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J Díez

Publications and source records attributed to J Díez.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Genetics and molecular biology in cardiology (IV). Myocardial response to biomechanical stress].

Biomechanical stress of the myocardium is the situation resulting from hypoxia, hypertension, and other forms of myocardial injury, that invariably lead to increased demands for cardiac work and/or loss of functional myocardium. As a consequence of biomechanical stress a number of responses develop involving all the myocardial cells, namely cardiomyocytes. As a result some myocardial phenotypic changes develop that are initially compensatory (i.e., hypertrophy) but which may mediate the eventual decline in myocardial function that occurs with the transition from hypertrophy to failure in conditions of persistent stress (i.e., apoptosis and fibrosis). This review focuses on the steps involved in the response of the myocardium to biomechanical stress and highlights the most recent developments in the molecular mechanisms involved in the development of heart failure.

Antibody Formation↗
PubMed2001

Group II metabotropic glutamate receptors are differentially expressed in the medial nucleus of the trapezoid body in the developing and adult rat.

The existence of a neuronal-glial signalling through the activation of neurotransmitter receptors expressed in glia is well-documented. In excitatory synapses, glutamate released from presynaptic terminals activates not only postsynaptic receptors, but also ionotropic and metabotropic glutamate receptors localized in the glia ensheathing the synapses. The medial nucleus of the trapezoid body of the auditory system is involved in the localization of sounds in the space. In this nucleus, the large excitatory synaptic terminals formed by the calyces of Held on the principal globular cell bodies are wrapped by astrocytic processes. Since these synapses are functional from early postnatal days, glia receiving excitatory synaptic signals from the calyces may participate in modulating the maturation and development of the system. Groups I and II of metabotropic glutamate receptors (mGluRs) have been localized in glial cells in different brain regions. To investigate whether group II mGluRs are present in the medial nucleus of the trapezoid body, we have studied the pattern of expression of mGluR2/3 in the developing and mature nucleus by means of immunocytochemichal methods. The most remarkable finding was the switch in the occurrence of mGluR2/3 from glial to neuronal compartments. Thus, a preferential localization of mGluR2/3 immunoreactivity was observed in astrocytic processes surrounding the calyces of Held during the early postnatal development. In contrast, the main feature in adult rats was the presence of the group II mGluRs in presynaptic calyces of Held and postsynaptic principal globular cells.From these observations we suggest a role for group II mGluRs in neuronal-glial signalling in the calyx of Held-principal globular neuron synapses. Activation of these receptors might be relevant to the maturation and modulation of synaptic transmission in the medial nucleus of the trapezoid body.

Aging↗
PubMed2001

Effects of loop diuretics on angiotensin II-stimulated vascular smooth muscle cell growth.

BACKGROUND: Torasemide and furosemide are diuretics that inhibit the Na(+), K(+), 2Cl(-) co-transporter localized in cells from the ascending limb of the loop of Henle. The effects of torasemide and furosemide on cell growth induced by angiotensin II (Ang II) were investigated in cultured vascular smooth muscle cells (VSMCs) obtained from the aorta of adult spontaneously hypertensive rats (SHR). METHODS: Cell growth was determined by DNA and protein synthesis as measured by [3H]thymidine and [3H]leucine incorporation, respectively. Proliferation of VSMCs was measured using a non-radioactive colorimetric cell proliferation assay. RESULTS: Ang II (10(-7) M) signficantly increased DNA and protein synthesis and cell proliferation in VSMCS: These effects were completely abolished by the Ang II type 1 receptor antagonist irbesartan (10(-6) M). Ang II-induced [3H]leucine incorporation was reduced in a dose-dependent way by torasemide (IC(50) value: 7.7+/-0.8x10(-7) M) but not by furosemide. Neither torasemide nor furosemide modified Ang II-stimulated [3H]thymidine incorporation or proliferation in VSMCs. CONCLUSIONS: These results indicate that torasemide, but not furosemide, inhibits Ang II-induced protein synthesis in VSMCs from SHR. Thus, it is suggested that the capacity of torasemide to block this trophic action of Ang II in rat VSMCs is not mediated by inhibition of the Na(+), K(+), 2Cl(-) co-transport mechanism.

Angiotensin II↗
PubMed2001

The loop diuretic torasemide interferes with endothelin-1 actions in the aorta of hypertensive rats.

