bluuebunny/crossref_metadata_2025_split huggingface dataset:
NADH/NADPH oxidase p22phox C242T polymorphism and coronary artery disease in the Australian population
Authors: Cai  , Duarte  , Wilcken  , Wang  
Published: March 2003

BackgroundOxidative stress induced by the superoxide anion (.O2−) has been implicated in atherogenesis. The NADH/NADPH oxidase system is involved in .O2− production and p22 phox is an essential component of that system.Material and methodsWe analysed the p22 phox C242T polymorphism in 689 consecutive Australian Caucasians aged ≤ 65 years with and without angiographically documented coronary artery disease (CAD)ResultsWe report the rare T allele frequency of 0.33, which is 3 fold higher than that reported in the Japanese population by Inoue et al. [
7]. The genotype distributions were not different among patients with CAD (CC:0.422, CT:0.459 and TT: 0.119 in men; 0.447, 0.439 and 0.114 in women) and without CAD (0.479, 0.420 and 0.101%, χ2 = 0.794, P = 0.672 in men; 0.443, 0.471 and 0.86, χ2 = 0.442, P = 0.802 in women). The frequencies of the rare TT homozygotes or of the ‘T’ allele frequency were also not associated with the number of significantly stenosed vessels (χ2 = 4.466, P = 0.614 in men; χ2 = 4.736, P = 0.578 in women) or with a myocardial infarction (MI) history (χ2 = 2.310, P = 0.315 in men; χ2 = 1.178, P = 0.555 in women). However, when the analysis was conducted in young male patients aged ≤ 45 years (n = 44), TT + TC patients tended to have an increased risk for CAD (odds ratio: 5.71 95% CI: 1.22–26.75, P = 0.0271).ConclusionThe p22 phox C242T polymorphism is not associated with the occurrence or severity of CAD or with a history of MI in Australian Caucasian patients aged ≤ 65 years. However, the polymorphism could be associated with an increased CAD risk in young patients, which requires confirmation in large populations.
Angiogenesis extent and expression of matrix metalloproteinase‐2 and ‐9 correlate with upgrading and myometrial invasion in endometrial carcinoma
Authors: Iurlaro  , Loverro  , Vacca  , Cormio  , Ribatti  , Minischetti  , Ria  , Bruno  , Selvaggi  
Published: March 2003

BackgroundChanges in angiogenesis and expression of extracellular matrix‐degrading enzymes have been substantiated during tumour changeover and progression.MethodsTissues from 64 biopsies of endometrial carcinoma (EC) and 15 biopsies of normal (control) endometrium were investigated immunohistochemically to determine their microvessel number, and by in situ hybridisation to determine the expression of mRNA of the matrix metalloproteinase‐2 (MMP‐2, gelatinase A) and metalloproteinase‐9 (MMP‐9 gelatinase B). EC were grouped according to both histological grade (G) G1 to G3 and depth of myometrial (M) invasion M1 to M3.ResultsEC as a whole gave significantly higher counts over control endometria. Counts of the G1 group overlapped those of the control group, increased significantly in the G2 and even more in the G3 group. G3 biopsies in particular also displayed most microvessels widely scattered in the tumour tissue, in close association with tumour cells, and as winding and arborized tubes, often dilated in microaneurysmatic segments. Counts also increased in M2 and M3. Expression of the MMP‐2 and MMP‐9 mRNA, evaluated as percentages of positive biopsies and intensity of expression, were upregulated with the transition from control and G1 groups to G2 and G3, and in relation to advancing depth of invasion. In EC, MMP‐2 and MMP‐9 mRNA were also expressed by host stromal cells, including microvascular endothelial cells, fibroblasts and macrophages. In the control biopsies, poor expression of MMP‐2 mRNA in few endothelial cells and no expression of MMP‐9 mRNA were detected.ConclusionThese in situ data suggest that angiogenesis and degradation of extracellular matrix occur simultaneously with EC upgrading and advancing depth of invasion, and that EC cells and some host stromal cell populations cooperate in tumour progression.
Complement activation by oxidatively modified low‐density lipoproteins
Authors: Wieland  , Dorweiler  , Bonitz  , Lieser  , Walev  , Bhakdi  
Published: March 2003

