Heavy metals and fertility

Heavy metals have been identified as factors affecting human fertility. This study was designed to investigate whether the urinary heavy metal excretion is associated with different factors of infertility. The urinary heavy metal excretion was determined in 501 infertile women after oral administration of the chelating agent 2,3-dimercaptopropane-1-sulfonic acid (DMPS). Furthermore, the influence of trace element and vitamin administration on metal excretion was investigated. Significant correlations were found between different heavy metals and clinical parameters (age, body mass index, nationality) as well as gynecological conditions (uterine fibroids, miscarriages, hormonal disorders). Diagnosis and reduction of an increased heavy metal body load improved the spontaneous conception chances of infertile women. The DMPS test was a useful and complementary diagnostic method. Adequate treatment provides successful alternatives to conventional hormonal therapy.     

DMPS-arsenic challenge test. I: Increased urinary excretion of monomethylarsonic acid in humans given dimercaptopropane sulfonate

The purpose of the present study was to evaluate in a novel manner the arsenic exposure of humans living in two towns in Northeastern Chile. Residents of one town drink water containing 593 microg As/l. Those in the control town drink water containing 21 microg As/l. Our hypothesis was that the administration of the chelating agent, 2,3-dimercaptopropane-1-sulfonic acid, Na salt (DMPS, DIMAVAL) would increase the urinary excretion of arsenic, alter the urinary profile of arsenic species and thus result in a better indication of the body load of arsenic and a better biomarker for arsenic exposure. The method used to evaluate these subjects was to give them 300 mg DMPS by mouth, after an overnight fast, and collect urine at specified time periods. The urine samples were analyzed for inorganic arsenic, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and total arsenic by hydride generation and atomic absorption spectrophotometry. The results indicated that: 1) During the 2-hr period after DMPS administration, MMA represented 42%, inorganic As, 20 to 22% and DMA, 37 to 38% of the total urinary arsenic. The usual range of the MMA percentage in human urine has been 10 to 20%. The % MMA increased almost equally for both the arsenic-exposed and control subjects. 2) The exposed subjects had a greater urinary excretion of total arsenic, before and after DMPS administration, than the control subjects. 3) Although buccal cells were obtained only from a few subjects, the prevalence of mononucleated buccal cells, an indication of genotoxicity, was 5-fold greater for those who consumed drinking water with the higher arsenic content than among control subjects. Our conclusions are that 1) DMPS has a highly specific effect in humans on MMA metabolism and/or urinary excretion; 2) the human body stores substantial amounts of arsenic; and 3) the urinary arsenic concentration after DMPS administration may be more indicative of the body burden of arsenic because it was greater than that found before DMPS was given.     

Beat frequency difference between the two flagella of Chlamydomonas depends on the attachment site of outer dynein arms on the outer-doublet microtubules

In vitro mercury induces a high proliferative response in splenic lymphocytes and in vivo it induces a systemic autoimmune disease in susceptible mouse strains. This disease is characterized by increased serum levels of IgE and IgG1 antibodies, by the production of anti-nucleolar antibodies and by the formation of renal immune complex deposits. We have previously found that the presence of 2-mercaptoethanol (2-ME) inhibited mercury-induced cell proliferation in vitro. In this study, we tested the effects of four other thiol compounds, namely dithiothreitol (DTT), L-cysteine, meso-2,3-dimercaptosuccinic acid (meso-DMSA) and 2,3-dimercapto-1-propanesulfonic acid, Na salt (DMPS) on mercury-induced immunological changes both in vitro and in vivo. We found that in vitro, the addition of all thiol compounds abrogated mercury-induced cell aggregation and proliferation. In vivo, injection of meso-DMSA and/or DMPS (s.c. or i.p.) immediately following exposure to mercury markedly decreased IgG1 synthesis in spleen cells and serum IgE levels in mercury-susceptible SJL mice. Treatment with DMPS also prevented mercury-induced IgG1 anti-nucleolar antibody synthesis and the development of mesangial IgG1 immune complex deposits in SJL mice.     

