Platelet Malondialdehyde Research Articles

Malondialdehyde (MDA) as a Marker of Platelet Function in Rats with CCl4-Induced Toxic Hepatopathy

Blood platelets are pivotal cells in the process of hemostasis and thrombosis. In the majority of patients with severe liver disease, platelet function appeared defective. We determinate platelet adhesiveness, aggregability and MDA level, in rats with acute and chronic hepatopathy induced by CCl4 administration. Our data relieves that platelet functions are not only affected in chronic toxic affectation, but also in acute intoxication (p[0.05). Icosanoids production (expressed in MDA levels) are significantly decreased only in chronic CCl4 intoxication (p[0.001). Significant correlation appears between aggregability and MDA (r = -0.78) and adhesiveness and MDA (r = -0.57) in group C, with chronic CCl4 intoxication. The complexity of these platelet functions related to the hepatic disease is still a matter of debate and needs further investigation.

Native High-Density Lipoprotein and Melatonin Improve Platelet Response Induced by Glycated Lipoproteins

Activated platelets and glycated lipoproteins are responsible for atherothrombosis in diabetics. Melatonin and native high-density lipoproteins are crucial in the preservation of pro/oxidant-antioxidant balance. The aim of the present study was to investigate the in vitro effects of native high-density lipoproteins and melatonin on altering the platelet response induced by glycated lipoproteins. Low-density lipoproteins and high-density lipoproteins were purified from plasma by ultracentrifugation and were glycated with glucose for three weeks. After incubation with or without melatonin/or native highdensity lipoproteins, low-density lipoproteins, glycated low-density lipoproteins/glycated high-density lipoproteins were added to ADP-induced platelets. Oxidative parameters, caspase-3/9 and nitric oxide levels were measured spectrophotometrically; CD62-P/ annexin-V expression was determined by flow cytometry. In glycated low-density lipoprotein/glycated high-density lipoprotein-treated groups, platelet malondialdehyde/ protein carbonyl, P-selectin, annexin-V, caspase-3/9 levels were increased (ranging from P < 0.001 to P < 0.01); glutathione and nitric oxide levels were reduced (ranging from P < 0.001 to P < 0.01). In glycated low-density lipoprotein/glycated high-density lipoprotein-treated groups, melatonin treatment reduced malondialdehyde, protein carbonyl, CD62-P, annexin-V and caspase-3/9 (P < 0.001, P < 0.01) levels and elevated nitric oxide (only glycated low-density lipoproteins). In glycated low-density lipoprotein/glycated high-density lipoprotein-treated groups, native high-density lipoprotein treatment reduced malondialdehyde, protein carbonyl, annexin-V, caspase-3/9 levels (P < 0.001, P < 0.01) and increased glutathione; nitric oxide levels (only with gly-HDL). Both melatonin and high-density lipoproteins should be regarded as novel promising mechanism-based potential therapeutic targets to prevent atherothrombosis in diabetics.

Platelet oxidative stress and systemic inflammation in chronic spontaneous urticaria

Recent studies implicate the role of immune-inflammatory responses in chronic spontaneous urticaria (CSU). Although it is well known that platelets release inflammatory mediators and reactive oxygen species upon activation, their role in CSU is poorly characterized. The present study was designed to evaluate platelet oxidative stress [platelet malondialdehyde (MDA), platelet superoxide dismutase (SOD), platelet glutathione peroxidase (GPx)] and systemic inflammatory markers [plasma Interleukin-6 (IL-6), high sensitivity C-reactive protein (hs-CRP)] in patients with CSU and their association with disease severity. Forty-five patients with CSU and 45 age- and gender-matched healthy controls were included in the study. Severity grading was completed according to the urticaria severity score (USS). Autologous plasma skin test (APST) was done in all patients with CSU. Platelet MDA, SOD and GPx and inflammatory markers plasma IL-6 and hs-CRP were assayed in all study participants. In patients with CSU, platelet SOD and GPx were significantly lowered, while platelet MDA levels were significantly elevated in comparison to healthy controls. Both IL-6 and hs-CRP were significantly elevated in patients with CSU and correlated with platelet oxidative stress parameters (p<0.05). Platelet MDA, SOD and GPx and inflammatory markers (plasma IL-6 and hs-CRP) showed a significant correlation with USS in patients with CSU. Our results indicate significant systemic inflammation and platelet oxidative stress in patients with CSU.

