| 1. |
- Sundkvist, Göran, et al.
(author)
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Sorbitol and myo-inositol levels and morphology of sural nerve in relation to peripheral nerve function and clinical neuropathy in men with diabetic, impaired, and normal glucose tolerance
- 2000
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In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 17:4, s. 259-268
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Journal article (peer-reviewed)abstract
- Aims: Sorbitol and myo-inositol levels and morphology of sural nerve were compared with nerve function and clinical neuropathy in men with diabetic, impaired (IGT), and normal glucose tolerance. Methods: After neurography of sural nerve and determinations of sensory thresholds for vibration, warm and cold on the foot, whole nerve sural nerve biopsy was performed in 10 men with Type 1 diabetes mellitus, 10 with IGT, and 10 with normal glucose tolerance. Polyol levels were assessed by gas-liquid chromatography/mass spectrometry. Results: Sural nerve amplitudes were significantly lower and sorbitol levels significantly higher in diabetic patients (median (interquartile range)) (3.7 (3.5) μV and 643 (412) pmol/mg protein, respectively) both compared with IGT (11.3 (10.6) μV; P = 0.04 and 286 (83) pmol/mg protein; P = 0.0032, respectively) and normally glucose tolerant (10.0 (11.6); P = 0.0142 and 296 (250) pmol/mg protein; P = 0.0191, respectively) subjects. There were no differences in nerve morphology between the three groups. Nerve myo-inositol levels correlated, however, positively with cluster density (r(s) = 0.56; P = 0.0054). In diabetic and IGT subjects, sural nerve amplitudes (2.6 (3.8) vs. 12.1 (10.6) μV; P = 0.0246) and myelinated nerve fibre density (MNFD; 4076 (1091) vs. 5219 (668) nerve fibres/mm2; P = 0.0021) were significantly lower in nine subjects with clinical neuropathy than in 10 without. Conclusions: Nerve degeneration (i.e. MNFD) correlated with clinical neuropathy but not with glucose tolerance status whereas nerve myo-inositol levels positively correlated with signs of nerve regeneration (i.e. increased cluster density).
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| 2. |
- Anwaar, I., et al.
(author)
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Increased plasma endothelin-1 and intraplatelet cyclic guanosine monophosphate in men with disturbed glucose metabolism
- 2000
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In: Diabetes Research and Clinical Practice. - 0168-8227. ; 50:2, s. 127-136
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Journal article (peer-reviewed)abstract
- 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-1 was 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/109 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. (C) 2000 Elsevier Science Ireland Ltd.
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| 3. |
- Gottsäter, A., et al.
(author)
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Homocysteine is related to neopterin and endothelin-1 in plasma of subjects with disturbed glucose metabolism and reference subjects
- 2000
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In: Angiology. - : SAGE Publications. - 0003-3197 .- 1940-1574. ; 51:6, s. 489-497
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Journal article (peer-reviewed)abstract
- 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 (HbA(1c)) (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.
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| 4. |
- Anwaar, I., et al.
(author)
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Hormone replacement therapy in healthy postmenopausal women. Effects on intraplatelet cyclic guanosine monophosphate, plasma endothelin-1 and neopterin
- 2000
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 247:4, s. 463-470
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Journal article (peer-reviewed)abstract
- 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, Malmo, 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 (0.423.40) 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.
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| 5. |
- Anwaar, I., et al.
(author)
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Intraplatelet cyclic 3'-5' guanosine monophosphate is related to serum cholesterol
- 1996
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In: International Angiology. - 0392-9590. ; 15:3, s. 201-206
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Journal article (peer-reviewed)abstract
- Nitric oxide (NO) exerts its vasodilator and antiaggregatory effects through activation of soluble guanylate cyclase and the consequent increase in the concentration of cGMP in target cells. We conducted this study in order to evaluate relationships between intraplatelet cGMP levels and risk factors for atherosclerosis in middle aged subjects. Intraplatelet cGMP was determined by radioimmunoassay and related to age, BMI, blood pressure, antihypertensive treatment, total, LDL and HDL cholesterol, triglycerides, blood glucose, HbA1c, smoking habit and intimal thickness of the common carotid artery in 265 subjects participating in a health survey (age 59 ± 6 years, range 48-68 years, 121 females, 144 males). Intraplatelet cGMP concentration was inversely correlated with total serum cholesterol (r = -0.18; p < 0.01) and HDL cholesterol (r = -0.14, p < 0.05) as well as with platelet count (r = -0.29; p < 0.001). When platelet count was adjusted for, only the correlation between total serum cholesterol and cGMP remained significant. No significant correlations could be demonstrated between intraplatelet cGMP levels and measurable parameters of atherosclerosis. Lower levels of the vasodilating and antiaggregating mediator cGMP in platelets are related to higher levels of serum total cholesterol. These results favour the hypothesis of a relationship between lipid levels and NO associated vasodilator and antiaggregating fuction in atherosclerosis.
