Moderate hyperhomocysteinaemia and immune activation in Parkinson's disease.

Moderate hyperhomocysteinaemia has been linked to an increased risk for cardiovascular diseases. Increased homocysteine concentrations may follow folate depletion due to insufficient dietary intake of the vitamin, but there is also some indication that immune activation could play a role. In this preliminary study, homocysteine, folate, and vitamin B(12) concentrations were measured in 19 patients with Parkinson's disease, 61-90 years of age, and compared to a healthy control group of similar age and to neopterin concentrations as an indicator of immune activation. A subgroup of patients presented with increased homocysteine and low folate concentrations. Homocysteine levels correlated inversely with vitamins folate and B(12) and positively with neopterin concentrations. Disturbed homocysteine metabolism in Parkinson's disease may be associated with vitamin deficiency and with immune system activation which may underlie folate depletion.

Is hyperhomocysteinemia due to the oxidative depletion of folate rather than to insufficient dietary intake?

Hyperhomocysteinemia is considered as a risk factor for cardiovascular diseases. Usually, an inverse relationship exists between homocysteine and folate levels, and supplementation with folate lowers homocysteine concentrations in patients. Therefore, hyperhomocysteinemia is mainly ascribed to the insufficient dietary intake of folate. Hyperhomocysteinemia has also been observed in infections and inflammatory diseases. Oxidative stress appears to be involved in the pathogenesis of these disorders, and associations have been found between homocysteine and e.g., neopterin concentration. Increased neopterin concentration indicates immune system activation and also allows an estimate of thus elicited oxidative stress. It may be relevant that the active cofactor, tetrahydrofolate, is very susceptible to oxidation. Immunologically induced oxidative stress could lead to folate depletion resulting in hyperhomocysteinemia. Thus, hyperhomocysteinemia in patients can be considered as an indirect consequence of hyperconsumption of antioxidant vitamins during prolonged states of immune activation.

Hyperhomocysteinemia in dementia.

Hyperhomocysteinemia is a strong risk factor for atherosclerotic vascular disease, and elevated serum homocysteine is correlated with vitamin B deficiency. In this pilot study, significantly elevated homocysteine levels were found in patients with Alzheimer's disease as well as in patients with vascular dementia, probably indicating similar pathophysiological pathways. We found significant correlations between low folic acid concentrations as well as high homocysteine concentrations and cognitive decline. Supplementation with folic acid may be an inexpensive way to reduce elevated homocysteine levels in demented patients.

Atrial natriuretic peptide-induced release of cyclic guanosine monophosphate by coronary bypass grafts.

BACKGROUND: Superior long-term patency rates of the internal mammary artery (IMA) versus saphenous vein (SV) after coronary artery bypass grafting are well documented. Higher production rates of vasodilating and platelet-inhibiting mediators (prostacyclin and nitric oxide) by the IMA seem to have a major impact on its long-term durability and resistance to coronary artery graft disease. For the right gastroepiploic artery (RGEA) marked release of protective mediators is reported as well. The vasodilating effect of cyclic guanosine monophosphate (cGMP) released after stimulation by atrial natriuretic peptide might serve as another graft protective system. The aim of the present study was to determine cGMP release by IMA, RGEA, and SV after atrial natriuretic peptide challenge. METHODS: Samples of human IMA (n = 19), RGEA (n = 7), and SV (n = 18) discarded during coronary artery bypass grafting were stimulated with 10(-6) mol/L atrial natriuretic peptide after a resting phase in nutrient medium. Release of cGMP was determined by 125-iodide radioimmunoassay. RESULTS: Basal cGMP production rates of the IMA (759.9 +/- 277.0 fmol/cm2) and RGEA (739.9 +/- 186.0 fmol/cm2) were higher than production rates of SV (281.2 +/- 64.0 fmol/cm2). Application of atrial natriuretic peptide led to a statistically significant increase of cGMP release in IMA grafts (1,939.3 +/- 778.0 fmol/cm2), whereas RGEA (618.4 +/- 141.3 fmol/cm2) and SV (221.7 +/- 64.5 fmol/cm2) remained at basal levels (p < 0.05). CONCLUSIONS: From these data we conclude that the IMA in comparison with the RGEA and SV produces more extracellular cGMP when stimulated by atrial natriuretic peptide. This effect might support the cGMP-mediated protective properties of nitric oxide and could underline the extraordinary suitability of the IMA as a bypass conduit.

Stimulated prostacyclin release by conduits used for coronary artery bypass grafting.

