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Biomedical subjects

A Gottsäter

Publications and source records attributed to A Gottsäter.

At least 19 recordsLinked to original sources
PubMed2003

Decreasing levels of tumour necrosis factor alpha and interleukin 6 during lowering of body mass index with orlistat or placebo in obese subjects with cardiovascular risk factors.

AIM: Obesity is associated with increased levels of inflammatory mediators. The objective of this study was to evaluate changes in the leucocyte derived inflammatory mediators tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and the isoprostane 8-epi-prostaglandin (PG) F2alpha during BMI lowering with orlistat (Xenical(R), Roche) or placebo. METHODS: TNF-alpha, IL-6, and 8-epi PGF2alpha evaluated in 376 subjects aged 18-75 years with BMI 28-38 kg/m2 before and after 1 year of double-blind, randomized treatment with orlistat 120 mg or placebo three times daily. RESULTS: Weight reduction was associated with decreasing (p < 0.001) levels of TNF-alpha and IL-6 in both orlistat and placebo groups. After 12 months, TNF-alpha was lower (p < 0.05) in the orlistat compared with the placebo group. In the orlistat group, the change in TNF-alpha correlated with change in s-glucose (r = 0.22; p = 0.01), and the change in 8-epi-PGF2alpha correlated with changes in s-cholesterol (r = 0.27; p < 0.001) and s-LDL-cholesterol (r = 0.28; p < 0.001). CONCLUSION: Weight reduction was associated with decreasing levels of both TNF-alpha and IL-6. After 12 months of treatment, TNF-alpha levels were lower in orlistat than in placebo-treated subjects. Whether these results translate into reduced incidence of cardiovascular disease remains to be elucidated.

Adolescent↗
PubMed2003

Cardiovascular autonomic neuropathy associated with carotid atherosclerosis in Type 2 diabetic patients.

AIMS: To clarify if cardiovascular autonomic neuropathy is associated with carotid artery atherosclerotic plaques in Type 2 diabetic patients. METHODS: Cardiovascular autonomic nerve function was related to carotid artery ultrasound in 61 Type 2 diabetic patients 5-6 years after diagnosis of diabetes. RESULTS: Cardiovascular autonomic neuropathy [abnormal age corrected expiration/inspiration (E/I) ratio or acceleration index (AI)] was found in 13/61 (21%) patients. Patients with cardiovascular autonomic neuropathy showed increased degree of stenosis in the common carotid artery (24.6 +/- 13.2% vs. 14.7 +/- 9.2%; P = 0.014) and a tendency towards a higher plaque score (4.0 +/- 1.7 vs. 3.2 +/- 1.6; P = 0.064). Controlled for age, AI correlated inversely with degree of stenosis (r = -0.39; P = 0.005), plaque score (r = -0.39; P = 0.005), and mean (r = -0.33; P = 0.018) and maximum (r = -0.39; P = 0.004) intima-media thickness in the common carotid artery. In contrast, E/I ratio correlated only slightly with mean intima-media thickness in the common carotid artery (r = -0.28; P = 0.049). CONCLUSIONS: Cardiovascular autonomic neuropathy was associated with carotid atherosclerosis in Type 2 diabetic patients. Abnormal E/I ratios reflect efferent structural damage to parasympathetic nerves whereas abnormal AI reflects afferent autonomic dysfunction possibly due to impaired baroreceptor sensitivity secondary to carotid atherosclerosis.

Adult↗
PubMed2002

Interleukin-1 receptor antagonist is detectable in human carotid artery plaques and is related to triglyceride levels and Chlamydia pneumoniae IgA antibodies.