BackgroundOxidatively modified low‐density lipoproteins (LDLs) have been implicated in the pathogenesis of atherosclerosis and are found in human vascular lesions. There is increasing evidence that complement activation may also play a role in atherogenesis. Activated complement proteins have been demonstrated to be present in early atherosclerotic lesions, and lipids isolated from lesions have been shown to activate complement, hence their designation as lesion complement activator (LCA). The question now arose whether oxidized LDLs would also activate complement.Material and methodsThe complement‐activating capacity of a lesion complement activator preparation and of minimally as well as heavily oxidized LDL was investigated by measuring SC5b‐9 formation in normal human serum. In addition, C3 conversion was followed using two‐dimensional immunoelectrophoresis.ResultsMinimally and heavily oxidized LDL generated small but significant amounts of SC5b‐9 (7.9 μg mL−1, SD 3.5, and 10.8 μg mL−1, SD 1.2, respectively; n = 6) compared with native LDL (3.3 μg mL−1, SD 1.4; P < 0.05), whereas LCA generated substantially larger amounts of the terminal complex (32.0 μg mL−1, SD 3.2). Both oxidized LDL preparations caused only minor C3 conversion.ConclusionsThese findings show that oxidation does not confer relevant complement‐activating properties on LDL, suggesting that the lesion complement activator is not directly related to oxidized LDL. Oxidized LDL is probably of minor importance for complement activation in atherosclerotic lesions.
Comparative inhibitory potential of differently modified antisense oligodeoxynucleotides on hepatitis C virus translation
Authors: Alt  , Eisenhardt  , Serwe  , Renz  , Engels  , Caselmann  
Published: March 2003

BackgroundA completely modified phosphorothioate antisense oligodeoxynucleotide (cS‐ODN 4) directed against nucleotides 326–348 of the hepatitis C virus (HCV) 5′ non‐coding region (NCR) efficiently inhibits viral gene expression. As cS‐ODN exerts undesired side‐effects in vivo, we synthesized partially modified ODN 4 that contained only six modified nucleotides which are located at the ODN termini or are scattered along the molecule. The tested modifications were polar phosphorothioates (S) and non‐polar methyl‐ (M) or benzylphosphonates (B).ResultsIn an in vitro translation system, specific inhibition of HCV gene expression by M‐ODN 4 or B‐ODN 4 was observed if terminally modified ODN were used; the maximal inhibition was 92.3% ± 1.9% and 87.1% ± 3.7%, respectively, at 10 μmol L−1 concentration. S‐ODN 4 specifically suppressed viral translation irrespective of the location of the modifications, resulting in a maximal inhibition of 86.3% ± 3.3%. For all terminally modified ODNs the therapeutic index was high, with tB‐ODN 4 the second best at 3.8. Inhibition correlated with efficient RNase H‐associated cleavage of target RNA. In transient co‐transfection experiments of HepG2 cells with a reporter gene construct and the ODN, terminally modified B‐ODN 4 was the most effective and specific inhibitor. At a concentration of 5 μmol L−1 the suppression of HCV translation was 96.3% ± 0.7%.ConclusionThese data demonstrate that terminally modified B‐ODN 4 is a potent inhibitor of HCV gene expression in vitro and in HepG2 cell culture and may be valuable for future antiviral treatment.
Short‐term hormone replacement therapy: reduced plasma levels of soluble adhesion molecules
Authors: Van Baal  , Emeis  , Kenemans  , Kessel  , Peters‐Muller  , Schalkwijk  , Van Der Mooren  , Stehouwer  
Published: March 2003