The benefits of hormone replacement therapy on plasma and platelet antioxidant status and fatty acid composition in healthy postmenopausal women

Oxidative stress is suggested to play an important role in the pathogenesis of cardiovascular disease (CVD). Various hormone replacement therapy (HRT) protocols are used to reduce the CVD risk in postmenopausal women. Recent studies found that HRT lowers lipid levels and improves vascular endothelial function in postmenopausal women. In this study the effects of HRT on plasma and platelet membrane fatty acid composition and the oxidant-antioxidant system in postmenopausal women are investigated. Blood samples were obtained from 50 postmenopausal women. Before starting treatment, all participants underwent clinical, biochemical and hormonal screening procedures including gynecologic and physical breast examination. Then oral HRT (2 mg estrodiol valerate + 1 mg cyproterone acetate) were given to all subjects for 1 year. Levels of malondialdehyde (MDA), total thiol (t-SH) and fatty acid contents, activities of glutathione-Stransferase (GST) and superoxide dismutase (SOD) were measured before and after treatment. Platelet membrane palmitic, stearic and oleic acid contents decreased (6.5%, 22.5% and 21.9% respectively) and linoleic and arachidonic acid contents increased (21.2% and 25.4% respectively) after HRT. Platelet MDA, GST and SOD levels were lower and t-SH content was higher than pre-treatment levels. These results indicate that hormone replacement therapy may affect platelet membrane fatty acid content and oxidant-antioxidant balance in postmenopausal women.

The Association of Oxidant Status and Antioxidant Capacity in Children With Acute and Chronic ITP

This study was undertaken to investigate oxidant and antioxidant systems in patients with immune thrombocytopenic purpura (ITP). With this purpose, we measured the levels of serum malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS), and other oxidative stress parameters. Fifty-two pediatric patients with ITP (25 acute, 27 chronic) and 21 healthy children were included in the study. Patients with acute ITP were studied, before and after, methylprednisolone treatment. Hemoglobin, hematocrit, platelet count, and TAC were statistically significantly lower in patients with acute ITP before treatment than those in the control group (P<0.05). In addition, in this group, MDA, TOS levels, and OSI (oxidative stress index) were found to be higher than those in the control group. In chronic ITP group, although hemoglobin hematocrit, platelet counts, and TAC levels were statistically significantly lower than those in the control groups,the mean platelet volume, MDA, TOS, and OSI were found to be statistically significantly higher (P<0.05). Platelet count and mean platelet volume values were statistically significantly lower in patients with acute ITP before treatment than after treatment (P<0.05). We also found a positive correlation between thrombocyte count and TAC, in patients with acute ITP before treatment (r: 0.601, P<0.001) and acute ITP after treatment (r: 0.601, P<0.001) and chronic ITP (r: 0.601, P<0.001). A negative correlation was found between thrombocyte count and serum MDA levels, in patients with acute ITP before treatment (r: -0.356, P<0.001) and acute ITP after treatment (r: -0.356, P<0.001) and chronic ITP (r: -0.356, P<0.001). We also found a negative correlation between thrombocyte count and serum OSI, in patients with acute ITP before treatment (r: -0.494, P<0.001) and acute ITP after treatment (r: -0.494, P<0.001) and chronic ITP (r: -0.494, P<0.001). A negative correlation was found between thrombocyte count and TOS, in patients with acute ITP before treatment (r: -0.470, P<0.001) and acute ITP after treatment (r: -0.470, P<0.001) and chronic ITP (r: -0.470, P<0.001). In conclusion, increased MDA, TOS and OSI, and decreased TAC levels were found in patients with acute and chronic ITP. On the basis of these findings, we suggest that free oxygen radicals may have an effect on the structural and functional damage of platelets, and on the mechanism of thrombocytopenia in both, acute and chronic ITP.

