Biomedical subjects

F Franconi

Publications and source records attributed to F Franconi.

At least 37 records · Page 2Linked to original sources

PubMed2000

An in-vivo magnetic resonance imaging study of the olfactory bulbectomized rat model of depression.

The olfactory bulbectomized (OB) rat is a well-accepted animal model of depression. The present magnetic resonance imaging (MRI) investigation demonstrates alterations in signal intensities in cortical, hippocampal, caudate and amygdaloid regions in OB animals, but not in sham operated controls. Ventricular enlargement was also evident in OB animals. These alterations have implications with regard to the face and construct validity of this model.

Amygdala↗

PubMed2000

Modulation by alpha- and gamma-tocopherol and oxidized low-density lipoprotein of apoptotic signaling in human coronary smooth muscle cells.

Apoptosis may play an important role in atherogenesis. Oxidized low-density lipoprotein (oxLDL) promotes apoptosis in the arterial wall in addition to several other proatherogenic effects. Tocopherol supplements have been suggested to protect against coronary heart disease (CHD) in epidemiological studies. The effects of oxLDL and alpha- and gamma-tocopherol on apoptotic signaling pathways are poorly understood. Thus, the goal of the study was to investigate these pathways in the presence of copper-oxidized LDL and tocopherols in human coronary smooth muscle cells (SMC). We showed that oxLDL-mediated apoptosis, assessed by DNA fragmentation, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, and caspase activation stimulated several transcription factors and proapoptotic dynamic movements of the Bcl-2 family proteins through the mitogen-activated protein kinase (MAPK) and Jun kinase pathways. alpha-Tocopherol and gamma-tocopherol significantly reduced these molecular events and cell death effectors caspase-3 and -8. Under our experimental conditions, alpha-tocopherol was significantly more effective than gamma-tocopherol, and oxLDL-mediated apoptosis increased c-Jun, cyclic AMP-responsive element-binding, Ets-like element kinase-dependent 7, and activating transcription factor-2 proteins as well as nuclear activity of the activated protein-1 complex in human coronary SMC. Moreover, our results demonstrate that tocopherols may exert their antiatherogenic effects at least in part via reduction of the MAPK and JunK cascade together with a protective profile of apoptotic genes of the Bcl-2 family. These data are consistent with the beneficial effects of tocopherols on atherogenesis seen in experimental studies and on CHD in epidemiological surveys.

Adult↗

PubMed2000

Clinical and pharmacological profile in a clenbuterol epidemic poisoning of contaminated beef meat in Italy.

Long-acting beta adrenergic agonists, such as clenbuterol accumulate in the liver, but not meat of treated farm animals, and result in epidemic poisonings in consumers. We describe an outbreak of poisoning in 15 people, following the consumption of meat. Clinical symptoms (distal tremors, palpitations, headache, tachipnoea-dyspnoea, and also moderate hyperglycaemia, hypokalemia and leucocytosis) were seen in nine hospitalised patients, starting about 0.5-3 h after poisoning, and disappearing within 3-5 days later. Clenbuterol was found in the urine of all the symptomatic patients, at higher levels than pharmacokinetic computing (mean level 28 ng/ml, 36 h after ingestion), based on the levels found in the meat (1140-1480 ng/g edible tissue). Thus, epidemic poisoning can be produced following the consumption of contaminated meat. The need for a better definition of pharmaco- and toxico-kinetics, not only for drugs ingested as parent drug, but also when ingested as residues with animal tissues, is recommended.

Adrenergic beta-Agonists↗

PubMed2000

Protease-activated receptor-2 modulates myocardial ischemia-reperfusion injury in the rat heart.