BackgroundEpidemiological data have suggested that the use of hormone replacement therapy (HRT) is associated with a decreased risk of cardiovascular disease. Vascular endothelium and adhesion molecules play an important role in the initiation and progression of atherosclerosis.Material and methodsProspective, randomized, placebo‐controlled 12‐week study. Sixty healthy, normotensive postmenopausal women received either micronised oestradiol 2 mg alone (n = 16, E2 group), or sequentially combined with a progestagen; E2 + P groups trimegestone 0.5 mg (E2 + T, n = 14) or dydrogesterone 10 mg (E2 + D group, n = 14) or placebo (n = 16). Data were collected at baseline and at 4 and 12 weeks.ResultsTwelve weeks of treatment with E2 or E2 + P was associated with a significant decrease in the plasma concentrations of soluble intercellular adhesion molecule‐1 (sICAM‐1), vascular cell adhesion molecule‐1 (sVCAM‐1), and thrombomodulin (sTM). The average decrease in these markers was about 9%. In women treated with trimegestone the decreases were larger than in those treated with dydrogesterone; for sICAM‐1 (−15% vs. −2%; P < 0.0001), sVCAM‐1 (−15% vs. +3%; P = 0.003) and sTM (−9% vs. −4%; P = 0.11). Plasma levels of endothelin‐1 (ET‐1) decreased (by 13%) only in women treated with E2 + P. In the E2 group, flow‐mediated, endothelium‐dependent vasodilatation increased by 6 percentage points after 12 weeks (P = 0.07 vs. baseline, P = 0.02 vs. E2 + P, and P = 0.17 vs. placebo).ConclusionShort‐term treatment with E2 or E2 + trimegestone reduces plasma levels of sICAM‐1, sVCAM‐1 and sTM. ET‐1 decreased only in the E2 + P groups. Different types of progestagens may differentially affect sICAM‐1, sVCAM‐1 and sTM levels, which may be relevant for the choice of type HRT.
Capillary permeability is increased in normo‐ and microalbuminuric Type 1 diabetic patients: amelioration by ACE‐inhibition
Authors: Oomen  , Jager  , Hoogenberg  , Dullaart  , Reitsma  , Smit  
Published: March 2003

BackgroundCapillary leakage of sodium‐fluorescein (NaF) in the skin reflects capillary permeability and may be a marker of diabetes‐associated microcirculatory abnormalities.DesignWe evaluated transcapillary skin NaF leakage by fluorescence videodensitometry in 10 normoalbuminuric, 10 microalbuminuric Type 1 diabetic men (diabetes duration > 10 years) and 10 healthy subjects. The microalbuminuric patients were restudied after 6 weeks treatment with the ACE‐inhibitor enalapril, 10 mg once daily. All measurements were performed at a blood glucose level of 5 mmol L−1.ResultsTranscapillary NaF leakage was strongly increased in normoalbuminuric Type 1 diabetic patients compared to healthy subjects (P < 0.001) and was still further increased in microalbuminuric Type 1 diabetic patients (P < 0.01 compared to normoalbuminuric patients). Enalapril reduced NaF leakage (P < 0.05), mean arterial blood pressure (P < 0.05) and microalbuminuria (P < 0.05). After treatment, NaF leakage was not different from that in normoalbuminuric patients.ConclusionsCapillary permeability, as determined by NaF leakage, is elevated in normoalbuminuric Type 1 diabetic patients with long‐standing disease, and the excess elevation in microalbuminuric Type 1 diabetic patients is ameliorated by ACE‐inhibition. Skin NaF videodensitometry seems a useful tool to document capillary permeability in intervention studies.
Pretreatment renal vascular tone predicts the effect of specific renin inhibition on natriuresis in essential hypertension
Authors: Van Paassen  , Navis  , De Jong  , De Zeeuw  
Published: March 2003