Milk production of Holstein heifers fed either alfalfa or corn silage diets at two rates of daily gain

OBJECTIVES: L-arginine exerts anti-atherosclerotic effects in hypercholesterolaemic rabbits via modulating endogenous NO production. We investigated whether L-arginine inhibits thromboxane formation in vivo and platelet aggregation ex vivo in this animal model. METHODS: The urinary excretion rates of 2,3-dinor-6-keto-PGF1 alpha (major urinary metabolite of PGI2) and 2,3-dinor-TXB2 (major urinary metabolite of thromboxane A2) were used as indicators of platelet-endothelial cell interactions in vivo. Rabbits were fed 1% cholesterol (Cholesterol group, N = 8), 1% cholesterol plus 2.25% L-arginine (Cholesterol + L-arginine, N = 8), or normal rabbit chow (Control, N = 4) for 12 weeks. Urine samples were collected in weekly intervals. At the end of the study period platelet aggregation ex vivo and endothelium-dependent and -independent vascular function of isolated aortic rings in vitro was assessed. RESULTS: Urinary 2,3-dinor-TXB2 excretion significantly increased in the cholesterol group (p < 0.05), and endogenous NO formation (measured as urinary nitrate excretion) decreased (p < 0.05). Both parameters were significantly correlated with each other (R = 0.48, p < 0.01). L-arginine partly restored urinary nitrate excretion and significantly reduced TXA2 production to values even below those in the control group (p < 0.001). Urinary 2,3-dinor-6-keto-PGF1 alpha excretion increased in early hypercholesterolaemia and returned to control values in the second half of the study period. The early increase in urinary 2,3-dinor-6-keto-PGF1 alpha excretion was attenuated by L-arginine. Platelet aggregation was significantly enhanced in cholesterol-fed rabbits and attenuated by dietary L-arginine. L-arginine also improved the impaired endothelium-dependent relaxations to ADP, and normalized the vasoconstrictor effects of 5-HT in isolated aortic rings. CONCLUSIONS: Cholesterol-feeding enhances platelet aggregation and TXA2 formation, and stimulates platelet-endothelial cell interaction in rabbits. These effects are probably due to impaired NO elaboration, as indicated by decreased urinary nitrate excretion. Chronic dietary supplementation with L-arginine elevates systemic NO elaboration and significantly increases the PGI2/TXA2 ratio. It thus beneficially influences the homeostasis between vasodilator and vasoconstrictor prostanoids in vivo.     

Effect of captopril on prostacyclin and nitric oxide formation in healthy human subjects: interaction with low dose acetylsalicylic acid

1. Angiotensin converting enzyme inhibitors have been suggested to act in part by potentiating the stimulatory effect of bradykinin on endothelial prostacyclin and/or nitric oxide (NO) formation. This may give rise to interaction with cyclo-oxygenase inhibiting drugs like acetylsalicylic acid, which is most often used in low doses in patients with cardiovascular diseases. 2. We investigated the effects of captopril (2 x 25 mg day-1), or ASA (1 x 100 mg day-1), or the combination of both drugs for 7 days, on blood pressure, prostanoid and NO formation rates in a double-blind, double dummy, randomized crossover study in 13 healthy female subjects. The urinary metabolites of thromboxane A2 (2,3-dinor-TXB2) and prostacyclin (2,3-dinor-6-keto-PGF1 alpha), and PGE2 were measured by gas chromatography/tandem mass spectrometry in urine on days 1, 6 and 7 of each medication. NO formation was assessed using urinary NO3- and cyclic GMP as indicators. 3. Urinary 2,3-dinor-6-keto-PGF1 alpha excretion was not significantly changed by either captopril, ASA, or their combination. Urinary 2,3-dinor-TXB2 excretion was inhibited by > 80% by ASA alone or in combination with captopril (each P < 0.05), but was not affected by captopril alone. Urinary PGE2 excretion was not significantly changed by either of the treatments. Urinary NO3- and cyclic GMP excretion rates were not significantly changed by captopril, ASA, or their combination. 4. Blood pressure was slightly reduced by captopril. ASA had no effect on blood pressure when given alone, nor did it modulate the effect of captopril on blood pressure during co-administration. Angiotensin II/angiotensin I ratio (index of ACE activity) was significantly decreased by captopril alone or in combination with ASA, but was unaffected by ASA alone. 5. Captopril does not stimulate prostacyclin formation in healthy human subjects in a dose sufficient to substantially inhibit ACE activity. Co-administration of ASA significantly inhibits 2,3-dinor-TXB2 excretion, but does not interfere with the blood pressure lowering effect of captopril in healthy human subjects.     

