RESUMEN

Sinorhizobium meliloti is a root-nodulating, nitrogen-fixing bacterium. An S. meliloti strain that is mutant for the rpoH(1) gene, which encodes a sigma(32)-like protein, elicits the formation of ineffective nodules on the host plant alfalfa. We characterized the rpoH(1) mutant for phenotypes related to symbiosis. Alfalfa nodules formed by the rpoH(1) mutant exhibited greatly reduced levels of acetylene reduction activity compared to the wild-type nodules. Whereas intracellular colonization by rhizobia was observed in a zone just below the apical meristem, we found ultrastructural abnormalities and signs of degeneration of bacteroids within many host cells in the proximally adjacent zone. In the proximal part of the nodule, only a few nodule cells contained bacteroids. In contrast, the rpoH(1) mutant showed normal induction of nitrogen fixation gene expression in microaerobic culture. These results suggest that the rpoH(1) mutation causes early senescence of bacteroids during the endosymbiotic process, but does not affect the invasion process or the synthesis of the nitrogenase machinery. The rpoH(1) mutant exhibited increased sensitivity to various agents and to acid pH, suggesting that RpoH(1) is required to protect the bacterial cell against environmental stresses encountered within the host. Since RpoH(1) was previously reported to be required for the synthesis of some heat shock proteins (Hsps), we examined the transcription of several genes for Hsp homologs. We found that transcription of groESL(5), lon, and clpB after heat shock was RpoH(1)-dependent, and conserved nucleotide sequences were found in the -35 and -10 regions upstream of the transcription start sites of these genes. Although groESL(5) expression is almost completely dependent on RpoH(1), we found that a groESL(5) mutant strain is still capable of normal symbiotic nitrogen fixation on alfalfa.

Asunto(s)

Proteínas de Choque Térmico/fisiología , Medicago sativa/fisiología , Fijación del Nitrógeno , Factor sigma/fisiología , Sinorhizobium meliloti/química , Simbiosis , Secuencia de Bases , Datos de Secuencia Molecular , Factor sigma/química , Factor sigma/genética , Factor sigma/metabolismo

RESUMEN

The purpose of this study was to evaluate whether or not cardiac sympathetic nerve activity, using (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging, and cardiac natriuretic peptides (atrial and brain, ANP and BNP) were independent predictors of cardiac events, and, if so, which was the stronger predictor. Planar (123)I-MIBG images were obtained from 62 patients with heart disease. Plasma ANP and BNP levels, left ventricular ejection fraction (LVEF) by echocardiography, serum total cholesterol and triglyceride were measured. (123)I-MIBG was assessed as the heart-to-mediastinum (H/M) ratio of the delayed image and the washout rate (WoR) from the early to the delayed image. Patients were followed up for an average of 16.2 months, and 12 of 62 patients had cardiac events. Patients with events had significantly lower LVEF and H/M ratio compared with those without events. They had significantly higher WoR, ANP and BNP. By multivariate Cox proportional hazard analysis, (123)I-MIBG (H/M or WoR), ANP and BNP were independent predictors for cardiac events. Event-free survival using a Kaplan-Meier model, with a threshold value of 2.0 for H/M and 45% for WoR, showed that patients with H/M<2.0 and/or WoR>45% had a significantly poorer prognosis. These results suggest that (123)I-MIBG imaging and cardiac natriuretic peptides are useful tools for the evaluation of patients with heart disease, and that cardiac sympathetic nerve activity is a stronger predictor of cardiac events.