OBJECTIVES: To investigate whether the interleukin-1 receptor antagonist (Il-1ra) and interleukin-1beta (Il-1beta) can be detected in human carotid artery tissue, and whether their presence is related to evidence of Chlamydia pneumoniae infection, risk factors for atherosclerosis, and clinical data. SETTING: Departments of Vascular Diseases and Surgical Pathophysiology, University Hospital, Malmö, Sweden. SUBJECTS: A total of 66 patients undergoing carotid endarterectomy (median age 74, range 53-89 years, 26 women). Il-1beta and Il-1ra were studied in carotid artery plaques and in Il-1ra in serum. RESULTS: Interleukin-1 receptor antagonist was detected in mononuclear cells in plaques from 37/66 (56%) patients. Patients with Il-1ra in plaques showed higher [2.04 (1.70-3.14) mmol x L(-1) vs. 1.69 (1.09-1.99) mmol x L(-1); P < 0.05] serum(s-)triglyceride(tg) levels, and a higher frequency of IgA seropositivity for C. pneumoniae (76% vs. 52%; P < 0.05) than those without. S-Il-1ra levels correlated with s-tg levels (r=0.38; P=0.047). There were no differences between patients with and without Il-1ra in plaques concerning s-Il-1ra, blood(b-)haemoglobin or leucocyte count, s-cholesterol, b-glucose, blood pressure, IgG seropositivity for C. pneumoniae, prevalence of neurological symptoms preceding operation, smoking, or diabetes mellitus. There were no differences in frequency of Il-1ra in plaques or in s-Il-1ra levels between patients with symptomatic and asymptomatic stenosis, between smokers and nonsmokers, or between diabetic and nondiabetic patients. Il-1beta was not detected in plaques in the current study. CONCLUSION: Interleukin-1 receptor antagonist can be detected in human atherosclerotic carotid artery plaques, and is related to s-triglyceride levels and IgA seropositivity for C. pneumoniae, but not to prevalence of neurological symptoms related to embolization.

Aged↗
PubMed2002

Platelet and leukocyte activation during aortoiliac angiography and angioplasty.

OBJECTIVE: to evaluate platelet and leukocyte activation during aortoiliac angiography and percutaneous transluminal angioplasty (PTA). METHODS: an observational study of 14 patients with aortoiliac atherosclerotic disease, nine of whom underwent PTA. The proportion of fibrinogen-, and P-selectin positive platelets, P-selectin expression on platelets, intraplatelet cGMP and cAMP, CD18 positive granulocytes, CD18 expression on granulocytes, plasma (p)-neopterin, p-TNF alpha and p- interleukin-6 were repeatedly measured in arterial blood during angiography and in venous blood before and after. RESULTS: compared to a previous venous sample, arterial intraplatelet cAMP was increased proximal to the atherosclerotic lesion before contrast infusion and PTA (median 18 [range: 14-22] vs 16 [15-21] pmol/10(9) platelets p<0.05), and intraplatelet cGMP was increased proximal to the lesion after contrast infusion and PTA (1.2 [0.8-3.9] vs 0.9 [0.6-2.5] pmol/10(9) platelets p<0.05). Four hours after angiography, both the proportion of P-selectin positive platelets (28[11-55]%) and platelet P-selectin expression (9[6-40]) had decreased (p<0.05), from arterial values distal to the lesion before contrast infusion and PTA (57 [24-78]% and 26 [10-83]). Granulocyte CD18 expression was lower during angiography than in a previous venous sample. CONCLUSIONS: the results are compatible with platelet but not leukocyte activation during peripheral angiography.

Aged↗
PubMed2002

Decreasing plasma endothelin-1 and unchanged plasma neopterin during folate supplementation in hyperhomocysteinemia.