Measurements of urinary prostaglandins in young ovulatory women during the menstrual cycle and in postmenopausal women

The purpose of the present work was to study the prostaglandin excretion in young nonpregnant ovulatory women during the menstrual cycle on the one hand and in postmenopausal women on the other hand and to investigate the influence of female sex hormones (estradiol, progesterone) on urinary prostanoid excretion. Urinary excretion rates of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, thromboxane B2 (TxB2) and their metabolites PGE-M (11 alpha-hydroxy-9, 15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid), 2,3-dinor-6-keto-PGF1 alpha, 2,3-dinor-TxB2 and 11-dehydro-TxB2 were determined by gas chromatography-triple stage quadrupole mass spectrometry (GC/MS/MS) in 41 young non-pregnant women during the follicular phase and during the luteal phase and in 23 postmenopausal women. Excretion rates of all urinary prostanoids were not significantly different in the follicular phase when compared with the luteal phase. In contrast to the young ovulatory women, PGE2 and TxB2 were significantly higher in postmenopausal women. Concerning the other prostaglandins significant differences between these groups of women did not exist. Although serum levels of estradiol and progesterone were different in young and postmenopausal women, sex hormones have not been shown to correlate with prostaglandins. Our data do not suggest sex hormones to be responsible for the difference in the prostaglandin excretion in women of reproductive age and in women in the menopause. Further systematic investigations into age dependency of prostaglandin excretion in women are necessary.     

(Vinylaryloxy)acetic acids. A new class of diuretic agents. 3. ((2-Nitro-1-alkenyl)aryloxy)acetic acids

A series of [(2-nitro-1-alkenyl)aryloxy]acetic acids was synthesized and tested in dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration; representative of these is (E)-[2,3-dichloro-4-(2-nitropropenyl)phenoxy]acetic acid (5). The most highly active compounds are qualitatively similar in action to [2,3-dichloro-4-(2-methylenebutyryl)phenoxylacetic acid (ethacrynic acid) in causing a prompt increase in the excretion of water and of sodium and chloride ions in approximately equimolar amounts but are three to five times as potent. Potassium ion excretion is increased but less markedly than sodium excretion.     

Heterogeneity of the hippocampus: effects of subfield lesions on locomotion elicited by dopaminergic agonists

Oriented calcium oxalate crystals have been grown beneath phospholipid monolayers at the air-solution interface from supersaturated calcium oxalate solutions. Mature calcium oxalate crystals grown beneath zwitterionic dipalmitoylphosphatidylcholine (DPPC) monolayers exhibit the characteristic morphology of calcium oxalate monohydrate (COM) crystals with the elongated (101) crystal face preferentially oriented parallel to the plane of the monolayer. Calcium oxalate crystals grown beneath negatively-charged dimyristoylphosphatidylserine (DMPS) monolayers also show a preferential orientation with respect to the monolayer; they do not, however, exhibit the characteristic COM morphology. Raman spectroscopy strongly suggests that the crystals grown beneath either DPPC or DMPS monolayers are the monohydrate phase of calcium oxalate; therefore, differences in crystal morphology are not due to differences in the crystalline phase. Dimyristoylphosphatidylethanolamine (DMPE), dimyristoylphosphatidic acid (DMPA), eicosanoic acid (C20), and eicosanol (C20-OH) monolayers have also been studied to help elucidate the mechanisms of interaction between the lipid monolayers and the calcium oxalate crystals. We discuss the roles of lattice matching, hydrogen bonding, stereochemistry and electrostatics on crystal orientation and morphology.     