Asunto(s)

3-Yodobencilguanidina , Factor Natriurético Atrial/sangre , Cardiopatías/sangre , Cardiopatías/diagnóstico por imagen , Péptido Natriurético Encefálico/sangre , Angina de Pecho , Cardiomiopatías , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Cardiopatías/diagnóstico , Enfermedades de las Válvulas Cardíacas , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Infarto del Miocardio , Valor Predictivo de las Pruebas , Cintigrafía , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estadística como Asunto

RESUMEN

We cloned and sequenced a cluster of genes involved in the biosynthesis of rhizobitoxine, a nodulation enhancer produced by Bradyrhizobium elkanii. The nucleotide sequence of the cloned 28.4-kb DNA region encompassing rtxA showed that several open reading frames (ORFs) were located downstream of rtxA. A large-deletion mutant of B. elkanii, USDA94 Delta rtx::Omega 1, which lacks rtxA, ORF1 (rtxC), ORF2, and ORF3, did not produce rhizobitoxine, dihydrorhizobitoxine, or serinol. The broad-host-range cosmid pLAFR1, which contains rtxA and these ORFs, complemented rhizobitoxine production in USDA94 Delta rtx::Omega 1. Further complementation experiments involving cosmid derivatives obtained by random mutagenesis with a kanamycin cassette revealed that at least rtxA and rtxC are necessary for rhizobitoxine production. Insertional mutagenesis of the N-terminal and C-terminal regions of rtxA indicated that rtxA is responsible for two crucial steps, serinol formation and dihydrorhizobitoxine biosynthesis. An insertional mutant of rtxC produced serinol and dihydrorhizobitoxine but no rhizobitoxine. Moreover, the rtxC product was highly homologous to the fatty acid desaturase of Pseudomonas syringae and included the copper-binding signature and eight histidine residues conserved in membrane-bound desaturase. This result suggested that rtxC encodes dihydrorhizobitoxine desaturase for the final step of rhizobitoxine production. In light of results from DNA sequence comparison, gene disruption experiments, and dihydrorhizobitoxine production from various substrates, we discuss the biosynthetic pathway of rhizobitoxine and its evolutionary significance in bradyrhizobia.

Asunto(s)

Proteínas Bacterianas/metabolismo , Bradyrhizobium/metabolismo , Genes Bacterianos , Complejos Multienzimáticos/genética , Oxidorreductasas/genética , Propanolaminas/metabolismo , Transaminasas/genética , Secuencia de Aminoácidos , Proteínas Bacterianas/genética , Bradyrhizobium/genética , Bradyrhizobium/fisiología , Cromatografía Liquida , Medios de Cultivo , Ácido Graso Desaturasas/genética , Ácido Graso Desaturasas/metabolismo , Prueba de Complementación Genética , Espectrometría de Masas , Datos de Secuencia Molecular , Complejos Multienzimáticos/química , Complejos Multienzimáticos/metabolismo , Mutagénesis , Fijación del Nitrógeno/efectos de los fármacos , Sistemas de Lectura Abierta , Oxidorreductasas/química , Oxidorreductasas/metabolismo , Propanolaminas/farmacología , Análisis de Secuencia de ADN , Transaminasas/química , Transaminasas/metabolismo

RESUMEN

Nitrogen-fixing bacteria were isolated from the stems of wild and cultivated rice on a modified Rennie medium. Based on 16S ribosomal DNA (rDNA) sequences, the diazotrophic isolates were phylogenetically close to four genera: Herbaspirillum, Ideonella, Enterobacter, and Azospirillum. Phenotypic properties and signature sequences of 16S rDNA indicated that three isolates (B65, B501, and B512) belong to the Herbaspirillum genus. To examine whether Herbaspirillum sp. strain B501 isolated from wild rice, Oryza officinalis, endophytically colonizes rice plants, the gfp gene encoding green fluorescent protein (GFP) was introduced into the bacteria. Observations by fluorescence stereomicroscopy showed that the GFP-tagged bacteria colonized shoots and seeds of aseptically grown seedlings of the original wild rice after inoculation of the seeds. Conversely, for cultivated rice Oryza sativa, no GFP fluorescence was observed for shoots and only weak signals were observed for seeds. Observations by fluorescence and electron microscopy revealed that Herbaspirillum sp. strain B501 colonized mainly intercellular spaces in the leaves of wild rice. Colony counts of surface-sterilized rice seedlings inoculated with the GFP-tagged bacteria indicated significantly more bacterial populations inside the original wild rice than in cultivated rice varieties. Moreover, after bacterial inoculation, in planta nitrogen fixation in young seedlings of wild rice, O. officinalis, was detected by the acetylene reduction and (15)N(2) gas incorporation assays. Therefore, we conclude that Herbaspirillum sp. strain B501 is a diazotrophic endophyte compatible with wild rice, particularly O. officinalis.