Protease-activated receptor-2 (PAR-2) is a member of seven transmembrane domain G protein-coupled receptors activated by proteolytic cleavage whose better known member is the thrombin receptor. The pathophysiological role of PAR-2 remains poorly understood. Because PAR-2 is involved in inflammatory and injury response events, we investigated the role of PAR-2 in experimental myocardial ischemia-reperfusion injury. We show for the first time that PAR-2 activation protects against reperfusion-injury. After PAR-2-activating peptide (2AP) infusion, we found a significant recovery of myocardial function and decrease in oxidation at reflow. Indeed, the glutathione cycle (glutathione and oxidized glutathione) and lipid peroxidation analysis showed a reduced oxidative reperfusion-injury. Moreover, ischemic risk zone and creatine kinase release were decreased after PAR-2AP treatment. These events were coupled to elevation of PAR-2 and tumor necrosis factor alpha (TNFalpha) expression in both nuclear extracts and whole heart homogenates. The recovery of coronary flow was not reverted by L-nitroarginine methylester, indicating a NO-independent pathway for this effect. Genistein, a tyrosine kinase inhibitor, did not revert the PAR-2AP effect. During early reperfusion injury in vivo not only oxygen radicals are produced but also numerous proinflammatory mediators promoting neutrophil and monocyte targeting. In this context, we show that TNFalpha and PAR-2 are involved in signaling in pathophysiological conditions, such as myocardial ischemia-reperfusion. At the same time, because TNFalpha may exert pro-inflammatory actions and PAR-2 may constitute one of the first protective mechanisms that signals a primary inflammatory response, our data support the concept that this network may regulate body responses to tissue injury.

Animals↗

PubMed2000

High-field quantitative transverse relaxation time, magnetization transfer and apparent water diffusion in experimental rat brain tumour.

The potential of quantitative parameter images of transverse relaxation time T(2), apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR) to characterize experimental brain tumours was studied. Necrosis or haemorrhage can be detected using either MTR, ADC or T(2) (necrosis-MTR reduced by 35%, ADC and T(2) increased respectively by 170% and 100% compared with normal brain tissue; haemorrhage-MTR increased by 60%, ADC and T(2) decreased by 40% and 20%, respectively). Normal brain tissue can only be distinguished from tumour on T(2) and MTR parameter images. However, for small tumours (10 microl), the best contrast is observed with MTR, ca. 30%, whereas for T(2) the contrast is ca. 10%.

Animals↗

PubMed2000

In vivo quantitative microimaging of rat spinal cord at 7T.

In vivo T(2), ADC, and MT properties of the GM and WM of the rat spinal cord were measured at 7T in the cervical region. The GM T(2), T(2GM) = 43.2 +/- 1.0 msec is significantly reduced compared to the WM T(2), T(2WM) = 57.0 +/- 1.6 msec. Diffusion is anisotropic for both GM and WM, with a larger ADC value along the cord axis (ADC(GM//) = 1.05 +/- 0.09 10(-9) m(2)sec(-1) and ADC(WM//) = 1.85 +/- 0.18 10(-9) m(2)sec(-1)) than perpendicular to this plane (ADC(GM)( perpendicular) approximately 0.50 * 10(-9) m(2)sec(-1) and ADC(WM)( perpendicular) approximately 0.18 * 10(-9) m(2)sec(-1)). The MT properties do not significantly differ between the WM and the GM, but allow one to distinguish the thin CSF layer from the WM. DWI with the sensitizing gradient perpendicular to the cord axis leads to the best contrast between GM and WM in the cervical region.

Analysis of Variance↗

PubMed2000

Relationship between metabolic glycaemic control and platelet content of glutathione and its related enzymes, in insulin-dependent diabetes mellitus.

The relationship between glycaemic metabolic control and intracellular concentration of reduced glutathione (GSH) and related enzymes GSH-peroxidase (GSH-Px), GSH-reductase (GSH-Red), GSH-transferase (GSH-Tr), glucose-6-P-dehydrogenase (G6PDH), and thioltransferase (TT) in patients with insulin-dependent diabetes mellitus (IDDM) is controversial. Choosing platelets as cell model (as commonly done in previous studies), the aim of this study was to relate the platelet content of GSH and related enzymes to glycaemic metabolic control, expressed as glycated haemoglobin (HbA1c), as well as to presence of retinopathy and nephropathy in 114 IDDM patients. As compared to controls, both GSH and GSH-Red (geometric means (95% CI)) were significantly increased in platelets of diabetic patients: 3.3 (0.7-9.6) vs. 2.4 (0.8-7.6) mmol 10(-9) platelets; P=0.01 for GSH, and 30.6 (14.7-61.6) vs. 22.2 (8.7-52.2) mU 10(-9) platelets, P=0.0002 for GSH-Red, and TT activity was marginally decreased in the IDDM group (P=0.06). While no clear relationship was present between GSH-related enzymes and HbA1c, a trend was present toward a non-linear relation between HbA1c and GSH, being significantly related by a parabolic curve (P=0.002). As compared to patients with normoalbuminuria (n=88), diabetic patients with increased urinary albumin excretion rate (n=26) had a significant decrease in platelet TT concentration (3.2 (0.9-6.7) vs. 5.1 (1.9-18.7) mU 10(-9) platelets; P=0.0002), whereas retinopathy was not associated to modifications in GSH or in the enzymatic pattern. In summary: (a) platelet GSH and GSH-Red are increased in IDDM, while other enzymes are unmodified; (b) GSH seems to be related to metabolic control according to non-linear parabolic curve; (c) presence of increased albuminuria is associated to a selective decrease in platelet TT content.