Interaction of a thrombin inhibitor and a platelet GP IIb/IIIa antagonist in vivo: evidence that thrombin mediates platelet aggregation and subsequent thromboxane A2 formation during coronary thrombolysis

We examined the effect of a specific thrombin inhibitor, Ro 46-6240, alone and combined with an antagonist of the platelet GP IIb/IIIa, Ro44-9883, on the response to tissue-type plasminogen activator in a canine model of thrombolysis. Platelet activity was determined by measuring the excretion of 2,3-dinorthromboxane (TX)B2, an enzymatic metabolite of TXA2. Ro 46-6240 administered before tissue-type plasminogen activator induced a dose-dependent prolongation of the activated partial thromboplastin time and prothrombin time. The time to reperfusion decreased dose-dependently (P < .01) to 10 +/- 6 min vs. 52 +/- 5 min in controls. Ro 46-6240 also prevented reocclusion, which occurred in every case in control experiments. Urinary excretion of 2,3-dinor-TXB2 increased from 3 +/- 1 to 37 +/- 9 ng/mg creatinine in controls after reperfusion. This increase was reduced in a dose-dependent fashion by Ro 46-6240, such that at the highest dose, urinary 2,3-dinor-TXB2 after reperfusion was 5.6 +/- 1 ng/mg creatinine. Similar functional and biochemical effects were seen when a subthreshold dose of Ro 46-6240 was combined with Ro 44-9883. At the dose used, Ro 44-9883 alone abolished platelet aggregation ex vivo but failed to modify the response to tissue-type plasminogen activator or the excretion of 2,3-dinor-TXB2 after reperfusion (51 +/- 6 ng/mg creatinine, n = 3). However, the combination of Ro 44-9883 and Ro 46-6240 reduced the time to reperfusion (40 +/- 8 vs. 68 +/- 15 min; n = 7, P < .05), prevented reocclusion and abolished the rise in urinary 2,3-dinor-TXB2 (5 +/- 1 ng/mg creatinine, n = 4). These findings suggest that thrombin mediates platelet activation during coronary thrombolysis. The increased platelet activity results in platelet aggregation and a subsequent increase in TXA2 formation.     

Na(+)-glucose cotransporter inhibitors as antidiabetic agents. III. Synthesis and pharmacological properties of 4'-dehydroxyphlorizin derivatives modified at the OH groups of the glucose moiety

To overcome hydrolysis by beta-glucosidase present in the digestive tract, the OH groups on the glucose moiety of the 4'-dehydroxyphlorizin derivatives (1, 2, 3) were modified with various kinds of patterns, and then the effects of the modified compounds on urinary glucose excretion were evaluated in rats. Among them, triacetyl (9), 2,3-O-diacetyl (17), 6-O-methoxycarbonyl (34), 4-O-methoxycarbonyl (38), and 2-O-acetyl (41) derivatives showed more potent effect than the parent compound 2 by oral administration (p.o.). The stabilities of the compounds 34, 38, and 41 against beta-glucosidase were higher than that of 2. The increase in oral activity was found to correlate with the enhancement of the stability against beta-glucosidase.     

