Síndrome metabólico en pacientes con enfermedad arterial periférica / Metabolic syndrome in patients with peripheral arterial disease

Antecedentes y objetivos. La prevalencia del síndrome metabólico (SM) en pacientes con enfermedad arterial periférica (EAP) y arteriosclerosis de otros territorios está incrementada, pero se desconoce si también lo está en pacientes con EAP aislada. En pacientes con EAP, sin otra enfermedad aterosclerótica, hemos evaluado la prevalencia del SM y el grado de control de los factores de riesgo y fármacos cardiovasculares en comparación con enfermos sin SM. Pacientes y métodos. Estudio transversal multicéntrico, subestudio del PERIFÉRICA, realizado en consultas de atención primaria y especializada en 2009. Se incluyeron 3.934 pacientes, con ≥45 años y EAP documentada mediante el índice tobillo-brazo <0,9, amputación o revascularización arterial, sin antecedentes de enfermedad coronaria y/o cerebrovascular. Resultados. La edad media fue 67,6 años y el 73,8% eran varones. La prevalencia del SM fue del 63% (IC95% 61,5-64,3%). Los pacientes con SM tenían mayor prevalencia de factores de riesgo, mayor comorbilidad, una EAP más grave y utilizaban más frecuentemente fármacos cardiovasculares. Tras ajustar por factores de riesgo y comorbilidad, los bloqueadores del sistema renina-angiotensina, betabloqueantes, diuréticos y estatinas eran los fármacos utilizados con mayor frecuencia. Los objetivos de presión arterial (22% vs. 41,5%, p<0,001) y de HbA1c en pacientes diabéticos (44% vs. 53,1%, p<0,001) se alcanzaron menos frecuentemente en los pacientes con SM que en los que no tenían esta condición, sin que hubiera diferencias en cuanto al colesterol-LDL (29,8% vs. 39,1%, p=0,265). Conclusión. Cerca de dos tercios de los pacientes con EAP padecen el SM. A pesar de utilizar más fármacos cardiovasculares los objetivos terapéuticos se alcanzan en una menor proporción que en los pacientes sin SM (AU)

Background and objective. The prevalence of metabolic syndrome (MS) in patients with peripheral arterial disease (PAD) and coronary or cerebrovascular disease is increasing, but it is not known whether this association also exists in patients with isolated PAD. The aim of the current study was to assess the prevalence of MS in patients with PAD who had no coronary or cerebrovascular disease, the prescription rate of evidence-based cardiovascular therapies and the attainment of therapeutic goals in patients with PAD and with and without MS. Patients and methods. Multicenter, cross-sectional study of 3.934 patients aged ≥ 45 years with isolated PAD who were treated in primary care and specialized outpatient clinics during 2009. A diagnosis of PAD was reached for ankle brachial indices <0.9, a previous history of amputation or revascularization. Results. In the overall population, the mean age was 67.6 years, 73.8% were males and 63% had MS (95% CI 61.5-64.3%). Patients with MS had a higher prevalence of cardiovascular risk factors and comorbidities, more severe PAD and higher prescription rate of evidence-based cardiovascular therapies. After adjusting for risk factors and comorbidity, there was a more frequent use of renin-angiotensin system blockers, beta-blockers, diuretics and statins among the patients with MS. A lower percentage of patients with MS achieved the therapeutic goals for blood pressure (22% vs. 41.5%, p<0.001). Similarly, a lower percentage of patients with diabetes achieved the glycated hemoglobin goals (44% vs. 53.1%, p<0.001), with no differences in LDL-cholesterol levels (29.8% vs. 39.1%, p=0.265). Conclusion. Patients with PAD have a high prevalence of MS. Patients with MS do not attain therapeutic goals as frequently as those without, despite taking more cardiovascular drugs (AU)

Metabolic syndrome in patients with peripheral arterial disease. / Síndrome metabólico en pacientes con enfermedad arterial periférica.