BACKGROUND: Hyperhomocysteinemia is a risk factor for atherosclerosis and venous thrombosis, probably exerting its effects through endothelial function. Homocysteine levels are lowered by folate supplementation, and such treatment improves endothelial function. However, whether folate supplementation decreases vascular risk and improves survival is unknown. The aim of this study was to evaluate endothelial function and mononuclear leukocyte inflammatory activity during homocysteine lowering in patients with hyperhomocysteinemia and vascular disease. METHODS: Endothelial function assessed as plasma (p-)endothelin(ET)-1 and intraplatelet cGMP and cAMP, and mononuclear leukocyte inflammatory activity, assessed as p-neopterin were studied during homocysteine lowering in 50 patients with hyperhomocysteinemia and vascular disease, randomized to folate supplementation or no treatment for 3 months. RESULTS: P-homocysteine decreased during the 3 months not only in patients on folate supplementation (from 27 [21-52] to 14 [8-41] micromol/l; p<0.001), but also in the untreated group (from 23 [20-35] to 19 [4-31] micromol/l; p<0.001). P-ET-1 decreased during folate supplementation (from 5.7 [2.7-11.6] to 4.1 [1.8-9.0] pg/ml; p<0.01), but was unchanged in the untreated group 4.1 [2.0-9.5] pg/ml and 4.5 [2.7-7.1] pg/ml). P-neopterin was unchanged in patients on folate supplementation (9.7 [5.1-54.4] and 7.6 [5.7-73.0] nmol/l), but increased in the untreated group (from 8.2 [4.7-19.5] to 8.6 [4.6-24.6] nmol/l; p<0.05). Intraplatelet cGMP decreased in patients on folate supplementation (from 0.86 [0.21-2.00] platelets to 0.56 [0.17-1.42] pmol/10(9) platelets; p<0.05), but was unchanged in the untreated group. No significant differences concerning intraplatelet cAMP occurred in either group. CONCLUSIONS: Folate supplementation in hyperhomocysteinemia is associated with decreasing levels of both ET-1 and intraplatelet cGMP, and the absence of an increase in the levels of the inflammatory mediator neopterin.

Aged↗
PubMed2002

Clinical manifestations of atherosclerosis in an elderly population are related to plasma neopterin, NGAL and endothelin-1, but not to Chlamydia pneumoniae serology.

BACKGROUND: Inflammatory mediators secreted by leukocytes are implicated in atherogenesis. Chlamydia (C.) pneumoniae infection has been suggested as a trigger of this process. We investigated relationships between C. Pneumoniae serology, inflammatory mediators and symptomatic cardiovascular disease in old age. METHODS: In a cross-sectional study at baseline with a prospective 4 year follow-up, intraplatelet cyclic 3'-5'adenosine monophosphate (cAMP) and cyclic 3'-5'guanosine monophosphate (cGMP), plasma neutrophil gelatinase associated lipocalin (NGAL), plasma soluble tumor necrosis factor receptor-1 (TNFR-1) plasma neopterin and plasma endothelin-1 (ET-1) were analysed together with IgG and IgA antibodies for C. Pneumoniae in an elderly reference population (n=140, median age 71 years, 71 females). Twenty-one subjects had clinical manifestations of cardiovascular disease at baseline and another 21 were diagnosed with cardiovascular disease during follow-up. RESULTS: In age adjusted logistic regression, subjects with cardiovascular disease showed higher plasma levels of neopterin (p=0.02), NGAL (p=0.04), and ET-1 (p<0.01). If subjects with cardiovascular disease at baseline were excluded from the analysis, higher plasma neopterin (p=0.01) and lower serum HDL cholesterol (p=0.03) predicted cardiovascular disease during follow-up. The presence of IgG or IgA against C. pneumoniae was not associated with cardiovascular disease. Neither were there any associations between inflammatory or endothelial parameters and C. pneumoniae serology. CONCLUSIONS: The inflammatory mediators neopterin and NGAL and endothelial derived vasoconstrictive ET-1 were increased in elderly subjects with symptomatic cardiovascular disease. Increased plasma neopterin predicted cardiovascular disease during follow-up. No relationships were found between C. Pneumoniae serology and cardiovascular disease.

Acute-Phase Proteins↗
PubMed2001

Clinically suspected pulmonary embolism: is it safe to withhold anticoagulation after a negative spiral CT?

