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Biomedical subjects

E Poch

Publications and source records attributed to E Poch.

At least 19 recordsLinked to original sources
PubMed2006

A coding polymorphism in the 12-lipoxygenase gene is associated to essential hypertension and urinary 12(S)-HETE.

The arachidonic acid-derived metabolite 12-(S)hydroxyeicosatetraenoic acid (12(S)-HETE), catalyzed by 12-lipoxygenase (12-LOX, ALOX12), exhibits a variety of biological activities with implications in cardiovascular disease. Previous studies have shown higher urinary excretion of this metabolite in essential hypertension. The aim of this study was to analyze the association of polymorphisms in ALOX12 with hypertension and urinary levels of 12(S)-HETE. We studied 200 patients with essential hypertension (aged 56+/-1 years, mean+/-s.e.m., 97 males) and 166 matched controls (aged 54+/-1 years, 91 males). Out of six polymorphisms in the coding region of ALOX12, only R261Q determined a nonconservative amino-acid change and was evaluated by polymerase chain reaction and restriction digestion. Urinary 12(S)-HETE was measured in Sep-Pack-extracted samples using specific enzyme-linked immunosorbent assay. The distribution of genotypes of the R261Q polymorphism was significantly different between patients and controls: patients 92 (0.46) GG, 84 (0.42) GA, 24 (0.12) AA vs controls 56 (0.34) GG, 78 (0.47) GA, 32 (0.19) AA (P=0.030). On the contrary, no association was observed for two intronic polymorphisms. The urinary excretion of 12(S)-HETE (ng/mg creatinine) was significantly higher in GG homozygous patients (13.0+/-1.5) than in GA (8.2+/-1.8) or in AA (8+/-1.5) patients (P=0.018). These results indicate that a nonsynonymous polymorphism in ALOX12 is associated to essential hypertension and to urinary levels of 12(S)-HETE, thus suggesting a role for this gene in this disease.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2006

[Quality indicators in Hypertension Care Units: indicators of structure in the QUALIHTA study].

AIM: To evaluate the minimum-required indicators of quality of care in Hypertension Units at two levels of delivered care (secondary and tertiary) in Spain. METHODS: A total of 51 quality indicators were included (N) in order to evaluate: architectural resources (8), material resources (12 on devices and 22 on supportive services) and human resources (9), which were presented as a formulary to the head of the corresponding Hypertension Unit. As a measure of the indicator, the accomplishment (yes/no) was registered. RESULTS: Data from 61 participating centers were collected and included in the analysis: 42 (68,9%) centers of tertiary level and 19 (31,1%) of secondary level. The degree of compliance of the different quality indicators in the global sample is (range): architecture, 60%-100%; material resources, 83.3%-100% (devices); 57.4-100% auxiliary services; 51.7% with respect to human resources and 69-100% with respect to continuing education and the dedication of the personnel. As expected, the differences between care levels were observed mainly in the availability of auxiliary services. CONCLUSIONS: The Hypertension Units in Spain comply with a series of structural indicators of care quality at an acceptable level. The degree of compliance in certain aspects of human resources, mainly percent of dedication, number and continuing education could be improved. The evaluation of these aspects of care quality could allow the Scientific Societies to define the recommendation in order to deliver the best quality of care in hypertension.

Cross-Sectional Studies↗
PubMed2006

[Baclofen-associated encephalopathy in a hemodialysis patient with hiccups].

Baclofen is a centrally acting gamma-ammino butyric acid agonist that is used like muscular relaxant in disorders with spasticity and intractable hiccups. Although encouraging and safe results were provided 5 mg/day in hemodialysis patients, his pharmacokinetic and pharmacodinamic properties are not well known in end stage renal disease. We present here the case of a hemodialysis patient with intractable hiccups who developed baclofen-associated encephalopathy with this recommended dose.

