bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexibility in the composition and concentration of amino acids in honeydew of the drepanosiphid aphidTuberculatus quercicola
Authors: Yao Izumi , Akimoto Shin‐Ichi
Published: March 2003

Abstract1. Mutualistic interactions between aphids and ants are mediated by honeydew that aphids produce. Previous work showed that when attended by the antFormica yessensisForel (Hymenoptera: Formicidae), nymphs of the aphidTuberculatus quercicola(Matsumura) (Homoptera: Aphididae) developed into significantly smaller adults with lower fecundity than did nymphs that were not ant attended.

2. This study tested the hypothesis that this cost of ant attendance arises through changes in the quality and quantity of honeydew. Ant‐attended and ant‐excluded aphid colonies were prepared in the field. The composition and concentration of amino acids were compared between the honeydew produced by ant‐attended colonies and that produced by ant‐excluded colonies.

3. The aphids excreted smaller droplets of honeydew, but also excreted them more frequently, in ant‐attended colonies than in ant‐excluded colonies. The honeydew of ant‐attended aphids contained more types of amino acid, and a significantly higher total concentration of amino acids, than did the honeydew of ant‐excluded aphids.

4. These results suggest that the increase in the concentration of amino acids in honeydew leads to a shortage of nitrogen available for aphid growth and reproduction, resulting in lower performance under ant attendance.

5. With the advance of seasons, a significant reduction was found in both the total free amino acid concentration in phloem sap and the frequency of honeydew excretion; however the total concentration of amino acids in the honeydew did not vary significantly during the seasons, suggesting that aphids keep the quality of honeydew constant in order to maintain ant visitation.
Gemfibrozil‐induced decrease in serum ubiquinone and α‐ and γ‐tocopherol levels in men with combined hyperlipidaemia
Authors: Åberg  , Appelkvist  , Bröijersén  , Eriksson  , Angelin  , Hjemdahl  , Dallner
Published: March 2003

Background

Low blood levels of antioxidants are associated with an increased risk of developing coronary artery disease. Lipophilic antioxidants are transported in lipoproteins, and hypolipidaemic therapy may therefore alter their blood concentrations.

Methods

The present randomized, placebo‐controlled cross‐over study of 21 men with combined hyperlipidaemia examines whether 10–12 weeks of gemfibrozil treatment affects the serum concentrations of the antioxidants ubiquinone‐10 or α‐ or γ‐tocopherol.

Results

Gemfibrozil treatment lowered plasma triglycerides and both total and very low‐density lipoprotein (VLDL)‐cholesterol (P < 0.001 for all by
ANOVA), whereas high‐density lipoprotein (HDL)‐cholesterol increased (P < 0.001). The median serum levels of ubiquinone‐10 decreased from 1.30 μmol L−1 (interquartile range 0.87–1.71 μmol L−1) with placebo to 0.76 μmol L−1 (0.66–0.95) with gemfibrozil treatment (P < 0.001). Corresponding levels for α‐ and γ‐tocopherol were: 68.5 μmol L−1 (51.1–84.7) vs. 40.8 μmol L−1 (30.3–55.0) and 8.6 μmol L−1 (5.2–16.7) vs. 4.3 μmol L−1 (3.5–7.0) respectively (P < 0.001 for both). The decrease in serum antioxidants was also evident when standardized for total cholesterol (P < 0.05) or LDL‐cholesterol (P < 0.001). Normolipaemic control subjects had significantly lower antioxidant levels than placebo‐treated patients: ubiquinone 0.63 μmol L−1 (0.41–1.05), α‐tocopherol 34.3 μmol L−1 (27.3–45.6) and γ‐tocopherol 3.2 μmol L−1 (2.5–4.2) (P < 0.001 for all). The association of antioxidants with lipoprotein lipids was further established by positive correlations between the levels of antioxidants and those of total cholesterol (r = 0.64, P < 0.001) or total triglycerides (r = 0.71, P < 0.001).

Conclusion

Gemfibrozil treatment of men with combined hyperlipidaemia reduces serum antioxidant levels to the levels seen in healthy normolipidaemic men. The mechanisms and the relevance of this finding remain unclear and need to be addressed in further studies.
Lack of influence of apolipoprotein E4 on lipoprotein levels in the island population of Sardinia
Authors: Deiana  , Pes  , Carru  , Errigo  , Pettinato  , Carcassi  , Baggio  , Contu
Published: March 2003

Background

In this study, the apolipoprotein E (apoE) genotypes as well as plasma lipid and lipoprotein levels have been determined for the first time in 633 healthy and unrelated inhabitants on the island of Sardinia (291 men and 342 women, age range 6–89 years), randomly selected in the four districts of Sardinia among healthy people having parents and grandparents born in the same geographic area. This island lies in the centre of the western Mediterranean sea with a well‐recognized peculiar and preserved genetic background. The ε3 allele frequency (0.897) is higher than that previously reported in southern and mainland Italy and is one of the highest in Europe and among Caucasians; ε2 allele frequency (0.040) is the lowest in Europe; ε4 (0.063) is unusually low and, most interestingly, does not change in the different age groups, i.e. does not decrease in old subjects.

Results

Lipid and lipoprotein analysis confirm that total cholesterol and low‐density lipoprotein (LDL)‐cholesterol levels are lower than those described in mainland Italy; moreover, in this large Sardinian series, accurately selected, ε4 allele did not influence total cholesterol (P = 0.270), LDL‐cholesterol (P = 0.667) and high‐density lipoprotein (HDL)‐cholesterol (P = 0.549) as in other populations. In contrast, subjects carrying the ε2 allele were found to have significantly lower total cholesterol (P = 0.001) and LDL‐cholesterol (P = 0.001) levels than ε3 carriers.