Effects of monoisoamyl meso-2,3-dimercaptosuccinate on arsenite-induced maternal and developmental toxicity in mice

The therapeutic efficacy of monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS), on arsenite-induced maternal and developmental toxicity was evaluated in the pregnant mouse. Sodium arsenite (12 mg/kg) was intraperitoneally injected into Swiss mice on day 9 of gestation, whereas Mi-ADMS was given subcutaneously at 0.25, 5, 24, and 48 hr after arsenite exposure. Amelioration by Mi-ADMS of arsenite-induced maternal and embryofetal toxicity was assessed at 23.8, 47.5, and 95 mg/kg/day. Controls received 0.9% saline with or without arsenite. Cesarean sections were performed on gestation day 18. In the positive control group (treated with arsenite only), 20.8% of the pregnant animals died, whereas 37.5% of the dams were carrying completely resorbed litters. No arsenite-induced maternal lethality was seen following treatment with Mi-ADMS at 23.8, 47.5 and 95 mg/kg/day. Also, administration of the drug at these doses significantly reduced the embryolethality, as well as the incidence of some skeletal variations provoked by sodium arsenite. Although based on these findings, Mi-ADMS might be suggested as a potential antidote to prevent the arsenite-induced maternal and developmental toxicity, due to their reduced toxicity compared to Mi-ADMS, DMSA and DMPS would probably be more advisable for pregnant women exposed to arsenite.     

Effect of symplasmic isolation and antigibberellin treatment on morphogenesis in Chara

We characterized the particle size distribution and the analyte transmission efficiency of a liquid chromatography/particle beam/mass spectrometry (LC/PB/MS) system as a function of experimental variations normally used to optimize the LC/PB/MS system. The particle size distribution was evaluated using an electrical differential mobility particle sizer (DMPS) and both the DMPS and the mass spectrometer were used to evaluate transmission. The latter results were correlated to provide evidence related to mechanisms which contribute to poor sample transmission. Addition of ammonium acetate buffer did not increase the aerosol particle mean diameter. However, it did lead to significant increases in caffeine transmission efficiency observed in both the DMPS and the mass spectrometer. Our results were interpreted to suggest a possible electrostatic cause for quantitative anomalies in LC/PB/MS rather than simple mass discrimination in the particle beam momentum separator.     

Pressure tuning infrared spectroscopic study of cisplatin-induced structural changes in a phosphatidylserine model membrane

The dynamic effect of cis-diamminedichloroplatinum(II) (DPP) and its aquated metabolite (DDP-OH) on a dimyristoylphosphatidylserine (DMPS) model membrane was investigated by pressure tuning vibrational spectroscopy. The native species (DDP-Cl) and the aquated species (DPP-OH) were both observed to bind to the carboxylate group of the serine as evidenced by a frequency shift of 1622-1620 cm-1. However, only DDP-OH was observed to bind to the phosphate group (PO(-)2). The binding of either drug to DMPS resulted in an increased pressure required to halt the reorientational fluctuations of the acyl chains, indicating that the distance between the chains were increased. The two drugs did not partition into the matrix of the hydrophobic section in the model membrane. Collectively, these data suggest that DDP-Cl and DDP-OH are capable of binding to the polar head group of DMPS, resulting in an enlargement of the area of the head and a subsequent increase in the intermolecular distance between the acyl chains.     

Dietary modification of omega 6 fatty acid intake and its effect on urinary eicosanoid excretion

A group of women were fed two separate diets in a crossover study and urinary eicosanoids were quantified. One diet contained 3.1% of total energy (en%) as polyunsaturated fatty acids (3.0 en% linoleic acid) and the other contained 8.4 en% polyunsaturated fatty acids (8.3 en% linoleic acid). Carbohydrate replaced fat in the low-polyunsaturated-fat diet. No changes were observed in the urinary excretion of 6-oxo-prostaglandin F1 alpha, its 2,3-dinor metabolite or thromboxane B2 by subjects on either of the diets. Urinary 2,3-dinor-thromboxane B2 excretion was lower (206.5 ng/24 h) when subjects were fed the high-omega 6 polyunsaturated fatty acid diet when compared with the lower-omega 6 polyunsaturated fatty acid diet (275.3 ng/24 h). Conversely, urinary prostaglandin E2 was higher (139.2 ng/g creatinine) during the higher-omega 6 polyunsaturated fatty acid diet when compared with the lower-omega 6 polyunsaturated fatty acid diet (94.4 ng/g creatinine).     