Aged↗
PubMed2006

[Hypertension in hemodialysis: prevalence and associated factors in Catalonia. The PRESDIAL study].

OBJECTIVE: To evaluate the prevalence of hypertension (HT) in prevalent hemodialysis (HD) patients in our region, and to analyze the associated clinical and biochemical variables. METHODS: Observational, cross-sectional and multicentric study including a representative sample of prevalent and stable (> 6 months) HD patients from all the HD centers (in and out of Hospitals) in Catalonia, Spain. Clinical and biochemical variables were recorded and predialysis blood pressure (BP) was determined (x3) in each dialysis session during 1 month, as well as the pre/post weight weekly. HT was defined as having at least one of these criteria: a mean (12 determinations) systolic BP > or = 140 mmHg or diastolic BP > or = 90 mmHg or antihypertensive treatment for at least 3 months. RESULTS: The sample comprised 387 patients from 32 of the 40 centers included, 231 of whom where men, with mean age of 63 +/- 14 years. The prevalence of HT in this sample was 67.4%, varying according to the etiology of End-Stage Renal Disease: diabetic 81%, vascular 81%, glomerulonephritis 61%, PKD 52%, unknown and others 64%. The prevalence of additional CV risk factors was 83%. One of each hypertensive 4 patients were treated, of whom 58% had systolic BP > or = 140 or dyastolic > or = 90, in contrast to 28% of untreated patients. The proportion of individuals according to the number of antihypertensive agents was 21% (no agents), 48% (1 agent), 20% (2 agents), 11% (3 agents). Blood pressure was higher among patients receiving higher number of antihypertensive agents. No differences according HT were found in age (64 +/- 13 in hypertensive patients versus 60 +/- 15 in normotensives), time on dialysis (4 +/- 4 vs 4 +/- 4 years), interdialysis weight gain (2.1 +/- 0.8 vs 2.1 +/- 0.8 kg), proportion of weight gain (3.3 +/- 1.4 vs 3.1 +/- 1.4%) or proportion of patients with > 5% weight gain with respect to dry weight (32.5 vs 27.3%). While 84% of hypertensive patients had an additional CV risk factor, this value was 67% in the patients without HT (p < 0.001). CONCLUSION: In HD patients HT has a high prevalence in our region and is poorly controlled. The causes of this poor control may be multiple, and weight gain parameters seem not to be a main factor in these stable patients. Due to the aggregation of risk factors in these patients, strategies in order to improve BP control in HD are mandatory.

Aged↗
PubMed2001

Role of Sp1 in the induction of p27 gene expression in vascular smooth muscle cells in vitro and after balloon angioplasty.

-The abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in atherosclerosis and restenosis. Although several studies have implicated the growth inhibitory protein p27(Kip1) (p27) in the control of myocyte growth and hypertrophy, little is known about the molecular mechanisms that regulate p27 expression in the cardiovascular system. In the present study, we demonstrate the interaction of the transcription factor Sp1 with 2 GC-rich sequences within the p27 promoter in cultured VSMCs. Importantly, point mutations that disrupted Sp1 binding markedly reduced p27 promoter activity, demonstrating that Sp1 is required for efficient p27 gene transcription in cultured VSMCs. Because p27 expression is upregulated after balloon angioplasty, we investigated Sp1 expression and activity in control and balloon-injured rat carotid arteries to assess the role of Sp1 as a physiological regulator of p27 expression. Although immunohistochemical analysis disclosed Sp1 protein expression in both control and balloon-injured arteries, a high level of Sp1 DNA-binding activity was found only in response to balloon angioplasty. Collectively, these results demonstrate that Sp1 is essential for maximum p27 promoter activity in VSMCs and suggest that posttranslational induction of Sp1 DNA-binding activity contributes to the induction of p27 expression and VSMC growth arrest at late time points after balloon angioplasty.

Angioplasty, Balloon↗
PubMed2001

Increased levels of 12(S)-HETE in patients with essential hypertension.