Asunto(s)

Betaproteobacteria/clasificación , Betaproteobacteria/crecimiento & desarrollo , Fijación del Nitrógeno , Oryza/microbiología , Acetileno/metabolismo , Betaproteobacteria/aislamiento & purificación , Betaproteobacteria/fisiología , Medios de Cultivo , ADN Bacteriano/análisis , ADN Bacteriano/genética , ADN Ribosómico/análisis , ADN Ribosómico/genética , Genes de ARNr , Datos de Secuencia Molecular , Oxidación-Reducción , Reacción en Cadena de la Polimerasa/métodos , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN

RESUMEN

OBJECTIVE: Many studies have reported that the resting heart rate (HR) is intimately related to the prognosis of cardiovascular disease. However, HR in the waking state is influenced by psychological and physical activity and has low reproducibility. To measure the base HR (minimum and stable HR during sleep) with ease, we developed a wristwatch-type HR recorder. We then investigated the pathophysiological significance of the base HR. SUBJECTS AND METHODS: The subjects were 158 patients (82 men and 76 women) with essential hypertension (HT) on no medication and 204 normotensive (NT) subjects (105 men and 99 women, matched for age). On the basis of pulse waves from the wristwatch-type photoelectric plethysmograph, using a blue sensor with a wavelength of 450 nm, HR was recorded easily minute by minute during sleep time. In addition, 40 (23 men and 17 women) of the HT patients were hospitalized. Their cardiac index (CI) and stroke volume index (SVI) were measured by means of the cuvette method during waking time and night-time deep sleep when their HR had reached a minimum level. RESULTS: Mean base HR (HRo) in NT subjects was 49+/-4 beats per minute (bpm) and tended to rise with increasing age (r = 0.51, P < 0.01). In HT patients, HR0 was significantly higher: 60+/-7 bpm (P < 0.01). CI of HT patients, measured during night-time deep sleep, maintained a stable value of 2.45+/-0.36 l/min per m2. SVI in patients whose HR0 was above 60 was significantly lower than that in patients whose HR0 was below 60 (37+/-4.5: 45+/-4.8 ml/m2, P < 0.01). Corresponding differences in mean HR and SVI during waking or night-time, became smaller. CONCLUSIONS: These findings suggest that there is a close relation between base HR and cardiac function caused by such conditions as age and hypertension. This relation became indistinct during waking time. Moreover, the wristwatch-type HR recorder appears to be a useful tool for measuring base HR.

Asunto(s)

Frecuencia Cardíaca/fisiología , Hipertensión/fisiopatología , Sueño/fisiología , Adulto , Anciano , Gasto Cardíaco , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/instrumentación , Pletismografía/instrumentación , Pronóstico , Volumen Sistólico