Conclusion

The low ε4 frequency and the lack of influence of this allele on lipid metabolism is a unique characteristic and, to date, has been described only in Sardinia among Caucasians; it might contribute to the low prevalence of coronary artery disease in this island.
A methylenetetrahydrofolate reductase gene polymorphism in ischaemic stroke and in carotid artery stenosis
Authors: Kostulas  , Crisby  , Huang  , Lannfelt  , Hagenfeldt  , Eggertsen  , Kostulas  , Hillert
Published: March 2003

Methods

A biallelic polymorphism of the methylenetretrahydrofolate reductase (MTHFR) gene, reported to influence the plasma level of homocysteine (Hcy), was investigated for a possible role in influencing the risk of ischaemic cerebrovascular disease (ICVD) and occlusive atherosclerosis in 126 patients with ischaemic stroke and 70 patients with internal carotid artery (ICA) stenosis.

Results

Only minor differences were observed between different groups of patients and control subjects. Although 47% of ICA stenosis patients had increased plasma Hcy, the MTHFR genotype did not correlate with levels of either Hcy, folic acid or vitamin B12. In addition, the MTHFR genotype did not affect Hcy levels, even in the presence of low blood folate.

Conclusion

We conclude that this common MTHFR gene polymorphism does not exert a significant influence on the risk of developing ICVD or ICA stenosis, and does not cause the increased level of Hcy observed in ICA stenosis.
Effect of air pollutants on the pulmonary surfactant system
Authors: Müller  , Seifart  , Barth
Published: March 2003

Air pollutants have been recognized to influence the structure and function of the surfactant system. Agents that have received the most attention include ozone, nitrogen dioxide, hyperoxia, diesel exhaust, tobacco smoke, silica and fibrous materials such as asbestos. The deleterious effects of air pollutants on the surfactant system depend on the size of the agent, on its solubility in aqueous solutions and chemical reactivity and on its concentration and the duration of exposure. Hereby the following general rules apply: the smaller the agent's size and the less water soluble the pollutant is, the greater the tendency to reach the alveoli during breathing. In addition, the reactivity also determines the depth of penetration into alveoli. Compounds with high reactivity such as O3, which also fulfil the earlier rules, will react with the upper respiratory tract compared with compounds with slightly reduced reactivity, such as NO2, which will penetrate the alveoli. The common consequence of exposure to air pollutants is an accumulation of surfactant phospholipids and surfactant‐specific proteins in the bronchoalveolar lavage fluid. These components also are structurally altered, mainly by oxidant gases, resulting in impairment of their biological activity. Thus, for surfactant phospholipids, there is impaired adsorption to the air–liquid interface due to oxidation of their fatty acids. Also, surfactant protein A, regarded as a modulator of the surfactant system, shows impaired functions after exposure to oxidants. It is likely that in addition to the effects described in this review not all effects are known because the molecular effects of several key components (e.g SP‐B and C) have not been well studied.
Investigation into thiol conjugation of transthyretin in hereditary transthyretin amyloidosis
Authors: Suhr  , Ando  , Ohlsson  , Olofsson  , Andersson  , Lundgren  , Ando  , Holmgren
Published: March 2003

Background

For all forms of amyloidosis, the amyloid‐generating mechanism is unknown. Familial amyloidotic polyneuropathy type I is caused by a variant transthyretin (TTR Met‐30). As electrospray ionization mass spectrometry (ESI‐MS) discloses both thiol‐conjugated and ‐unconjugated forms of wild‐type and variant TTR, we wanted to investigate the relationship between TTR conjugation and clinically overt amyloid disease.

Methods

Plasma from 35 individuals (12 symptomatic TTR Met‐30 carriers, nine asymptomatic and 14 healthy control subjects) were analysed using ESI‐MS.

Results

The total TTR concentration was significantly lower in symptomatic TTR Met‐30 carriers than in control subjects. An increased percentage of conjugated TTR Met‐30 was found in symptomatic carriers compared with asymptomatic, whereas the percentage conjugated wild‐type TTR was similar for control subjects, asymptomatic and symptomatic TTR Met‐30 carriers.

Conclusion

The finding of a decreased ratio of unconjugated to conjugated TTR Met‐30 in plasma samples from symptomatic TTR Met‐30 carriers indicates that thiol conjugation of TTR could be involved in amyloid formation.
Cardiovascular risk factors associated with clinically isolated and diffuse atherosclerosis in Spanish patients with coronary artery disease
Authors: Meco  , Pintó  , Escribà  , Vela  , Jara  , Pallarés  , Castiñeiras  , Pujol
Published: March 2003

Background

Patients with coronary artery disease (CAD) associated with peripheral (PAD) or cerebrovascular disease (CVD), a condition called diffuse atherosclerosis, have a higher risk of death than patients with isolated CAD. The prevalence of diffuse atherosclerosis and the atherogenic risk factors associated with this condition in our geographic area have not been described previously.

Methods

A cohort of 2597 patients (62 ± 10.8 years, 665 women) consecutively admitted at Bellvitge Hospital because of acute coronary syndromes were studied. CAD patients were divided in two groups with diffuse and located atherosclerosis according to whether they had or they had not an associated PAD or CVD. Baseline history, physical data and lipid profile were recorded in each patient according to a standardized questionnaire.

