The plasma homocysteine/creatinine ratio can be used to study the implication of (C677T) MTHFR genetic variants in homocysteine homeostasis.
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Adult↗
Biomedical subjects
G Durand
Publications and source records attributed to G Durand.
Functional specialization of stable and dynamic microtubules in protein traffic in WIF-B cells.
We found that the magnesium salt of ilimaquinone, named 201-F, specifically disassembled dynamically unstable microtubules in fibroblasts and various epithelial cell lines. Unlike classical tubulin- interacting drugs such as nocodazole or colchicine which affect all classes of microtubules, 201-F did not depolymerize stable microtubules. In WIF-B-polarized hepatic cells, 201-F disrupted the Golgi complex and inhibited albumin and alpha1-antitrypsin secretion to the same extent as nocodazole. By contrast, 201-F did not impair the transport of membrane proteins to the basolateral surface, which was only affected by the total disassembly of cellular microtubules. Transcytosis of two apical membrane proteins-the alkaline phosphodiesterase B10 and dipeptidyl peptidase IV-was affected to the same extent by 201-F and nocodazole. Taken together, these results indicate that only dynamically unstable microtubules are involved in the transport of secretory proteins to the plasma membrane, and in the transcytosis of membrane proteins to the apical surface. By contrast, stable microtubules, which are not functionally affected by 201-F treatment, are involved in the transport of membrane proteins to the basolateral surface. By specifically disassembling highly dynamic microtubules, 201-F is an invaluable tool with which to study the functional specialization of stable and dynamic microtubules in living cells.
Albumins↗
Chronic n-3 polyunsaturated fatty acid diet-deficiency acts on dopamine metabolism in the rat frontal cortex: a microdialysis study.
The effects of alpha-linolenic acid diet deficiency on rat dopaminergic metabolism were investigated in the frontal cortex of male 2-3 month-old rats using the microdialysis method. Increased basal levels of dopamine metabolites were observed in the frontal cortex of awake deficient rats, without modification of dopamine levels. Moreover, using KCl perfusion which releases newly synthesized dopamine, no difference was observed in anaesthetized deficient rats versus control rats. In addition, a decrease in dopamine release was observed in anaesthetized deficient rats versus control rats after tyramine stimulation, which is known to induce release of dopamine from vesicular stores. A working model is proposed which suggests that a chronic n-3 polyunsaturated fatty acids (PUFA) deficiency may lead to modifications in the internalization of dopamine in the storage pool in the frontal cortex.
Analysis of Variance↗
Chronic dietary n-3 polyunsaturated fatty acids deficiency affects the fatty acid composition of plasmenylethanolamine and phosphatidylethanolamine differently in rat frontal cortex, striatum, and cerebellum.
As chronic consumption of a diet devoid of n-3 fatty acid induced modification of neurotransmission pathways in the frontal cortex of rats, plasmalogen alteration could occur in this area. Because of the propensity to facilitate membrane fusion, plasmenylethanolamine (PmE), a major plasmalogen of brain, may be involved in synaptic transmission. Female rats were fed diet containing peanut oil [(n-3)-deficient diet] through two generations. Two weeks before mating, half of the female rats of the second generation received a diet containing peanut oil and rapeseed oil (control group). The distribution and acyl composition of major phospholipids, phosphatidylethanolamine and PmE, were measured in the frontal cortex, striatum, and cerebellum of the male progeny of the two groups at 60 d of age. The n-3 polyunsaturated fatty acid (PUFA) deficiency had no effect on the distribution of phospholipids in all brain regions but affected their acyl composition differently. The level of 22:6n-3 was significantly lower and compensated for by higher levels of n-6 fatty acids in all regions and phospholipids studied. However, docosahexaenoic acid, being more concentrated in the PmE of frontal cortex, is also more decreased in the n-3-deficient rats compared to the striatum. By contrast, striatum PmE has retained more 22:6n-3 than PmE of the other regions. In addition, the increase of n-6 PUFA was significantly lower in frontal cortex PmE compared to the striatum and cerebellum PmE. In association with altered neurotransmission observed in frontal cortex of n-3-deficient rats, our results suggest that frontal cortex PmE might be more affected in chronically alpha-linolenic-deficient rats. However, by retaining 22:6n-3, striatum PmE could be most resilient.
