Search PubMed⌕ Search

Biomedical subjects

Jorge Joven

Publications and source records attributed to Jorge Joven.

At least 19 recordsLinked to original sources
PubMed2006

Serum paraoxonase-1 activity and concentration are influenced by human immunodeficiency virus infection.

BACKGROUND: Higher high-density lipoprotein concentrations are associated with a better disease course in HIV-infected patients. Paraoxonase-1, an enzyme contained within high-density lipoproteins, is thought to hydrolyse oxidised lipids. The aim of the present study was to investigate the relationships between HIV infection and the circulating activity and concentration of paraoxonase-1, and the concentration of high-density lipoproteins, apolipoprotein A-I and oxidised low-density lipoproteins. METHODS: We studied patients with HIV infection (n=212) and healthy subjects (n=409). In all the participants we measured the relevant biochemical and genetic variables. The statistical associations between these variables and paraoxonase-1 activity and concentration were assessed using multiple linear regression analysis. RESULTS: Serum paraoxonase-1 activity was decreased (P<0.001) and its concentration was increased (P=0.017) in HIV-patients compared to the controls. HIV infected patients had lower HDL-cholesterol and apolipoprotein A-I concentrations. Multivariate regression analysis showed that serum paraoxonase-1 activity was associated with the CD4+ T lymphocyte count (P<0.05), apolipoprotein A-I (P<0.001), and paraoxonase-1 genetic polymorphisms (P<0.001). Paraoxonase-1 concentration was associated with that of serum beta-2-microglobulin (P<0.001). CONCLUSIONS: Both, paraoxonase-1 activity and concentration were influenced by HIV-infection and these were related to alterations in HDL composition and the immunological status of the patients.

Adult↗
PubMed2006

Manipulation of inflammation modulates hyperlipidemia in apolipoprotein E-deficient mice: a possible role for interleukin-6.

There are increasing evidences showing that inflammation participates in atherosclerosis. Therefore, the therapeutic use of anti-inflammatory agents should be considered. We have induced chronic, aseptic inflammation upon the injection of turpentine and tested the effect of dexamethasone on lipoprotein metabolism and, consequently, atherosclerosis in apolipoprotein E-deficient mice. Aseptic inflammation caused a significant decrease in hyperlipidemia. Treatment with dexamethasone elicited the opposite effect increasing hyperlipidemia through mechanisms related to the increase in the synthesis of triglyceride-rich lipoproteins. Changes in plasma lipids correlated with those observed in the size of atherosclerotic lesions. Our data suggest the presence of a common mechanism present in both observations and which is probably related to the cytokine secretion. Among the candidates, we chose to test the effect of interleukin-6 because it is involved in both processes, atherosclerosis and inflammation, and its expression is efficiently repressed by corticosteroids. The injection of recombinant interleukin-6 in our mice elicited the same effects observed in our model of inflammation. We conclude that manipulation of inflammation-related mechanisms modulates lipid homeostasis and development of atherosclerotic plaque in rodents.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

Effects of rosiglitazone and metformin on postprandial paraoxonase-1 and monocyte chemoattractant protein-1 in human immunodeficiency virus-infected patients with lipodystrophy.

Highly active antiretroviral therapy in Human Immunodeficiency Virus (HIV) has been associated with lipodystrophy, insulin resistance and atherosclerosis. We investigated the effects of rosiglitazone or metformin on fasting and postprandial inflammatory and antioxidant variables in HIV-infected males with lipodystrophy. Thirty-one patients were randomly assigned to receive either rosiglitazone (4 mg twice daily) or metformin (1 g twice daily) for 26 weeks. At baseline and after treatment, standardized 10-h oral fat loading tests were performed. Before treatment, inflammatory variables remained unchanged but there was a postprandial decrease in high density lipoprotein (HDL)-cholesterol and paraoxonase (PON1) activity. Rosiglitazone and metformin reduced homeostasis model assessment index (HOMA) similarly (-34% and -37%, respectively, P<0.05 for each). Both treatments increased fasting and postprandial PON1 activity and decreased postprandial monocyte chemoattractant protein 1 (MCP-1) concentrations. However, plasma C-reactive protein (CRP) and Interleukin-6 (IL-6) concentration did not change throughout the study. To decrease insulin resistance results in a higher anti-oxidant and consequent lower pro-inflammatory action of HDL. This may confer protection against accelerated atherosclerosis in these patients.

Adult↗
PubMed2006

HIV-infected patients with lipodystrophy have higher rates of carotid atherosclerosis: the role of monocyte chemoattractant protein-1.