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| 6. |
- Elmståhl, S., et al.
(author)
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The Malmö food study : The relative validity of a modified diet history method and an extensive food frequency questionnaire for measuring food intake
- 1996
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In: European Journal of Clinical Nutrition. - 0954-3007. ; 50:3, s. 143-151
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Journal article (peer-reviewed)abstract
- Objective: To assess the relative validity of two diet assessment methods, an extensive quantitative food frequency questionnaire (method A) and a novel shorter quantitative food frequency questionnaire with a 14 day food record (method B). Design: A randomized prospective cohort study. Setting: General community. Subjects: 206 residents of the town of Malmö, aged between 50-69 years, 101 men and 105 women who completed the methods during one year. Methods: Both diet methods were designed to cover the whole diet and portion sizes were estimated using a booklet with 120 photographs; method A comprised 250 items and method B combined a two-week food record measuring lunch and dinner meals and a shorter 130 item quantitative food frequency questionnaire for average consumption of foods, snacks and beverages during the past year. An 18 day dietary record comprising six 3-day weighed records evenly distributed over one year served as a reference method. Results: Pearson's correlation coefficients varied from 0.25 for fat intake to 0.84 for milk products for method A and from 0.32 for fish to 0.88 for meat for method B. Correlations for most food groups ranged between 0.50-0.80, and were higher for method B. Only small changes were noted after adjustment for energy intake. On average for most food groups categorization of subjects into quartiles, 55% of subjects belonging to the lowest quartile, and 57-59% of those belonging to the highest quartile for method A and B were correctly classified. Conclusion: A combined food record with a quantitative food frequency questionnaire is a better tool for food assessment than an extensive food frequency questionnaire. Sponsorship: This study was supported by the Swedish Medical Research Council (K84-19X-7010-01) and the International Agency for Research on Cancer (Collaborative Research Agreement DEB/85/43).
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| 7. |
- Elmståhl, S., et al.
(author)
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The Malmö food study : The reproducibility of a novel diet history method and an extensive food frequency questionnaire
- 1996
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In: European Journal of Clinical Nutrition. - 0954-3007. ; 50:3, s. 134-142
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Journal article (peer-reviewed)abstract
- Objective: To assess the reproducibility of two diet assessment methods, an extensive quantitative food frequency questionnaire (method A) and a novel shorter quantitative food frequency questionnaire with a 14 day food record (method B). Design: A randomized prospective cohort study. Setting: General community. Subjects: 241 residents of the town of Malmö, aged between 50-69 years, 126 men and 115 women who completed the methods one year apart. Methods: Both diet methods were designed to cover the whole diet and portion sizes were estimated using a booklet with 120 photographs; method A comprised 250 items and method B combined a two-week food record measuring lunch and dinner meals and a shorter 130 item quantitative food frequency questionnaire for average consumption of foods, snacks and beverages during the past year; Results: The percent difference between estimated energy intake one year apart were for men 10.7% for method A and 0.2% for method B, corresponding values for women 13.7% and 1.1%. Method B showed a good agreement between measurements for energy-providing nutrients, micronutrients and major food groups, i.e. meat products, edible fats, milk, fish, fruits and vegetables with correlation coefficients between 0.70-0.90 for women. The percent difference of average intake of edible fat was about 10%. Average energy-adjusted Pearson's correlation coefficients were of the order of 0.50-0.80 for most nutrients including 14 fatty acids. The correlation for the ratio between polyunsaturated and saturated fatty acids were about 0.70 for men and 0.80 for women; Conclusion: A modified diet history method combining a food record and a food frequency questionnaire shows good reproducibiiity. Sponsorship: This study was granted by the Swedish Medical research Council (Grant K 84-19X-7010-1) and by the International Agency for Research on cancer (Collaborative research agreement DEB/85/43).
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| 8. |
- Elneihoum, A. M., et al.