BACKGROUND: The direct effects of torasemide and furosemide on vasoconstriction and increases in intracellular free calcium concentration ([Ca(2+)]i) induced by endothelin-1 (ET-1) were investigated in the aorta of spontaneously hypertensive rats (SHR). METHODS: Vascular responses were assessed in endothelium-denuded aortic rings using an organ bath system. Changes of [Ca(2+)]i in cultured vascular smooth muscle cells (VSMCs) were assessed using fura-2 methodology. RESULTS: ET-1-induced vasoconstriction was reduced in a dose-dependent way by torasemide and furosemide (IC(50) values: 4.3+/-1.4x10(-5) and 9.8+/-5.6 x10(-5) M, respectively). The ET-1-induced biphasic [Ca(2+)]i increase was blocked by torasemide (IC(50)=2.0+/-0.2x10(-8) and 2.7+/-0.6x10(-6) M, respectively). Furosemide inhibited the initial rise in [Ca(2+)]i induced by ET-1, with no effect on the second rise. The specific chloride (Cl(-)) channel blocker diphenylamine-2-carboxylate inhibits both ET-1-induced responses in VSMCs (IC(50)=8.0+/-0.3x10(-9) and 2.5+/-0.7x10(-7) M, respectively). CONCLUSIONS: These results suggest that the ability of loop diuretics to interfere with the vascular actions of ET-1 may involve different molecular mechanisms. The ability of torasemide to block the vasoconstrictive action of ET-1 could include an inhibitory action on Cl(-) channels.

Animals↗
PubMed2001

Is the balance between nitric oxide and superoxide altered in spontaneously hypertensive rats with endothelial dysfunction?

BACKGROUND: Increases in oxidant stress, i.e. excessive production of superoxide anion (O2(.-)), have been reported in different models of hypertension. This study was designed to test the hypothesis that increased O2(.-) production, more than diminished nitric oxide (NO) generation, plays a critical role in endothelial dysfunction present in spontaneously hypertensive rats (SHR). METHODS: The study was performed in 30-week-old normotensive Wistar-Kyoto rats (WKY) and SHR. In addition, 16-week-old SHR were treated with oral irbesartan (average dose 20 mg/kg per day) for 14 weeks (SHR-I). Aortic nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase activity was determined by use of chemiluminescence with lucigenin. Aortic constitutive nitric oxide synthase (cNOS) activity was determined by measuring the conversion of L-arginine to L-citrulline. Vascular responses to acetylcholine were determined by isometric tension studies. RESULTS: Whereas systolic blood pressure (SBP) was significantly increased in SHR compared with WKY, no differences were observed in SBP between SHR-I and WKY. In SHR compared with WKY, we found significantly greater NADH/NADPH-driven O2(.-) production, similar cNOS-mediated NO production and an impaired vasodilation in response to acetylcholine. Treated SHR had similar NADH/NADPH oxidase activity and significantly lower cNOS activity than the WKY group. Vasodilation in response to acetylcholine was improved in SHR-I. CONCLUSIONS: These findings suggest that a diminished availability of NO secondary to an enhanced NADH/NADPH oxidase-dependent O2(.-) production may play a critical role in endothelial dysfunction of adult SHR.

Acetylcholine↗
PubMed2001

Clinical aspects of hypertensive myocardial fibrosis.

Myocardial fibrosis is one of the histologic constituents of myocardial remodeling present in hypertensive patients with hypertensive heart disease. In fact, an exaggerated interstitial and perivascular accumulation of fibrillar collagens type I and type III has been found in the myocardium of patients with arterial hypertension and left ventricular hypertrophy. Hypertensive myocardial fibrosis has been shown to facilitate abnormalities of cardiac function, coronary reserve, and electrical activity that adversely affect the clinical outcome of hypertensive patients. Therefore, development of noninvasive tools for the monitoring of myocardial fibrosis and pharmacological strategies aimed to promote the regression of fibrosis could be of particular relevance in the clinical treatment of patients with hypertensive heart disease.

Antihypertensive Agents↗
PubMed2001

Biochemical assessment of myocardial fibrosis in hypertensive heart disease.

Fibrous tissue accumulation is an integral feature of the adverse structural remodeling of cardiac tissue seen with hypertensive heart disease. Given the importance of fibrous tissue in leading to myocardial dysfunction and failure, noninvasive monitoring of myocardial fibrosis by use of serological markers of collagen turnover could prove a clinically useful tool, particularly given the potential for cardioprotective and cardioreparative pharmacological strategies. An emerging experimental and clinical experience holds promise for the use of radioimmunoassays of various serological markers of fibrillar collagen type I and type III turnover in arterial hypertension. More specifically, the measurement of serum concentrations of procollagen type I C-terminal propeptide (a peptide that is cleaved from procollagen type I during the synthesis of fibril-forming collagen type I) may provide indirect diagnostic information on both the extent of myocardial fibrosis and the ability of antihypertensive treatment to diminish collagen type I synthesis and reduce myocardial fibrosis. This approach represents an exciting and innovative strategy, and available data set the stage for larger trials, in which noninvasive measures of fibrosis in hypertensive heart disease could prove useful.