BackgroundIn essential hypertension an elevated renal vascular resistance (RVR) may be a marker of renin‐angiotensin‐aldosterone system‐mediated impairment of renal sodium excretion. This hypothesis was tested by investigating whether, in subjects with essential hypertension, the natriuretic response to specific renin‐angiotensin‐aldosterone system (RAAS) blockade by renin‐inhibitor remikiren could be predicted from pretreatment renal vascular tone.Materials and methodsRenal hemodynamics, and the effects of single (n = 17) and multiple doses (n = 8, 8 days) of remikiren (600 mg day−1) on sodium excretion were studied under conditions of carefully controlled sodium balance.ResultsPretreatment renal vascular tone showed considerable individual differences: filtration fraction (FF) ranged from 21.2 to 30.3% and RVR from 18.8 to 33.5 10−2 mmHg min mL−1 in the single dose study, and FF from 20.8 to 24.9% and RVR from 14.8 to 28.8 10−2 mmHg min mL−1 in the multiple dose study. Remikiren induced a fall in blood pressure, FF and RVR, with considerable interindividual variability in natriuretic response. During single dose, cumulative sodium loss was 5.1 mmol per 5 h (−8.8 to +24.6), whereas after 8 days treatment cumulative sodium loss was 72 ± 30 mmol (−46 to +187). The natriuretic response to remikiren during single as well as multiple dose significantly correlated with pretreatment renal vascular tone (estimated from FF and RVR) but not with remikiren‐induced changes in renal hemodynamics or in hormonal parameters. Cumulative sodium loss was largest in patients with a higher pretreatment FF and RVR (r = 0.74, P < 0.001 and r = 0.52, P < 0.05, respectively, single dose; and r = 0.75, P < 0.05 and r = 0.73, P < 0.05, respectively, multiple dose).ConclusionThese data support the hypothesis that in essential hypertension an elevated renal vascular tone is a marker of RAAS‐mediated impairment of sodium excretion.
Suppression of the nocturnal rise in growth hormone reduces subsequent lipolysis in subcutaneous adipose tissue
Authors: Samra  , Clark  , Humphreys  , Macdonald  , Bannister  , Matthews  , Frayn  
Published: March 2003

BackgroundThe aim of this study was to examine the effect of the nocturnal rise in growth hormone (GH) concentration on lipolysis in adipose tissue the following morning.MethodsEight healthy subjects were studied on two occasions (control vs. suppression of GH secretion) and six were studied on a third occasion (control vs. replacement of GH). Lipolysis in the whole body was assessed by measurement of systemic glycerol turnover. Lipid metabolism in the subcutaneous adipose tissue of the anterior abdominal wall was studied by measurement of arterio‐venous differences.ResultsSuppression of the nocturnal rise in GH did not affect systemic glycerol turnover. However, in subcutaneous abdominal adipose tissue it led to a significant reduction in the veno‐arterial differences in nonesterified fatty acid (NEFA, P = 0.041) and glycerol (P = 0.014) concentrations, reflecting a reduction in intracellular lipolysis (P = 0.011). Although arterialized plasma triacylglycerol (TG) concentrations were reduced in the absence of the nocturnal GH pulse, the extraction of TG in subcutaneous abdominal adipose tissue remained unchanged.ConclusionWe conclude that the normal nocturnal rise in plasma GH concentration leads to site‐specific regulation of lipolysis in adipose tissue on the following day, with preferential fat mobilization from central depots.
Cholesteryl ester transfer protein gene polymorphisms are associated with carotid atherosclerosis in men
Authors: Kakko  , Tamminen  , Päivänsalo  , Kauma  , Rantala  , Lilja  , Reunanen  , Kesäniemi  , Savolainen  
Published: March 2003