The platelet-type 12-lipoxygenase (12-LO) catalyzes the transformation of arachidonic acid into 12-hydroperoxyeicosatetraenoic acid [12-(S)HPETE], which is reduced to 12-hydroxyeicosatetraenoic acid [12-(S)HETE]. These metabolites exhibit a variety of biological activities such as mediation of angiotensin II-induced intracellular calcium transients in cultured rat vascular smooth muscle cells. It has recently been reported that platelet 12(S)-HETE production is enhanced in the spontaneously hypertensive rat. The pronounced hypotensive effect of LO inhibition in SHR suggests that LO activity may play a role in this form of hypertension. The aim of this study was to determine the basal and thrombin-induced platelet 12(S)-HETE production and the urinary 12(S)-HETE excretion in essential hypertension. We studied 19 patients with this disease (57+/-2 years of age) and 9 normotensive control subjects (48+/-5 years of age) (P:=0.074). 12(S)-HETE was measured in Sep-Pack-extracted samples with specific ELISA and high-performance liquid chromatography. The platelet basal level of 12(S)-HETE was significantly higher in patients than in control subjects (3.56+/-1.22 versus 0.64+/-0.13 ng/10(6) platelets, P:<0.025). In contrast, there were no differences in thrombin-stimulated (1 U/mL) 12(S)-HETE generation: 7.66+/-2.14 in patients versus 4.87+/-1.46 in control subjects (P:=0.61). Platelet 12-LO protein levels, measured by Western blotting with a polyclonal antibody, were higher in the patients than in the control subjects. The urinary excretion of 12(S)-HETE was higher in patients than in control subjects: 36.8+/-7.24 versus 17.1+/-3.14 ng/mg creatinine (P:<0.01). These results indicate that 12(S)-HETE levels and 12-LO protein are increased in patients with essential hypertension, suggesting a role for this metabolite in human hypertension.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2001

Molecular basis of salt sensitivity in human hypertension. Evaluation of renin-angiotensin-aldosterone system gene polymorphisms.

We analyzed the association between salt sensitivity in essential hypertension and 8 genetic polymorphisms in 6 genes of the renin-angiotensin aldosterone system. Seventy-one patients with essential hypertension were classified as salt sensitive or salt resistant by means of the 24-hour ambulatory blood pressure (BP) change to high salt intake. The polymorphisms evaluated correspond to the following genes: ACE (I/D), angiotensinogen (M235T), angiotensin II type 1 receptor (A1166C), 11beta-Hydroxysteroid dehydrogenase type 2 (11betaHSD2) (G534A), aldosterone synthase (C-344T and Intron 2 conversion), and the mineralocorticoid receptor (G3514C and A4582C); all were determined using standard polymerase chain reaction methods. Thirty-five patients (49%) were classified as salt sensitive. We analyzed the BP response to high salt intake among genotypes and found a significant association for ACE I/D and 11betaHSD2 G534A polymorphisms. Patients homozygous for the insertion allele of the ACE gene (II) had a significantly higher BP increase with high salt intake than did patients homozygous for the deletion allele (DD). Heterozygous patients (ID) exhibited an intermediate response. The prevalence of salt-sensitive hypertension was also significantly higher (P=0.003) in II (68%) and DI patients (59%) compared with DD hypertensives (19%). With respect to 11betaHSD2 G534A, patients with the GG genotype had a significantly higher systolic BP increase with high salt intake than did GA patients. In addition, plasma renin activity suppression in response to high salt was significantly greater in GA patients than in GG patients. The prevalence of salt-sensitive hypertension was 14.3% in GA patients and 50.8% in GG patients (P=0.067). In conclusion, the I allele of ACE I/D polymorphism is significantly associated to salt-sensitive hypertension. The BP response to high salt intake was different among genotypes of ACE I/D and 11betaHSD G534A, suggesting that these polymorphisms may be potentially useful genetic markers of salt sensitivity.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2000

Control of vascular smooth muscle cell growth by cyclin-dependent kinase inhibitory proteins and its implication in cardiovascular disease.