Animals↗
Diagnostic approach to mediastinal masses.
Mediastinal masses represent a vast group of tumours and pseudo-tumours which can involve the various compartments of the mediastinum. The authors propose a radiologic diagnostic approach starting from the plain thoracic radiograph with study of the mediastinal lines and oesophageal transit and going on to the classifications made possible by modern CT and MR imaging. The proposed diagnostic procedure is based on nine mediastinal lines and two 'threads of Ariadne' which are the compartments where the masses are located and their behaviour at CT (densitometry before and after administration of an iodinated bolus) and at MRI (T1, T2, gadolinium-enhanced T1-weighted sequences). The definitive aetiological diagnosis may be established by surgery, but also in certain cases by percutaneous needle biopsy.
Absorptiometry, Photon↗
Cardiac troponin I in diagnosis of perioperative myocardial infarction after cardiac surgery.
OBJECTIVE: The diagnosis of perioperative myocardial infarction (PMI) after cardiac surgery remains an important issue. The present study was designed to determine the relevance of the measurement of serum cardiac troponin I (cTnI, a biochemical marker with high cardiospecificity. Therefore, cTnI was compared with creatine kinase-MB (CK-MB) mass and to the other classical signs of myocardial infarction after cardiac surgery. DESIGN: A prospective study. SETTING: A university hospital. PARTICIPANTS: Forty-one patients undergoing coronary artery bypass grafting (CABG) (n = 17) or valvular replacement (n = 24). These patients were separated into three groups according to postoperative complications: group 1, Q-wave PMI (n = 5); group 2, nonspecific changes (non-Q wave) on the electrocardiogram (ECG) and/or need of inotropic support (n = 12); group 3, no postoperative complication (n = 24). INTERVENTIONS: Postoperative follow-up consisted of serial determination of different biochemical markers (CK, CK-MB, cTnI), ECGs, and echocardiography. Blood samples were drawn before (H0) and 3 (H3), 12 (H12), 20 (H20), 24 (H24), and 48 (H48) hours after the onset of cardiopulmonary bypass (CPB). MEASUREMENTS AND MAIN RESULTS: In all patients in group 3, CK-MB and cTnI concentrations increased, and peaked at H12 after CPB (13.4 +/- 7.7 and 7.1 +/- 4.1 micrograms/L for CK-MB and cTnI, respectively). In group 1, cTnI concentrations were significantly higher than in group 3 from H12 until H48 (p < 0.002), peaked later (H24; 59.0 +/- 38.8 micrograms/L), and remained in plateau. In group 2, cTnI peak concentrations were significantly different than in groups 1 and 3 (26.2 +/- 14.8 micrograms/L) and occurred at H24 (as in patients with Q-wave PMI). CONCLUSION: A cTnI concentration less than 15 micrograms/L (mean + 2 standard deviations [SDs] of peak cTnI in group 3) within 24 to 48 hours after cardiac surgery is highly suggestive of the absence of perioperative myocardial necrosis. Because of its higher cardiospecificity than CK-MB mass, and its prolonged release after myocardial necrosis, cTnI might be a useful tool in the diagnosis of PMI after cardiac surgery.
Biomarkers↗
Docosahexaenoic acid concentrations in retinal phospholipids of piglets fed an infant formula enriched with long-chain polyunsaturated fatty acids: effects of egg phospholipids and fish oils with different ratios of eicosapentaenoic acid to docosahexaenoic acid.