The goal of this study was 3-month clinical outcome in nonanticoagulated patients with clinically suspected acute pulmonary embolism (PE) following a negative spiral CT. During a 6-month period 305 patients underwent spiral CT, of whom only 8 also had a lung scintigraphy. In patients with a final CT report read as not positive for acute PE, all hospital records and answers to a patient questionnaire were analyzed for episodes of venous thrombembolism (VTE). Acute PE was diagnosed at spiral CT in 61 patients (20%). Twenty-six of the remaining 244 patients were excluded from further analysis because of (a) long-term anticoagulation due to symptomatic acute deep venous thrombosis (n = 5), clinically diagnosed acute PE (n = 2), chronic recurrent VTE (n = 4), and cardiac disorders (n = 5); and (b) a normal perfusion scintigram (n = 4) or a negative pulmonary arteriogram (n = 6). Three patients were lost to follow-up. Among the remaining 215 patients only 10 had undergone a negative lower extremity venous study. Sixteen patients (7%) died during the follow-up period, 6 of whom underwent autopsy. Venous thrombembolism was diagnosed in three of the 215 patients (1.4%, 95% confidence limits: 0.5-4.0%), one causing the patient's death. Two patients had advanced thoracic malignancies and the third severe chronic obstructive pulmonary disease (84 years old). A negative spiral CT may be able to exclude clinically significant acute PE with the same accuracy as a normal lung scintigraphy or a negative pulmonary arteriography.

Acute Disease↗
PubMed2001

Hormone replacement therapy in healthy postmenopausal women: a randomized, placebo-controlled study of effects on coagulation and fibrinolytic factors.

OBJECTIVES: To evaluate effects of postmenopausal hormone replacement therapy (HRT) on von Willebrand factor, factor (F)VIII, factor (F)VII, fibrinogen, antithrombin (AT) III, prothrombin fragments 1 and 2, protein C, total and free protein S, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and resistance to activated protein C. DESIGN: Part 1: double blind randomized trial for 3 months. Part 2: open study for 9 months. SETTING: Department of Endocrinology, University Hospital, Malmö, Sweden. SUBJECTS: Fifty-one postmenopausal women with a history of amenorrhoea of at least 6 months and body mass index > or = 24 kg m-2 participated in part 1 and 46 participated in part 2. INTERVENTION: Randomization for placebo (n=24) or HRT (n=27). HRT was given as 2 mg oestradiol valerate for the first 3 months, with the addition of 10 mg medroxyprogesterone for 10 days every third month thereafter. MEASUREMENTS: At baseline and after 3 and 12 months. RESULTS: During 0-3 months in the HRT group, FVII increased (P < 0.01), whereas fibrinogen, AT III and total protein S all decreased (P < 0.001 for all). Changes in variables were expressed as Delta-values. After 3 months Delta-values differed between groups for fibrinogen (P < 0.05), AT III (P < 0.001), total protein S (P < 0.001), and PAI-1 (P < 0.001). During 0-12 months, fibrinogen, total protein S, tPA (P < 0.01 for all) and AT III (P < 0.05) decreased. In the control group, all variables were unchanged during the study, except for increases (P < 0.05) in total protein S after 3 and 12 months, and a decrease (P < 0.01) in FVIII after 12 months. After 12 months Delta-values differed for fibrinogen (P < 0.05), AT III (P < 0.05) and total protein S (P < 0.001). CONCLUSIONS: Unopposed oestrogen substitution was associated with both potentially beneficial effects, such as decreases in fibrinogen, and potentially thrombogenic effects such as decreasing AT III and protein S and increasing FVII. During prolonged follow-up and addition of progesterone, differences between groups concerning FVII were attenuated. These data suggest that effects of HRT upon coagulation are most pronounced early after institution of unopposed treatment.

Blood Coagulation↗
PubMed2001

High levels of antigen-specific islet antibodies predict future beta-cell failure in patients with onset of diabetes in adult age.