Adult↗

PubMed2000

Resveratrol inhibition of lipid peroxidation.

To define the molecular mechanism(s) of resveratrol inhibition of lipid peroxidation we have utilized model systems that allow us to study the different reactions involved in this complex process. Resveratrol proved (a) to inhibit more efficiently than either Trolox or ascorbate the Fe2+ catalyzed lipid hydroperoxide-dependent peroxidation of sonicated phosphatidylcholine liposomes; (b) to be less effective than Trolox in inhibiting lipid peroxidation initiated by the water soluble AAPH peroxyl radicals; (c) when exogenously added to liposomes, to be more potent than alpha-tocopherol and Trolox, in the inhibition of peroxidation initiated by the lipid soluble AMVN peroxyl radicals; (d) when incorporated within liposomes, to be a less potent chain-breaking antioxidant than alpha-tocopherol; (e) to be a weaker antiradical than alpha-tocopherol in the reduction of the stable radical DPPH*. Resveratrol reduced Fe3+ but its reduction rate was much slower than that observed in the presence of either ascorbate or Trolox. However, at the concentration inhibiting iron catalyzed lipid peroxidation, resveratrol did not significantly reduce Fe3+, contrary to ascorbate. In their complex, our data indicate that resveratrol inhibits lipid peroxidation mainly by scavenging lipid peroxyl radicals within the membrane, like alpha-tocopherol. Although it is less effective, its capacity of spontaneously entering the lipid environment confers on it great antioxidant potential.

Antioxidants↗

PubMed2000

MRI study of transient cerebral ischemia in the gerbil: interest of T2 mapping.

RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the diagnostic use of MRI and, more precisely, the use of quantitative T2 imaging at 7 T for the early detection of neuronal cerebral alterations after transient ischemia in the gerbil. METHODS: One hundred forty-seven Mongolian gerbils were separated into four groups for which a bicarotid artery occlusion lasted for 4, 6, 8, or 10 minutes, respectively. The animals were scanned before carotid artery occlusion and at 3, 6, 10, 24, and 48 hours and 5 days after the ischemic incident. MR images were acquired on a Bruker Avance DRX300 mini-imaging system. RESULTS: Our results show that T2 mapping is able to localize brain damage induced by transient ischemia and to detect early perturbations in water content (as early as 6 hours after ischemia). CONCLUSIONS: T2 measurements in the striata are correlated with the severity of the ischemic incident, since the changes observed on the T2 images are directly proportional to the duration of occlusion.

Animals↗

PubMed1999

Idazoxan does not prevent but worsens focal hypoxic-ischemic brain damage in neonatal Wistar rats.

We examined the neuroprotective efficacy of a post-treatment with idazoxan (Idaz): an alpha2-adrenoceptor antagonist with activity at the I1- and I2-subtypes of the imidazoline receptor (I-receptor), in an experimental model of perinatal hypoxic-ischemic (HI) brain damage. Seventy-two, 7-day-old Wistar rats were subjected to permanent unilateral ligation of the common carotid artery and transient (2 hr) hypoxia (8% O(2)). The surviving animals were sub-divided into 3 groups: one "control" group received intraperitoneal (i.p.) injection of saline (Sigma; n = 21) and two "treated" groups received, 10 min post-HI, i.p. treatments with Idaz (I3: 3 mg/kg; n = 19) or (I8: 8 mg/kg; n = 20). Idaz effects were assessed by TTC-staining 72 hr post-HI for Sigma (n = 13), I3 (n = 11), and I8 (n = 12) groups and by MRI-examination 5 weeks post-HI for Sigma (n = 8), I3 (n = 8), and I8 (n = 6) groups. Total ratio of brain infarct areas were significantly (P < 0.01) different between Sigma and Idaz-treated rats: 20.9 +/- 4.0%, 35.6 +/- 5.9 % and 36.8 +/- 5.8% for Sigma, I3 and I8, respectively, when determined with TTC-staining and; 23.3 +/- 3.7%, 39.8 +/- 4.2%, and 43.2 +/- 10.1%, for Sigma, I3, and I8, respectively, when assessed by MRI. Our results suggest that Idaz, given as a post-HI treatment, does not exert neuroprotective effects but enhances the brain injury induced by focal neonatal cerebral HI. The deleterious mechanism may result from an overactivity of sympathetic tone and/or the immaturity of central I-receptors in newborn rats.