Inhibitory Effect of Seabuckthorn (Hippophea rhamnoides) on Platelet Aggregation and Oxidative Stress

Extracts from seabuckthorn (Hippophea rhamnoides) leaves, fruit and seed oil were screened for anti-platelet properties in-vitro using human platelets stimulated with 0.2 mM ADP. Half maximal inhibitory concentration was found to be 55 microg/ml platelet rich plasma(PRP) for leaf extract, 47.7 microg/ml PRP for fruit extract and 0.62 microl/ml PRP for seed oil. In-vitro incubation of platelets with increasing concentrations of seed oil was found to inhibit oxidative stress in resting as well as agonist stimulated platelets as evident by decreased formation of peroxide and superoxide radicals. Leaf extract and seed oil were further evaluated for antiplatelet and antioxidant action in-vivo in cholesterol-induced experimental atherosclerosis in rabbits. Rabbits fed on diet supplemented with cholesterol (0.5% or 1%) for 60 days showed statistically significant increase in platelet aggregation stimulated by ADP and collagen as compared to platelet aggregation in control rabbits. Malondialdehyde levels in platelets of cholesterol fed rabbits were significantly higher than those of control rabbits. Both leaf extract and seed oil supplementation prevented cholesterol induced alterations in platelet aggregation and platelet malondialdehyde levels. The study shows that SBT leaf extract and seed oil inhibit oxidative stress and hyperactivity of platelets both in-vitro as well as in-vivo and plausibly attenuate atherogenesis.

Spice active principles as the inhibitors of human platelet aggregation and thromboxane biosynthesis

Spice active principles are reported to have anti-diabetic, anti-hypercholesterolemic, antilithogenic, anti-inflammatory, anti-microbial and anti-cancer properties. In our previous report we have shown that spices and their active principles inhibit 5-lipoxygenase and also formation of leukotriene C4. In this study, we report the modulatory effect of spice active principles viz., eugenol, capsaicin, piperine, quercetin, curcumin, cinnamaldehyde and allyl sulphide on in vitro human platelet aggregation. We have demonstrated that spice active principles inhibit platelet aggregation induced by different agonists, namely ADP (50 μM), collagen (500 μg/ml), arachidonic acid (AA) (1.0 mM) and calcium ionophore A-23187 (20 μM). Spice active principles showed preferential inhibition of arachidonic acid-induced platelet aggregation compared to other agonists. Among the spice active principles tested, eugenol and capsaicin are found to be most potent inhibitors of AA-induced platelet aggregation with IC50 values of 0.5 and 14.6 μM, respectively. The order of potency of spice principles in inhibiting AA-induced platelet aggregation is eugenol>capsaicin>curcumin>cinnamaldehyde>piperine>allyl sulphide>quercetin. Eugenol is found to be 29-fold more potent than aspirin in inhibiting AA-induced human platelet aggregation. Eugenol and capsaicin inhibited thromboxane B2 (TXB2) formation in platelets in a dose-dependent manner challenged with AA apparently by the inhibition of the cyclooxygenase (COX-1). Eugenol-mediated inhibition of platelet aggregation is further confirmed by dose-dependent decrease in malondialdehyde (MDA) in platelets. Further, eugenol and capsaicin inhibited platelet aggregation induced by agonists—collagen, ADP and calcium ionophore but to a lesser degree compared to AA. These results clearly suggest that spice principles have beneficial effects in modulating human platelet aggregation.

Malondialdehyde and coenzyme Q10 in platelets and serum in type 2 diabetes mellitus: correlation with glycemic control

This study investigated the level of platelet malondialdehyde (MDA) as a marker of oxidative stress and coenzyme Q10 (CoQ10) as an index of antioxidant capacity in patients with type 2 diabetes mellitus and their relation to glycemic control. The study group consisted of 28 patients with type 2 diabetes mellitus (10 men and 18 women) with mean age of 48 +/- 2 years. Ten healthy individuals, age and sex matched with the patients, were used as a control group. Laboratory investigations in the form of lipid profile, glycosylated hemoglobin, plasma MDA, platelet MDA and plasma CoQ10 were assessed for all patients and controls. The study revealed that plasma and platelet MDA, as a marker of oxidative stress, were significantly higher in diabetic patients than in controls. The level of CoQ10, as antioxidant capacity, was significantly lower in diabetic patients than in controls. There was a negative correlation between plasma CoQ10 concentrations and glycosylated hemoglobin. Type 2 diabetic patients are at increased risk of oxidative stress manifested by increased plasma MDA as well as platelet MDA and decreased CoQ10, and this oxidative stress increases with poor glycemic control.