RESUMEN

Trandolapril is the prodrug of an angiotensin-converting enzyme (ACE) inhibitor. It has been proposed that its active metabolite, trandolaprilat, is mainly excreted in bile, but this has not been clearly demonstrated. Recently it has been reported that temocaprilat, an active metabolite of the ACE inhibitor temocapril, is effectively excreted in bile via an ATP-dependent active transporter (canalicular multispecific organic anion transporter: cMOAT). To investigate whether trandolaprilat has the pharmacological ability to affect the cMOAT system in a manner similar to temocaprilat. The lipophilicity of trandolaprilat and temocaprilat was measured to determine the n-octanol-water partition coefficients. The dose-dependent inhibition of the up-take of [3H]-estradiol-17beta-D-glucuronide and [3H]-2,4-dinitrophenyl-S-glutathione, which are good substrates for cMOAT, in canalicular membrane vesicles (CMVs) prepared from Sprague-Dawley rats was determined in the presence of trandolaprilat and temocaprilat. The partition coefficient of trandolaprilat (log Po/w - 1.1) was about 30 times higher than that of temocaprilat (log Po/w - 2.5). The uptake of [3H]-estradiol-17beta-D-glucuronide and [3H]-2,4-dinitrophenyl-S-glutathione was dose-dependently inhibited by the presence of temocaprilat, but trandolaprilat had no effect on the transport of [3H]-estradiol-17beta-D-glucuronide or [3H]-2,4-dinitrophenyl-S-glutathione into CMVs even at concentrations as high as 200 microM. It could be concluded that trandolaprilat has a higher lipophilicity than temocaprilat. But the hepatobiliary excretion system via cMOAT may not contribute to the excretion of trandolaprilat in bile.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Bilis/metabolismo , Estradiol/análogos & derivados , Glutatión/análogos & derivados , Indoles/farmacocinética , Proteínas de Transporte de Membrana , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Adenosina Trifosfato/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/química , Animales , Canalículos Biliares/metabolismo , Estradiol/farmacocinética , Glutatión/farmacocinética , Indoles/química , Masculino , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Ratas , Ratas Sprague-Dawley , Tiazepinas/química , Tiazepinas/farmacocinética , Vesículas Transportadoras/metabolismo , Tritio

RESUMEN

We identified two rpoH-related genes encoding sigma32-like proteins from Sinorhizobium meliloti, a nitrogen-fixing root-nodule symbiont of alfalfa. The genes, rpoH1 and rpoH2, are functionally similar to rpoH of Escherichia coli because they partially complemented an E. coli rpoH null mutant. We obtained evidence indicating that these genes are involved in the heat shock response in S. meliloti. Following an increase in temperature, synthesis of several putative heat shock proteins (Hsps) was induced in cultures of wild-type cells: the most prominent were 66- and 60-kDa proteins, both of which are suggested to represent GroEL species. The other Hsps could divided into two groups based on differences in synthesis kinetics: synthesis of the first group peaked 5-10 min, and expression of the other group 30 min, after temperature upshift. In the rpoH1 mutant, inducible synthesis of the former group was markedly reduced, whereas that of the latter group was not affected. Synthesis of both the 66- and 60-kDa proteins was partially reduced. While no appreciable effect was observed in the rpoH2 single mutant, the rpoH2 mutation had a synergistic effect on the 60-kDa protein in the rpoH1- background. The results indicate that two distinct mechanisms are involved in the heat shock response of S. meliloti: one requires the rpoH1 function, while rpoH2 can substitute in part for the rpoH1 function. Moreover, the rpoH1 mutant and rpoH1 rpoH2 double mutant exhibited Nod+ Fix- and Nod- phenotypes, respectively, on alfalfa.

Asunto(s)

Proteínas de Choque Térmico/genética , Filogenia , Factor sigma , Sinorhizobium meliloti/genética , Factores de Transcripción/genética , Agrobacterium tumefaciens/genética , Secuencia de Aminoácidos , Clonación Molecular , Escherichia coli/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/fisiología , Genotipo , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/fisiología , Medicago sativa/microbiología , Datos de Secuencia Molecular , Plásmidos , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiología , Proteínas Recombinantes/química , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Sinorhizobium meliloti/crecimiento & desarrollo , Simbiosis , Temperatura , Factores de Transcripción/química , Factores de Transcripción/fisiología

Asunto(s)

Anestesia/métodos , Hipertensión/complicaciones , Procedimientos Quirúrgicos Operativos/métodos , Femenino , Humanos , Embarazo , Complicaciones Cardiovasculares del Embarazo

RESUMEN

Macroptilium atropurpureum is a model legume with a broad symbiont range for nodulation. We have achieved the first in vitro plant regeneration of this species using cv. Siratro. Hypocotyl explants excised from dark-grown seedlings generated slimy, friable calli after three weeks' culture on B5 medium containing 1-2 mg/l kinetin and 0.05 mg/l alpha-naphthaleneacetic acid. This was followed by the generation of green organogenic callus with shoot buds by subculturing the explants to hormone-free B5 medium 20 days after the start of culture. The green organogenic calli with shoot buds were maintained as organogenic callus by subculturing on the same medium, and shoots were elongated on hormone-free B5 medium. Elongated shoots were rooted on half-strength B5 medium. Most regenerated plants were morphologically normal, diploid and fertile, although tetraploid plants appeared at a low frequency (8%).

