bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of acute exogenous hyperinsulinaemia on very low density lipoprotein subfraction composition in normal subjects
Authors: Annuzzi G. , Iovine C. , Mandarino B. , Patti L. , Di Marino L. , Riccardi G. , Rivellese A. A. 
Published: March 2003

Subtle abnormalities of very‐low‐density lipoprotein (VLDL) composition and distribution seem to be associated with increased cardiovascular risk. The aims of this study were first, to evaluate whether hyperinsulinaemia per se is able to produce VLDL abnormalities and second, whether this occurs through a stimulation of lipolytic enzymes.Eight normal male volunteers, age 36 ± 7 years (M ± SD), body mass index (BMI) 26±3 kg m−2, underwent a 5‐h euglycaemic hyperinsulinaemic clamp (1·2 mU insulin/kg b.w. min−1). Nine sex, age and BMI comparable subjects underwent control experiments (saline infusion). Three VLDL subfractions of decreasing size were isolated by density gradient ultracentrifugation; lipoprotein lipase (LPL) and hepatic lipase (HL) post‐heparin plasma activities were determined by the 3H‐labelled triolein method.Hyperinsulinaemia (∼65 mU mL−1) produced the expected plasma free fatty acid suppression. Triglyceride levels were reduced in total VLDL (− 27 ± 32% vs. + 38 ± 52% after saline, P < 0·05) and in the larger VLDL (− 56 ± 19 vs. + 34 ± 38, P < 0·001). Moreover the relative contribution of the larger subfraction was decreased (− 39 ± 15% vs. − 3 ± 21%, P < 0·01), while the percentage of smaller particles was increased (+17 ± 20 vs. − 9 ± 22, P < 0·05). LPL and HL activities were decreased to the same degree during either insulin or saline infusion.Exogenous hyperinsulinaemia produced lipoprotein abnormalities partially similar to those previously shown in type 1 diabetic patients, indicating that these abnormalities may be secondary to insulin therapy.
Macrophage migration inhibitory factor in the sera and at the colonic mucosa in patients with ulcerative colitis: clinical implications and pathogenic significance
Authors: Murakami H. , Akbar SK. MD. Fazle , Matsui H. , Onji M. 
Published: March 2003

Background Inflammatory cytokines produced by activated macrophages are implicated in the pathogenesis of ulcerative colitis (UC). With the theory that macrophage migration inhibitory factor (MIF) may have a role in the accumulation of macrophages, we studied MIF in UC.Materials and methods A total of 27 patients with UC, 14 patients with Crohn's diseases (CD), 11 patients with other forms of colitis and 26 normal controls were enrolled in the study. The levels of MIF in the sera and culture supernatant were measured by an enzyme‐linked immunosorbent assay. MIF, macrophages and T cells were localized at the colonic mucosa by immunohistochemistry.Results The levels of MIF in the sera were significantly higher in UC than in normal controls (P < 0·05), in serum C‐reactive protein (CRP) ‐positive cases with UC than in CRP‐negative cases with UC (P < 0·05), and in patients with severe colitis with UC than in mild colitis with UC (P < 0·05). There was a positive relationship between serum MIF levels with the CRP levels and activities of colitis. However, the levels of MIF in patients with CD and other forms of colitis were not significantly different from their levels in normal controls and UC. Infiltrating cells at the colonic mucosa in UC and CD expressed MIF.Conclusions These data suggest a role of MIF in the pathogenesis of UC. MIF may be used as a marker of disease activity in UC and control of MIF production may have therapeutic implications.
Noninvasive diagnosis of the degree of hepatic fibrosis using ultrasonography in patients with chronic liver disease due to hepatitis C virus
Authors: Hirata M. , Akbar S. M. F. , Horiike N. , Onji M. 
Published: March 2003