BACKGROUND AND OBJECTIVE: The prevalence of metabolic syndrome (MS) in patients with peripheral arterial disease (PAD) and coronary or cerebrovascular disease is increasing, but it is not known whether this association also exists in patients with isolated PAD. The aim of the current study was to assess the prevalence of MS in patients with PAD who had no coronary or cerebrovascular disease, the prescription rate of evidence-based cardiovascular therapies and the attainment of therapeutic goals in patients with PAD and with and without MS. PATIENTS AND METHODS: Multicenter, cross-sectional study of 3.934 patients aged ≥ 45 years with isolated PAD who were treated in primary care and specialized outpatient clinics during 2009. A diagnosis of PAD was reached for ankle brachial indices <0.9, a previous history of amputation or revascularization. RESULTS: In the overall population, the mean age was 67.6 years, 73.8% were males and 63% had MS (95% CI 61.5-64.3%). Patients with MS had a higher prevalence of cardiovascular risk factors and comorbidities, more severe PAD and higher prescription rate of evidence-based cardiovascular therapies. After adjusting for risk factors and comorbidity, there was a more frequent use of renin-angiotensin system blockers, beta-blockers, diuretics and statins among the patients with MS. A lower percentage of patients with MS achieved the therapeutic goals for blood pressure (22% vs. 41.5%, p<0.001). Similarly, a lower percentage of patients with diabetes achieved the glycated hemoglobin goals (44% vs. 53.1%, p<0.001), with no differences in LDL-cholesterol levels (29.8% vs. 39.1%, p=0.265). CONCLUSION: Patients with PAD have a high prevalence of MS. Patients with MS do not attain therapeutic goals as frequently as those without, despite taking more cardiovascular drugs.

Basic characterization and partial purification of ß-glucosidase from cell-free extracts of Oenococcus oeni ST81.

AIMS: This study was designed to characterize a ß-glucosidase of Oenococcus oeni ST81, a strain isolated from a Spanish wine of the origin appellation Ribeira Sacra. METHODS AND RESULTS: The ß-glucosidase of O. oeni ST81 seems to have a periplasmic localization into the cells. This activity was strongly inhibited by gluconic acid, partially inhibited by glucose and not inhibited by fructose, lactate, malate, mannitol or sorbitol. Ethanol increased the activity of this enzyme up to 147%. Among the several metal ions assayed, only Fe²âº (10 mmol l⁻¹) and Cu²âº (5 mmol l⁻¹) exhibited a partial inhibitory effect (40%). This enzyme was partially purified using a combination of ammonium sulfate precipitation and chromatographic methods. The single peak because of ß-glucosidase in all chromatographic columns indicates the presence of a single enzyme with an estimated molecular mass of 140 kDa. The calculated K(m) and V(max) values for 4-nitrophenyl-ß-D-glucopyranoside were 0·38 mmol l⁻¹ and 5·21 nmol min⁻¹, respectively. The enzyme was stable at pH 5·0 with a value of t(1/2) = 50 days for the crude extract. CONCLUSIONS: The ß-glucosidase of O. oeni ST81 is substantially different from those characterized from other wine-related lactic acid bacteria (LAB), such as Lactobacillus plantarum and Lactobacillus brevis; however, it appears to be closely related to a ß-glucosidase from O. oeni ATCC BAA-1163 cloned into Escherichia coli. The periplasmic localization of the enzyme together with its high tolerance to ethanol and fructose, the low inhibitory effect of some wine-related compounds on the enzymatic activity and long-term stability of the enzyme could be of interest for winemaking. SIGNIFICANCE AND IMPACT OF THE STUDY: Information regarding a ß-glucosidase from O. oeni ST81 is presented. Although the release of aroma compounds by LAB has been demonstrated, little information exists concerning the responsible enzymes. To our knowledge, this study contains the first characterization of a native ß-glucosidase purified from crude extracts of O. oeni ST81.

Characterization of lactic acid bacteria from musts and wines of three consecutive vintages of Ribeira Sacra.