RESUMEN

Inhibitors of ethylene synthesis or its physiological function enhanced nodulation in Lotus japonicus and Macroptilium atropurpureum. In contrast, the application of 1-aminocyclopropane-1-carboxylic acid, a precursor of ethylene biosynthesis, reduced the nodule number in these legumes. These results suggest that an ethylene-mediated signaling pathway is involved in the nodulation process even in the determinate nodulators.

Asunto(s)

Etilenos/metabolismo , Fabaceae/metabolismo , Fijación del Nitrógeno , Plantas Medicinales , Rosales/metabolismo , Bradyrhizobium/fisiología , Etilenos/antagonistas & inhibidores , Fabaceae/crecimiento & desarrollo , Fabaceae/fisiología , Rosales/crecimiento & desarrollo , Rosales/fisiología

RESUMEN

We isolated 11 low-indole-3-acetic acid (IAA)-producing mutants of Bradyrhizobium elkanii by Tn5 mutagenesis. The amount of IAA produced by each mutant was 2.2-13.6% of that of the wild-type. It was found by resting cell reactions that the biosynthetic step to convert indole-3-pyruvic acid to indole-3-acetaldehyde was blocked in all the mutants.

Asunto(s)

Bradyrhizobium/metabolismo , Ácidos Indolacéticos/metabolismo , Bradyrhizobium/genética , Bradyrhizobium/aislamiento & purificación , ADN Bacteriano/análisis , Mutagénesis , Mapeo Restrictivo/métodos , Transposasas

RESUMEN

Application of 1-aminoocyclopropane-1-carboxylic acid, an ethylene precursor, decreased nodulation of Macroptilium atropurpureum by Bradyrhizobium elkanii. B. elkanii produces rhizobitoxine, an ethylene synthesis inhibitor. Elimination of rhizobitoxine production in B. elkanii increased ethylene evolution and decreased nodulation and competitiveness on M. atropurpureum. These results suggest that rhizobitoxine enhances nodulation and competitiveness of B. elkanii on M. atropurpureum.

Asunto(s)

Aminoácidos Cíclicos , Bradyrhizobium/metabolismo , Fabaceae/microbiología , Fijación del Nitrógeno/efectos de los fármacos , Plantas Medicinales , Propanolaminas/metabolismo , Aminoácidos/farmacología , Bradyrhizobium/genética , Bradyrhizobium/fisiología , Etilenos/biosíntesis , Etilenos/farmacología , Plásmidos/genética , Propanolaminas/farmacología

RESUMEN

Lipochito-oligosaccharides (Nod factors) produced by Rhizobium or Bradyrhizobium are the key signal molecules for eliciting nodulation in their corresponding host legumes. To elucidate the signal transduction events mediated by Nod factors, we investigated the effects of Nod factors on the cytosolic [Ca2+] of protoplasts prepared from roots and suspension-cultured cells of soybean (Glycine max and G. soja) using a fluorescent Ca2+ indicator, Fura-PE3. NodBj-V (C18:1, MeFuc), which is a major component of Nod factors produced by Bradyrhizobium japonicum, induces transient elevation of cytosolic [Ca2+] in the cells of soybean within a few minutes. This effect is specific to soybean cells and was not observed in the tobacco BY-2 cells. Furthermore, NodBj-V without MeFuc did not induce any cytosolic [Ca2+] elevation in soybean cells. Exclusion of Ca2+ from the medium, as well as pre-treatment of the cells with an external Ca2+ chelator or with a plasma membrane voltage-dependent Ca2+ channel inhibitor, suppressed the Nod factor-dependent cytosolic [Ca2+] elevation. These results indicate that transient Ca2+ influx from extracellular fluid is one of the earliest responses of soybean cells to NodBj-V (C18:1, MeFuc) in a host-specific manner.