It is unclear whether high levels of antigen-specific islet antibodies [GADA (glutamic acid decarboxylase 65 antibodies) and IA2-ab (protein tyrosine phosphatase-like protein antibodies)] predict beta-cell failure in patients with onset of diabetes in adult age. Therefore, GADA and IA2-ab levels at the diagnosis of diabetes were related to fasting plasma C-peptide levels 5 yr later in 148 patients with diabetes onset in adult age (age at onset, 20-77 yr; median, 57 yr). Classical islet cell antibodies (ICA) were also determined. Complete beta-cell failure (undetectable fasting plasma C-peptide) was only present in 4 patients at diagnosis of diabetes, but in 21 patients 5 yr thereafter. At diagnosis, ICA were detected in 20 of 21 (95%) patients with beta-cell failure after 5 yr and in only 7 of 127 (5%) without, whereas GADA and/or IA2-ab (>97.5 percentile of healthy controls) were detected in all 21 (100%) with but also in 23 of 127 (18%) patients without beta-cell failure after 5 yr. Thus, ICA had a higher positive predictive value (74%) than GADA and/or IA2-ab (47%; P < 0.05). With high cutoff values for GADA and IA2-ab, however, GADA and/or IA2-ab were detected in 19 of 21 (90%) patients with beta-cell failure vs. only in 5 of 127 (4%) without, giving a positive predictive value of 79%. Slightly elevated GADA levels in IA2-ab-negative patients were associated with progressive but not complete beta-cell failure within the study period. Hence, high GADA and/or IA2-ab levels predict a future complete beta-cell failure, whereas low GADA levels predict slowly progressive beta-cell insufficiency.

Adult↗
PubMed2001

Predictors of carotid endarterectomy in middle-aged individuals.

The objective was to investigate which screening variables in a population study predicted carotid endarterectomy. Among 793 carotid endarterectomies performed at Malmö University Hospital between 1991 and 1998, 85 patients (14 females) were identified that had participated in a population screening between 1974 and 1991. Median time from screening to operation was 16 years (range 6-26 years). Screening variables were compared with corresponding values from the background screening population (n = 33261). As operated patients were older than the background population at screening (49 [37-60] vs. 46 [26-61] years; p < 0.0001), comparisons were age-adjusted. Operated patients had higher systolic blood pressure (SBP; 130 [126-133] vs. 125 [125-125] mmHg; p < 0.01), serum total cholesterol (6.1 [5.9-6.3] vs. 5.7 [5.7-5.7] mmol/l; p < 0.0001), serum triglyceride (1.4 [1.3-1.6] vs. 1.1 [1.1-1.1] mmol/l; p < 0.0001), serum glutamic acid transferase (0.46 [0.40-0.53] vs. 0.40 [0.40-0.41] microkat/l; p < 0.05), and plasma fibrinogen (3.77 [3.42-4.16] vs. 3.35 [3.30-3.41] mmol/l; p < 0.05) levels, a lower 120-min insulin/glucose ratio at an oral glucose tolerance test (OGTT; 0.48 [0.38-0.58] vs. 0.60 [0.59-0.61]; p < 0.05) and forced vital lung capacity (3.7 [3.6-3.9] vs. 3.9 [3.9-4.0] l/min; p < 0.05), and a higher prevalence of smoking at screening (68% vs. 45%; p < 0.0001). Smoking, SBP, serum total cholesterol, and the 120-min insulin/glucose ratio remained independent predictors for carotid surgery in multivariate analysis. No differences existed among patients operated on because of symptomatic and asymptomatic stenosis. In conclusion, increased SBP and total cholesterol, lower 2-h insulin/glucose ratio at an OGTT, and smoking predict carotid surgery at long-term follow-up.

Acyltransferases↗
PubMed2000

Increased plasma endothelin-1 and intraplatelet cyclic guanosine monophosphate in men with disturbed glucose metabolism.