AIMS: This study was designed to isolate and characterize the lactic acid microbiota of the musts and wines of a young denomination of origin area, Ribeira Sacra in north-west Spain. METHODS AND RESULTS: Over three consecutive years (2007, 2008 and 2009), we examined musts and wines from four cellars in different zones of the region. Through biochemical and genetic tests, 459 isolates of lactic acid bacteria (LAB) were identified as the following species: Lactobacillus alvei (0·7%), Lactobacillus brevis (1·7%), Lactobacillus frumenti (0·9%), Lactobacillus kunkeei (12%), Lactobacillus plantarum (6·5%), Lactobacillus pentosus (0·9%), Lactococcus lactis ssp. lactis (3%), Leuconostoc citreum (0·7%), Leuconostoc fructosum (synon. Lactobacillus fructosum) (3·7%), Leuconostoc mesenteroides ssp. mesenteroides (2·8%), Leuconostoc pseudomesenteroides (0·2%), Oenococcus oeni (59%), Pediococcus parvulus (7%) and Weisella paramesenteroides (synon. Leuconostoc paramesenteroides) (0·9%). Of these species, O. oeni was the main one responsible for malolactic fermentation (MLF) in all cellars and years with the exception of Lact. plantarum, predominant in 2007, in one cellar, and Lact. brevis, Lact. frumenti and Ped. parvulus coexisting with O. oeni in one cellar in 2009. Different strains (84) of LAB species (14) were identified by biochemical techniques (API strips, the presence of plasmids, enzyme activities and MLF performance) and molecular techniques (PCR). All assays were carried out with every one of the 459 isolates. To select candidates for use as culture starters, we assessed malolactic, ß-glucosidase and tannase activities, the presence of genes involved in biogenic amine production and plasmid content. CONCLUSIONS: A high diversity of LAB is present in the grape musts of Ribeira Sacra but few species are responsible for MLF; however, different strains of such species are involved in the process. As far as we are aware, this is the first report of Lact. frumenti thriving in wine. SIGNIFICANCE AND IMPACT OF THE STUDY: Information on LAB populations in must and wine is presented. A large collection of well-characterized strains of LAB are available as starter cultures to winemakers.

Nodular regenerative hyperplasia of the liver and Hodgkin's disease: a case report.

Nodular regenerative hyperplasia (NRH) of the liver is a rare entity characterized by the presence of nodules in the hepatic parenchyma, not surrounded by fibrous septa. The pathogenesis and etiology are unknown but an association with different diseases including some hematological disorders has been described. Its association with Hodgkin's disease is infrequent. We report the case of a 63 years old man who presented symptoms and signs of portal hypertension, hepatocellular failure with progressive deterioration and death. Postmortem examination disclosed Hodgkin's disease with hepatosplenic involvement and NRH of the liver. The association of these entities could be explained by the presence of portal infiltration contributing to portal venous obliteration and leading to portal hypertension and formation of the parenchymal nodules characteristic of this entity. Other mechanisms that could cause or influence this association can not be ruled out.

Nucleotide sequence analysis of pRS2 and pRS3, two small cryptic plasmids from Oenococcus oeni.

Nucleotide sequence analysis of two cryptic plasmids, pRS2 (2544 bp) and pRS3 (3948 bp), from Oenococcus oeni revealed the presence in both of three major open reading frames with significant similarity to other small cryptic plasmids from O. oeni. The results suggest that those plasmids could be separated into two subfamilies, one represented by pLo13 and pRS3, the other represented by pOg32, pRS1, and pRS2.

Nucleotide sequence analysis of pRS1, a cryptic plasmid from Oenococcus oeni.

A new cryptic plasmid, pRS1, from an Oenococcus oeni strain isolated from Spanish wines is reported. Nucleotide sequence analysis (2523 bp) revealed the presence of three major open reading frames (ORFs) whose nucleotide sequence and encoded proteins exhibit high homology with those of pOg32, a previously described plasmid of O. oeni. Common features in other plasmids from O. oeni (i.e., pLo13 and pOg32) have been found in pRS1. They have three major ORFs in the same strand; the putative encoded proteins by two of these ORFs exhibit homology with the replication (Rep) and the recombination (Pre) proteins, respectively, of the pT181 plasmid family and related gram-positive bacteria plasmids; these plasmids contain the DNA sequences required for plasmid replication by the rolling circle mechanism and for recombination (i.e., double-strand origin, DSO; single-strand origin, SSO; recombination-specific sites, RSA and RSB); and finally, all these plasmids have a third ORF of unknown function. These features suggest that pRS1 could constitute together with pLo13 and pOg32 a family of small cryptic plasmids of O. oeni.

Cloning of Frankia species putative tRNA(Pro) genes and their efficacy for pSAM2 site-specific integration in Streptomyces lividans.

pSAM2 is a conjugative Streptomyces ambofaciens mobile genetic element that can transfer and integrate site specifically in the genome. The chromosomal attachment site (attB) for pSAM2 site-specific recombination for two Frankia species was analyzed. It overlaps putative proline tRNA genes having a 3'-terminal CCA sequence, an uncommon feature among actinomycetes. pSAM2 is able to integrate into a cloned Frankia attB site harbored in Streptomyces lividans. The integration event removes the 3'-terminal CCA sequence and introduces a single nucleotide difference in the T psi C loop of the putative Frankia tRNA(Pro) gene. Major differences between the attP sequence from pSAM2 and the Frankia attB sequence restrict the identity segment to a 43-bp-long region. Only one mismatch is found between these well-conserved att segments. This nucleotide substitution makes a BstBI recognition site in Frankia attB and was used to localize the recombination site in a 25-bp region going from the anticodon to the T psi C loop of the tRNA(Pro) sequence. Integration of pSAM2 into the Frankia attB site is the first step toward introduction of pSAM2 derivatives into Frankia spp.