Animals↗
PubMed2001

Effects of antihypertensive agents on the left ventricle: clinical implications.

Hypertensive heart disease (HHD) is characterized by left ventricular hypertrophy (LVH), alterations of cardiac function, and coronary flow abnormalities. LVH is an independent cardiovascular risk factor related to cardiovascular complications in patients with hypertension. Therefore, a decrease in left ventricular mass is a therapeutic goal in these patients. The effect of the different antihypertensive agents on LVH regression has been studied in nearly 500 clinical trials. Most studies conclude that there is regression of LVH after significant decrease in blood pressure with most commonly prescribed antihypertensive agents. However, the ability to regress LVH is different between antihypertensive drug classes. ACE inhibitors and calcium channel antagonists are more potent in reducing left ventricular mass than beta-blockers, with diuretics falling in the intermediate group. Recent data suggest that angiotensin AT(1) receptor antagonists reduce left ventricular mass to a similar extent as ACE inibitors or calcium channel antagonists. Although a large number of studies have established that reversal of LVH decreases the occurrence of adverse cardiovascular events in patients with hypertension, the hypothesis that LVH regression is beneficial has not yet been conclusively proven. On the other hand, the time has come to revisit the current management of HHD simply focused on controlling blood pressure and reducing left ventricular mass. In fact, it is necessary to develop new approaches aimed to repair myocardial structure and protect myocardial perfusion and function and, in doing so, to reduce in a more effective manner, adverse risk associated with HHD. The identification of genes involved in both the process of HHD and the response to therapy may be critical for the development of these new approaches. This article will review briefly the available data on the effects of antihypertensive agents on HHD. In addition, the emerging new concepts on the pharmacology of hypertensive myocardial remodeling and the pharmacogenetic basis of the treatment of HHD will be also considered.

Animals↗
PubMed2001

Identification of factors associated with poor peripheral blood progenitor cell mobilization in Hodgkin's disease.

BACKGROUND AND OBJECTIVES: Although the use of drugs which damage stem cells is common in patients with Hodgkin's disease (HD), factors affecting peripheral blood progenitor cell (PBPC) mobilization have not been clearly established in this group of patients. The aim of this study was to identify factors associated with poor PBPC mobilization in patients with HD. DESIGN AND METHODS: In order to address this issue we have evaluated in 54 patients with HD mobilized with G-CSF alone the following factors: sex, age, histologic subtype, B symptoms at diagnosis, status of remission, previous chemotherapy and radiotherapy, interval from diagnosis and last chemotherapy cycle to harvest, and dose of G-CSF. Univariate analysis was performed using Student's t-test, Pearson's correlation and Spearman's correlation. A stepwise regression model was used to determine which of the variables was the most predictive of PBPC mobilization. RESULTS: In univariate analysis poorer PBPC mobilization was observed in patients who had previously received at least two courses of mini-BEAM (p=0.006), a high number of different chemotherapy regimens (p=0.002), a chemotherapy score >30 (p=0.02) and more than 9 months of alkylating agents (p=0.07). We did not find radiotherapy to be a significant factor affecting progenitor cell yield (p=0.59). In the stepwise regression model, only the previous administration of two or more mini-BEAM cycles predicted a poor PBPC yield (p=0.006). INTERPRETATION AND CONCLUSIONS: Previous chemotherapy, principally exposure to a mini-BEAM regimen, seems to be the principal factor affecting collection of PBPC in patients with HD mobilized with G-CSF alone. Since mini-BEAM is an effective salvage regimen in relapsed or refractory HD, collection of PBPC should be planned when there has been no or only minimal exposure to a mini-BEAM regimen.

Adolescent↗
PubMed2000

The metabotropic glutamate receptor subtype mGluR 2/3 is located at extrasynaptic loci in rat spinal dorsal horn synapses.

The position of neurotransmitter receptors relative to active neurotransmitter release sites may be a major factor influencing neuronal responses. The location of the metabotropic glutamate receptor subtype mGluR2/3 was investigated in synaptic structures in the rat superficial spinal dorsal horn laminae by using a pre-embedding immunogold technique. Immunostaining for mGluR2/3 occurred in laminae I through III. Gold particles were encountered both in the cytosol and along the plasma membrane. Distinctive plasmalemmal immunodeposits were detected in vesicle-containing profiles, where they were located to membrane compartments distant from active release sites rather than in the close vicinity of synaptic specialisations. No distinct immunolabelling was observed in profiles meeting characteristics of primary afferent terminals. The extrasynaptic occurrence of mGluR2/3 suggests a presynaptic heteroreceptor role for these receptor subtypes in the spinal dorsal horn.