While quiescence is a defining characteristic of differentiated vascular smooth muscle cells (VSMCs) residing within the medial layer of elastic arteries in the adult organism, mature VSMCs can undergo phenotypic modulation and reenter the cell cycle in response to several physiological and pathological stimuli. Abnormal VSMC proliferation is thought to contribute to the pathogenesis of vascular occlusive lesions, including atherosclerosis, vessel renarrowing after successful angioplasty (restenosis), and graft atherosclerosis after coronary transplantation. Therefore, elucidating the molecular mechanisms limiting VSMC growth is currently the subject of active research. This review will focus on the role of cyclin-dependent kinase inhibitory proteins in the regulation of VSMC proliferation and its implication in intimal lesion formation during the pathogenesis of vascular proliferative diseases.

Arteriosclerosis↗
PubMed2000

Genetic variation of the gamma subunit of the epithelial Na+ channel and essential hypertension. Relationship with salt sensitivity.

We evaluated the association of a common polymorphism in gammaENaC, consisting in a C to G transversion in codon 649, with essential hypertension and to the pressor response to salt in whites. Two hundred fifteen essential hypertensive patients, and 137 normotensive controls were genotyped for the gamma649 ENaC polymorphism by polymerase chain reaction method and diagnostic restriction enzyme digestion. The genotype distribution of the gamma649 ENaC polymorphism in the hypertensives, 129 CC (60%) and 86 CG/GG (40%) was not significantly different from that of the control group, 84 CC (61%) and 53 CG/GG (39%) (P = .81). Salt sensitivity was assessed in a group of 48 patients by 24-h mean blood pressure response to changes in salt intake. Nineteen patients were diagnosed as salt sensitive, whereas 29 had salt-resistant hypertension. The gamma649 ENaC genotype distribution in salt-sensitive patients was 12 CC (63%) and 7 CG/GG (37%), not significantly different from the distribution in the salt-resistant group, 19 CC (65%) and 10 CG/GG (35%), P = .87. The changes in systolic, diastolic, and mean blood pressure as measured by ambulatory blood pressure monitoring, and in plasma renin activity and plasma aldosterone induced by high salt diet were not different among the gamma649 ENaC genotypes. In the present study we found no association between the gamma649 ENaC polymorphism and essential hypertension or salt sensitivity. Although these data do not support a major causative role for this polymorphism, we cannot exclude that a functional mutation elsewhere in ENaC might be associated with essential hypertension.

Adult↗
PubMed2000

Lack of association between ACE gene polymorphism and left ventricular hypertrophy in essential hypertension.

The possible association between the insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene and left ventricular hypertrophy (LVH) was investigated in a group of essential hypertensive patients. Seventy-one essential hypertensive patients (35 men and 36 women), aged 51 +/- 1 years, were genotyped by PCR for the I/D polymorphism of the ACE gene. Cardiac morphology and function were assessed by means of M-mode echocardiography. The relative frequencies of the three genotypes, DD, DI, and II, were respectively: 24%, 55%, and 21%. Mean values of left ventricular mass index were 145, 144, and 150 g/m2 for DD, DI, and II genotypes, without significant differences among them (P = 0.82). Likewise, the prevalence of LVH (76%, 64%, and 87%) was not significantly different among the three genotypes (P = 0.23). We conclude that the ACE gene I/D polymorphism is not associated with LVH in essential hypertension. Journal of Human Hypertension (2000) 14, 47-49.

Adolescent↗
PubMed2000

Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment.