Results

A total of 370 patients (14.2%) had diffuse atherosclerosis. Among them, there were more men and women older than 55 years than among those with isolated CAD. Patients with diffuse atherosclerosis were more frequently hypertensive, diabetic and former smokers than those with isolated CAD (60.5% vs. 49.4%, P < 0.01; 37.4% vs. 24.5%, P < 0.01; and 47% vs. 35.7%, P < 0.01, respectively). There were no significant differences in the mean values of total cholesterol (TC), low‐density cholesterol (LDL‐C), high‐density cholesterol (HDL‐C) and triglycerides between both groups of patients, but patients with diffuse atherosclerosis had a lower HDL‐C/TC ratio, with borderline statistical significance (0.18 ± 0.06 vs. 0.19 ± 0.06, P = 0.06). Using multiple logistic regression analysis, the variables associated with diffuse atherosclerosis in men were age greater than 55 years (OR 1.97, CI 1.33–2.93), hypertension (OR 1.50, CI 1.14–2.20), diabetes (OR 1.78, CI 1.20–2.70), smoking (former smokers) (OR 2.09, CI 1.36–3.24) and HDL‐C/TC < 0.20 (OR 1.60, CI 1.18–2.17); and in women hypertension (OR 3.43, CI 1.48–7.94) and diabetes (OR 2.58, CI 1.55–4.80).

Conclusions

Clinically overt diffuse atherosclerosis is a relatively common disease. Older patients and those with hypertension, diabetes or low HDL‐C/TC ratio are more likely to have diffuse atherosclerosis than those without these conditions.
Carbohydrate‐deficient transferrin and gamma‐glutamyltransferase are inversely associated with lipid markers of cardiovascular risk
Authors: Nikkari  , Koivu  , Anttila  , Raunio  , Sillanaukee
Published: March 2003

Background

A variety of epidemiological studies have suggested a U‐shaped association between alcohol consumption and atherosclerosis progression and incidence events. Moderate intake of alcohol is considered beneficial, whereas heavy drinking increases cardiovascular disease risk.

Methods

Alcohol and cardiovascular risk‐related laboratory tests were carried out in 70 consecutive male employees in connection with an occupational health survey in 1996. Carbohydrate‐deficient transferrin (CDT) and gamma‐glutamyltransferase (GGT) were used as markers for alcohol consumption. The subjects were divided into quartiles on the basis of CDT or GGT value.

Results

The highest CDT quartile had significantly higher serum high‐density lipoprotein (HDL)‐cholesterol (P < 0.05) than the lowest quartile. The highest GGT quartile had significantly higher serum total cholesterol (P < 0.01), lower serum HDL‐cholesterol (P < 0.05), higher serum low‐density lipoprotein (LDL)‐cholesterol (P < 0.01) and higher serum triglyceride (P < 0.01) than the lowest quartile.

Conclusions

An explanation for the findings is that high alcohol consumption without significant liver induction increases the level of HDL‐cholesterol, whereas high alcohol consumption with induction of liver may have adverse effects on lipoprotein metabolism. The results were interpreted to indicate that CDT and GGT detect different populations of drinkers in regard to cardiovascular lipid risk factors.
Scopolamine model of dementia: electroencephalogram findings and cognitive performance
Authors: Ebert  , Kirch
Published: March 2003

Background

Memory and cognitive functions are known to decline with advancing age. Studies have suggested that this may be due to a decrease in cholinergic function in the brains of elderly people. This review aims to assess studies documented in the literature dealing with the ‘scopolamine model’ of dementia.

Methods

Sources included MedLine searches from the last 10 years (search for ‘scopolamine model’, ‘dementia’, ‘electroencephalogram’, ‘cognition’) and references from original and review articles. The aim was to include human and animal studies occupying the cholinergic hypothesis in cognitive dysfunction. Electroencephalographic (EEG) and cognition findings were considered.

Results

Scopolamine influences delta, theta, alpha and beta activity in EEG and partially mimics the EEG changes found in patients with senile dementia or dementia of the Alzheimer type. Effects on different cognitive functions have been extensively documented.

Conclusion

Scopolamine produces similar memory deficits seen in the elderly, but the drug cannot induce the full range of deficits seen in patients with Alzheimer's disease. Various aspects of memory were unaffected by scopolamine administration. Memory improvements in elderly subjects can be achieved after cholinergic stimulation.
Growth factor receptor expression in human gastroenteropancreatic neuroendocrine tumours
Authors: Wulbrand  , Wied  , Zöfel  , Göke  , Arnold  , Fehmann
Published: March 2003

Background

Human gastroenteropancreatic neuroendocrine tumours are functionally and biologically heterogeneous, but their exact growth factor receptor expression pattern, important for onco‐ and carcinogenesis, remains unknown.

Methods

This study searched for the mRNA expression pattern of six tyrosine‐ and serine/threonine kinase receptors [hepatocyte growth factor (HGFR), fibroblast growth factor (FGFR), epidermal growth factor (EGFR), insulin‐like growth factor (IGF)‐1R, transforming growth factor (TGF)‐βR1, TGF‐βR2] together with the five somatostatin receptors in human gastroenteropancreatic neuroendocrine tumours (gastrinomas, insulinomas, tumours with carcinoid syndrome, functionally inactive neuroendocrine tumours) using reverse transcriptase‐polymerase chain reaction (RT‐PCR).