Resistance to spiramycin in Streptomyces ambofaciens, the producer organism, involves at least two different mechanisms.

During its stationary phase, Streptomyces ambofaciens produces the macrolide antibiotic spiramycin, and has to protect itself against this antibiotic. Young mycelia, not yet producing spiramycin, are sensitive to it, but they become fully resistant when production begins. In a sensitive mycelium, resistance could be induced by exposure to sub-inhibitory concentrations of spiramycin, and these induced mycelia, like producing mycelia were resistant not only to spiramycin but also to several other macrolide antibiotics. Ribosomes extracted from these resistant mycelia were shown in vitro to be more resistant to spiramycin than ribosomes extracted from sensitive mycelium, indicating that S. ambofaciens possesses a spiramycin-inducible ribosomal resistance to spiramycin and to macrolide antibiotics. Studies with spiramycin non-producing mutants showed that, in these mutants, resistance to spiramycin also varies during cultivation, in that an old culture was much more resistant than a young one. But with these non-producing mutants, the spectrum of resistance was narrower, and in vitro data showed that resistance was not due to ribosomal modification. These results suggest that S. ambofaciens presents at least two distinct mechanisms for spiramycin resistance; a spiramycin-inducible ribosomal resistance, and a second resistance mechanism which might be temporally regulated and which could involve decreased permeability to, or export of, the antibiotic. The two mechanisms are probably at work simultaneously in the producing mycelium, the spiramycin-inducible resistance being induced by endogenous spiramycin. In non-producing mutants, in the absence of self-induction by spiramycin, only the second mechanism is observed.

Organization and nucleotide sequence analysis of a ribosomal RNA gene cluster from Streptomyces ambofaciens.

The Streptomyces ambofaciens genome contains four rRNA gene clusters. These copies are called rrnA, B, C and D. The complete nucleotide (nt) sequence of rrnD has been determined. These genes possess striking similarity with other eubacterial rRNA genes. Comparison with other rRNA sequences allowed the putative localization of the sequences encoding mature rRNAs. The structural genes are arranged in the order 16S-23S-5S and are tightly linked. The mature rRNAs are predicted to contain 1528, 3120 and 120 nt, for the 16S, 23S and 5S rRNAs, respectively. The 23S rRNA is, to our knowledge, the longest of all sequenced prokaryotic 23S rRNAs. When compared to other large rRNAs it shows insertions at positions where they are also present in archaebacterial and in eukaryotic large rRNAs. Secondary structure models of S. ambofaciens rRNAs are proposed, based upon those existing for other bacterial rRNAs. Positions of putative transcription start points and of a termination signal are suggested. The corresponding putative primary transcript, containing the 16S, 23S and 5S rRNAs plus flanking regions, was folded into a secondary structure, and sequences possibly involved in rRNA maturation are described. The G + C content of the rRNA gene cluster is low (57%) compared with the overall G + C content of Streptomyces DNA (73%).

Resistance to macrolides, lincosamides and streptogramin type B antibiotics due to a mutation in an rRNA operon of Streptomyces ambofaciens.

Streptomyces ambofaciens produces spiramycin, a macrolide antibiotic and expresses an inducible resistance to macrolides, lincosamides and streptogramin B antibiotics (MLS). From a mutant of S.ambofaciens exhibiting a constitutive MLS resistance phenotype a resistance determinant was cloned on a low copy number vector (pIJ61) through its expression in Streptomyces lividans. Further characterization has shown that this determinant corresponded to a mutant rRNA operon with a mutation in the 23S rRNA gene. In different organisms, mutations leading to MLS resistance have been located at a position corresponding to the adenine 2058 of Escherichia coli 23S rRNA. In the 23S rRNA from S.ambofaciens a similar position for the mutation has been postulated and DNA sequencing of this region has shown an adenine to guanine transition at a position corresponding to 2058. S.ambofaciens possesses four rRNA operons which we have cloned. In Streptomyces, contrary to other bacteria, a mutation in one among several rRNA operons confers a selectable MLS resistance phenotype. Possible reasons for this difference are discussed.