Docosahexaenoic acid (DHA; 22:6n-3) is the major fatty acid in the phosphatidylethanolamine of photoreceptor cells. The supply of preformed DHA in milk may play an important role in early human visual development. We examined the effect of adding dietary DHA from yolk or fish oil on its accretion in the retina of newborn piglets fed artificially for 2 wk. DHA-enriched eggs from hens fed rapeseed oil and two fish oils with a high or low ratio of eicosapentaenoic acid (EPA; 20:5n-3) to DHA were used. The basic (conventional) formula contained (% by wt of total fatty acids) 17% linoleic acid (18:2n-6) and 1.3% alpha-linolenic acid (18:3n-3). The yolk-enriched formula also contained 0.5% arachidonic acid (AA; 20:4n-6) and 0.4% DHA. The fish-oil-enriched formulas contained either 0.3% EPA and 0.2% DHA (from salmon oil) or < 0.1% EPA and 0.3% DHA (low-EPA fish oil used at a low concentration), or 0.1% AA, 0.3% EPA, and 0.9% DHA (low-EPA fish oil used at a high concentration). The low-EPA fish oil used at a low concentration can supply the DHA required without increasing the EPA status but only the yolk-enriched formula allowed the artificially reared piglets to attain the same AA status in blood lipids as with sow milk feeding. The DHA concentration plateaued in the retina when it reached 7.5% by wt of total fatty acids in plasma phospholipids. Yolk phospholipids and fish oils are equally potent sources for supplying the highest retinal DHA concentration, which was found to be 41.7% by wt of total fatty acids in phosphatidylethanolamine (compared with 35% without supplementation). Inclusion of 0.2-0.3% DHA ensures maximal DHA accretion in the retina but cosupplementation with AA is necessary to achieve the status with maternal feeding in blood lipids and to prevent any possible imbalance between n-6 and n-3 fatty acids.
Animals↗
Dietary fish oil affects monoaminergic neurotransmission and behavior in rats.
We studied the effects of a fish oil enriched diet on fatty acid composition of cerebral membranes and on several neurochemical and behavioral variables of monoaminergic function in rats. The frontal cortex, striatum, hippocampus and cerebellum were studied in rats fed fish oil (FPO, 50% salmon oil + 50% palm oil), which provided an (n-6)/(n-3) polyunsaturated fatty acid (PUFA) ratio of 0.14 versus 6. 19 in controls fed a diet containing a mixture of African peanut oil and rapeseed oil. In the FPO group compared to the control group, the major modifications in fatty acid composition of cerebral membranes included the following: higher levels in 22:6(n-3), lower levels in 20:4(n-6) and a significantly greater proportion of phosphatidylserine. Dopamine levels were 40% greater in the frontal cortex of rats fed FPO than from those fed the control diet. In this cerebral region there was also a reduction in monoamine oxidase B (MAO-B) activity and greater binding to dopamine D2 receptors. By contrast, a lower binding to dopamine D2 receptors (-7%) was observed in the striatum. Ambulatory activity was also reduced in FPO-fed rats, possibly related to observed changes in striatal dopaminergic receptors. This suggested that the level of (n-6) PUFA, which was considerably lower in the FPO diet than in the control diet, could act on locomotion through an effect on striatal dopaminergic function, whereas the high level of (n-3) PUFA could act on cortical dopaminergic function.
Animals↗
Alpha-linolenic acid deficiency modifies distractibility but not anxiety and locomotion in rats during aging.
In rodents, chronic dietary alpha-linolenic acid deficiency decreases learning and memory and alters dopaminergic and serotoninergic neurotransmission. However, these two neurotransmitter systems are related mainly to attention, emotion and locomotion. Therefore, we decided to investigate the effects of dietary alpha-linolenic acid deficiency in rats tested with animal models of distractibility (the distractometer procedure), anxiety (the elevated plus maze) and ambulatory activity (a circular corridor). Moreover, because these neurochemical modifications persist during aging, we decided to study the effects of aging on these behaviors by using rats aged 2, 6, 12 and 24 mo. An age-related decline in distractibility was observed that was accelerated by linolenic acid deficiency. Indeed, an age-related reduction in distractibility was found in so far as distraction time was reduced at the age of 12 mo in controls and at the age of 24 mo in deficient groups compared with 2-mo-old rats. Moreover, distraction time was significantly lower in 6- and 24-mo-old rats fed a deficient diet compared with age-matched controls. Anxiety was not modified by diet or age. Finally, a parallel decrease in locomotion was exhibited by rats fed both diets between 6 and 12 mo of age. Locomotion was not modified by diet. These results show that dietary alpha-linolenic deficiency alters behavior in a very specific way; distractibility is modified by diet, whereas anxiety and locomotion are not, suggesting that particular brain areas may be altered.