Oxidized-LDL and Fe3+/Ascorbic Acid-Induced Oxidative Modifications and Phosphatidylserine Exposure in Human Platelets are Reduced by Melatonin

Low-density lipoprotein (LDL) modifications and platelet activation are major risk factors for cardiovascular diseases. When platelets are exposed to oxidative stress, they become activated. Oxidized LDL (ox-LDL) and metal-catalysed oxidation systems such as Fe3+/ascorbic acid increase free radical production. We wanted to verify whether melatonin has a protective effect against oxidative modifications and phosphatidylserine externalization in platelets induced by ox-LDL and Fe3+/ascorbic acid. For in vitro effects of melatonin on platelets, ADPactivated platelets were incubated with ox-LDL or Fe3+/ascorbic acid for 1 h at 37 °C with or without melatonin. Then platelet malondialdehyde, protein carbonyl and glutathione levels were measured. Platelet phosphatidylserine exposure was measured with annexin-V using flow cytometry. Malondialdehyde, protein carbonyl and phosphatidylserine levels of platelets treated with Fe3+/ascorbic acid significantly increased compared to the control group. Glutathione contents of Fe3+/ascorbic acid-treated platelets significantly decreased. Melatonin pre-treatment of Fe3+/ascorbic acid-treated platelets caused a marked reduction in malondialdehyde and phosphatidylserine levels and a marked increase in glutathione levels. Melatonin also caused non-significant reduction in protein carbonyl contents of Fe3+/ascorbic acid-treated platelets. Malondialdehyde, protein carbonyl and phosphatidylserine levels of platelets treated with ox-LDL also significantly increased compared to the control group. Platelet glutathione levels non-significantly decreased with ox-LDL. With addition of melatonin, malondialdehyde, protein carbonyl and phosphatidylserine levels of platelets treated with ox-LDL significantly decreased. These data suggest that melatonin may protect platelets from iron overload-induced and ox-LDL-induced oxidative modifications and also from the triggering signals of apoptosis activation, possibly due to its scavenger effect on toxic free radicals.

Do platelet apoptosis, activation, aggregation, lipid peroxidation and platelet–leukocyte aggregate formation occur simultaneously in hyperlipidemia?

Objectives: The circulating lipoproteins may cause some abnormalities in platelet composition and function in hypercholesterolemia. The aim of this study was to investigate whether platelet apoptosis, platelet activation, platelet aggregation, platelet–leukocyte aggregate (PLA) formation and lipid peroxidation occur simultaneously in hyperlipidemia. Design and methods: Expression of GpIIb/IIIa (CD41a), P-selectin (CD62-P), platelet-bound fibrinogen (antifibrinogen), platelet membrane phosphatidylserine (PS), platelet–monocyte aggregates (mono-PLA) and platelet–neutrophil aggregates (neut-PLA) was measured in eight hyperlipidemic and eight normal subjects using flow cytometry. ADP (10 μM) was used to activate platelets. Furthermore, ADP induced platelet aggregation responses, platelet malondialdehyde (MDA) and glutathione (GSH) levels were determined. Results: Before platelet activation, platelet CD62-P, antifibrinogen, annexin-V, mono-PLA, neut-PLA and platelet MDA levels as well as platelet aggregation responses in the hyperlipidemics were significantly higher than those in the controls ( P < 0.01, P < 0.01, P < 0.01, P < 0.001, P < 0.001, P < 0.01, P < 0.001, respectively), whereas GpIIb/IIIa expression and GSH levels were not different significantly ( P > 0.05). In the control group, CD62-P, antifibrinogen and annexin-V levels increased significantly after ADP activation ( P < 0.05, P < 0.05, P < 0.01, respectively). In hyperlipidemic subjects, annexin-V expression increased significantly after activation ( P < 0.01), whereas expression of GpIIb/IIIa, CD62-P and antifibrinogen remained unchanged ( P > 0.05). The levels of total cholesterol (T-CHO), low density lipoprotein cholesterol (LDL-C), serum fibrinogen (S-FGN) and high density lipoprotein cholesterol (HDL-C) in patients were found to be correlated with platelet CD62-P, antifibrinogen, annexin-V, mono-PLA and MDA. Conclusions: In conclusion, it seems that in hyperlipidemia, some platelets are in an activated state in circulation, and that increased lipid peroxidation, early apoptosis, platelet–leukocytes aggregate formation and platelet aggregation altogether accompany this process.