(author)
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Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases
- 1996
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In: Stroke: a journal of cerebral circulation. - 0039-2499. ; 27:10, s. 1734-1738
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Journal article (peer-reviewed)abstract
- Background and Purpose: Leukocytes have been implicated in the development of ischemia atherosclerotic vascular disease. In a prospective study we investigated whether the plasma concentration of inflammatory mediator, ie, proteases and cytokine, as markers for systemic leukocyte activation, are increased in patient with acute ischemic cerebrovascular diseases. Methods: Using enzyme-linked immunosorbent assays, we measured the plasma level of neutrophil gelatinase-associated lipocalin (NGAL), neutrophil proteinase 4 (NP4), tumor necrosis factor-α (TNF)m and soluble TNF receptor protein-1 p55 (sTNFR-1) in 120 patients with acute ischemic cerebrovascular insult (72 with and 48 stroke and 48 with transient ischemic attack (TIAl) and in 35 age-and sex-matched healthy subject. Results: Compared with the control group, plasma NGAL levels were higher in the stroke group (P<.0001) and the TIA group (P<.01); plasma NP4 levels were higher in the stroke group (P<.0001) and the TIA group (P<.01); and plasma sTNFR-1 levels wee higher in the stroke group (P<.04). There was significant correlation between the plasma levels of fibrinogen and those of both sTNFR-1 (r=.32; P=32; P=.005) and NGAL 9r=.40; P=.0001) and between the erythrocyte sedimentation rate and the plasma levels of both sTNFR-1 (r=.35; P=.001) and NGAL (r=.34;P=.002). Conclusions: Our study demonstrated that marker for systemic leukocyte activation, ie, plasma levels of cytokine and protease, were higher in patients with acute ischemic cerebrovascular disease than in healthy control subject. Activated leukocytes and leukocytic mediator may have an important role in acute cerebrovascular ischemia and it consequences.
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| 9. |
- Gottsäter, Anders, et al.
(author)
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Increasing plasma fibrinogen, but unchanged levels of intraplatelet cyclic nucleotides, plasma endothelin-1, factor VII, and neopterin during cholesterol lowering with fluvastatin
- 1999
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In: Blood Coagulation and Fibrinolysis. - : Ovid Technologies (Wolters Kluwer Health). - 0957-5235. ; 10:3, s. 133-140
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Journal article (peer-reviewed)abstract
- 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/109 platelets (-0.17 to 0.24); NS], cAMP [decrease by 0.13 pmol/109 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.
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| 10. |
- Lindgärde, F, et al.
(author)
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Overweight is associated with lower serum leptin in Peruvian Indian than in Caucasian women : A dissociation contributing to low blood pressure?
- 2001
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In: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 50:3, s. 325-329
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Journal article (peer-reviewed)abstract
- We tested whether plasma levels of leptin and insulin are associated with the lower blood pressure in women of Peruvian Indian heritage compared with Caucasian women. A total of 181 women from Peru and 85 from Sweden, aged 20 to 60 years, with normal plasma glucose levels participated in the study. Measurements of anthropometry, blood pressure, and blood tests were performed after overnight fasting. Compared with women from Umeå in Sweden, women from Lima, Peru had higher body mass index (BMI) (26.2 +/- 4.9 v 24.4 +/- 3.8 kg/m(2)), waist circumference (85 +/- 11 v 79 +/- 10 cm), lower systolic blood pressure (99 +/- 15 v 114 +/- 14 mm; P <.001) and diastolic blood pressure (67 +/- 7 v 74 +/- 10 mm; P <.001). In addition, they had a reduction of the ratio of plasma leptin to BMI (0.52 +/- 0.22 v 0.61 +/- 0.36; P <.001), greater plasma insulin (80 +/- 42 v 41 +/- 21 pmol/L), but lower plasma glucose (4.2 +/- 0.5 v 5.1 +/- 0.5 mmol/L; P <.001). Furthermore, the 181 women from Lima had higher plasma triglyceride levels (1.5 +/- 0.8 v 1.3 +/- 0.7; P =.039), but lower plasma high-density lipoprotein (HDL)-cholesterol (1.0 +/- 0.2 v 1.5 +/- 0.4 mmol/L; P <.001) and total plasma cholesterol (5.0 +/- 1.1 v 5.9 +/- 1.3 mmol/L; P <.001) levels. Plasma leptin correlated with blood pressure and BMI in both populations (P <.001). In multiple regression analysis, BMI, but not log leptin, emerged as the determinant for systolic blood pressure. We concluded that women living in Lima have significant lower blood pressure levels in association with elevated plasma insulin concentrations, but lower plasma leptin values adjusted for BMI in comparison with women from northern Sweden. This may suggest that the concept of metabolic syndrome is different among women with Peruvian Indian heritage in comparison to a Caucasian population.
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