Individuals with HIV-1 infection are at increased risk for cardiovascular events, and lipodystrophy is generally associated with pro-atherogenic metabolic disturbances. We conducted a case-control study to assess the presence of sub-clinical atherosclerosis in HIV-1-infected patients with or without lipodystrophy (LD) and to evaluate the influence of monocyte chemoattractant protein-1 (MCP-1) on the development of both carotid atherosclerosis and LD. The study population consisted of 43 patients with LD and 86 patients without LD. We determined carotid intima-media thickness (IMT), MCP-1 concentrations in plasma, and MCP-1 genotype (presence or absence of the -2518G allele). HIV-1-infected patients with LD showed increased risk (OR=3.71, 95% CI=1.10-12.47, p=0.03) for sub-clinical atherosclerosis, and MCP-1 plasma concentration was significantly correlated with IMT in these patients (Pearson=0.31, p=0.03). Furthermore, presence of LD was a determinant for MCP-1 plasma concentration (beta=0.18, p=0.05). In summary, HIV-1-infected patients with clinically manifest LD are at higher risk for atherosclerosis and our observations support the relationship between inflammation and atherosclerotic disease.

Adult↗
PubMed2006

Functional and structural markers of atherosclerosis in human immunodeficiency virus-infected patients.

OBJECTIVES: We investigated functional and structural markers of atherosclerosis in human immunodeficiency virus (HIV)-infected patients in relation to the presence of the metabolic syndrome (MS). BACKGROUND: Antiretroviral combination therapy in HIV has been associated with cardiovascular risk factors that cluster in the MS. METHODS: Thirty-seven HIV-infected patients underwent assessment of flow-mediated vasodilation (FMD), aortic pulse-wave velocity (PWV), and carotid intima-media thickness (IMT). Age-matched type 2 diabetic patients (n = 13) and healthy controls (n = 14) served as reference groups. RESULTS: Fifteen HIV-infected patients (41%) fulfilled the National Cholesterol Education Program criteria of the MS. The FMD was similarly impaired in HIV-infected patients without the MS (MS- group) and the diabetic patients (5.1 +/- 0.4% and 4.9 +/- 0.6%, respectively) compared with controls (8.8 +/- 0.7%). The HIV-infected patients with the MS (MS+ group) had even more impaired FMD (2.5 +/- 0.3%). Carotid IMT was similarly increased in the MS+ group and the diabetic patients compared with the other groups. Aortic PWV was increased in the diabetic patients only. In HIV-infected patients, FMD was related to metabolic parameters, whereas aortic PWV and IMT were related to parameters of HIV infection, time on antiretroviral combination therapy, inflammatory (C-reactive protein and leukocytes) and metabolic parameters. CONCLUSIONS: The data of the present study suggest an increased cardiovascular risk in HIV-infected patients, even in the absence of clustering of metabolic risk variables. The presence of the MS in HIV is associated with even more advanced atherosclerotic changes. Presumably, both HIV infection and antiretroviral therapy may promote atherosclerosis through mechanisms involving endothelial cells, either directly or indirectly via metabolic risk factors.

Adolescent↗
PubMed2006

Paraoxonase-1 is associated with oxidative stress, fibrosis and FAS expression in chronic liver diseases.

BACKGROUND/AIMS: We previously reported that paraoxonase-1 activity measurement may be useful for the evaluation of liver diseases. Because oxidative stress plays a role in liver apoptosis, and lipid peroxides are hydrolyzed by paraoxonase-1, we have extended our studies to explore the relationships between this enzyme and oxidative stress, fibrosis and apoptosis. METHODS: We measured paraoxonase-1 activity and concentration, soluble FAS concentration, serum fibrosis markers, and total peroxides in a group of patients with minimal hepatic changes (n=25), chronic hepatitis (n=51), or liver cirrhosis (n=17). We also measured the Knodell activity index in liver biopsies and performed FAS and PON1 immunostaining. RESULTS: Patients with liver diseases showed an increase in soluble FAS, fibrosis markers and paraoxonase-1 concentrations, as well as a decrease in PON1 activity. Paroxonase-1 activity and concentration were correlated with soluble FAS (r=-0.43, P<0.001 and r=0.27, P=0.007, respectively). Paraoxonase-1 concentration showed a significant inverse association with FAS immunostaining (P=0.013) and a direct association with PON1 immunostaining (P<0.001). CONCLUSIONS: These results suggest an active role of PON1 in the regulation of oxidative stress, fibrosis and hepatic cell apoptosis in chronic liver diseases.