Short-term oral ingestion of Ginkgo biloba extract (EGb 761) reduces malondialdehyde levels in washed platelets of type 2 diabetic subjects

We have recently reported that ingestion of Ginkgo biloba extract (EGb 761) (a) significantly reduced collagen-induced platelet aggregation and thromboxane B 2 (TXB 2) production in both non-diabetic individuals as well as those with type 2 diabetes mellitus (T2DM), (b) significantly reduced platelet malondialdehyde (MDA), an index of lipid peroxidation, in non-diabetic subjects. In the present study we report that ingestion of EGb 761 (120 mg daily for 3 months), significantly decreased platelet MDA-thiobarbituric acid reacting substances (TBARS) (41 ± 9 pmol/10 7 platelets versus 30 ± 11 pmol/10 7 platelets) ( p < 0.005) in T2DM subjects with normal cholesterol levels (total cholesterol, 164 ± 22 mg/dl; age, 54 ± 9 years; BMI, 35.0 ± 8.8 kg/m 2, n = 12). In T2DM subjects with high cholesterol (total cholesterol, 218 ± 15 mg/dl; age, 52 ± 5 years; BMI, 36.2 ± 6.6 kg/m 2, n = 7), EGb 761 ingestion reduced the platelet TBARS from 29 ± 9 to 22 ± 9 pmol/10 7 platelets ( p < 0.04). Because ingestion of EGb 761 did not alter platelet counts it is concluded that EGb 761, probably due to the flavonoid fraction, reduced the TBARS by inhibiting cyclooxygenase (COX)-1-mediated arachidonic acid oxygenation or by reducing the arachidonic acid pool. This is likely to lead to a reduction of platelet hyperactivity, a significant contributor to the development of cardiovascular disease in T2DM patients. Because of other reported beneficial properties of EGb 761, such as stimulation of pancreatic β-cell function in T2DM subjects with pancreatic exhaustion, it appears that T2DM subjects might benefit from ingesting EGb 761 as a dietary supplement.

Retinal Neovascularization in Eales Disease

A study was undertaken, using fluorescein angiography, to correlate the area of capillary nonperfusion (CNP) with the occurrence of retinal neovascularization in 20 cases of Eales disease. Neovascularization elsewhere and neovascularization of the disc were found in eyes with greater than 20 and 60 disc areas CNP, respectively. The role of lipid peroxides in neovascularization was also studied biochemically. A significant increase in platelet malondialdehyde levels was observed in cases with neovascularization.

Coagulation profile and platelet function in patients with extrahepatic portal vein obstruction and non-cirrhotic portal fibrosis.

Coagulation disorders commonly develop in patients with cirrhosis of the liver. They have also been reported in patients with non-cirrhotic portal fibrosis (NCPF) and extra-hepatic portal venous obstruction (EHPVO); the two conditions with portal hypertension and near-normal liver functions. The spectrum and prevalence of coagulation abnormalities and their association with the pathogenesis of these diseases and with hypersplenism was prospectively studied. Eighteen EHPVO patients that included an equal number of NCPF patients and 20 healthy controls were prospectively studied. The coagulation parameters assessed included: international normalized ratio, partial thromboplastin time, and fibrinogen and fibrinogen degradation products. Platelet aggregation and malondialdehyde levels were measured. Both EHPVO (83%) and NCPF (78%) patients had a significantly prolonged international normalized ratio and a decrease in fibrinogen and platelet aggregation. The EHPVO patients had a significant prolongation in partial thromboplastin time (67% patients), with increased levels of fibrinogen degradation product levels occurring in all patients; these were normal in NCPF patients. Platelet malondialdehyde levels were normal in both groups. Hypersplenism was present in four EHPVO and seven NCPF patients. It did not significantly influence the coagulation profile in either NCPF or EHPVO patients. Coagulation anomalies are common and significant in both NCPF and EHPVO patients, suggestive of a mild disseminated intravascular coagulation disorder. These imbalances could be caused by chronic subclinical endotoxemia and cytokine activation after the initial portal thromboembolic event. The persistence of these abnormalities in adolescent patients indicates an ongoing coagulation derangement.