Determination and metabolism of dithiol chelating agents. XV. The meso-2,3-dimercaptosuccinic acid-cysteine (1:2) mixed disulfide, a major urinary metabolite of DMSA in the human, increases the urinary excretion of lead in the rat

Meso-2,3-dimercaptosuccinic acid (DMSA) in humans is an effective p.o. therapeutically useful chelating agent of Pb. In humans given DMSA p.o., the major urinary metabolite is DMSA-cysteine (1:2) mixed disulfide. In order to determine its efficacy in mobilizing Pb and increasing urinary Pb excretion, the mixed disulfide was given to rats treated previously with Pb acetate. The mixed disulfide was as effective as DMSA in increasing the urinary excretion of Pb and mobilizing Pb from the kidney. DMSA, however, appears to be superior for mobilizing Pb from the liver and the brain. After the mixed disulfide was given s.c. to rats, DMSA was found in the blood and urine. Twenty-four hours after administration, 0.7% of the administered mixed disulfide was found in the urine as DMSA, indicating the mixed disulfide can be reduced to DMSA. The mixed disulfide was also reduced in vitro to DMSA during incubation with rat blood. Although in the rat the DMSA-cysteine (1:2) mixed disulfide mobilized Pb from the kidney, increased the urinary excretion of Pb and was to some extent reduced to DMSA, its fate and pharmacological properties in the human, where it is found after DMSA administration, are unknown.     

The end of the continuum. Bereavement care for the adult

A method has been developed for the simultaneous analysis of the isomeric N-acetyl-S-(dichlorophenyl)cysteines (also known as dichlorophenylmercapturic acids, DCPMAs) in urine. This procedure allows the determination of 2,3- and 3,4-DCPMAs at the concentrations expected in the urine samples of employees occupationally exposed to 1,2-dichlorobenzene (1,2-DCB). The results of a 1,2-DCB exposure study under standardized conditions show a first-order kinetic for the excretion of DCPMAs, as well as acceptable linear correlations between the urinary concentrations of DCPMAs and the amount of inhaled 1,2-DCB. It therefore seems it would be possible to derive a biological tolerance value for 1,2-DCB based on isomeric DCPMAs as analytical parameters.     

Prognostic significance of normal dobutamine-atropine stress sestamibi scintigraphy in women with chest pain

The high risk of vaso-occlusive events in children younger than 4 years with cyanotic congenital heart disease and polycythaemia has been attributed to increased thromboxane (Tx) A2 formation. In older children with cyanotic congenital heart disease, however, the risk of vaso-occlusive events is much lower. We therefore hypothesized that the formation of TxA2 and prostacyclin is not disturbed in this age group. We measured urinary excretion of stable index metabolites of in vivo TxA2 and prostacyclin formation by gas chromatography-mass spectrometry in nine children (age 5.9-14.4, median 8.7 years) with cyanotic congenital heart disease, and in nine healthy, age-matched control subjects. The patients excreted less 2,3-dinor-TxB2 (systemic TxA2 formation, P = 0.03), 2,3-dinor-6-keto-PGF1 alpha (systemic prostacyclin formation. P = 0.03) and TxB2 (renal TxA2 formation, P = 0.01) than the control subjects. We conclude that in children older than 5 years with cyanotic congenital heart disease, endogenous synthesis of TxA2 and prostacyclin is not stimulated. This result may explain the lower risk of vaso-occlusive events in this age group as compared with younger children. In addition, our results suggest that chronic hypoxaemia may affect the in vivo formation of TxA2 and prostacyclin and the metabolic disposition of TxB2.     