Aging↗
Effect of two types of fish oil supplementation on plasma and erythrocyte phospholipids in formula-fed term infants.
We studied the effect of docosahexaenoic acid (DHA) supplementation of infant formulas on fatty acid composition of blood phospholipids in term infants. Two fish oil supplemented formulas containing 0.45 wt% DHA and high (0.35%) or low (0.10%) eicosapentaenoic acid (EPA) were fed for 42 days and compared with a standard formula and breast milk. Infants fed supplemented formulas and breast milk had similar time-dependent changes for DHA from birth to day 42, i.e., slight decreases in plasma phospholipids and erythrocyte phosphatidylcholine and no change in erythrocyte phosphatidylethanolamine. Low-EPA formula prevented EPA accumulation but did not limit the significant decrease in arachidonic acid (AA) noted in infants fed high-EPA formula. These results suggest that term infant formulas should be supplemented with DHA-rich EPA, low fish oil and AA to achieve a fatty acid status in formula-fed infants similar to that of breast-fed infants.
Arachidonic Acid↗
Oncostatin M is a potent stimulator of alpha1-antitrypsin secretion in lung epithelial cells: modulation by transforming growth factor-beta and interferon-gamma.
alpha1-Antitrypsin (alpha1-AT) plays a key role in lung homeostasis. Although the hepatocyte is considered as the primary source of alpha1-AT, we have previously demonstrated that rat alveolar epithelial type II cells as well as the human A549 cell line synthesize alpha1-AT, suggesting its local production within the lung. In the present study, we showed that oncostatin M, as opposed to interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), or IL-6, is a potent stimulator of alpha1-AT synthesis in the human A549 cell line. The oncostatin M-induced alpha1-AT secretion is modulated by interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta) at both the protein and mRNA levels. IFN-gamma decreases oncostatin M-induced alpha1-AT secretion. By contrast, TGF-beta in combination with oncostatin M induces a dramatic and synergistic upregulation that is not observed in the HepG2 hepatocyte cell line. Our results suggest that during an inflammatory process, alveolar epithelial cells may contribute to the antiprotease defense within the lung.
Animals↗
A proposal for basic management of HIV disease in west Africa: use of clinical staging and haemogram data.
Our objective was to propose a strategy to screen HIV-infected African people for biological immunodeficiency easily. In a cross-sectional study, we analysed the patterns of diseases and of CD4 counts among 266 HIV-infected adults. Peripheral facial paralysis and chronic cutaneo-mucous diseases were the earlier B-stage diseases. Pulmonary tuberculosis was close to B-stage diseases, and chronic diarrhoea was borderline between B and C stages. Cachexia was the most frequent C-stage symptom (47.8%). Ninety per cent of CDC-C stage people had CD4 counts below 350/microliter, whereas only 75% had CD4 counts below 200/microliter. Regression analysis identified the lymphocyte count, clinical stage and platelet count as predictors of CD4 count below 350/microliter. A simple score (lymphocyte count < or = 2500/microliter and clinical stage > or = B) is proposed to determine this CD4 threshold (positive predictive value: 83%) and to determine those patients needing treatment to prevent wasting and opportunistic infections.
AIDS-Related Opportunistic Infections↗
Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study.