Effects of antiepileptic drugs on rat platelet aggregation: ex vivo and in vitro study

The influence of conventional antiepileptic drugs (valproate, phenobarbital, diazepam, clonazepam, carbamazepine and diphenylhydantoin) on rat platelet activation induced by arachidonic acid (AA) or adenosine-5′-diphosphate (ADP) was investigated both ex vivo and in vitro on platelet-rich plasma (PRP). It was found that only diazepam, and to a smaller extent clonazepam, impaired rat platelet function. These benzodiazepines did not affect ex vivo platelet aggregation induced by ADP but dose-dependent inhibition of platelet aggregation and malondialdehyde (MDA) synthesis were observed, when the platelets were stimulated with AA (ED 50 of diazepam for aggregation was 2.7 mg/kg and that for MDA synthesis — 3.9 mg/kg). In in vitro study, diazepam was found to be a potent inhibitor of AA-induced platelet aggregation (IC 50 1.2 μg/ml) and MDA synthesis (IC 50 4.0 μg/ml). Higher concentrations of diazepam were required to inhibit ADP-induced aggregation (IC 50 29.0 μg/ml). Clonazepam also exhibited a concentration-dependent inhibitory effect on AA-induced platelet aggregation and MDA synthesis but this effect was weaker when compared to diazepam. The present data demonstrate that diazepam possesed a strong inhibitory effect on rat platelet activation. The correlation between the reduction of platelet aggregation and the synthesis of MDA may suggest that the observed effect of diazepam is due to the inhibition of the cyclooxygenase pathway of the AA metabolism in platelet.

Comparative assessment of lacidipine and nifedipine GITS: Effects on blood pressure, platelet function, and insulin sensitivity in patients with hypertension

ObjectiveThe aim of the present study was to assess the effects on blood pressure, platelet aggregation, and insulin sensitivity of lacidipine and nifedipine gastrointestinal therapeutic system (GITS) given once daily in a parallel-group, double-blind, randomized study of patients with mild to moderate hypertension. MethodsTwenty patients (12 men, 8 women) with mild to moderate hypertension aged 45 to 56 years (average age, 50 ± 2.3 years) were included. They received placebo for 4 weeks and were then randomly divided into 2 groups of 10 patients each. Nifedipine GITS 30 mg and lacidipine 4 mg were given for 16 weeks. Blood pressure and heart rate were measured at the clinic in the supine, sitting, and standing positions 24 ± 1 hours after the last dose. At the end of the placebo and active phases the following procedures were performed: a platelet aggregation test; determination of platelet malondialdehyde production; and determination of tolerance to 100 g of glucose by measuring plasma insulin. ResultsBoth drugs significantly reduced systolic and diastolic blood pressures to the same level; however, observable differences in the rate of reduction were noted. In week 1, systolic blood pressure decreased 15.15% in the nifedipine GITS group and 6.54% in the lacidipine group. Heart rate was increased slightly but significantly in the standing position in the nifedipine GITS group only. Neither of the drugs reduced platelet aggregation ex vivo, however, both modified malondialdehyde production, indicating an effect at the arachidonic acid metabolic pathway. ConclusionsThe effects of the drugs on the metabolism of carbohydrates were inconclusive. However, a tendency for lacidipine to improve insulin sensitivity and for nifedipine GITS to have the opposite effect was observed.

Purine metabolites and malondialdehyde in platelets of diabetic patients

The concentration of some of the purine nucleotides and their metabolites together with that of malondialdehyde (MDA) have been measured in resting and stimulated platelets of type 1 and type 2 diabetic patients. While control platelets show a net decrease of guanosine triphosphate (GTP) (3.1 vs. 2.3 nmol per 10 9 platelets) and guanosine diphosphate (GDP) (3.0 vs. 2.0 nmol per 10 9 platelets) and a significant increase of adenosine (0.04 vs. 0.55 nmol per 10 9 platelets) with platelet stimulation, platelets of type 1 and type 2 diabetic patients have a lesser change of these metabolites (GTP, 2.6 vs. 2.4; GDP, 2.3 vs. 2.4; adenosine, 0.04 vs. 0.30 ( P<0.05 vs. control) nmol per 10 9 platelets in type 1 diabetics; GTP, 2.4 vs. 2.7; GDP, 2.4 vs. 2.1; adenosine, 0.08 vs. 0.32 ( P<0.05 vs. control) nmol per 10 9 platelets in type 2 diabetics). These results indicate that the change (stimulated minus resting) of GTP, GDP and adenosine in diabetic platelets is significantly different from that of controls ( P<0.001). Moreover, the amount of MDA produced during platelet activation seems to be lower than controls only in type 2 diabetes (1.81 vs. 2.86 nmol per 10 9 platelets, P<0.05). These results seem to indicate that a difference in the pattern of platelet nucleotides could be an important feature even in well-controlled diabetes, while MDA is probably modified only in association with the late vascular complications of diabetes.