Background Chronic liver disease is characterized by progressive hepatic fibrosis and changes in hepatic haemodynamics. This study has addressed the possibility of a noninvasive diagnosis of the degree of hepatic fibrosis by evaluating the velocity of blood in the hepatic vasculature. Materials and methods The maximum velocity of blood at the portal vein and hepatic artery was measured in 80 patients with chronic liver diseases (19 with liver cirrhosis; 61 with chronic hepatitis) and in 20 normal volunteers by Doppler ultrasonography. The arterio‐portal ratio (A/P ratio) was calculated by dividing the maximum velocity of blood (Vmax) in the hepatic artery with the Vmax in the portal vein. Multivariate analysis was used to disclose the independent predictors of the degree of hepatic fibrosis. Results The levels of A/P ratio were significantly higher in patients with liver cirrhosis (LC) compared to those with chronic hepatitis (CH) and normal controls. Probit analysis revealed that the value of A/P ratio at which CH becomes LC was A/P ≥ 3·5. The levels of A/P ratio were also significantly higher in patients with severe fibrosis compared with mild (P < 0·0001) and moderate (P < 0·0001) fibrosis. Multivariate analysis disclosed right A/P ratio (P = 0·0001), left A/P ratio (P = 0·013), and platelet counts (P = 0·0172), as the only independent predictors of the degree of hepatic fibrosis. Conclusions A/P ratio may be used for the noninvasive diagnosis of the degree of hepatic fibrosis in patients with chronic liver diseases.
Two newly identified SNPs in the APO AI‐CIII intergenic region are strongly associated with familial combined hyperlipidaemia
Authors: Groenendijk M. , Cantor R. M. , Funke H. , Dallinga‐Thie G. M. 
Published: March 2003

Background We previously reported linkage and association of the apoAI‐CIII‐AIV gene region on chromosome 11 with familial combined hyperlipidaemia (FCHL). However, the observed epistasis resulting in an increased susceptibility to FCHL still remains unexplained. We hypothesize that the region between the apo AI and apo CIII genes may harbour functional mutations that might be in linkage disequilibrium with the already identified SstI and MspI polymorphisms, and provide an alternative explanation for the observed relationship.Methods Using sequence analysis, we identified four new single nucleotide polymorphisms (SNPs) in the apo AI‐CIII intergenic region. These four variants, T3213C, A3235C, T3287C and A5132C, were studied in 30 FCHL probands, 159 hyperlipidaemic relatives, 327 normolipidaemic relatives, and 218 spouses from the same families in which the original results were obtained.Results The allele frequencies were significantly different between probands and spouses (P < 0·05). Transmission/disequilibrium test (TDT) analyses revealed more frequent transmission of the minor alleles to the affected offspring. The minor genotype was associated with elevated plasma cholesterol and triglyceride levels. The T3213C and MspI, and the A3235C and SstI SNPs were in complete linkage disequilibrium, resulting in two different major haplotypes 2‐2‐1‐2‐2‐1 and 1‐1‐2‐2‐2‐2 (MspI‐T3213C‐A3235C‐T3287C‐A5132C‐SstI). Both haplotypes appear to predispose to FCHL independently, and account, together with the wild‐type, for almost 90% of those occurring in these FCHL families, extending the high‐risk combination of haplotypes that were reported previously.Conclusion These newly identified additional intergenic SNPs therefore provide an alternative explanation for the observed association of the SstI and MspI polymorphisms to the increased susceptibility for FCHL.
In vitro effect of advanced glycation end‐products on human polymorphonuclear superoxide production
Authors: Bernheim J. , Rashid G. , Gavrieli R. , Korzets Z. , Wolach B. 
Published: March 2003

Background Advanced glycation end‐products (AGEs) are elevated in the sera of diabetic patients. The latter are prone to severe bacterial infections. Advanced glycation end‐products have been shown to modulate immune competent cell activities. In this study we examined the in vitro effect of advanced glycation end‐products on superoxide anion generation by human polymorphonuclear leukocytes.Materials and methods Advanced glycation end‐products were prepared by incubation of bovine serum albumin (BSA) with glucose for 90 days. Superoxide production was measured as the superoxide dismutase‐inhibitable reduction of ferricytochrome c. The effect of advanced glycation end‐products on superoxide production was evaluated in both baseline (nonstimulated) and stimulated (by either formyl‐methionyl‐leucyl‐phenylalanine, or phorbol‐myristate‐acetate) polymorphonuclear leukocytes.Results The baseline superoxide production of polymorphonuclear leukocytes was significantly increased by advanced glycation end‐products in a dose–dependent manner. In contrast, in stimulated polymorphonuclear leukocytes advanced glycation end‐products significantly inhibited superoxide production, again in a dose–dependent manner. This inhibitory effect of advanced glycation end‐products was observed after dialyzing AGE‐BSA, thereby eliminating the possible influence of reactive carbohydrates. No modification of superoxide production was seen with BSA and only a mild inhibitory effect of glucose at high concentrations.Conclusions Advanced glycation end‐products depress superoxide production by stimulated polymorphonuclear leukocytes. As superoxide plays an essential role in bactericidal activity, this polymorphonuclear leukocyte dysfunction may be a contributory factor to the increased prevalence and severity of bacterial infection seen in diabetic patients.
Effects of long‐term octreotide treatment on the response of portal‐systemic collaterals to vasopressin in portal hypertensive rats
Authors: Wang S.‐S. , Chan C.‐C. , Lee F.‐Y. , Chang F.‐Y. , Lin H.‐C. , Chen C.‐T. , Huang H.‐C. , Tai C.‐C. , Lai I.‐N. , Lee S.‐D. 
Published: March 2003