Asunto(s)

Señalización del Calcio/efectos de los fármacos , Glycine max/efectos de los fármacos , Glycine max/metabolismo , Lipopolisacáridos/farmacología , Bradyrhizobium/metabolismo , Células Cultivadas , Citosol/metabolismo , Lipopolisacáridos/metabolismo , Fijación del Nitrógeno , Plantas Tóxicas , Protoplastos/metabolismo , Glycine max/microbiología , Nicotiana

RESUMEN

From Bradyrhizobium japonicum highly reiterated sequence-possessing (HRS) strains indigenous to Niigata and Tokachi in Japan with high copy numbers of the repeated sequences RSalpha and RSbeta (K. Minamisawa, T. Isawa, Y. Nakatsuka, and N. Ichikawa, Appl. Environ. Microbiol. 64:1845-1851, 1998), several insertion sequence (IS)-like elements were isolated by using the formation of DNA duplexes by denaturation and renaturation of total DNA, followed by treatment with S1 nuclease. Most of these sequences showed structural features of bacterial IS elements, terminal inverted repeats, and homology with known IS elements and transposase genes. HRS and non-HRS strains of B. japonicum differed markedly in the profiles obtained after hybridization with all the elements tested. In particular, HRS strains of B. japonicum contained many copies of IS1631, whereas non-HRS strains completely lacked this element. This association remained true even when many field isolates of B. japonicum were examined. Consequently, IS1631 occurrence was well correlated with B. japonicum HRS strains possessing high copy numbers of the repeated sequence RSalpha or RSbeta. DNA sequence analysis indicated that IS1631 is 2,712 bp long. In addition, IS1631 belongs to the IS21 family, as evidenced by its two open reading frames, which encode putative proteins homologous to IstA and IstB of IS21, and its terminal inverted repeat sequences with multiple short repeats.

Asunto(s)

Bradyrhizobium/genética , Elementos Transponibles de ADN/genética , Secuencia de Aminoácidos , Proteínas Bacterianas/genética , Secuencia de Bases , Bradyrhizobium/aislamiento & purificación , ADN Bacteriano/genética , ADN Bacteriano/aislamiento & purificación , Japón , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , Endonucleasas Específicas del ADN y ARN con un Solo Filamento , Microbiología del Suelo

RESUMEN

Rhizobitoxine is synthesized by the legume symbiont Bradyrhizobium elkanii and the plant pathogen Burkholderia andropogonis. Rhizobitoxine competitively inhibited 1-aminocyclopropane-1-carboxylate (ACC) synthase bLE-ACS2 from the tomato, a key enzyme in the pathway of ethylene biosynthesis. Based on this inhibition of ACC synthase, we have developed a new assay for rhizobitoxine.

RESUMEN

This study was conducted to examine whether imidaprilat, an active diacid of the angiotensin-converting enzyme (ACE) inhibitor imidapril, preferentially inhibits angiotensin I degradation rather than bradykinin degradation, and whether imidapril is less active than other ACE inhibitors in inducing cough in patients with hypertension. The effect of imidaprilat on the inhibition of pressor response to angiotensin I and augmentation of depressor response to bradykinin was compared with that of enalaprilat and captopril in anesthetized rats. To determine the incidence of cough associated with imidapril, patients with a history of ACE inhibitor-induced dry cough were enrolled in a randomized, open-labeled, crossover trial with two 6-week periods to be treated with imidapril or amlodipine, a calcium-channel blocker. The recurrence of cough was assessed during both treatments. In the animal study, there were no significant differences in the ratio of inhibition of pressor response to angiotensin I and the augmentation of depressor response to bradykinin among the ACE inhibitors. In the cough-challenge trial, a total of 60 patients with hypertension were enrolled in the study. Cough and cough related symptoms recurred in 98.3% of the patients (59/ 60) during imidapril therapy. In contrast, only two patients reported cough during treatment with amlodipine. These results indicate that imidapril has no selectivity in inhibiting angiotensin I- and bradykinin-degradation in rats, and that clinically it is not different from other ACE inhibitors in inducing cough in patients with hypertension.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Tos/inducido químicamente , Hipertensión/tratamiento farmacológico , Imidazoles/uso terapéutico , Imidazolidinas , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Animales , Presión Sanguínea/efectos de los fármacos , Bradiquinina/efectos de los fármacos , Bradiquinina/metabolismo , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Imidazoles/efectos adversos , Masculino , Persona de Mediana Edad , Ratas , Ratas Wistar