Prostaglandin cyclooxygenase products but not thromboxane A2 are involved in the pathogenesis of ewthromelalgia in thrombocythaemia

Fluid of artificial blisters from erythromelalgic skin areas in primary thrombocythaemia contained a high amount of prostaglandin-E-like activity. Dazoxiben did not alleviate the erythromelalgia in patients with primary thrombocythaemia despite complete inhibition of platelet malondialdehyde and thromboxane B2 synthesis and no inhibition of prostaglandin-E-like material. During a 10-day dazoxiben treatment period, persistent erythromelalgia was associated with a significant shortened mean platelet life span of 3.2 days. During subsequent treatment with low dose acetylsalicylic acid daily complete relief of erythromelalgia was associated with inhibition of platelet prostaglandin endoperoxide production and correction of platelet mean life span to normal, 7.9 days. These observations indicate that prostaglandin E2, or another prostaglandin endoperoxide metabolite, is involved in the pathogenesisof erythromelalgia. The presented study does not give one single clue as to the origin (platelet, vessel wall or other) of the prostanoid, but very likely originates from platelets because a very low dose of acetylsalicylic acid (250 to 500 mg every other day), which irreversibly inhibits platelet cyclooxygenase, is highly effective in the prevention of erythromelalgia in thrombocythaemia.

Red blood cells and platelet membrane fatty acids in non-dialyzed and dialyzed uremies

Three groups of patients with chronic renal failure (CRF), 16 non-dialyzed, 16 undergoing haemodialysis (HD), 16 undergoing continuous ambulatory peritoneal dialysis (CAPD), and 48 controls were examined. We analyzed the fatty acid composition in membranes from erythrocytes and platelets and the platelet malondialdehyde (MDA) production as an index of thromboxane metabolism. Marked differences in erythrocytes fatty acid composition were observed between patients with CRF and controls and, particularly, among the three groups of patients with CRF. Patients on CAPD were characterized by an increase in oleic acid, while haemodialyzed had a marked increase in arachidonic acid. Platelet fatty acid composition showed similar differences, suggesting a ‘systemic’ membrane abnormality. Platelet MDA was increased in haemodialyzed and positively correlated with the platelet arachidonate content.

The antihistamine drug cimetidine and arachidonic acid metabolism

Results of our previous study showed that the antihistamine drug cimetidine inhibited functions of blood platelets. The aim of the present paper was to analyse in detail the mechanism of this action. We focussed our attention on the effect of cimetidine on three steps of arachidonic acid metabolism-liberation of arachidonate, biosynthesis of thromboxane A2 and malondialdehyde formation. Cimetidine in the concentration range from 0.01 to 1 mmol/l did not inhibit either thrombin-stimulated liberation of3H-arachidonic acid from individual platelet phospholipids nor malondialdehyde production. Cimetidine at the concentration of 1 mmol/l, however, significantly inhibited the production of thromboxane B2, the stable metabolite of TXA2. Cimetidine appears to inhibit platelet functions by inhibiting arachidonic acid metabolism at the step of conversion of cyclic endoperoxides, PGG2 and PGH2, to thromboxane A2.

Age-related changes in arachidonic acid peroxidation and glutathione-peroxidase activity in human platelets

Lipid peroxidation, vitamin E level and glutathione-peroxidase activity were determined in platelets from elderly (>68 years) and young (21–43 years) people. To further assess the platelet lipid peroxidation, the metabolism of endogenous arachidonic acid in unstimulated platelets as well as that of the exogenous one were measured in the two groups. The oxygenated metabolites of arachidonic acid were enhanced in the elder population under both conditions tested. In addition, the platelet malondialdehyde content, a marker of the overall lipid peroxidation, was also found significantly increased in platelets from aged subjects. On the other hand, the platelet vitamin E level and the glutathione-peroxidase activity were significantly depressed in the elder group compared to the young one. These results suggest that the increased platelet activation observed with age could be linked to the accumulation of lipoxygenase-dependent peroxides associated with the decreased antioxidative defence of the cells, especially glutathione-peroxidase activity.