Plasma endothelin-1, the nitric oxide (NO) mediator intraplatelet cyclic guanosine monophosphate (cGMP), the prostacyclin mediator cyclic adenosine monophosphate (cAMP) and the macrophage derived inflammatory mediator plasma neopterin were measured in men with Type 2 diabetes mellitus (n=91), impaired glucose tolerance (IGT; n=51), previously abnormal glucose tolerance (PAGT; n=20), and 34 healthy control men. Plasma endothelin-1was higher in men with Type 2 diabetes mellitus than in controls [4.1 (1.0-14.3) vs. 2.1 (0.2-8. 7) ng/l; P<0.001). Intraplatelet cGMP was higher in men with PAGT [0. 84 (0.57-2.76) pmol/10(9) platelets; P<0.05], IGT [0.85 (0.48-3.53); P<0.001] and Type 2 diabetes mellitus [0.90 (0.47-3.86); P<0.001] than in controls [0.70 (0.42-1.70]. No differences existed between groups concerning intraplatelet cAMP or plasma neopterin. Plasma endothelin-1 correlated with fasting plasma glucose (r=0.33; P<0.001) and HbA1(c) (r=0.29; P<0.001). In conclusion, elevated plasma endothelin-1 in Type 2 diabetes mellitus and its relationship to glucose and HbA1(c) suggest a putative role for endothelin-1 in diabetic endothelial cell damage. Increased cGMP indicating enhanced production/activity of NO suggests that factors other than reduced NO activity contribute to enhanced platelet aggregation in diabetes.

Aged↗
PubMed2000

Hormone replacement therapy in healthy postmenopausal women. Effects on intraplatelet cyclic guanosine monophosphate, plasma endothelin-1 and neopterin.

OBJECTIVES: To evaluate beneficial effects of postmenopausal hormone replacement therapy (HRT) on endothelial function, measured as intraplatelet cyclic guanosine monophosphate (cGMP, mediator of nitric oxide), cyclic adenosine monophosphate (cAMP, mediator of prostacyclin) and plasma endothelin-1 (ET-1), and on monocyte activation, measured as plasma neopterin. DESIGN: Part 1: double-blind randomized trial for 3 months; part 2: open study for 9 months. SETTING: The study was performed at the Department of Endocrinology, University Hospital, Malmö, Sweden. SUBJECTS: Fifty-one postmenopausal women participated in part 1 and 46 in part 2. Inclusion criteria included a history of amenorrhoea for at least 6 months before the study and body mass index >/= 24 kg m-2. INTERVENTION: Randomization for either placebo (n = 24) or HRT (n = 27). HRT was given as 2 mg oestradiol valerate for the first 3 months with the addition of 10 mg medroxyprogesterone for 10 days every third month thereafter. MEASUREMENTS: Performed at baseline and after 3 and 12 months of the study. RESULTS: In the HRT group, intraplatelet cGMP increased from 0.56 (0.35-0.94) to 0.61 (0.42-3. 40) and 0.65 (0.43-1.08) pmol (109 platelets)-1 after 3 and 12 months, respectively (P = 0.01), whereas plasma ET-1 decreased from 3.2 (1.1-6.8) to 2.0 (0.8-5.1) and 1.8 (0.4-15.4) pg mL-1 (P < 0. 001). Intraplatelet cAMP and plasma neopterin were unchanged. When smokers (n = 15) and non-smokers (n = 12) in the HRT group were analysed separately, significant effects were seen only amongst smokers. The control group showed unchanged levels of cGMP, cAMP, ET-1 and neopterin. CONCLUSIONS: These data suggest beneficial effects of HRT on endothelial function which may account for anti-atherogenic effects of HRT in postmenopausal women, especially in smokers. No effects of HRT were seen upon monocyte activation.

Blood Platelets↗
PubMed2000

Homocysteine is related to neopterin and endothelin-1 in plasma of subjects with disturbed glucose metabolism and reference subjects.