Adult↗
PubMed2006

The influence of HIV infection on the correlation between plasma concentrations of monocyte chemoattractant protein-1 and carotid atherosclerosis.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in atherosclerosis and it has been recently proposed as a surrogate biomarker of long-term clinical outcomes in patients with acute myocardial infarction. Little is known of the factors that may influence plasma MCP-1 concentrations. METHODS: We studied 384 healthy volunteers and 226 HIV-infected patients as a model of chronic inflammatory condition that predisposes to sub-clinical atherosclerosis. RESULTS: In healthy participants there were significant associations between plasma MCP-1 concentration and age, smoking status, and serum triglyceride concentrations that were not observed in the HIV-infected patients. The plasma concentration of MCP-1 was significantly associated with the polymorphism at position -2518 of the MCP-1 gene and, in patients, with the carotid artery intima-media thickness. There were also significant correlations indicating a close association between MCP-1 and HIV disease activity. However, in a multiple regression model, only age, the MCP-1 genotype and smoking status showed significant, and independent, associations with plasma MCP-1 concentrations. CONCLUSION: Plasma MCP-1 concentration is genetically determined and associated with age and smoking habit and it also correlates with subclinical atherosclerosis in HIV-infected patients.

Adult↗
PubMed2006

New variants in the mitochondrial genomes of schizophrenic patients.

The impaired mitochondrial function hypothesis in schizophrenia is based on evidence of altered brain metabolism, morphology, biochemistry and gene expression. Mitochondria have their own genome, which is needed to synthesize some of the subunits of the respiratory chain enzymes. Mitochondrial DNA (mtDNA) is maternally inherited and we observed an excess of maternal transmission of schizophrenia in a set of parent-offspring affected pairs. We therefore hypothesized that mutations in the mtDNA may contribute to the complex genetic basis of schizophrenia. The entire mtDNA of six schizophrenic patients with an apparent maternal transmission of the disease was sequenced and compared to the reference sequence. We have identified 50 variants and among these six have not been previously reported. Three of them were missense variants: MTCO2 7750C>A, MTATP6 8857G>A and MTND4 12096T>A. These were maternally inherited because they were also present in the mtDNA of their respective schizophrenic mothers and none of them were found in 95 control individuals. The MTND4 12096T>A (Leu446His) is a heteroplasmic variant present in five of the six mother-offspring patient pairs that triggers a non-conservative substitution in the ND4 subunit of complex I. Sequence alignment of 110 ND4 peptides from all eukaryotic kingdoms shows that only hydrophobic amino acids are found in this position. Moreover, leucine was conserved or substituted by an isoleucine in all mammalian species. This indicates that the presence of histidine could affect complex I activity in patients with schizophrenia.

Adult↗
PubMed2006

Rosiglitazone modulates fasting and post-prandial paraoxonase 1 activity in type 2 diabetic patients.

1. In the present study, we have explored the effect of rosiglitazone on post-prandial paraoxonase (PON)-1, an enzyme with potent anti-oxidant properties that may protect against atherosclerosis because increased post-prandial lipaemia, although sometimes understated, is part of the diabetic dyslipidaemia. 2. A randomized, cross-over, placebo-controlled, double-blind clinical trial was performed. Participants (19 type 2 diabetic patients on oral antihyperglycaemic agents) were randomly assigned to receive either placebo or rosiglitazone 4 mg twice daily for 8 weeks. After a 6 week wash-out, the alternative treatment was implemented. Standardized 6 h oral fat-loading tests were performed after each treatment period. 3. Patients assigned to rosiglitazone had increased fasting PON-1 activity (from 331 +/- 29 to 362 +/- 32 U/L before treatment vs after treatment, respectively; P = 0.015), although the PON-1 mass did not change (68.8 +/- 21.1 vs 64.2 +/- 25.4 mg/L before treatment vs after treatment, respectively). In addition, rosiglitazone significantly decreased fasting plasma peroxides compared with placebo (162 +/- 25 vs 214 +/- 28 mmol/L, respectively; P = 0.019). The post-prandial fall in PON-1 activity, expressed as area under the curve, was attenuated by rosiglitazone (-97 +/- 14 vs-161 +/- 24 Uh/L for rosiglitazone vs placebo, respectively; P = 0.02) and the increase in PON-1 activity caused by rosiglitazone correlated with reductions in fasting plasma glucose (r = -0.42; P < 0.05), homeostatic model assessment index (r = -0.59; P < 0.01) and peroxides (r = -0.40; P = 0.07). 4. The present data indicate that rosiglitazone may convey increased protection against the oxidative modification that represents increased post-prandial lipaemia.