OBJECTIVE: To evaluate the effect of a moderate dose of fish oil on glycemic control and in vivo insulin action in type 2 diabetic men with elevated plasma triacylglycerols and to determine the effect of the same treatment on gene expression of GLUT4, lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL) in the abdominal adipose tissue. RESEARCH DESIGN AND METHODS: A total of 12 type 2 diabetic men were randomly allocated to 2 months of 6 g daily of either fish oil or sunflower oil, separated by a 2-month washout interval, in a double-blind crossover design. RESULTS: For glucose metabolism, 2 months of fish oil supplementation compared with sunflower oil led to similar fasting plasma insulin, glucose, and HbA1c. Basal hepatic glucose production did not increase after fish oil. There was no difference in insulin suppression of hepatic glucose production nor in insulin stimulation of whole-body glucose disposal measured by the euglycemic-hyperinsulinemic clamp. Fish oil did not ameliorate the low mRNA level of GLUT4 in adipose tissue of these patients. For lipid profile, fish oil lowered plasma triacylglycerol more than sunflower oil (P < 0.05) and tended to increase the amount of mRNA of both LPL and HSL in adipose tissue. CONCLUSIONS: A moderate dose of fish oil did not lead to deleterious effects on glycemic control or whole-body insulin sensitivity in type 2 diabetic men, with preserved triacylglycerol-lowering capacities.
Basal Metabolism↗
[Radiologic analysis of known-interval cancers after 2 years of organized mass screening for breast cancer in Ille-et-Vilaine].
The first thirty-two known interval breast cancers (appearing within the first or second year after a negative screen) occurring during a two-year breast screening round were reviewed and the radiograms analyzed. Five classes were established: true interval cancers (13/32 cases), radiologically occult cancers (2/32), cancers with no specific sign (7/32), false negative cancers (5/32) and unclassifiable cancers (5/32). In more than 50% of the cases, there was no abnormality on the initial radiographic test, although the literature reports that the rate of false-negatives in interval cancers is less than 20%. Standard classification (by at least 3 readers) is very important to provide a possible explanation of cancer development. Action should be initiated to reduce their number.
Adult↗
Gene expression of a protein, JB70, related to rat alpha1-acid glycoprotein in Euglena gracilis.
Antibodies directed against rat alpha1-acid glycoprotein (AGP) recognize a 70 kDa antigen, designated JB70, present in extracts of achlorophyllous Euglena gracilis cells as well as in their culture medium. By using 2-dimensional electrophoresis, JB70 appears to be composed of two acidic polypeptides. Additionally, Northern blot analysis reveals the presence in E. gracilis cells of a 2.3 kb mRNA hybridizing with a cDNA probe specific for rat AGP mRNA. Moreover, elevated mRNA levels are detected in dexamethasone-treated E. gracilis cells, indicating a response to this inducer similar to that observed for hepatic AGP. These results strongly suggest that polypeptides closely related to hepatic rat AGP are expressed in E. gracilis cells. They also indicate that, like other gene families implicated in natural defense processes such as heat-shock protein and metallothionein genes, the AGP gene appears to be conserved down to this early diverging eucaryote.
Animals↗
Modifying the n-3 fatty acid content of the maternal diet to determine the requirements of the fetal and suckling rat.
During perinatal development, docosahexaenoic acid (22:6n-3) accumulates extensively in membrane phospholipids of the nervous system. To evaluate the n-3 fatty acid requirements of fetal and suckling rats, we investigated the accumulation of 22:6n-3 in the brain and liver of pup rats from birth to day 14 postpartum when their dams received increasing amounts of dietary 18:3n-3 (from 5 to 800 mg/100 g diet) during the pregnancy-lactation period. The fatty acid composition of brain and liver phospholipids of pups, as well as that of dam's milk, was determined. At birth, 22:6n-3 increased regularly to reach the highest level when the maternal diet contained 800 mg 18:3n-3/100 g. On days 7 and 14 postpartum, brain 22:6n-3 plateaued at a maternal dietary supply of 200 mg/100 g. Docosapentaenoic acid (22:5n-6) had the opposite temporal pattern. The unusually high concentration of eicosapentaenoic acid (20:5n-3) in liver and dam's milk observed at the highest 18:3n-3 intake suggests an excessive dietary supply of this fatty acid. All these data suggest that the n-3 fatty acid requirements of the pregnant rat are around 400 mg 18:3n-3 and those of the lactating rat at 200 mg (i.e., 0.9 and 0.45% of dietary energy, respectively). The values of 18:3n-3 and 22:6n-3 milk content which allowed brain 22:6n-3 to reach a plateau value in suckling pups were 1% of total fatty acids and 0.9% (colostrum) to 0.2% (mature milk), respectively. These levels are similar to those recommended for infant formulas.