Correlation between protein kinase C alpha activity and membrane phase behavior

Lipid activation of protein kinase C alpha (PKC alpha) was studied by using a model mixture containing 1, 2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1, 2-dimyristoyl-sn-glycero-3-phosphoserine (DMPS), and 1, 2-dimyristoyl-sn-glycerol (1,2-DMG). This lipid mixture was physically characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and 31P-nuclear magnetic resonance (31P-NMR). Based on these techniques, a phase diagram was constructed by keeping a constant DMPC/DMPS molar ratio of 4:1 and changing the concentration of 1,2-DMG. This phase diagram displayed three regions and two compounds: compound 1 (C1), with 45 mol% 1,2-DMG, and compound 2 (C2), with 60 mol% 1,2-DMG. When the phase diagram was elaborated in the presence of Ca2+ and Mg2+, at concentrations similar to those used in the PKC alpha activity assay, the boundaries between the regions changed slightly and C1 had 35 mol% 1,2-DMG. The activity of PKC alpha was studied at several temperatures and at different concentrations of 1,2-DMG, with a maximum of activity reached at 30 mol% 1,2-DMG and lower values at higher concentrations. In the presence of Ca2+ and Mg2+, maximum PKC alpha activity occurred at concentrations of 1,2-DMG that were close to the boundary in the phase diagram between region 1, where compound C1 and the pure phospholipid coexisted in the gel phase, and region 2, where compounds C1 and C2 coexisted. These results suggest that the membrane structure corresponding to a mixture of 1,2-DMG/phospholipid complex and free phospholipid is better able to support the activity of PKC alpha than the 1,2-DMG/phospholipid complex alone.     

Effects of dietary fat saturation on eicosanoid production, platelet aggregation and blood pressure

The effects of dietary fat saturation on eicosanoid urinary excretion, platelet aggregation (PA) and blood pressure (BP) were studied in 42 healthy subjects. They consumed four consecutive diets differing in their fat saturation [saturated (SFA); monounsaturated (MUFA); polyunsaturated n-6 (PUFA n-6); and polyunsaturated n-6/n-3, (PUFA n-3)]. Each diet period lasted 5 weeks. There were no differences in 24-h 2,3-dinor-6- keto-prostaglandin F1 alpha excretion among dietary periods. A significant effect was noted regarding the excretion of 11-dehydro-thromboxane B2 (P < 0.0001). During the PUFA n-6 phase the excretion was significantly higher than during SFA and MUFA periods. Dietary fatty acid composition had a significant effect on ADP (1 mumolL-1) and collagen (2 mgL-1) induced PA. Dietary fat also had a significant effect on systolic and diastolic blood pressure (P < 0.0001). Both were significantly higher during the SFA period than during the other three periods. Our findings suggest that changes in dietary fatty acids may have mild, but significant, effects on eicosanoid production, platelet aggregation and blood pressure.     

GABA(A) receptor function in the cerebral cortex of alcohol-naive P and NP rats

In our previous paper (Biochim. Biophys. Acta 1379 (1998) 257-263), we demonstrated that bicarbonate promotes a cleavage of lactone ring of dehydroascorbate (DHA) on the basis of in vitro experiments. In the present study, we examined the degradation of DHA in blood circulation in vivo by using a high-performance liquid chromatographic method for the determination of ascorbate (AsA), DHA and 2,3-diketogulonate (2,3-DKG), which required no pretreatment of biological fluids. When DHA was intravenously administered to rats, a rapid disappearance of DHA (t1/2 < 1 min) and a concomitant appearance of 2,3-DKG in blood circulation were observed. Approximately 90% of the administered DHA were excreted into urine as resulting 2,3-DKG (55%) and AsA (31%), respectively. Furthermore, we elucidated that rat plasma lacks an enzyme having an aldonolactonase-like activity. The result of the present study suggests that this DHA disappearance is a function of both a chemical degradation to 2,3-DKG and a reduction to AsA.