Cystatin C is a nonglycosylated basic protein produced at a constant rate by all investigated nucleated cells. It is freely filtered by the renal glomeruli and primarily catabolized in the tubuli (not secreted or reabsorbed as an intact molecule). Because serum cystatin C concentration is independent of age, sex, and muscle mass, it has been postulated to be an improved marker of glomerular filtration rate (GFR) compared with serum creatinine level. We compared serum cystatin C level with other markers of GFR, such as serum creatinine level and creatinine clearance, and analyzed their variations based on iothalamate labeled with iodine 125 ((125)I-iothalamate) clearance ((125)I-ICl), used as the gold standard for GFR. The concentrations of the two different markers of GFR in patients with impaired renal function were classified according to (125)I-ICl. Twenty individuals with normal renal function ((125)I-ICl, 128 +/- 23 mL/min/1.73 m(2)) were used as the control group. Serum cystatin C level showed a greater sensitivity (93.4%) than serum creatinine level (86.8%). Also, serum cystatin C showed the greatest proportion of increased values in patients with impaired renal function (100%) compared with serum creatinine level (92.15%). Serum cystatin C levels started to increase to greater than normal values when GFR was 88 mL/min/1.73 m(2), whereas serum creatinine level began to increase when GFR was 75 mL/min/1.73 m(2). These data suggest that measurement of serum cystatin C may be useful to estimate GFR, especially to detect mild reductions in GFR, and therefore may be important in the detection of early renal insufficiency in a variety of renal diseases for which early treatment is critical.

Biomarkers↗
PubMed2000

G-Protein beta(3) subunit gene variant and left ventricular hypertrophy in essential hypertension.

A functional genetic variant consisting of a C825T substitution in the GNB3 gene, encoding for the G-protein beta(3) subunit, has been associated with enhanced G-protein activation and cell growth. The aim of the study was to investigate the association of this polymorphism with left ventricular hypertrophy (LVH) in a sample of patients with essential hypertension. Left ventricular mass was assessed by 2-mode echocardiography in 86 patients with essential hypertension, and GNB3 C825T genotype was determined by polymerase chain reaction and restriction digestion. Thirty-seven (0.43) patients were homozygous for the C allele (CC), 40 (0.47) were heterozygous (CT), and 9 (0.10) were homozygous for the T allele (TT). The genotype distribution among the patients was in Hardy-Weinberg equilibrium. Values of left ventricular end-diastolic diameter (52.0+/-0.7 versus 48.9+/-0.9 mm, P=0.007), posterior wall thickness (11.3+/-0.2 versus 10.6+/-0.2 mm, P=0.042), and left ventricular mass index (152.7+/-4.4 versus 135.2+/-6.4 g/m(2), P=0. 023) were significantly higher in patients with CT and TT genotypes considered together (CT+TT) than in CC patients. The distribution of the genotypes was significantly different when comparing patients with LVH: 20 (0.33) CC and 40 (0.67) CT+TT patients had this complication, and 17 (0.65) CC and 9 (0.35) CT+TT patients did not (P<0.01). The frequency of the T allele was significantly different among patients with (0.40) and without (0.20) LVH (P<0.01). A logistic regression analysis showed that the association between the T allele and LVH was independent of age, mean blood pressure, body mass index, and alcohol consumption. The relative risk of LVH in patients bearing the T allele (CT+TT group) compared with CC hypertensive patients was 3.03 (95% CI 1.14 to 8.05). The findings suggest an association between LVH and the 825T allele in hypertensive patients.

Adult↗
PubMed2000

Renin-angiotensin system genetic polymorphisms and salt sensitivity in essential hypertension.