Animal Nutritional Physiological Phenomena↗
High frequency of a deletion polymorphism of the angiotensin-converting enzyme gene in asthma.
BACKGROUND: An insertion-deletion polymorphism of the angiotensin-converting enzyme (ACE) gene has been shown to be associated with levels of ACE. Because ACE is heavily expressed in the lungs and plays a key role in the metabolism of angiotensin II and bradykinin, which are potentially involved in the pathogenesis of asthma, we tested the hypothesis of an association between the polymorphism of the ACE gene and asthma. METHODS: Seventy-nine patients with asthma, 54 healthy subjects, and 33 patients with nonasthmatic lung disease were studied. Pulmonary function tests were performed in patients with asthma, and the ACE genotypes were determined in all subjects by the polymerase chain reaction. RESULTS: The ACE genotype distribution was similar in healthy subjects and in patients without asthma. By contrast, the population of patients with asthma was characterized by a higher prevalence of the DD genotype of ACE (odds ratio, 2.09; 95% confidence interval, 1.05 to 4.16; p = 0.023). No difference in pulmonary function test results was detected in asthmatic patients according to the distribution of ACE genotypes. CONCLUSION: This study reports an association between the DD genotype of ACE and asthma, which is not related to the degree of airway obstruction. These results need to be confirmed by a larger case-control study.
Adult↗
Sequential study of serum glycoprotein fucosylation in acute hepatitis.
BACKGROUND: alpha-Fetoprotein is a useful diagnostic marker in hepatocellular carcinoma, during which its serum level increases and its glycan structure is hyperfucosylated. Normally-expressed glycoproteins (alpha 1-antitrypsin and transferrin) are also hyperfucosylated in hepatocellular carcinoma. alpha-fetoprotein serum levels are also increased in conditions associated with hepatic regeneration, such as acute hepatitis. We conducted a longitudinal study of the alpha 1-6 fucosylation pattern of serum alpha-fetoprotein in ten patients with acute hepatitis and compared it to that of transferrin and alpha 1-antitrypsin. METHODS: Protein levels were measured by using immunochemical assays. Crossed affinoimmunoelectrophoresis in the presence of Lens culinaris agglutinin was performed for each protein, and the fucosylation index, corresponding to the agglutinin reactive fraction, was determined. The results were compared to those in 25 healthy donors and five newborns. RESULTS: alpha-Fetoprotein was hyperfucosylated and remained stable throughout the course of the disease. In contrast, serum transferrin and alpha 1-antitrypsin gradually became hyperfucosylated during the course of acute hepatitis. The transferrin and alpha 1-antitrypsin fucosylation indexes correlated with each other, but not with the alpha-fetoprotein fucosylation index. No correlation was found between alpha-fetoprotein, alpha 1-antitrypsin and transferrin fucosylation indexes and the corresponding glycoprotein serum levels. CONCLUSIONS: Hyperfucosylation of alpha-fetoprotein is not specific to hepatocellular carcinoma. Increased alpha 1-6 fucosylation should not be considered solely as a tumour marker, but might also reflect cell proliferation. The study of alpha 1-6 hyperfucosylation process of normally-expressed glycoproteins awaits further investigation, to test its usefulness as a new marker of liver regeneration during the follow-up of acute hepatitis.
Acute Disease↗