Results

EGF receptor was expressed almost exclusively in gastrinomas. Among the four tumour subtypes, expression frequencies of the somatostatin receptors 1 and 5, HGF‐, IGF‐1‐, TGF‐βR1, TGF‐βR2 and the EGF‐receptor varied significantly.

Conclusions

In spite of the common cellular origin of these tumours, differences in growth factor receptor expression suggest the existence of different pathways during tumour subtype development.
T‐cell receptor gene usage in patients with fibrosing alveolitis and control subjects
Authors: Lympany P. A. , Southcott A. M. , Welsh K. I. , Black C. M. , Boylston A. W. , Du Bois R. M.
Published: March 2003

Background

Fibrosing alveolitis is characterized by inflammation, fibrosis and increased numbers of activated CD4+ T‐cells in the lower respiratory tract. The aims of this study were to compare the T‐cell antigen receptor repertoire in the lungs of subjects with fibrosing alveolitis systemic sclerosis (FASSc) with cryptogenic fibrosing alveolitis (CFA) and normal control subjects, to determine whether FASSc is driven by a specific T‐cell trigger and is determined by a T‐cell driven immune response, and to assess the clonality of CD4+ and CD8+ TcR usage in subjects with FASSc.

Materials and methods

We used reverse transcription polymerase chain reaction with specific Vα‐ and Vβ‐chain primers to identify the TcR gene usage in biopsy material, bronchoalveolar lavage fluid or peripheral blood from our subjects.

Results

We found individual‐specific restriction of Vα‐ and Vβ‐chain usage in lung biopsies from patients and control subjects. To establish whether this was due to expression bias in the CD4+ or CD8+ T‐cells and was restricted to the lung, the αβ‐T‐cell receptor chain usage was assessed in T‐cell subsets separated from the lungs of patients with fibrosing alveolitis and was compared with that of the peripheral blood. There was no consistent difference in the expression of any variable family chain among the population studied, although there was a significant difference between lung and peripheral blood lymphocyte Vβ‐families in CD8+ T‐cells (P = 0.0007).

Conclusion

We conclude that there is individual TcR Vα‐ and Vβ‐expression bias in subjects with fibrosing alveolitis.
Physicochemical and functional modifications induced by obesity on human erythrocyte membranes
Authors: Faloia  , Garrapa  , Martarelli  , Camilloni  , Lucarelli  , Staffolani  , Mantero  , Curatola  , Mazzanti
Published: March 2003

Background

Na+,K+‐ATPase activity was evaluated in relation to membrane composition and molecular organization in erythrocyte membranes from obese patients by the amphyphylic molecule 6‐dodecanoyl‐2‐dimethylamino‐naphthalene (Laurdan). Its possible relationship with fat distribution and hyperinsulinaemia was also investigated.

Design

Subjects were 10 obese men (OM), 12 women with subcutaneous obesity (FSO), 10 women with abdominal obesity (FAO) and 41 healthy lean subjects, 26 women (FC) and 15 men (MC). An oral glucose tolerance test was administered to all subjects to evaluate insulin secretion and glucose tolerance.

Results

Na+,K+‐ATPase activity was increased in all obese patients. Values were higher in FSO and FAO than in FC (with FAO greater than FSO) and in OM than in MC. The erythrocyte membrane cholesterol‐to‐phospholipid ratio was increased in obese patients and was significantly different in FSO patients compared with FC. The erythrocyte membrane protein‐to‐phospholipid ratio was also increased in all obese subjects, reaching statistical significance only in FSO vs. FC. The liquid crystalline phase, as tested by Laurdan generalized polarization (GP), was decreased in obese patients, indicating the presence of greater molecular environmental order; all patients groups showed lower GP values than control subjects, but only FAO reached statistical significance compared with FC. There was no evident correlation between membrane Na+,K+‐ATPase activity and insulin levels, nor did membrane composition and properties show any evident relationship with insulin levels.

Conclusion

Both increased Na+,K+‐ATPase activity and altered fluidity and lipid composition were observed in the erythrocyte membrane of all obese patients. These findings are in line with previous observations by our group and indicate that the changes in Na+,K+‐ATPase activity observed in obese patients could be related to changes in plasma membrane organization and composition.
Endothelial activation and response in patients with hand arm vibration syndrome
Authors: Kennedy  , Khan  , McLaren  , Belch
Published: March 2003

Background

Hand–arm vibration syndrome (HAVS) is a form of secondary Raynaud's phenomenon (RP) of occupational origin. In other forms of RP, blood and blood vessel wall interaction is one factor in the pathophysiology. Cytokines and cell adhesion molecules both play an important role in this interaction, and basal vascular tone and vasodilatation are regulated by nitric oxide.

Methods

Blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) and levels of soluble intercellular adhesion molecule‐1 (sICAM‐1) and the inflammatory cytokine interleukin 8 (IL‐8) were measured in eight male patients with vibration white finger disease, which is part of HAVS, and in eight healthy matched male control subjects.

Results

sICAM‐1 levels were statistically higher (P = 0.02, Mann–Whitney U‐test) and IL‐8 levels (P < 0.01, Mann–Whitney) were significantly lower in the patient group. The patients with HAVS had significantly reduced vascular responses to SNP (P < 0.05,
anova).