RESUMEN

Dietary sodium restriction has a variety of effects on metabolism, including activation of the renin-angiotensin system. Angiotensin II has complex metabolic and cardiovascular effects, and these may be relevant to the effects of both nonpharmacological and pharmacological interventions in noninsulin-dependent diabetes mellitus (NIDDM). We have assessed the effect of dietary sodium restriction on insulin sensitivity and endogenous glucose production in eight normotensive patients with diet-controlled NIDDM who underwent hyperinsulinemic clamp studies in a randomized, double-blind, placebo-controlled cross-over protocol after two 4-day periods on sodium replete (160 mmol/day) and sodium deplete (40 mmol/day) diets. Mean +/- SD 24-h urinary sodium was 197 +/- 76.0 mmol (replete) and 67 +/- 19.5 mmol (deplete), P = 0.03. Insulin sensitivity was 42.0 +/- 11.3 mumol/kg.min (replete) and 37.0 +/- 11.6 mumol/kg.min (deplete), P = 0.04 (a reduction of 12%). Blood pressure was 130 +/- 21/78 +/- 11 mmHg (replete) and 128 +/- 12/73 +/- 10 mmHg (deplete). Dietary sodium restriction may result in a decrease in peripheral insulin sensitivity in normotensive patients with NIDDM, possibly via an elevation in prevailing angiotensin II concentrations.

Asunto(s)

Diabetes Mellitus Tipo 2/dietoterapia , Dieta Hiposódica , Insulina/farmacología , Anciano , Aldosterona/sangre , Angiotensina II/sangre , Estudios Cruzados , Diabetes Mellitus Tipo 2/sangre , Método Doble Ciego , Electrólitos/sangre , Femenino , Glucosa/biosíntesis , Técnica de Clampeo de la Glucosa , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Placebos , Renina/sangre , Triglicéridos/sangre

RESUMEN

In a survey of DNA fingerprints of indigenous Bradyrhizobium japonicum with the species-specific repeated sequences RS alpha and RS beta, 21 isolates from three field sites showed numerous RS-specific hybridization bands. The isolates were designated highly reiterated sequence-possessing (HRS) isolates, and their DNA hybridization profiles were easily distinguished from the normal patterns. Some HRS isolates from two field sites possessed extremely high numbers of RS alpha copies, ranging from 86 to 175 (average, 128), and showed shifts and duplications of nif- and hup-specific hybridization bands. The HRS isolates exhibited slower growth than normal isolates, although no difference in symbiotic properties was detected between the HRS and normal isolates. Nucleotide sequence analysis of 16S rRNA genes showed that HRS isolates were strains of B. japonicum. There was no difference in the spectra of serological and hydrogenase groupings of normal and HRS isolates. Some HRS isolates possessed a tandem repeat RS alpha dimer that is similar to the structure of (IS30)2, which was shown to cause a burst of transpositional rearrangements in Escherichia coli. The results suggest that HRS isolates are derived from normal isolates in individual fields by genome rearrangements that may be mediated by insertion sequences such as RS alpha.