Animals↗

PubMed1999

Anisotropy of water diffusion in corona radiata and cerebral peduncle in patients with hemiparesis.

Diffusion tensor imaging is a magnetic resonance method which provides quantitative measurements of the directionality (anisotropy) of diffusion. Anisotropy measurements can be used to obtain quantitative information about the microstructural integrity of white matter tracts. In intact tracts diffusion is restricted and directional because water molecules move predominantly longitudinally to tracts. The aim of this study was to measure the anisotropy of diffusion in patients with chronic hemiparesis. We measured in the corona radiata and the cerebral peduncle in 10 patients with a chronic hemiparesis and supratentorial lesions and 10 control subjects in regions of interest. In all patients anisotropy was reduced in the coronal radiata contralateral to the hemiparesis by more than 3 SD compared to control subjects. In three patients, each of which had a severe hemiparesis, anisotropy in the cerebral peduncle was reduced by more than 3 SD compared to normal control subjects. Our findings suggest that reduced anisotropy is associated with chronic hemiparesis.

Adult↗

PubMed1999

Improving the detection of low concentration metabolites in magnetic resonance spectroscopy by digital filtering.

In vivo detection and quantitation of metabolites is often limited by their low concentration. As far as magnetic resonance spectroscopy (MRS) is concerned, detection and quantitation can be significantly improved by reduction of the observed spectral width (SW). The reduction is limited to the spreading of resonances in the bandwidth unless high performance digital filters are used. Indeed, these filters avoid the folding of unwanted resonances such as water peak into the main frequency spectrum and therefore allow reduction of the spectral width to its optimal value. These filters are now available on most MRS systems but their use is not common even if, as we show in the particular case of proton MRS, a significant increase in signal-to-noise ratio (two-fold factor for SW reduction from 5000 Hz to 1351 Hz) can be achieved. This signal-to-noise improvement allows better quantitation accuracy.

Humans↗

PubMed1999

Cerebral MRI on fetuses submitted to repeated cocaine administration during the gestation: an ovine model.

The aim of this study was to determine the role of Magnetic Resonance Imaging (MRI) in investigating fetal cerebral lesions induced by long term exposure to cocaine during sheep pregnancy. Cerebral Magnetic Resonance Imaging was performed on two groups of fetuses at 125 days of gestation (normal gestation: 145 days). The control group consisted of eight fetuses of four pregnant ewes. The study group consisted of eight fetuses of four pregnant ewes receiving daily 140 mg/kg injection of cocaine from day 60 until delivery. The following MR sequences were applied: T1-weighted FLASH, and T2-weighted Fast-Spin-Echo. Cerebral images were evaluated semi quantitatively using the following criteria: Heterogenicity, contrast between grey and white matter, contours irregularity, hyposignal, lateral ventricle sizes. The brightness distribution and homogenicity of the images were analysed by means of edge pair distributions using a new computerized method originally designed for ultrasound images analysis developed by Ultrasight inc (USA). (1) Flash T1: Heterogenic areas and irregular contours were more frequent in cocaine exposed fetuses. The contrast between grey and white matter was more important in the cocaine group. Hyposignal was found only in the cocaine group. Enlarged lateral ventricle occurred more frequently in the cocaine group. (2) Spin echo T2: The contrast between grey and white matter was higher and the contours of the brain more irregular in the cocaine group. Heterogenicity and hyposignal were also more frequent in this group but the difference with the control group was not significant. The computerized analysis of the contrast density on the cerebral images showed that 88% of the areas exceeding the reference level concerned the cocaine group, while only 14% of the areas exceeding the reference level concerned the control group. Long term exposure to cocaine induces cerebral tissue modifications, in favor of an advanced maturation and the development of hypoxic lesions. The histology of the brains confirmed in the cocaine group, the existence of hypoxic lesions with gliosis, perivascular edema and hemorrhages, and neuronal death.

Animals↗

PubMed1999

Beneficial effects of ACE-inhibition with zofenopril on plaque formation and low-density lipoprotein oxidation in watanabe heritable hyperlipidemic rabbits.