Animals↗
PubMed2000

Identification and characterization of a host protein required for efficient template selection in viral RNA replication.

Biochemical studies suggest that positive-strand RNA virus replication involves host as well as viral functions. Brome mosaic virus (BMV) is a member of the alphavirus-like superfamily of animal and plant positive-strand RNA viruses. Yeast expressing the BMV RNA replication proteins 1a and 2a supports BMV RNA replication and mRNA synthesis. Using the ability of BMV to replicate in yeast, we show that efficient BMV RNA replication requires Lsm1p, a yeast protein related to core RNA splicing factors but shown herein to be cytoplasmic. Haploid yeast with an Lsm1p mutation was defective in an early template selection step in BMV RNA replication, involving the helicase-like replication protein 1a and an internal viral RNA element conserved with tRNAs. Lsm1p dependence of this interaction was suppressed by adding 3' poly(A) to the normally unpolyadenylated BMV RNA. Our results show Lsm1p involvement in a specific step of BMV RNA replication and connections between Lsm1p and poly(A) function, possibly through interaction with factors binding mRNA 5' ends.

Amino Acid Sequence↗
PubMed2000

Serum carboxy-terminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease.

BACKGROUND: This study was designed to investigate whether the serum concentration of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type I synthesis, is related to myocardial fibrosis in hypertensive patients. METHODS AND RESULTS: The study was performed in 26 patients with essential hypertension in which ischemic cardiomyopathy was excluded after a complete medical workup. Right septal endomyocardial biopsies were performed in hypertensive patients to quantify collagen content. Collagen volume fraction (CVF) was determined on picrosirius red-stained sections with an automated image analysis system. The serum concentration of PIP was measured by specific radioimmunoassay. Compared with normotensives, both serum PIP and CVF were increased (P<0.001) in hypertensives. A direct correlation was found between CVF and serum PIP (r=0.471, P<0.02) in all hypertensives. Histological analysis revealed the presence of 2 subgroups of patients: 8 with severe fibrosis and 18 with nonsevere fibrosis. Serum PIP was higher (P<0.05) in patients with severe fibrosis than in patients with nonsevere fibrosis. Using receiver operating characteristic curves, we observed that a cutoff of 127 microg/L for PIP provided 78% specificity and 75% sensitivity for predicting severe fibrosis with a relative risk of 4.80 (95% CI, 1.19 to 19.30). CONCLUSIONS: These results show a strong correlation between myocardial collagen content and the serum concentration of PIP in essential hypertension. Although preliminary, these findings suggest that the determination of PIP may be an easy and reliable method for the screening and diagnosis of severe myocardial fibrosis associated with arterial hypertension.

Adult↗
PubMed2000

Vascular oxidant stress: molecular mechanisms and pathophysiological implications.

The term oxidative stress refers to a situation in which cells are exposed to excessive levels of either molecular oxygen or chemical derivatives of oxygen (ie, reactive oxygen species). Three enzyme systems produce reactive oxygen species in the vascular wall: NADH/NADPH oxidase, xanthine oxidoreductase, and endothelial nitric oxide synthase. Among vascular reactive oxygen species superoxide anion plays a critical role in vascular biology because it is the source for many other reactive oxygen species and various vascular cell functions. It is currently thought that increases in oxidant stress, namely excessive production of superoxide anion, are involved in the pathophysiology of endothelial dysfunction that accompanies a number of cardiovascular risk factors including hypercholesterolemia, hypertension and cigarette smoking. On the other hand, vascular oxidant stress plays a pivotal role in the evolution of clinical conditions such as atherosclerosis, diabetes and heart failure.

Animals↗
PubMed2000

[Apoptosis in cardiovascular diseases].

Apoptosis consists of a distinct form of cell death that displays characteristic alterations in cell morphology and cell fate which are different than death due to oncosis or necrosis. In terms of tissue kinetics, apoptosis may be considered a mechanism that counterbalances the effect of cell proliferation by mitotic division. In fact, deregulated apoptosis has been implicated in the development a wide variety of human diseases. Excessive apoptotic cell death may cause organ atrophy and organ failure. On the other hand, insufficient elimination of redundant cells may lead to organ and tissue structural remodeling. In recent years, apoptosis has become a highly fashionable and competitive area of research. Fortunately, it has not escaped the attention of the cardiovascular community. Sightings of apoptosis have been reported from every corner of cardiovascular medicine ranging from conduction system defects to congestive heart failure, and from atherosclerosis to aneurysms. There is no question that these sightings will eventually be converted into mechanistic etiopathogenic and physiopathological insights and will form the basis for designing new diagnostic modalities and novel therapies.

