35% plant 'escape' frequency was achieved with selection on 4 mg l(-1) gluphosinate ammonium after shoot initiation. Mean co-transformation frequency with various genes-of-interest was 66%. The estimated number of insertions of the uidA gene in 25 lines were; 1-2 in 32%, 3-5 in 52%, and 6-8 in 16% of lines. In T(1) progenies, marker genes segregated in a Mendelian fashion in 50% of 39 lines analysed, as determined by transgene activity assays. Based on PCR analysis, it appeared that in some lines the occurrence of distorted segregation was due to poor transmission of the transgenes.
Subject(s)
Biolistics , Transformation, Genetic , Triticum/genetics , Base Sequence , Culture Techniques , DNA Primers , Genes, Plant , Plants, Genetically Modified/genetics , TransgenesABSTRACT
BACKGROUND: The aim of the present study was to investigate the effect of losartan on the progression of renal function in non-diabetic patients with chronic renal failure in an open, prospective, follow-up study of 1 year. METHODS: Twenty-nine hypertensive patients (14 females and 15 males; mean age 63 years.) with non-diabetic chronic renal failure of several causes received losartan 50 mg/day (plus other antihypertensive agents if needed) and were followed-up prospectively during 13+/-1 months. Eighteen patients received angiotensin-converting enzyme inhibitors plus other antihypertensive drugs at baseline. Patients had been followed-up for 44+/-4 months prior to the treatment with losartan. The rate of progression of renal insufficiency was evaluated as the slope of the reciprocal of serum creatinine vs time in months. RESULTS: Blood pressure, creatinine clearance and urinary protein excretion at baseline and after 1 year of treatment with losartan were: 149+/-3/90+/-1 vs 142+/-2/84+/-1 mmHg (P<0.01/P<0.05), 29+/-3 vs 29+/-3 ml/min (P=NS), and 1.7+/-0.4 vs 1.2+/-0.2 g/24 h (P=0.11, NS). Serum creatinine at baseline, and after 6 months and 1 year of treatment with losartan was: 3.18+/-0.24, 3.24+/-0.27 (P=NS vs baseline) and 3.49+/-0.32 mg ml (P<0.05 vs baseline). The rate of progression of renal disease before and after 1 year of treatment with losartan was -0.0039+/-0.0058 vs -0.0012+/-0.0073 mg/month (P<0.01). Changes in proteinuria after 1 year of treatment with losartan correlated with the change in renal disease progression (r=-0.519, P<0.01). CONCLUSIONS: The rate of progression of renal function in patients with non-diabetic chronic renal failure is slowed down after 1 year of treatment with losartan. The results of this preliminary study suggest that AT1 receptor blockade treatment offers renoprotection in this subset of patients, although these results need to be confirmed in appropriate controlled trials.