BackgroundThe cholesteryl ester transfer protein (CETP) is involved in the reverse cholesterol transport and is therefore a candidate gene for atherosclerosis.DesignThe prevalences of the I405V and the R451Q polymorphisms were studied in a population sample of 515 men and women. Genotypes were determined by PCR and carotid atherosclerosis by ultrasonography as the mean intima‐media thickness (IMT) of the carotid arteries.ResultsThe Q451 allele was associated with significantly lower intima media thickness in men (P = 0.001). The Q451 allele was, in our earlier study, associated with high plasma CETP activity in men. The VV405 genotype was associated with lower plasma CETP activity compared with the II405 genotype (P < 0.01 for the difference). In the general linear model general factorial procedure the interaction between alcohol consumption and the I405V genotype on IMT was significant (P = 0.013) in men, and when the interaction term was taken into the model the I405V genotype also significantly affected IMT (P = 0.008). The VV405 genotype seems to be most harmful for men with the highest alcohol consumption.ConclusionsWe describe two polymorphisms of the CETP gene associated with intima media thickness in men. A significant interaction was found between alcohol consumption and the I405V genotype on IMT.
Association of serum sialic acid and MMP‐9 with lipids and inflammatory markers
Authors: Kalela  , Pönniö  , Koivu  , Höyhtyä  , Huhtala  , Sillanaukee  , Nikkari  
Published: March 2003

BackgroundInflammation of the arterial wall has emerged to be an important contributor to the process of atherosclerosis, the major cause of coronary heart disease. Several factors are currently under investigation as inflammatory markers of atherosclerosis. Serum sialic acid and matrix metalloproteinase‐9 may provide such markers. We studied their association with the lipid profile and with the inflammatory markers C‐reactive protein and leukocyte count in a clinically healthy population of men.Materials and methodsCardiovascular risk‐related laboratory tests were carried out in 65 consecutive male employees in connection with an occupational health survey in 1996. The subjects were divided into tertiles on the basis of serum sialic acid or matrix metalloproteinase‐9 concentration.ResultsIn a stepwise polychotomous logistic regression model adjusting for coronary heart disease risk factors, serum sialic acid concentration was not associated with markers of inflammation but rather with the lipid risk factors of atherosclerosis: inversely with HDL cholesterol (OR = 0.081, 95% CI 0.0068–0.97) and positively with total cholesterol (OR = 2.4, 95% CI 1–5.6). Matrix metalloproteinase‐9 levels had a significant positive correlation with the leukocyte count (OR = 2.3, 95% CI 1.4–4).ConclusionsSerum sialic acid does not appear to be an indicator of inflammation but is somehow connected with the level of total and HDL cholesterol. Serum matrix metalloproteinase‐9 may provide a useful marker of inflammation because it correlates with the leukocyte count and is not associated with the lipid profile.
Alcohol consumption and insulin resistance in young adults
Authors: Flanagan  , Moore  , Godsland  , Cockington  , Robinson  , Phillips  
Published: March 2003

BackgroundAlcohol may have a cardioprotective effect. One possible mechanism is by reducing insulin resistance, a known cardiovascular risk factor. The aim of this study was to assess the relationship between alcohol consumption, insulin resistance and other parameters determining glucose tolerance in 154 young men and women.Subjects and methodsSubjects completed a questionnaire documenting weekly alcohol consumption. Insulin sensitivity and glucose tolerance were measured using the intravenous glucose tolerance test with minimal model analysis. Height, weight, usual level of exercise, smoking habits and socio‐economic status were also recorded.ResultsInsulin sensitivity correlated inversely with body mass index (r = − 0.529, P < 0.001) but not with level of physical fitness. Women were significantly less insulin sensitive than men (4.19 and 5.63 104 min−1 pmol−1 L−1, respectively; P < 0.001). Insulin sensitivity correlated positively with alcohol consumption and this trend remained significant allowing for body mass index and gender (β = 0.17, P < 0.014). First‐phase insulin secretion showed a weak but non‐significant trend in the opposite direction. Fasting glucose, fasting insulin and glucose tolerance showed no relationships with alcohol consumption.ConclusionThese data suggest a close relationship between alcohol consumption and insulin resistance in young adults. Regular alcohol consumption is associated with decreased insulin resistance and this may partly explain the cardioprotective effect of alcohol.
Subcutaneous adipose tissue expression of tumour necrosis factor‐α is not associated with whole body insulin resistance in obese nondiabetic or in type‐2 diabetic subjects
Authors: Koistinen  , Bastard  , Dusserre  , Ebeling  , Zegari  , Andreelli  , Jardel  , Donner  , Meyer  , Moulin  , Hainque  , Riou  , Laville  , Koivisto  , Vidal  
Published: March 2003