AbstractBackground Chronic portal hypertension is associated with the development of portal‐systemic collaterals. Long‐term octreotide treatment has been shown to enhance the constrictive response to vasopressin in the mesenteric arteries of portal hypertensive rats. This study investigated the effects of long‐term octreotide treatment on the response of portal‐systemic collaterals to vasopressin in portal hypertensive rats.Methods Partially portal vein‐ligated rats were divided into two groups to receive subcutaneous injection of either placebo (5% dextrose in water) or octreotide (30 µg kg−1) twice daily for 7 days. Two series of experiments were performed to measure: (a) the systemic and portal hemodynamics and cumulative concentration‐response curves of collateral vessels to vasopressin (10−10 to 10−7 M) and (b) the slopes of the flow‐pressure curves of collaterals (an index of portal‐systemic shunting). The cumulative concentration‐response curves and flow pressure curves were determined by the in situ collateral perfusion.Results Long‐term octreotide treatment significantly lowered the portal pressure without changes in the mean arterial pressure. Vasopressin significantly and similarly increased the perfusion pressure of collateral vessels in both the placebo‐ and octreotide‐treated groups. In addition, long‐term octreotide treatment exerted no effect on the EC50 of vasopressin (−8·25 ± 0·19 vs. –8·20 ± 0·10, P > 0·05) and the slopes of flow‐pressure curves (0·97 ± 0·02 vs. 0·94 ± 0·04, P > 0·05) in the collaterals.Conclusion Despite lowering the portal pressure, long‐term octreotide treatment did not enhance the vasoconstrictive effect of vasopressin in the collateral vessels of portal hypertensive rats and ameliorate the degree of portal‐systemic shunting.
Allelic polymorphism −491A/T in apo E gene modulates the lipid‐lowering response in combined hyperlipidemia treatment
Authors: García‐Otín A.‐L. , Civeira F. , Aristegui R. , Díaz C. , Recalde D. , Sol J. M. , Masramon X. , Hernández G. , Pocoví M. ,   the ATOMIX Study Group
Published: March 2003

AbstractBackground Combined hyperlipidemia (CHL) is one of the dyslipidemias more frequently found in clinical practice, and lipid‐lowering drugs are often necessary in its management. Some genetic loci have been associated with CHL expression, and some studies have shown modulation of drugs efficiency in the treatment of dyslipidemias by genetic polymorphisms. We have investigated whether common polymorphisms and mutations in the apolipoprotein (apo) E, lipoprotein lipase (LPL), and apo CIII genes influence atorvastatin or bezafibrate responses in patients with CHL.Design One hundred and sixteen subjects participating in the ATOMIX study (Atorvastatin in Mixed dyslipidemia) were randomized to treatment with either atorvastatin or bezafibrate. Apolipoprotein E genotype and common −491A/T and −219T/G polymorphisms in the apo E gene promoter region, Sst I polymorphism in the apo CIII gene (3238C/G), and D9N and N291S common mutations in the LPL gene were determined by polymerase chain reaction (PCR) and restriction enzyme digestion.Results Statistical analysis showed the influence of the −491A/T polymorphism in atorvastatin and bezafibrate treatments. Subjects carrying the −491T allele showed an increased LDL‐cholesterol‐lowering effect with atorvastatin compared with −491T allele noncarriers (−35% vs. −27%, P = 0·037). Subjects carrying the −491T allele, when on bezafibrate treatment, showed a lower triglyceride reduction compared with −491T allele noncarriers (−23% vs. −39%, P = 0·05).Conclusions In our study, the −491A/T polymorphism in the apo E gene promoter region modulated the lipid‐lowering efficiency of atorvastatin and bezafibrate in CHL patients. Such influence might explain some of the interindividual response variabilities observed for the two drugs, and could help in CHL management.
Sodium bicarbonate treatment and ubiquitin gene expression in acidotic human subjects with chronic renal failure
Authors: Roberts R. G. , Redfern C. P. F. , Graham K. A. , Bartlett K. , Wilkinson R. , Goodship T. H. J. 
Published: March 2003