The effects of angiotensin-converting enzyme (ACE)-inhibition with zofenopril on the development of atherosclerosis and low-density lipoprotein (LDL) oxidation were determined in Watanabe Heritable Hyperlipidemic (WHHL) rabbits. Rabbits received either placebo (n = 6) or 0.5 mg/kg/day of zofenopril (n = 6). After 6 weeks of treatment, the computer-assisted analysis revealed that zofenopril reduced the aortic and common carotid corrected cumulative lesion area by 34% and 39%, respectively (p < 0.05 vs placebo-treated group). The intimal/medial ratio of the largest fatty streaks was 0.426+/-0.158 in the zofenopril-treated group and 0.875+/-0.238 in the placebo-treated group (p < 0.05). Furthermore, we found in the zofenopril-treated group smaller lesions with an intimal/medial ratio of zofenopril also reduced plasmatic LDL oxidation, as shown by significant reduction of malondialdehyde content (p < 0.01) and relative agarose gel mobility (p < 0.05), as well as by the prolongation of the lag-time (p < 0.05). Compared to zofenopril-treated rabbits, arterial sections of the placebo-group had significant increase in the intimal presence of macrophages-derived foam cells (p < 0.05), ox-LDL (p < 0.01), and native LDL (p < 0.01) detected by immunocytochemistry with RAM-11, MDA2 and NP1533975 monoclonal antibodies, respectively. To investigate the amount of platelet accumulation in the atherosclerotic plaque we also measured platelet-associated radioactivity. Autologous platelets were labeled with 111Indiumoxine and injected intravenously. After 2 hours, WHHL were sacrificed and arterial sections were counted for platelet-associated radioactivity. In the placebo-treated group, platelet radioactivity was 0.52+/-0.12 equivalent of radioactivity per mg of tissue in the common carotid and 0.25+/-0.18 in the abdominal aorta; in contrast, rabbits treated by zofenopril had 0.20+/-0.12 in the common carotid and 0.06+/-0.01 in the abdominal aorta. These data indicate that ACE-inhibition with zofenopril has antiatherosclerotic and antioxidant effects in WHHL-rabbits. Our results also shows that these effects could be linked to a reduced wall-associated platelet deposition at the site of atherosclerotic lesions.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Reduced anisotropy of water diffusion in structural cerebral abnormalities demonstrated with diffusion tensor imaging.

We used diffusion tensor imaging (DTI) to investigate the behavior of water diffusion in cerebral structural abnormalities. The fractional anisotropy, a measure of directionality of the molecular motion of water, and the mean diffusivity, a measure of the magnitude of the molecular motion of water, were measured in 18 patients with longstanding partial epilepsy and structural abnormalities on standard magnetic resonance imaging and the results compared with measurements in the white matter of 10 control subjects. Structural abnormalities were brain damage (postsurgical brain damage, nonspecific brain damage, perinatal brain damage, perinatal infarct, ischemic infarct, perinatal hypoxia, traumatic brain damage (n = 3), mitochondrial cytopathy and mesiotemporal sclerosis), dysgenesis (cortical dysplasia (n = 2) and heterotopia) and tumors (meningioma (n = 2), hypothalamic hamartoma and glioma). Anisotropy was reduced in all structural abnormalities. In the majority of abnormalities this was associated with an increased mean diffusivity; however, 30% of all structural abnormalities (some patients with brain damage and dysgenesis) had a normal mean diffusivity in combination with a reduced anisotropy. There was no correlation between fractional anisotropy and mean diffusivity measurements in structural abnormalities (r = -0.1). Our findings suggest that DTI is sensitive for the detection of a variety of structural abnormalities, that a reduced anisotropy is the common denominator in structural cerebral abnormalities of different etiologies and that mean diffusivity and fractional anisotropy may be, in part, independent. Combined measurements of mean diffusivity and fractional anisotropy are likely to increase the specificity of DTI.

Adolescent↗

PubMed1999

Wallerian degeneration in the optic radiation after temporal lobectomy demonstrated in vivo with diffusion tensor imaging.