Conclusions

In this study, we reveal differences in vascular responses to SNP that suggest there may be an impairment of the smooth muscle response to nitric oxide in patients with HAVS. The increase in sICAM‐1 that occurs in patients with HAVS suggests that leucocyte adhesion is increased and that adherent neutrophils may contribute to the microvascular damage seen in this disease. The impeded flow of blood cells through the microcirculation may result in the low levels of circulating IL‐8 due to the cytokine binding to erythrocytes. The possible role of NO activity in HAVS warrants further investigation.
Skin perfusion in patients with erythromelalgia
Authors: Littleford  , Khan  , Belch
Published: March 2003

Background

Erythromelalgia (EM) is a chronic disorder characterized by intermittent pain, warmth and erythema of the extremities. Symptoms can be precipitated by increasing the temperature of the affected limb and can be partially relieved by direct cooling.

Materials and methods

Microvascular assessment was conducted under ‘hot’ (28°C) environmental conditions in 61 EM (EMI) patients and 30 control subjects. Twenty patients with many of the symptoms of EM were enrolled as an active control group (EMII). Using laser Doppler flowmetry, basal skin erythrocyte flux (SkEF) and the hyperaemic response to local heating (44°C) were measured.

Results

Compared with control subjects, basal SkEF was reduced at the toe (P < 0.001), index finger (P < 0.05), dorsal and plantar aspects of the foot (P < 0.01) in both patient groups and at the medial mid‐calf (P < 0.05) in EMI patients. Both EM groups also had a significantly reduced maximum SkEF at the dorsum of foot and medial mid‐calf (all P < 0.001) compared with control values. In a subset of patients and control subjects, transcutaneous carbon dioxide levels were raised in EMI patients (P < 0.02) compared with levels in control subjects. Toe temperature was significantly reduced in both EM groups compared with control subjects (both P < 0.001).

Conclusion

Our study indicates for the first time that there is a vasoconstrictor tendency in patients with EM, which may be related to functional or structural changes in skin microvessels. Thus, the previous hypothesis that the pathophysiology of EM relates to vasodilatation is not supported in our patients. We believe that, in EM, vasoconstriction precedes reactive hyperaemia, similar to that seen in Raynaud's phenomenon.
[13C]‐Galactose breath test: correlation with liver fibrosis in chronic hepatitis C
Authors: Mion  , Rousseau  , Scoazec  , Berger  , Minaire
Published: March 2003

Background

The galactose elimination capacity test is a quantitative liver function test that has been shown to be a potential surrogate marker for death in advanced chronic liver diseases. However, this test lacks sensitivity in early liver disease. The goal of this study was to evaluate a [13C]‐galactose breath test (GBT) in a population of patients with chronic hepatitis C.

Design

The GBT was performed in 10 control subjects and 50 patients with chronic hepatitis C; the results were compared with the METAVIR pathological scoring of liver biopsy specimens and with standard biochemical liver function tests.

Results

In 10 patients, oral vs. intravenous administration of galactose yielded similar results for the GBT (3.01% ± 0.12% dose h−1 for oral galactose vs. 2.98 ± 0.21 for intravenous). The GBT was then performed orally in the remaining 40 patients and 10 control subjects. A significant difference was observed between control subjects and patients (4.51% ± 0.18% vs. 2.97% ± 0.14% dose h−1, P < 0.0001). A significant difference for GBT results was observed between each fibrosis stage, but not with regard to the activity score.

Conclusions

The GBT results are dependent on the severity of liver fibrosis in chronic hepatitis C. Further studies are needed to evaluate the usefulness of the GBT for the follow‐up of chronic hepatitis C.
Plasma acylation stimulating protein, adipsin and lipids in non‐obese and obese populations
Authors: Maslowska  , Vu  , Phelis  , Sniderman  , Rhode  , Blank  , Cianflone
Published: March 2003

Background

Acylation stimulating protein (ASP) is a potent stimulator of TG synthesis in human adipocytes.

Design

In the present study, we have analysed plasma ASP and adipsin levels and their relationships to plasma lipids in non‐obese and obese groups.

Results

The results show that the frequency distribution of ASP is skewed but that of adipsin is normal in both groups. In the non‐obese population, the mean levels of plasma ASP and adipsin were 20.2 nmol L−1 (median) and 66.6 ± 19 nmol L−1 (mean) respectively. No difference was observed between men and women for each of the parameters. In the obese population, the median plasma ASP was increased by 246% (69.9 nmol L−1) and adipsin by 31% (87.0 ± 22.7 nmol L−1) above that of the control group. Although the levels for men and women were not statistically different for adipsin, the median ASP plasma concentration was 1.9‐fold higher in obese women than in obese men (71.8 nmol L−1 vs. 37.6 nmol L−1, P < 0.05). Best subset regression analysis provided a model with variables that best predict plasma ASP [r2 = 0.160, P < 0.008 for body mass index (BMI), P < 0.05 for triacylglycerol (TG), P < 0.03 for free fatty acid (FFA)] and plasma adipsin (r2 = 0.057, P < 0.017 for BMI) in a non‐obese population. In obese subjects, the model was different for plasma ASP (P = NS for any of the variables) and plasma adipsin (r2 = 0.356, P < 0.008 for FFA, P < 0.0002 for BMI, P < 0.02 for age). There was no correlation between ASP and adipsin in either the non‐obese or the obese group.

Conclusion

The present data suggest involvement of the ASP/adipsin pathway in the pathogenesis of obesity.
Angiotensin II increases erythropoietin production in healthy human volunteers
Authors: Freudenthaler  , Schreeb  , Körner  , Gleiter
Published: March 2003

Background

A number of animal studies and our own clinical trials point towards a possible influence of the renin‐angiotensin‐system (RAS) on erythropoietin (EPO) production. In this study we investigated the role of angiotensin II in the regulation of EPO production in humans.