AbstractBackground In chronic renal failure, metabolic acidosis is associated with increased whole body protein degradation. In rats this effect of acidosis occurs in skeletal muscle and is associated with increased ubiquitin mRNA expression. This has not been demonstrated in humans.Materials and methods Six patients with chronic renal failure and acidosis underwent muscle biopsy before and after 1 month's treatment with sodium bicarbonate. RNA was extracted from the biopsy, and the expression of the genes for ubiquitin and the proteasome component, C2, were measured by Northern blotting.Results and conclusions There was no significant difference in the expression of ubiquitin or C2 after bicarbonate treatment. This is contrast with results from animal models of acidosis and some other catabolic conditions in humans. This may reflect the complexity of the ubiquitin‐dependent pathway, and it may be that changes in ubiquitin expression are only seen with more severe and/or acute changes in pH.
The relation between Helicobacter pylori and atherosclerosis cannot be explained by a high homocysteine concentration
Authors: Bloemenkamp D. G. M. , Mali W. P. Th. M. , Tanis B. C. , Rosendaal F. R. , Van Den Bosch M. A. A. J. , Kemmeren J. M. , Algra A. , Visseren F. L. J. , Van Der Graaf Y. 
Published: March 2003

AbstractBackground Recent studies have suggested that a chronic infection with Helicobacter pylori might be an independent risk factor for atherosclerosis. However, a direct role in atherogenesis is not plausible, since the bacterium has not been isolated from atherosclerotic lesions. An indirect mechanism that could link H. pylori with atherosclerosis might be through an increase in plasma homocysteine concentration caused by deficiencies of vitamin B12 and folate in plasma.Materials and methods  In 150 female patients with peripheral arterial disease (PAD) and in 412 healthy control women from a nation‐wide population‐based case–control study, blood samples were collected to determine the antibody titre against H. pylori and to measure plasma homocysteine, folate and vitamin B12 levels. First, the odds ratio for PAD in women with a positive antibody titre against H. pylori was calculated and adjusted for homocysteine level. Secondly, mean concentrations of vitamin B12, folate and homocysteine were compared in healthy controls with a positive or negative antibody titre against H. pylori. Thirdly, the relation between H. pylori and PAD in individuals with a normal or high homocysteine level was investigated.Results  A positive immunoglobulin G antibody titre against H. pylori was found in 42% of the PAD patients and in 27% of the controls. The age‐ and socio‐economic‐status (SES) adjusted odds ratio for PAD was 1·5 (95%CI; 1·0–2·2). Additional adjustment for homocysteine plasma concentration did not essentially change the odds ratio. Secondly, among the healthy controls, the homocysteine plasma concentration did not depend on the immunoglobulin G titre, neither did the folate plasma concentration. The concentration of vitamin B12 was slightly higher in women with a positive titre. Thirdly, H. pylori infection was a risk factor for PAD in subjects with a normal homocysteine concentration [OR 2·0 (95%CI 1·3–3·1)].Conclusions  This study shows a relationship between a positive immunoglobulin G antibody titre against H. pylori and PAD in young women. Moreover, this study does not support the hypothesis that H. pylori infection is related to atherosclerosis via an increase in plasma homocysteine concentration.
Cardiovascular involvement in thalassaemic patients with Pseudoxanthoma elasticum‐like skin lesions: a long‐term follow‐up study
Authors: Cianciulli P. , Sorrentino F. , Maffei L. , Amadori S. , Cappabianca M. P. , Foglietta E. , Carnevali E. , Pasquali‐Ronchetti I. 
Published: March 2003

AbstractBackground Congenital haemolytic anaemia may be associated with pseudoxanthoma elasticum (PXE)‐like clinical manifestations.Methods The cardiovascular system of 14 homozygous and double heterozygous β‐thalassaemia patients with skin and retinal vessel alterations similar to those in genetic PXE was analysed over a period of 12 years and compared with that of 13 relatives (five sets of parents, one single parent, two thalassaemic brothers), and that of the control group composed of 16, age‐ and sex‐matched, thalassaemic patients.Results All patients with clinical PXE‐like skin lesions exhibited, by light and electron microscopy, dermal alterations and mineralization of elastic fibres identical to those typical of inherited PXE. None of the relatives and none of the control group showed clinical or structural findings of PXE. The follow‐up started in 1988. After 12 years of clinical observation, six patients showed dramatic progression of skin involvement, angioid streaks had progressed in two subjects. One patient had recurrent gastrointestinal bleeding and underwent partial stomach removal for gastric artery aneurysm, one underwent colon resection for intestinal infarct, one patient had a transitory ischaemic attack, one died after an intracranial haemorrhage, two patients died from cardiovascular disease and one from neoplasia.Conclusions Thalassaemic patients with PXE‐like skin lesions also manifest PXE‐like vessel alterations that progress with time. Considering the severe outcome of these lesions, accurate monitoring should be routinely performed on the cardiovascular system of thalassaemic patients with PXE‐like skin manifestations.
Effect of endothelin‐1 on intracellular glutathione and lipid peroxide availability and on the secretion of vasoactive substances by human umbilical vein endothelial cells
Authors: Scalera F. , Dittrich R. , Beckmann M. W. , Beinder E. 
Published: March 2003