Adult↗
PubMed2006

Longitudinal changes in serum paraoxonase-1 activity throughout normal pregnancy.

The aim of this study was to investigate the longitudinal changes in serum paraoxonase-1 (PON1) activity from preconception throughout normal pregnancy and their relationships with maternal dietary vitamin C and E intake. The study was performed in 35 women (studied at preconception, at 8, 20 and 32 weeks of pregnancy, and at labour). PON1 activity decreased significantly from 145.8 (109.8-198.8) U/L at preconception to 111.1 (85.3-179.9) U/L (p<0.01) at 32 weeks and 100.4 (54.7-171.4) U/L (p<0.001) at labour. There was a direct association between vitamin C intake and PON1 at week 32 (p=0.018). We conclude that adequate vitamin C intake in pregnant women may merit consideration, since vitamin C supplementation has proved beneficial in the prevention of preeclampsia in women at increased risk of this condition.

Adult↗
PubMed2005

Dietary cholesterol and differential monocyte chemoattractant protein-1 gene expression in aorta and liver of apo E-deficient mice.

In humans, hypercholesterolemia, steatohepatitis, and risk for arteriosclerosis are associated. Apolipoprotein E-deficient mice, a widely used animal model, show both arteriosclerosis and steatohepatitis in response to high-fat and cholesterol diets. We have found a relationship between these conditions and a higher mRNA aortic and hepatic monocyte chemoattractant protein-1 (mcp-1) gene expression. Both tissues respond in a similar way when dietary cholesterol is provided for a few weeks but differently if the conditions persist for a protracted period of time. After 8 months of treatment, the mcp-1 gene expression in the aorta continues increasing but in the liver decreases. This coincides with a significant increase in hepatic ppar-delta anti-inflammatory gene expression. Apparently, the arterial wall cannot prevent the deleterious effects of higher mcp-1 expression by increasing ppar-delta gene expression and the lesion progress. However, in the liver, the activation of anti-inflammatory genes may reduce the hepatic mcp-1 expression which significantly decreases the inflammatory response. This differential inflammatory gene expression in aorta and liver may support the idea that anti-inflammatory transcription factors are involved in the response to diet and inflammation. Therefore, the use of cholesterol-enriched diets should be carefully considered in the apolipoprotein E-deficient mice because they may trigger different stimuli and seriously hinder the interpretation of possible findings.

Animals↗
PubMed2005

The stromal derived factor-1 mutated allele (SDF1-3'A) is associated with a lower incidence of atherosclerosis in HIV-infected patients.

BACKGROUND: HIV-infected patients have higher rates of subclinical atherosclerosis. The chemokine stromal derived factor 1 (SDF-1) is the natural ligand for the CXCR4 HIV co-receptor, is highly expressed in atherosclerotic plaques, and the plasma concentration is lower in individuals homozygous for the mutant allele (SDF1-3'A). We tested the influence of SDF1-3'A on atherosclerosis in HIV-infected patients. METHODS: We performed carotid ultrasonography and determined the SDF1-3'A DNA polymorphism in 183 HIV-infected patients. Classical cardiovascular risk factors and antiretroviral therapy were also recorded. From these patients, we selected a group of 134 patients taking protease inhibitor-based antiretroviral therapy and in whom the lipid profile over an 18-month follow-up was collated. RESULTS: We found atherosclerosis in 113 (61.7%) and a lower number of patients with the SDF-1 mutated allele in the group with carotid atherosclerosis compared to those without (41.6% versus 57.1%; P = 0.04). Using a logistic regression analysis, age and dyslipidaemia were significantly associated with atherosclerosis but the SDF1-3'A allele exerted a protective effect on the development of atherosclerosis (odds ratio, 0.45; 95% confidence interval, 0.14-1.02; P = 0.05). Further, we observed that, in the selected group of patients there were lower plasma low-density lipoprotein cholesterol concentrations [mean +/- SEM, 2.06 +/- 0.34 mmol/l] throughout follow up in those patients without carotid lesions and who also carried the mutated SDF1-3'A allele (P = 0.04). CONCLUSION: The SDF1-3'A allele is associated with a lower presence of subclinical carotid atherosclerosis in an HIV-infected population.

Adult↗
PubMed2005

The role of circulating monocyte chemoattractant protein-1 as a marker of hepatic inflammation in patients with chronic liver disease.