Methods

After a hemorrhage of 750 ml as a basic physiological stimulus 72 healthy male volunteers received in a parallel design either placebo (physiologic electrolyte solution) for 6 h, angiotensin II i.v. for 6 h (1–3 μg min−1, sufficient to increase systolic blood pressure by 20 mmHg), the selective AT1‐receptor antagonist losartan, the ACE‐inhibitor captopril, angiotensin II + losartan, or angiotensin II + captopril.

Results

Administration of angiotensin II alone and in combination with captopril resulted in a significantly higher CmaxEPO (67% higher vs. placebo, P < 0.05) and AUCEPO (0–24h) (40% higher vs. placebo, P < 0.05). In the groups receiving losartan or captopril alone or the combination of angiotensin II + losartan no significant difference of CmaxEPO and AUCEPO(0–24h) compared to placebo could be detected.

Conclusions

This study shows in a model of controlled, basic physiological stimulation of renal EPO production that angiotensin II is able to increase EPO levels in humans. This effect of angiotensin II can be blocked by the specific AT1‐receptor antagonist losartan but not by the ACE‐inhibitor captopril. The result may be interpreted as a hint that one signal for the control of EPO production in humans may be mediated by angiotensin II (AT1)‐receptors.
Insulin: new roles for an ancient hormone
Authors: Ferrannini  , Galvan  , Gastaldelli  , Camastra  , Sironi  , Toschi  , Baldi  , Frascerra  , Monzani  , Antonelli  , Nannipieri  , Mari  , Seghieri  , Natali
Published: March 2003

Recent research has greatly expanded the domain of insulin action. The classical action of insulin is the control of glucose metabolism through the dual feedback loop linking plasma insulin with plasma glucose concentrations. This canon has been revised to incorporate the impact of insulin resistance or insulin deficiency, both of which alter glucose homeostasis through maladaptive responses (namely, chronic hyperinsulinaemia and glucose toxicity). A large body of knowledge is available on the physiology, cellular biology and molecular genetics of insulin action on glucose production and uptake.  More recently, a number of newer actions of insulin have been delineated from in vitro and in vivo studies. In sensitive individuals, insulin inhibits lipolysis and platelet aggregation. In the presence of insulin resistance, dyslipidaemia, hyper‐aggregation and anti‐fibrinolysis may create a pro‐thrombotic milieu. Preliminary evidence indicates that hyperinsulinaemia per se may be pro‐oxidant both in vitro and in vivo. Insulin plays a role in mediating diet‐induced thermogenesis, and insulin resistance may therefore be implicated in the defective thermogenesis of diabetes. In the kidney, insulin spares sodium and uric acid from excretion; in chronic hyperinsulinaemic states, these effects may contribute to high blood pressure and hyperuricaemia. Insulin hyperpolarises the plasma membranes of both excitable and non‐excitable tissues, with consequences ranging from baroreceptor desensitisation to cardiac refractoriness (prolongation of QT interval). Under some circumstances insulin is vasodilatory—the mechanism involving both the sodium‐potassium pump and intracellular calcium transients. Finally, by crossing the blood–brain barrier insulin exerts a host a central effects (sympatho‐excitation, vagal withdrawal, stimulation of corticotropin releasing factor), collectively resembling a stress reaction.  Description and understanding of these new roles, their interactions, the interplay between insulin resistance and hyperinsulinaemia, and their implications for cardiovascular disease have only begun.
The type and time of menopause as decisive factors for bone mass changes
Authors: Hadjidakis  , Kokkinakis  , Sfakianakis  , Raptis
Published: March 2003

Background

Early menopause, whether it be natural or surgical, is one of the established risk factors for osteoporosis. Surgical menopause, however, differs from natural menopause owing to the abrupt cessation of estrogen secretion. This study attempts to investigate the influence of menopause type on bone mineral density (BMD) changes.

Methods

Four groups, each consisting of 30 women, were compared: early menopause (EMP), surgical menopause (SUMP) and two groups of natural menopause. The two groups share a similar number of years since menopause (YSM) but have a different chronological age (NMPO), or share a similar age but different YSM (NMPY) to the EMP and SUMP. BMD was measured by the DXA method at L2–L4 vertebrae and proximal femur.

Results

Mean vertebral BMD of EMP was lower than that of SUMP (P < 0.05) and of NMPY (P < 0.001) women. Femoral neck BMD did not differ between SUMP and EMP women but both exhibited significantly lower BMD than either natural menopause groups. BMD of SUMP and vertebral BMD of NMPY women was inversely correlated to chronological age and to number of YSM. Pertaining to T‐score values according to the osteoporotic range, NMPO, EMP and SUMP women being homogeneous exhibited significantly lower values than NMPY in the vertebrae (F‐ratio = 7.84, P < 0.001). Whereas, in the femoral neck and the trochanter major, EMP and SUMP categories presented significantly lower T‐score values than the NMPO and NMPY (F = 3.61, P < 0.01 and 2.8, P < 0.05 respectively).

Conclusion

Women with early menopause exhibit lower vertebral BMD than women of similar age after either surgical or natural menopause. In women of similar age, surgical menopause results in lower vertebral and femoral neck densities compared to natural menopause. Chronological age and the interval after menopause negatively affects bone density in women with similar age whether in surgical or natural menopause.
The effect of coffee on gastric emptying and oro‐caecal transit time
Authors: Boekema  , Lo  , Samsom  , Akkermans  , Smout
Published: March 2003

Background

The consumption of coffee allegedly induces or aggravates gastrointestinal symptoms. In order to investigate the effect of coffee on gastrointestinal motility we studied the effect of coffee on gastric emptying and oro‐caecal transit time.