Hyperhomocysteinemia is an independent risk factor for vascular disease. In order to evaluate relations between hyperhomocysteinemia and endothelial and leukocyte function, the investigators related homocysteine to indices of endothelial function (plasma endothelin-1 [p-ET-1] and intraplatelet levels of the nitric oxide [NO] and prostacyclin mediators 3'-5' guanosine monophosphate [cGMP] and cyclic 3'-5' adenosine monophosphate [cAMP]) and the monocyte-derived inflammatory mediator neopterin in 168 men (mean age 69, range 49-72 years) with disturbed glucose metabolism and a reference group of 52 male subjects (mean age 70, range 61-79 years). Among the 168 patients with disturbed glucose metabolism plasma (p)-homocysteine correlated significantly with age (r=0.20; p<0.01), glycosylated hemoglobin (HbA1c) (r=0.17; p<0.05), triglycerides (r=0.20; p<0.05), intraplatelet GMP (r=0.16; p<0.05), p-ET-1 (r=0.21; p<0.05), and p-neopterin (r=0.31; p<0.001). The correlation between p-homocysteine and p-ET-1 persisted (p<0.01) in multiple regression analysis. Among the 52 reference subjects p-homocysteine correlated significantly with p-ET-1 (r=0.32; p<0.05) and p-neopterin (r=0.37; p<0.01). The correlation between p-homocysteine and p-neopterin persisted (p<0.05) in multiple regression analysis. In conclusion, homocysteine is related to neopterin and endothelin-1 in plasma of subjects with disturbed glucose metabolism and in reference subjects, suggesting that homocysteine exerts its deleterious effects on vascular function through interference with endothelial and leukocyte function.

Aged↗
PubMed1999

Autonomic neuropathy in Type 2 diabetic patients is associated with hyperinsulinaemia and hypertriglyceridaemia.

AIMS: To clarify whether parasympathetic neuropathy in Type 2 diabetic patients is associated with features of the insulin resistance syndrome. METHODS: Blood pressures, glycaemic control (HbA1c), plasma lipids, residual beta-cell function (fasting plasma C-peptide), autonomic nerve function, urinary albumin excretion and glomerular filtration rate (Cr-EDTA clearance) were evaluated in 82 Type 2 diabetic patients (age 63+/-years) 5 years after diagnosis of diabetes. RESULTS: Parasympathetic neuropathy (an abnormal age corrected E/I ratio) was found in 24/82 (29%) patients. After adjustment for body mass index (BMI), patients with parasympathetic neuropathy had elevated fasting plasma C-peptide (P < 0.001) and triglyceride (Tg) (P < 0.05) levels compared with patients without parasympathetic neuropathy. In addition, the age corrected E/I ratio correlated inversely with Tg (r=-0.31; P<0.01) and fasting plasma C-peptide (r=-0.32; P < 0.01) in the Type 2 diabetic patients. CONCLUSION: Autonomic neuropathy 5 years after diagnosis of Type 2 diabetes is associated with an unfavourable metabolic risk profile.

Autonomic Nervous System Diseases↗
PubMed1999

Increasing neopterin and decreasing endothelin-1 in plasma during insulin infusion in women.

Leukocyte-derived inflammatory mediators and endothelial production of vasoconstrictive factors, such as endothelin-1, and vasodilatory and platelet anti-aggregatory factors, such as nitric oxide (NO) and prostacyclin (PGI2), may have a role in the pathogenesis of atherosclerosis. In this study we evaluated whether insulin affects the monocyte-derived inflammatory mediator neopterin and endothelin- in plasma (p), and NO and PGI2 mediators cyclic 3'-5' guanosine monophosphate (cGMP) and cyclic 3'-5' adenosine monophosphate (cAMP) in platelets. P-neopterin was measured by enzyme linked immunosorbent assay (ELISA), and p-endothelin-1, intraplatelet cAMP and cGMP were measured by radioimmunoassay (RIA) before and after euglycaemic hyperinsulinaemic clamping in 51 healthy postmenopausal women aged 53-54 years. "Placebo clamping" with NaCl infusion was performed in a subgroup of 5/51 women. During euglycaemic hyperinsulinaemic clamping, p-endothelin-1 decreased (from 3.3+/-0.2 pg/ml to 2.4+/-0.2 pg/ml; p<0.01), whereas p-neopterin (from 5.0+/-1.1 nmol/l to 6.2+/-1.4 nmol/l; p<0.001) and both intraplatelet cGMP (from 0.61+/-0.03 to 0.68+/-0.03 pmol/10(9) platelets; p<0.05) and cAMP (from 4.00+/-0.14 to 4.76+/-0.20 pmol/10(9) platelets; p<0.001) increased. Increases in cGMP (from 0.79+/-0.05 to 1.07+/-0.15 pmol/10(9) platelets; p = 0.14) and cAMP (from 4.76+/-0.15 to 5.52+/-0.36 pmol/10(9) platelets; p = 0.08) also occurred during NaCl infusion, whereas neopterin and endothelin-1 values were unchanged. In conclusion, insulin administration was associated with decreasing p-endothelin-1 levels and increasing levels of p-neopterin and intraplatelet cyclic nucleotides in accordance with vasodilatation and monocyte activation.