PURPOSE: Diffusion tensor imaging allows the quantitative assessment of the microstructural organization of tracts in vivo (MR tractography). We used the new technique of MR tractography to demonstrate the effects of temporal lobectomy on the optic radiation. METHODS: Spatially normalised maps encoding magnitude of the bias (anisotropy) of diffusion of three patients with temporal lobe resections were compared with spatially normalised diffusion maps of 22 control subjects. All three patients were operated on for the treatment of medically intractable temporal lobe epilepsy and had a normal neurologic examination before surgery. One patient had an amygdalocorticectomy. Two patients had standard en bloc resections, one of whom developed a homonymous hemianopia after surgery. RESULTS: In the patient with hemianopia, a significant reduction of diffusion anisotropy (greater than mean+/-2 SD) consistent with wallerian degeneration was demonstrated in the optic radiation on the side of the temporal lobectomy, extending from the temporal to the occipital lobe. In the other patient with standard en bloc resection but clinically no hemianopia, the optic radiation was only marginally affected. In the third patient (amygdalocorticectomy), the diffusion anisotropy was within the normal range in the expected position of the optic radiation. CONCLUSIONS: Our findings show that MR tractography may be a useful tool to demonstrate wallerian degeneration in the optic radiation after temporal lobectomy in patients with hemianopia. This is the first time that this new method has been applied in postoperative imaging; it enables us to visualise the morphologic correlate of dysfunctional pathways after epilepsy surgery in vivo. The potential for using MR tractography to study other aspects of epilepsy is discussed.

Anisotropy↗

PubMed1998

Further insights into the anti-aggregating activity of NMDA in human platelets.

1. In the present study the effect of N-methyl-D-aspartate (NMDA) on thromboxane B2 synthesis and on [Ca2+]i was studied in human platelets. 2. NMDA (10(-7) M) completely inhibited the synthesis of thromboxane B2 from exogenous arachidonic acid (AA), while it did not interfere with the aggregating effect of the thromboxane A2 receptor agonist U-46619. 3. NMDA (0.1 microM - 10 microM) dose-dependently increased intracellular calcium in washed platelets preloaded with fura 2 AM, and this effect was not additive with that of AA. 4. NMDA shifted the dose-response curve of AA to the right. At the highest AA concentrations platelet aggregation was not inhibited. 5. The antiaggregating effect of NMDA was not antagonized by N(G)-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase (NOS) inhibitor. 6. Finally, NMDA (0.01 nM - 100 nM) associated with either aspirin or indomethacin significantly potentiated the antiaggregating activity of both cyclo-oxygenase inhibitors. 7. It was concluded that NMDA is a potent inhibitor of platelet aggregation and thromboxane B2 synthesis in human platelet rich plasma (PRP).

Aspirin↗

PubMed1998

Plasma and platelet ascorbate pools and lipid peroxidation in insulin-dependent diabetes mellitus.

BACKGROUND: As diabetes mellitus represents a situation in which production of peroxides is increased, the aim of this study was to investigate the relationship between plasma and platelet levels of ascorbic acid (AA)/dehydroascorbic acid (DHA) and those of malonyldialdehyde (MDA), an indirect marker of lipoperoxides, both assayed using high-performance liquid chromatography (HPLC), in 59 patients with insulin-dependent diabetes mellitus (IDDM) compared with 51 healthy control subjects matched for sex, age, smoking habits, as well as for dietary intake of energy, alcohol and vitamin C. RESULTS: Mean plasma and platelet MDA were significantly higher in the patients affected with IDDM than in control subjects. Moreover, the diabetic group was characterized by a huge decrease in plasma AA [8.45 +/- 5.5 mumol L-1 (SD) vs. 33.4 +/- 7.6 mumol L-1, P = 0.0001], mirrored by a significant increase in plasma DHA (11.9 +/- 3.9 mumol L-1 vs. 3.9 +/- 2.5 mumol L-1, P = 0.0001). No detectable DHA was observed in the platelets from both diabetic and control subjects, whereas AA was significantly increased in platelets from diabetic patients compared with control subjects (42.6 +/- 7.4 vs. 34.8 +/- 5.1 nmol 10(-9) platelets, P = 0.0001). Platelet AA in the diabetic group was significantly inversely correlated with glycated haemoglobin (r = -0.34; P = 0.04) and directly with plasma AA (r = 0.39; P = 0.02), the sum of plasma AA + DHA (r = 0.44; P = 0.009) and with platelet MDA (r = 0.38; P = 0.02). CONCLUSION: (a) The ratio plasma AA/DHA is significantly lowered in IDDM in association with an increase in MDA levels; (b) only AA is detected in platelets, being augmented in the diabetic group; (c) plasma ascorbate depletion does not reflect platelet levels of AA; and, finally, (d) metabolic control, as well as intracellular lipoperoxides, modulates platelet AA in IDDM.

Adult↗