BackgroundAn association with subcutaneous adipose tissue TNFα expression and insulin resistance has been suggested in obesity/type‐2 diabetes, but this has not been examined directly. In the first part of the study we investigated whether this association is present in 7 lean, 10 obese nondiabetic and 9 type‐2 diabetic men. In the second part of the study we examined the relationship between adipose tissue TNFα mRNA levels and BMI in 81 nondiabetic subjects spanning a wide range of BMIs.MethodsSubcutaneous adipose tissue TNFα mRNA levels and insulin sensitivity were determined with quantitative RT‐competitive PCR and hyperinsulinaemic clamp, respectively.Results.Subcutaneous adipose tissue TNFα mRNA levels were similar in 7 lean and 10 obese nondiabetic and 9 type‐2 diabetic men (P = 0.68), and did not change in response to 240‐min hyperinsulinaemia. TNFα mRNA levels and insulin sensitivity were not correlated. Unexpectedly, no correlation between TNFα mRNA and BMI was found. The relationship between adipose tissue TNFα mRNA and BMI was examined further in 31 male and 50 female nondiabetic subjects. The subcutaneous adipose tissue TNFα mRNA level correlated with BMI in all subjects (rS = 0.32, P < 0.01), and in a subgroup analysis in men (rS = 0.55, P < 0.01) but not in women (rS = − 0.08). The correlation in men was dependent on a fourfold higher TNFα mRNA level in 5 morbidly obese men while there was no difference in TNFα mRNA levels in lean or obese men.ConclusionsSubcutaneous adipose tissue TNFα expression does not correlate with insulin sensitivity in nondiabetic or type‐2 diabetic men; is not regulated by acute hyperinsulinaemia; and is increased only in morbidly obese men.
Effects of glucose ingestion on cardiac autonomic nervous system in healthy centenarians: differences with aged subjects
Authors: Paolisso  , Manzella  , Rizzo  , Barbieri  , Gambardella  , Varricchio  
Published: March 2003

BackgroundSpectral analysis of heart rate variability (HRV) investigates the cardiac autonomic nervous system (ANS) activity. In particular, low frequency/high frequency (LF/HF) is considered an index of cardiac sympatho‐vagal balance and is stimulated by glucose ingestion in healthy subjects. No studies have evaluated the effect of glucose ingestion on cardiac ANS in centenarians.Materials and methodsIn 30 healthy centenarians (HC) and 25 aged subjects (AS) power spectral analysis of HRV was investigated during an oral glucose ingestion.ResultsGlucose ingestion rose LF/HF ratio in both groups studied. Such stimulatory effects were restrained to the first 60 min of the study. Independent of age, gender, body mass index (BMI) and fasting plasma norepinephrine and FT3 concentrations, HC had basal total power (1318 ± 546 vs. 1918 ± 818 msec2, P < 0.01), lower low frequency (LF) (33 ± 21 vs. 50 ± 11 n.u. , P < 0.03), and higher high frequency (HF) (74 ± 18 vs. 43 ± 15 n.u., P < 0.05) than AS. Consequently, LF/HF ratio (0.43 ± 0.07 vs. 0.91 ± 0.05, P < 0.02) was also lower in HC than in AS. In AS, but not in HC, the baseline LF/HF ratio correlated significantly with BMI (r = 0.48, P < 0.01), waist‐hip‐ratio (WHR) (r = 0.45, P < 0.02), fasting plasma insulin (r = 0.49, P < 0.01) and norepinephrine (r = 0.57, P < 0.02) concentration. Glucose ingestion was associated with a significant rise in LF/HF ratio in both groups studied but per cent changes in glucose mediated stimulation of LF/HF was lower in HC than in AS. In a control study, water administration did not affect power spectral parameters of HRV.ConclusionOur study demonstrates that basal‐ and glucose‐stimulated LF/HF, an indirect index of cardiac sympatho‐vagal balance, are lower in HC than in AS.