Methods

In a randomised, controlled, cross‐over study gastric emptying and oro‐caecal transit time were studied in 12 healthy volunteers, using applied potential tomography and lactulose hydrogen breath test, respectively. After 1 day of coffee abstinence and an overnight fast, coffee or the control drink (water) was drunk and 10 min thereafter a liquid nutrient meal was ingested together with lactulose. During 150 min, recordings were made with applied potential tomography and breath samples were taken every 5 min. Lag‐phase duration and gastric half‐emptying time were determined by two blinded observers.

Results

The lag‐phase duration after coffee (median 19.8 min, range 6–47 min) was not significantly different from that after water (median 19.3 min, range 11–37.5), nor was the gastric half‐emptying time (median 75.7 min, range 56–157.6 vs. median 83.4 min, range 64.6–148.4). Likewise, coffee had no significant effect on oro‐caecal transit time (median 135 min, range 60–270 vs. median 140 min, range 55–270). No significant correlation between any of these parameters and mean daily coffee intake was found.

Conclusions

Coffee does not affect gastric emptying of a liquid meal or small bowel transit.
Fast, simple and highly sensitive double‐rounded polymerase chain reaction assay to detect medically relevant fungi in dermatological specimens
Authors: Turin  , Riva  , Galbiati  , Cainelli
Published: March 2003

Background

Early detection of fungal infection is essential for beginning of prompt and specific therapy. In this study we describe a rapid and sensitive procedure to detect, by polymerase chain reaction (PCR) assays, a wide range of medically important opportunistic and pathogenic fungi in dermal specimens from dermatomycoses‐affected patients.

Materials and methods

Three primer pairs, amplifying fragments of the highly conserved gene coding for small ribosomal RNA (18S rDNA) and the adjacent internal transcribed spacer (ITS) rDNA, previously published by others, were probed on DNA from pure cultures of medically relevant human and animal fungal species. In order to evaluate the specificity of the assay, amplifications of control DNAs from other eukaryotes and prokaryotes were also carried out, and they gave negative results.

Results

These primer sets, in single amplification or double‐rounded PCR assays, allowed specific amplification when applied to a wide number of fungal DNA from human and animal tissue specimens, including dermatophytes (genera Trichophyton, Microsporum), several yeast species (Candida, Saccharomyces, Cryptococcus, Malassezia) and moulds (Aspergillus, Penicillium). The PCR assay was able to detect as little as 10 pg of fungal DNA, corresponding to approximately 25 fungal genomes per sample specimen. A small‐scale DNA extraction method was also developed. This simple, time‐saving and sensitive procedure was successfully applied to 40 human and veterinary specimens, and the diagnosis was confirmed with cultural techniques, being shown to work even in the presence of other lesions or contaminating organisms.

Conclusions

This method allows early recognition of fungal pathogen cells in clinical samples as an alternative tool to conventional detection techniques.
Clinical importance of antibodies against platelet activating factor in antiphospholipid syndrome manifestations
Authors: Tektonidou  , Petrovas  , Ioannidis  , Vlachoyiannopoulos  , Moutsopoulos
Published: March 2003

Background

We assessed whether antibodies against platelet activating factor (PAF) are related to the presence of antiphospholipid syndrome (APS) clinical manifestations, in particular thrombosis, in patients with connective tissue diseases.

Materials and methods

Anti‐PAF, anticardiolipin (aCL), antiβ2 glycoprotein I (antiβ2GPI) and antiphosphatidylcholine (anti‐PC) antibodies were determined in 52 patients with APS, 29 patients with systemic lupus erythematosus (SLE) aCL but without APS, 30 patients with SLE without aCL, and 30 patients with scleroderma. A new enzyme‐linked immunosorbent assay (ELISA) was developed for determining anti‐PAF antibodies in a bovine serum‐free fashion.

Results

The ELISA showed high specificity. Homologous inhibition experiments showed 60–70% inhibition. Anti‐PAF antibodies were found in 18/52 APS patients, 10/29 SLE/aCL+ patients, 9/30 SLE/aCL− patients and 3/30 scleroderma patients. Anti‐PAF antibodies were significantly associated with anti‐PC antibodies (odds ratio [OR] 12.7, P < 0.01), and there was a modest association with immunoglobulin G (IgG) aCL (OR 3.1, P > 0.10), but not with IgM aCL or antiβ2GPI. Three SLE/aCL+ patients and five SLE/aCL− patients had clinical manifestations characteristic of APS. All these patients had anti‐PAF antibodies, while none had high titres of aCL or antiβ2GPI antibodies and only one had anti‐PC antibodies. Among the combined APS and SLE groups, the presence of anti‐PAF antibodies was significantly associated with clinical manifestations which are characteristic of APS (OR 2.6, P = 0.02). The effect was independent of IgG aCL and antiβ2GPI antibodies.