Asunto(s)

ADN Bacteriano/química , Dosificación de Gen , Secuencias Repetitivas de Ácidos Nucleicos , Rhizobium/genética , Fenotipo , ARN Ribosómico 16S/genética , Rhizobium/clasificación , Simbiosis

RESUMEN

Fosinopril is a phosphorus-containing ester prodrug of an angiotensin-converting enzyme (ACE) inhibitor. It is hydrolysed mainly in the gastrointestinal mucosa and liver to the active diacid, fosinoprilat, which has unique pharmacological properties. The majority of the active moieties of other ACE inhibitors are excreted in the urine. This means that an adjustment in either the dosage and/or the administration interval is needed in patients with moderate to severe renal dysfunction, in order to reduce drug accumulation and the possibility of an excessive decrease in blood pressure or other adverse effects. On the other hand, fosinoprilat is excreted both in urine and bile (as with temocaprilat, zofenoprilat and spiraprilat), and thus an adjustment of dosage and/or administration interval may be unnecessary in patients with moderate to severe renal dysfunction, as impaired renal function influences little of the pharmacokinetics of fosinoprilat. Furthermore, the available evidence suggests that the pharmacokinetic variables of fosinoprilat in patients receiving haemodialysis were similar to those in patients with moderate to severe renal dysfunction. Dosage modifications or supplemental dose administration following dialysis may be unnecessary. The hypotensive effect of the combination of fosinopril and a diuretic is synergistic. Pharmacokinetic interactions with fosinopril are unlikely in patients receiving thiazide or loop diuretics. Fosinopril has beneficial effects for patients with hypertension and left ventricular hypertrophy because it produces an adequate reduction in blood pressure and reversal of left ventricular hypertrophy. There are a large number of studies of the pharmacokinetics of fosinopril. However studies of its pharmacokinetic drug interactions with other drugs are far fewer. Further investigations are needed in several clinical settings.

Asunto(s)

Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Antihipertensivos/farmacocinética , Fosinopril/farmacocinética , Absorción , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Interacciones Farmacológicas , Femenino , Fosinopril/farmacología , Fosinopril/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Hemodinámica/efectos de los fármacos , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/metabolismo , Riñón/metabolismo , Enfermedades Renales/metabolismo , Enfermedades Renales/fisiopatología , Hígado/metabolismo , Hepatopatías/metabolismo , Hepatopatías/fisiopatología , Masculino , Isquemia Miocárdica/tratamiento farmacológico , Isquemia Miocárdica/metabolismo , Diálisis Peritoneal Ambulatoria Continua , Diálisis Renal

RESUMEN

The pharmacokinetics and pharmacodynamics of nisoldipine (CAS 63675-72-9, isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, Bay k 5552), a calcium antagonist, were investigated after administration of a single oral 10 mg dose and after 7 same doses on consecutive days to hypertensive patients with normal renal function (NRF) and those with mild to moderate renal dysfunction (impaired renal function, IRF). A significant decrease in blood pressure was observed after consecutive dosing of nisoldipine compared to baseline values over 24 h in both groups. There were no significant differences in plasma profiles of nisoldipine in both groups after either single or consecutive dosing. The plasma concentration-time profiles of the active metabolite, Bay r 9425, were similar to those of nisoldipine in both groups. The pharmacokinetic parameters of nisoldipine and its active metabolite in the NRF and IRF groups did not differ after the single and the consecutive dosing. In addition, there were neither prolongation of apparent elimination half-life (t1/2), nor increases in peak plasma levels (Cmax), or the area under the plasma concentration-time curve (AUC0-infinity) after consecutive dosing in both groups. Cumulative urinary excretion rates of the major metabolites, Bay s 4755 and Bay s 1869, did not differ significantly between the NRF and IRF groups in both single and consecutive studies. In the present study, mild flushing was observed in one patient with IRF. There was no deterioration in renal function during the study. These results suggest that nisoldipine may have a long-lasting antihypertensive effect during consecutive dosing and that it can be used in hypertensive patients regardless of presence of renal dysfunction.

Asunto(s)

Hipertensión/metabolismo , Enfermedades Renales/metabolismo , Nisoldipino/farmacocinética , Presión Sanguínea/efectos de los fármacos , Femenino , Semivida , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Nisoldipino/efectos adversos , Nisoldipino/uso terapéutico , Diálisis Renal