Blood Platelets↗
PubMed1999

Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclic nucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin.

Lipid-lowering statin treatment reduces cardiovascular morbidity and mortality and improves endothelial function in patients with hypercholesterolemia. The aim of the present study was to evaluate plasma levels of fibrinogen, factor VII, and the macrophage-derived inflammatory mediator neopterin during lipid lowering. In addition, the endothelial production of platelet antiaggregatory and vasodilatory factors such as nitric oxide and prostacyclin, and vasoconstrictive factors such as endothelin-1, was assessed. Plasma fibrinogen, factor VII, endothelin-1, and the neopterin and intraplatelet nitric oxide and prostacyclin mediators cyclic 3'-5'guanosine monophosphate (cGMP) and cyclic 3'-5'adenosine monophosphate (cAMP) were measured before and 6 months after the institution of treatment with fluvastatin in 17 patients (eight men and nine women, median age 60 years) with vascular disease and previously untreated hypercholesterolemia. After 6 months, a decrease of 1.62 mmol/l [1.26-2.18 (19%); P < 0.01] was noted in levels of total cholesterol, and a decrease of 1.70 mmol/l [1.52-2.30 (28%); P < 0.01] in levels of low-density lipoprotein cholesterol. Plasma levels of fibrinogen had increased [from 4.81 g/l (4.26-5.27) to 5.17 g/l (4.81-5.67); P < 0.05], whereas no significant changes had occurred in intraplatelet levels of cGMP [decrease by 0.05 pmol/10(9) platelets (-0.17 to 0.24); NS], cAMP [decrease by 0.13 pmol/10(9) platelets (-0.37 to 0.86); NS], plasma endothelin-1 [decrease by 0.05 pg/ml (-0.60 to 0.70); NS], plasma factor VII [from 1.14 IE/ml (0.58-1.38) to 1.22 IE/ml (0.96-1.46); NS], or plasma neopterin [from 8.6 nmol/l (7.1-11.5) to 8.7 nmol/l (7.9-11.3); NS]. In conclusion, during cholesterol-lowering treatment with fluvastatin, plasma levels of fibrinogen increased whereas intraplatelet cyclic nucleotide levels and plasma endothelin-1, factor VII and neopterin levels were unchanged.

Aged↗
PubMed1999

Increasing plasma neopterin and persistent plasma endothelin during follow-up after acute cerebral ischemia.

Release of inflammatory mediators from leukocytes and endothelial release of vasoactive factors are both important in the pathogenesis of atherosclerosis. To evaluate the concentrations of a specific marker for macrophage activation, neopterin, and the potent endothelial derived vasoconstrictive peptide endothelin-1 (ET-1), during the acute and chronic stages of cerebral ischemia, plasma concentrations of neopterin and ET-1 were measured in 59 patients with acute cerebral infarction or transient ischemic attack (median age 73 years, range 43-93, 27 men) and after a 1-year follow-up in 57/59 (97%) of patients. Plasma neopterin was higher at follow-up (6.3 nmol/L [3.7-21.6] vs 5.6 nmol/L [3.5-17.2]; p < 0.05) than at the acute stage, whereas the plasma ET-1 concentration was unchanged. Plasma concentrations of both neopterin and ET-1 correlated directly with age both in the acute stage (r = 0.42 and r = 0.35, respectively; p < 0.01) and after follow-up (r = 0.34; p < 0.05 and r = 0.27; p = 0.05, respectively). In conclusion, plasma neopterin increased after acute cerebral ischemia, indicating chronic inflammatory activity and continuous macrophage activation in ischemic cerebrovascular diseases.

Acute Disease↗