We investigated the relationships between plasma monocyte chemoattractant protein-1, serum C-reactive protein, and the degree of hepatic inflammation in patients with chronic liver disease. Monocyte chemoattractant protein-1 concentration was correlated with the histological hepatic inflammation (estimated by the Knodell index) and with standard liver function tests (P<0.01). C-reactive protein was not correlated with any of the variables studied. These results underline the role of monocyte chemoattractant protein-1 in the pathogenesis of liver impairment and suggest that this chemokine may be a reliable marker of inflammation in hepatic derangements.

Adult↗
PubMed2005

Comparison of rosiglitazone and metformin for treating HIV lipodystrophy: a randomized trial.

BACKGROUND: The use of antiretroviral combination therapy in HIV has been associated with lipodystrophy and cardiovascular risk factors. OBJECTIVE: To compare the effects of the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone and metformin for treating HIV lipodystrophy. DESIGN: An open, randomized, 6-month clinical trial. SETTING: University Medical Center, Utrecht, the Netherlands. PATIENTS: 39 HIV-infected men with lipodystrophy. INTERVENTION: Rosiglitazone, 8 g/d, or metformin, 2 g/d [DOSAGE ERROR CORRECTED] MEASUREMENTS: Insulin sensitivity estimated by the oral glucose tolerance test, subcutaneous and visceral abdominal fat measured by single-slice computed tomography, endothelial function measured by flow-mediated vasodilation, and fasting plasma measurements. Two patients in the metformin group withdrew from the study. Complete case analysis was performed. RESULTS: Compared with metformin, rosiglitazone increased subcutaneous abdominal fat (between-treatment change from baseline, 27 cm2 [95% CI, 7 cm2 to 46 cm2]) and visceral abdominal fat (between-treatment change from baseline, 24 cm2 [CI, 6 cm2 to 51 cm2]). The area under the curve for insulin after the oral glucose tolerance test decreased similarly with both agents, but only rosiglitazone increased adiponectin levels. Metformin showed greater benefits on fasting lipid profile than rosiglitazone. Flow-mediated vasodilation statistically significantly increased with metformin (mean change, 1.5% [CI, 0.4% to 3.3%]) and not with rosiglitazone (mean change, 0.7% [CI, -1.1% to 2.7%]). The metformin versus rosiglitazone increases did not statistically differ. Rosiglitazone and metformin did not change C-reactive protein levels. LIMITATIONS: This small trial was not blinded or placebo-controlled and did not measure clinical outcomes. CONCLUSIONS: The findings emphasize the importance of individualized care in HIV-infected patients. Although rosiglitazone may partly correct lipoatrophy, metformin improves visceral fat accumulation, fasting lipid profile, and endothelial function.

Adipose Tissue↗
PubMed2005

The efavirenz-induced increase in HDL-cholesterol is influenced by the multidrug resistance gene 1 C3435T polymorphism.

Efavirenz treatment has been associated with increases in HDL-cholesterol concentrations, and the circulating levels of the drug have been related to the multidrug resistance gene 1 (MDR-1) C3435T polymorphism. The changes in the measured lipid parameters were evaluated in 59 HIV-infected patients initiating efavirenz-based treatment at baseline and at 12 months of follow-up. Efavirenz treatment increased HDL-cholesterol. The changes in concentrations appeared to be influenced by the MDR-1 gene polymorphism, in which CC > CT > TT.

Adult↗
PubMed2005

Turpentine-induced inflammation reduces the hepatic expression of the multiple drug resistance gene, the plasma cholesterol concentration and the development of atherosclerosis in apolipoprotein E deficient mice.

We aimed to investigate the effect of turpentine-induced inflammation in an atherosclerosis-prone murine model. We have induced a chronic aseptic inflammation in apolipoprotein E-deficient mice, with or without a dietary supplement of aspirin (n = 10, each), by the injection of a mixture (1:1) of turpentine and olive oil in the hind limb twice weekly for a period of 12 weeks. Control animals were injected with olive oil alone (n = 10). The control mice did show any alteration neither in plasma nor at the site of injection. Turpentine-treated mice showed a significant increase in plasma TNF-alpha and SAA concentrations which indicated a systemic inflammatory response that was not substantially affected by aspirin. Also, turpentine injections significantly reduced the plasma cholesterol concentration, probably decreasing intestinal cholesterol re-absorption, and attenuated the size of atherosclerotic lesion. Both effects were minimally influenced by aspirin. The burden of atherosclerosis correlated with plasma lipid levels but not with plasma inflammatory markers. Finally, there was a concomitant decrease in the expression of the hepatic mdr1b gene that correlated with the decrease in plasma cholesterol concentration. Therefore, we conclude that mdr1 is an additional factor to consider in the complexity of alterations in cholesterol metabolism that occur in this model.

Animals↗