A direct comparison of the three coronary artery bypass conduits internal mammary artery (IMA), right gastroepiploic artery (RGEA), and saphenous vein (SV) concerning arachidonic acid (AA) stimulated release of the vasodilating and platelet inhibiting mediator prostacyclin was the aim of the present study. Pieces of saphenous vein (n = 16), right gastroepiploic artery (n = 8), and internal mammary artery (n = 19) were obtained from patients undergoing coronary artery bypass grafting. After a resting phase of 30 min in HEPES medium arachidonic acid (AA) was added in order to stimulate prostacyclin release. Time-dependent production of the stable prostacyclin metabolite 6-keto-prostaglandin F1 alpha was determined following stimulation. Under basal conditions the IMA (12.4 ng/cm2) and RGEA (12.0 ng/cm2) released more prostacyclin than saphenous vein (4.0 ng/cm2). After AA stimulation 6-keto-prostaglandin F1 alpha release at 30 min was as follows: IMA 806.0 ng/cm2, RGEA 35.9 ng/cm2, SV 82.3 ng/cm2 (p < 0.0001 within grafts, p < 0.0001 between grafts, ANOVA for repeated measures). The internal mammary artery in comparison with the right gastroepiploic artery and saphenous vein seems to be better protected against local thrombotic events and development of coronary artery graft disease with the aid of the vasodilating and platelet inhibiting mediator prostacyclin.

Diatomaceous earth lowers blood cholesterol concentrations.

In this study a potential influence of diatomaceus earth to lower blood cholesterol was investigated. During 12 weeks we monitored serum lipid concentrations in 19 healthy individuals with a history of moderate hypercholesterinemia (9 females, 10 males, aged 35 - 67 years). Individuals administered orally 250 mg diatomaceous earth three-times daily during an 8 weeks observation period. Serum concentrations of cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides levels were measured before study entry, every second week during the period of diatomaceous earth intake and 4 weeks after stop of intake. Compared to baseline (285.8 +/- 37.5 mg/dl = 7.40 +/- 0.97 mM) diatomaceous earth intake was associated with a significant reduction of serum cholesterol at any time point, reaching a minimum on week 6 (248.1 mg/dl = 6.43 mM, -13.2% from baseline; p<0.001). Also low-density lipoprotein cholesterol (week 4: p<0.05) and triglycerides levels decreased (week 2: p<0.05, week 4: p<0.01). Four weeks after intake of diatomaceous earth was stopped, serum cholesterol, low-density lipoprotein cholesterol and triglycerides still remained low and also the increase of high-density lipoprotein cholesterol became significant (p<0.05). Diatomaceous earth, a bioproduct, is capable of reducing blood cholesterol and positively influencing lipid metabolism in humans. Placebo-controlled studies will be necessary to confirm our findings.

The activated immune system and the renin-angiotensin-aldosterone system in congestive heart failure.

OBJECTS: The aim of the study was to investigate a possible relationship between plasma renin activity, angiotensin II, serum levels of angiotensin-converting enzyme, aldosterone and markers of immune activation in congestive heart failure (CHF). PATIENTS AND METHODS: Fifty-three patients (50 male, three female, mean age 46 +/- 16 years) with congestive heart failure were studied. Twenty-eight patients had I or II NYHA class of CHF and 25 patients had III or IV NYHA class (NYHA class, mean +/- SD: 2.3 +/- 0.9). Serum neopterin concentration and hormones were measured by commercial radioimmunoassays. Serum soluble receptors of tumour necrosis factor and interleukin-2 were determined by ELISA. RESULTS: All analytes significantly correlated with NYHA classes (P < 0.05). There existed correlations between neopterin and angiotensin-converting enzyme or aldosterone (rs = 0.35 and rs = 0.36, P < 0.05). The soluble tumour necrosis factor receptor concentrations correlated with plasma renin activity (rs = 0.38, P < 0.05). CONCLUSION: The result of our study suggest that there exists some relationship between the renin-angiotensin-aldosterone system and immune activation in severe congestive heart failure, however, the associations found are rather weak.

Rebound increase of plasminogen activator inhibitor type I after cessation of thrombolytic treatment for acute myocardial infarction is independent of type of plasminogen activator used.

Plasma concentrations of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), and D-dimer were investigated in 50 patients treated intravenously for acute myocardial infarction with either streptokinase (n = 23), urokinase (n = 17), or recombinant t-PA (rt-PA, n = 10). The fibrinolytic variables were measured by enzyme immunoassay on admission; 1, 2, 4, 6, 8, 12, and 24 h later; and then daily until day 7 after admission. In each subgroup of patients treated with different thrombolytic agents, PAI-1 increased significantly (P < 0.01) approximately 3 h after cessation of thrombolytic therapy. PAI-1 peak concentrations did not differ significantly (P = 0.82) among these three subgroups. t-PA and D-dimer did not differ significantly (P > 0.14) among subgroups except for higher t-PA in the rt-PA group attributable to detection of the therapeutically administered exogenous rt-PA by the t-PA assay. Our findings demonstrate a marked PAI-1 increase after thrombolytic therapy for acute myocardial infarction, which seems to be a common, drug-independent antifibrinolytic rebound phenomenon in response to thrombolytic treatment.