We evaluated the association between salt-sensitive hypertension and 3 different genetic polymorphisms of the renin-angiotensin system. Fifty patients with essential hypertension were classified as salt sensitive or salt resistant, depending on the presence or absence of a significant increase (P<0.05) in 24-hour ambulatory mean blood pressure (BP) after high salt intake. The insertion/deletion (I/D) angiotensin-converting enzyme (ACE) gene, the M235T angiotensinogen (AGT) gene, and the A1166C angiotensin II type 1 (AT1) receptor gene polymorphisms were determined with the use of standard polymerase chain reaction methods. Twenty-four (48%) patients with significantly increased (P<0.05) 24-hour mean BP with high salt intake (from 107.3+/-9.4 to 114.8+/-10.6 mm Hg) were classified as salt sensitive. In the remaining 26 patients (52%), high salt intake did not significantly modify 24-hour mean BP (from 107.6+/-10 to 107. 8+/-9 mm Hg), and they were classified as having salt-resistant hypertension. We did not find any significant association between either M235T AGT or A1166C AT1 receptor genotypes and the BP response to high salt intake. However, patients with essential hypertension homozygous for the insertion allele of the ACE gene (II) had a significantly higher BP increase with high salt intake (9. 8+/-8.1 mm Hg for systolic BP and 5.2+/-4.2 mm Hg for diastolic BP) than that observed in patients homozygous for the deletion allele (DD) (1.2+/-5.9 mm Hg for systolic BP; P=0.0118 and -0.2+/-4.2 mm Hg for diastolic BP; P=0.0274). Heterozygous patients (ID) exhibited an intermediate response. The prevalence of salt-sensitive hypertension also was significantly higher (P=0.012) in II (67%) and DI patients (62%) compared with DD hypertensives (19%). We conclude that a significant association exists between the I/D polymorphism of the ACE gene and salt-sensitive hypertension. Patients with II and DI genotypes have significantly higher prevalence of salt sensitivity than DD hypertensives.

Adult↗
PubMed2000

Inhibition of cellular proliferation by drug targeting of cyclin-dependent kinases.

Abnormal cellular proliferation is associated with the pathology of several diseases, including cancer, atherosclerosis and restenosis post-angioplasty. Therefore, antiproliferative therapies may be a suitable approach to treat these disorders. Candidate targets for such strategies include specific components of the cell cycle machinery. Progression through the cell cycle in mammalian cells requires the activation of several cyclin-dependent protein kinases (CDKs) through their association with regulatory subunits called cyclins. Active CDK/cyclin holoenzymes phosphorylate cellular proteins including the retinoblastoma susceptibility gene product (pRb) and the related pocket proteins p107 and p130. Several compounds have been described that directly or indirectly inhibit the activity of CDKs, which results in a suppression of cell growth. In this review, we will discuss the use of drugs targeting CDKs and their therapeutic application in animal models and clinical trials.

Animals↗
PubMed1999

[Genetic polymorphisms of the renin-angiotensin system and essential hypertension].

BACKGROUND: The renin-angiotensin system (RAS) plays an important role in blood pressure (BP) regulation. A number of RAS polymorphisms have been linked to essential hypertension (EH), but there is uncertainty about this association in other studies. We examined whether the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene, and the M235T and T174M polymorphisms of the angiotensinogen (AGT) gene are associated with EH in a Spanish sample of hypertensive patients. MATERIAL AND METHODS: We studied 75 patients with EH (BP > 160/100 mmHg), aged 55 (8.5) years, 30 males, systolic BP (SBP) 182 +/- (22.1) mmHg, diastolic BP (DBP) 109 +/- (9.9) mmHg (mean [SD]) and a strong family history of the disease. As a control group, 75 healthy subjects with no family history of cardiovascular disease were studied. The polymorphisms were determined by PCR amplification of genomic DNA, followed by enzyme digestion for the AGT gene polymorphisms. RESULTS: The genotype distribution and the frequencies of the alleles of the three RAS polymorphisms were similar in hypertensive and control subjects. In addition, we did not find any compound effect of the I/D ACE gene and M235T AGT gene polymorphisms on BP levels in hypertensive and control subjects. CONCLUSIONS: In this sample, the contribution of the ACE I/D polymorphism and the AGT M235T and T174M polymorphisms in the development of EH seems to be less important than previously estimated.

Adult↗