Apoptosis↗
PubMed2000

Radiocaesium and radiostrontium uptake by fruit bodies of Pleurotus eryngii via mycelium, soil and aerial absorption.

There has been an extraordinary increase in interest concerning the transfer of radioactive contamination to the fruit bodies of fungi since the Chernobyl nuclear power plant accident. These investigations, however, have focused exclusively on field studies aimed fundamentally at quantifying the behaviour of the radiocaesium component of the contamination. The results have shown great variability. As a contribution towards this body of knowledge, we have made a comparative study of the temporal evolution of the transfer of 85Sr and 134Cs via three routes of radioactive contamination--from the mycelium, from the surface layer of the soil, and directly onto the caps of the fruit bodies--for the saprophyte species, Pleurotus eryngii, under controlled laboratory conditions. The results indicate that the last of the above three uptake routes is the most efficient, and that the temporal evolution of the transfer is closely related to the radionuclide and the radioactive contamination route being considered.

Air Pollutants, Radioactive↗
PubMed2000

Factors influencing collection and engraftment of CD34+ cells in patients with breast cancer following high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation.

Although autologous PBPC transplantation is being used increasingly for the treatment of breast cancer, there are few data on factors influencing mobilization and engraftment in these patients. We have analyzed these factors in 70 patients with advanced or metastatic breast cancer undergoing autologous PBPC transplantation. All patients were mobilized after stimulation with G-CSF, and a median of 3.16 x 10(6)/kg CD34+ cells (range 0.75-23.33) were infused. All patients received conditioning with a combination of cyclophosphamide, thiotepa, and carboplatin, and postinfusion G-CSF was administered to 60 patients. The median times to reach 0.5 x 10(9)/L and 1 x 10(9)/L neutrophils were 10 and 11 days, respectively. The median times to obtain 20 x 10(9)/L and 50 x 10(9)/L platelets were 12 and 18 days, respectively. An analysis of factors that influence CD34+ cell collection was performed by linear regression. Previous radiation therapy and increasing age were associated with lower numbers of CD34+ cells collected. Those variables that could influence the tempo of engraftment were examined by multivariate analysis using Cox regression models. The number of CD34+ cells infused was found to influence both neutrophil and platelet recovery. The use of G-CSF after transplant, accelerated neutrophil recovery, and having more than six cycles of previous chemotherapy was an unfavorable factor for recovering >50 x 10(9)/L platelets.

Adult↗
PubMed2000

Vascular NADH/NADPH oxidase is involved in enhanced superoxide production in spontaneously hypertensive rats.

This study was designed to test the hypothesis that stimulation of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase is involved in increased vascular superoxide anion (*O(2)(-)) production in spontaneously hypertensive rats (SHR). The study was performed in 16-week-old and 30-week-old normotensive Wistar-Kyoto rats (WKY(16) and WKY(30), respectively) and in 16-week-old and 30-week-old SHR (SHR(16) and SHR(30), respectively). In addition, 16-week-old SHR were treated with oral irbesartan (average dose 20 mg/kg per day) for 14 weeks (SHR(30)-I). Aortic NADH/NADPH oxidase activity was determined by use of chemiluminescence with lucigenin. The expression of p22phox messenger RNA was assessed by competitive reverse transcription-polymerase chain reaction. Vascular responses to acetylcholine were determined by isometric tension studies. Aortic wall structure was studied, determining the media thickness and the cross-sectional area by morphometric analysis. Whereas systolic blood pressure was significantly increased in the 2 groups of hypertensive animals compared with their normotensive controls, no differences were observed in systolic blood pressure between SHR(30) and SHR(16). No other differences in the parameters measured were found between WKY(16) and SHR(16). In SHR(30) compared with WKY(30), we found significantly greater p22phox mRNA level, NADH/NADPH-driven *O(2)(-) production, media thickness, and cross-sectional area and an impaired vasodilation in response to acetylcholine. Treated SHR had similar NADH/NADPH oxidase activity and p22phox expression as the WKY(30) group. The vascular functional and morphological parameters were improved in SHR(30)-I. These findings suggest that an association exists between p22phox gene overexpression and NADH/NADPH overactivity in the aortas of adult SHR. Enhanced NADH/NADPH oxidase-dependent *O(2)(-) production may contribute to endothelial dysfunction and vascular hypertrophy in this genetic model of hypertension.

Animals↗