Conclusions

Anti‐PAF antibodies are common in APS and SLE and comprise an independent factor for the development of thrombosis. Several patients experiencing thromboses have anti‐PAF antibodies without other antiphospholipid specificities.
Homocysteine: an emergent cardiovascular risk factor?
Authors: Medina  , Amores‐Sánchez
Published: March 2003

Cardiovascular disease is the leading cause of mortality and disability in the western world. In the last years, the accumulation of evidence coming from both retrospective and prospective clinical studies has led to an increased interest in the potential role of mild hyperhomocysteinemia as a major, independent risk factor for cardiovascular disease. The present paper reviews the position of homocysteine in metabolism to understand the pathogenesis of hyperhomocysteinemia, as well as the clinical data pointing to its proposed role as an independent cardiovascular disease risk factor.
Virological and immunological effects of antioxidant treatment in patients with HIV infection
Authors: Müller F. , Svardal A. M. , Nordøy I. , Berge R. K. , Aukrust P. , Frøland S. S.
Published: March 2003

Background

Intracellular oxidative stress in CD4+ lymphocytes due to disturbed glutathione homeostasis may lead to impaired lymphocyte functions and enhanced HIV replication in patients with HIV infection, especially in those with advanced immunodeficiency. The aim of the present study was to assess whether short‐term, high‐dose antioxidant treatment might have effects on immunological and virological parameters in patients with HIV infection.

Materials and methods

In this pilot study, we examined virological and immunological effects of antioxidant combination treatment for 6 days with high doses of N‐acetylcysteine (NAC) and vitamin C in 8 patients with HIV infection. The following were assayed before, during and after antioxidant treatment: HIV RNA plasma levels; numbers of CD4+, CD8+, and CD14+ leukocytes in blood; plasma thiols; intracellular glutathione redox status in CD4+ lymphocytes and CD14+ monocytes; lymphocyte proliferation; lymphocyte apoptosis and plasma levels of tumour necrosis factor (TNF)α; soluble TNF receptors and neopterin in plasma.

Results

No significant changes in HIV RNA plasma levels or CD4+ lymphocyte counts in blood were noted during antioxidant treatment in the patient group. However, in the 5 patients with the most advanced immunodeficiency (CD4+ lymphocyte counts < 200 × 106 L−1), a significant rise in CD4+ lymphocyte count, a reduction in HIV RNA plasma level of 0.8 log, an enhanced lymphocyte proliferation and an increased level of intracellular glutathione in CD4+ lymphocytes were found. No change in lymphocyte apoptosis was noted.

Conclusions

Short‐term, high‐dose combination treatment with NAC and vitamin C in patients with HIV infection and advanced immunodeficiency lead to immunological and virological effects that might be of therapeutic value.
N‐acetylcysteine replenishes glutathione in HIV infection
Authors: De Rosa S.C. , Zaretsky M.D. , Dubs J.G. , Roederer M. , Anderson M. , Green A. , Mitra D. , Watanabe N. , Nakamura H. , Tjioe I. , Deresinski S.C. , Moore W.A. , Ela S.W. , Parks D. , Herzenberg L.A. , Herzenberg L.A.
Published: March 2003

Background

Glutathione (GSH) deficiency is common in HIV‐infected individuals and is associated with impaired T cell function and impaired survival. N‐acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection.

Design

Oral NAC administration in a randomized, 8‐week double‐blind, placebo‐controlled trial followed by optional open‐label drug for up to 24 weeks.

Subjects

HIV‐infected, low GSH, CD4 T cells < 500 μL−1, no active opportunistic infections or other debilitation; n = 81. Study conducted prior to introduction of protease inhibitors.

Results

Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 m m to 0.98 m
m, bringing GSH levels in NAC‐treated subjects to 89% of uninfected controls (P = 0.03). Baseline GSH levels in the placebo group (0.91) remained essentially the same during the 8 week placebo‐controlled trial. T cell GSH, adjusted for CD4 T cell count and β2‐microglobulin levels, also increased in the NAC‐treated subjects (P = 0.04). Adverse effects were minimal and not significantly associated with NAC ingestion.

Conclusion.

NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV‐infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.
Smoking or its cessation does not alter the susceptibility to in vitro LDL oxidation
Authors: Van Den Berkmortel F. W. P. J. , Demacker P. N. M. , Wollersheim H. , Thien T. , Stalenhoef A. F. H.
Published: March 2003

Background

Enhanced induction of low density lipoprotein (LDL) oxidation may play a role in the increased cardiovascular risk in smokers. We determined LDL oxidisability in vitro in non‐smokers, smokers and in subjects after smoking cessation.

Patients and Methods

Plasma lipids and copper induced LDL oxidation in vitro were measured in 31 persistent smokers, 47 smokers who tried to stop smoking and 25 non‐smokers. In the smoking cessation group, blood was collected before then 1, 3, 6 and 12 months after smoking cessation, and in the persistent smoking and non‐smoking groups at baseline and after 12 months. Plasma thiobarbituric acid reactive substances (TBARS) were measured 3 times (at baseline then after 1 and 3 months) in all subjects who refrained from smoking (controlled by urinary cotinine concentrations) for at least 3 months.

Results

At baseline, no differences in mean age, body mass index and lipid profiles between groups were present. Seventeen subjects of the smoking cessation group (36%) managed to quit during 12 months. Smoking cessation was associated with an increase in mean weight (P ≤ 0.001) and waist‐hip ratio (P ≤ 0.001). No major differences in LDL oxidisability were found between groups. A significant transient increase in high density lipoprotein (HDL) cholesterol was seen (from 1.20 ± 0.39 to 1.34 ± 0.42 mmol L−1) after 1 month of smoking cessation that disappeared after 3 months. However, after 1 month of smoking cessation, plasma TBARS decreased significantly (P < 0.05).

Conclusions

Neither the previously observed increased cardiovascular risk in smokers nor the decreased risk in those who stopped smoking seem to be mediated by permanent changes in lipid profiles or by alterations in the susceptibility to in vitro oxidation of LDL.