AbstractBackground The major pathophysiologic changes observed in preeclampsia suggest that endothelial cell dysfunction plays an important role in this disorder. The pathway mediating endothelial cell layer dysfunction is unknown. The concentration of endothelin‐1 (ET‐1), a potent mammalian vasoconstrictor peptide produced by the vascular endothelium, has been observed to be significantly increased in preeclampsia. In this study, we determined the in vitro effect of endothelin‐1 on glutathione and lipid peroxide levels and on the secretion of vasoactive substances by human umbilical vein endothelial cells (HUVECs).Methods Human umbilical vein endothelial cells were incubated for 24 h in the presence of different concentrations of ET‐1 (0–1000 pmol L−1), which were shown in an earlier experiment to have no effects on vitality and proliferation rate of HUVECs. The levels of glutathione (GSH) and lipid peroxides (LPO) were measured in endothelial cell lysates. For the measurement of vasoactive substances, levels of nitric oxide (NO), prostacyclin (PGI2) and thromboxane A2 (TXA2) were measured in endothelial cell supernatants.Results At lower concentrations (5–50 pmol L−1), ET‐1 increases the intracellular content of LPO, stimulates the secretion of TXA2, but inhibits the secretion of PGI2 in endothelial cells compared with control cells. At higher concentrations (100–1000 pmol L−1), ET‐1 increases the intracellular content of GSH, but results in a decrease of LPO, and increase of PGI2, back to control levels. ET‐1 has no effect on NO secretion.Conclusion These findings demonstrate that at concentrations corresponding to values in plasma from preeclamptic women, ET‐1 induces oxidative stress and results in altered secretion of vasoactive substances in human endothelial cells. We conclude that ET‐1 may participate in the pathway leading to endothelial cell dysfunction seen in preeclampsia.
Calcium affects biomarkers of colon carcinogenesis after right hemicolectomy
Authors: Van Gorkom B. A. P. , Van Der Meer R. , Karrenbeld A. , Van Der Sluis T. , Zwart N. , Termont D. S. M. L. , Boersma‐van Ek W. , De Vries E. G. E. , Kleibeuker J. H. 
Published: March 2003

AbstractBackground In Western societies colonic cancer most frequently develops in the distal colon, largely as a result of the composition of the diet. Modulation of dietary factors is therefore an attractive modality to reduce colorectal cancer risk. This study aims to evaluate the potentially protective effects of calcium in right hemicolectomy patients.Materials and methods A randomized controlled cross‐over intervention trial was performed with 1000 mg of elemental calcium per day for 2 months in 15 right hemicolectomy patients. Primary endpoints were proliferative activity, determined by immunohistochemical detection of BrdU‐labeled cells (LI) in rectal biopsies, and cytotoxicity and alkaline phosphatase activity of faecal water. Secondary endpoints were bile acid composition in faeces.Results Calcium‐reduced LI in the superficial one‐third of the crypt (from 0·84 ± 0·27% to 0·37 ± 0·08%, P = 0·04) and a trend towards a lower total LI and LI in the mid one‐third of the crypt was observed. Alkaline phosphatase activity was reduced from 6·2 ± 2·6 U mL−1 in the placebo period to 4·6 ± 2·2 in the calcium period (P = 0·02), and a trend toward a lower cytotoxicity of faecal water was observed. No effect on total bile acids in faeces was observed, but calcium increased the percentage of deoxycholic acid (from 49·6 ± 7·0% to 56·5 ± 6·2%, P = 0·03) and decreased the percentages of cholic acid (from 10·3 ± 4·7% to 5·8 ± 2·7%, P = 0·05) and lithocholic acid (from 26·7 ± 3·4% to 23·9 ± 2·9%, P = 0·04).Conclusion Calcium may have a protective effect against colorectal cancer risk in right hemicolectomy patients.