[Thiamine deficiency in infants: a case report]. / Béribéri du nourrisson : à propos d'un cas.

Thiamine deficiency is recognized in varied parts of the world. In Asia, it remains an important public health problem where highly polished rice is the major staple food and where other primary dietary sources of thiamine are in short supply. Beriberi, or clinically apparent thiamine deficiency, may present a variety of syndromes including myocardial dysfunction or wet beriberi, dry beriberi with neurological symptoms, and the more severe form Shoshin beriberi with cardiac failure and lactic acidosis. Infantile thiamine deficiency is a very rare condition in developed countries today. It occurs mainly in breastfed infants of mothers who have inadequate intake of thiamine. Clinical symptoms in such infants include gastrointestinal symptoms, cardiac failure, and lactic acidosis. We report the case of a 10-week-old girl, admitted with diarrhea, vomiting, acidosis, and cardiac failure. After excluding other etiologies of cardiomyopathy, biochemical thiamine deficiency confirmed the diagnosis of beriberi in an infant of a thiamine-deficient mother from Reunion Island, a French island where recently, with Mayotte Island, epidemic cases of beriberi have been described. This case is important to highlight the manifestations in young infants and to alert physicians to the possibility of thiamine deficiency in developed countries.

[Orange skin and xanthomas associated with lycopenaemia in a setting of type III dyslipoproteinemia]. / Coloration orangée des téguments et des xanthomes au cours d'une lycopénémie associée à une dyslipoprotéinémie de type III.

BACKGROUND: Type III hyperlipoproteinaemia (HLP) is a rare form of dyslipidaemia characterized by skin lesions such as palmar crease xanthoma and tuberous xanthomas. To our knowledge, there have been no previous reports of yellow-orange discoloration of the skin and xanthomas associated with this disease. CASE REPORT: A 61-year-old woman consulted for palmar crease xanthoma and tuberous xanthomas of the elbows with odd yellow-orange discoloration. Laboratory investigations demonstrated type-III HLP and a high serum lycopene level. After 14 weeks of lipid-lowering treatment, the xanthomas and discoloration showed improvement. In addition, lipid levels and serum lycopene had returned to normal. DISCUSSION: All cases of lycopenaemia reported in the literature followed excessive ingestion of lycopene in foods. We describe the first case of lycopenaemia with orange discoloration of xanthomas following raised serum lycopene but not involving excessive dietary intake. Type-III HLP was doubtless instrumental in the physiopathogenesis of these orange lesions.

Weight-dependent changes of immune system in adipose tissue: importance of leptin.

Ancestral lymphoid cells reside in adipose tissues, and their numbers are highly altered in obesity. Leptin, production of which is correlated to fat mass, is strongly involved in the relationships between adipose tissues and immune system. We investigated in epididymal (EPI) and inguinal (ING) fat pads to determine whether 1) lymphocyte phenotypes were correlated to the tissue weight and 2) leptin was involved in such relationships. Immunohistological analyses revealed a tight relationship between the T and NK lymphocytes of the stromal vascular fraction and adipocytes. We identified a significant negative and positive correlation between EPI weight and the percentage of NK and total T cells respectively by cytofluorometric analyses. The NK and ancestral gammadelta T cell contents were directly dependent of leptin since they increased significantly in high-fat (HF) diet mice but not in leptin-deficient (ob/ob) mice as compared to control. By contrast, the alphabeta T cell content seemed independent of leptin because their percentages increased significantly with the EPI weight whatever the type of mice (control, HF, ob/ob). The present study suggests that adipose tissues present, according to their localization, different immunological mechanisms that might be involved in the regulation of adipose cells functions and proliferations.

Biological validation of coenzyme Q redox state by HPLC-EC measurement: relationship between coenzyme Q redox state and coenzyme Q content in rat tissues.

The properties of coenzymes Q (CoQ9 and CoQ10) are closely linked to their redox state (CoQox/total CoQ) x 100. In this work, CoQ redox state was biologically validated by high performance liquid chromatography-electrochemical measurement after modulation of mitochondrial electron flow of cultured cells by molecules increasing (rotenone, carbonyl cyanide chlorophenylhydrazone) or decreasing (antimycin) CoQ oxidation. The tissue specificity of CoQ redox state and content were investigated in control and hypoxic rats. In control rats, there was a strong negative linear regression between tissular CoQ redox state and CoQ content. Hypoxia increased CoQ9 redox state and decreased CoQ9 content in a negative linear relationship in the different tissues, except the heart and lung. This result demonstrates that, under conditions of mitochondrial impairment, CoQ redox control is tissue-specific.

Total parenteral nutrition decreases liver oxidative metabolism and antioxidant defenses in healthy rats: comparative effect of dietary olive and soybean oil.

BACKGROUND: Total parenteral nutrition (TPN) is used for critically ill patients undergoing surgery, after trauma, or during disease conditions that favor oxidative stress. We studied the effect of TPN on liver oxidative metabolism and antioxidant defenses in rats, and we compared the effect of soybean oil- and olive oil-based diets. METHODS: Seven-week-old rats (n = 28) were divided into four groups. Two experimental groups received a TPN solution containing soybean oil (TPN-S) or a mixture of olive/soybean oil, 80/20 (TPN-O), IV for 6 days. Orally fed animals received a solid diet including soybean oil (Oral-S) or olive/soybean oil, 80/20 (Oral-O). The following parameters were measured: DL-alpha-tocopherol, vitamin A, malondialdehyde and thiobarbituric acid reactive substances (MDA-TBARS), and total radical-trapping antioxidant parameter (TRAP) in serum; DL-alpha-tocopherol, vitamin A, glutathione (GSH), and catalase (Cat) activity in liver homogenate; fatty acids from phospholipid, cytochrome P-450 content, NADPH-cytochrome c2 reductase activity in liver microsomes; superoxide dismutase (SOD), glutathione peroxidase (Gpx), glutathione reductase (GR), glutathione transferase (GST), and glucose-6-phosphate dehydrogenase (G6PD) in liver cytosol. RESULTS: The soybean or olive oil diets modified the liver microsomal fatty acid phospholipid composition, but the unsaturation index remained unchanged. TPN specifically increased the saturation of the membrane. The cytochrome P-450 level and the NADPH-cytochrome c2 reductase, SOD, Gpx, Cat, and GST activities were unchanged by soybean oil or olive oil diet but decreased receiving TPN. CONCLUSIONS: In rats, TPN decreased the liver oxidative metabolism and enzymatic antioxidant defenses. This may be related to saturation of the liver microsomal fatty acids.

Hepatic hyper-vitaminosis A: importance of retinyl ester level determination.

We report the case of a 32-year-old man with portal hypertension without cirrhosis due to chronic vitamin A intoxication. Portal hypertension revealed by oesophageal varice rupture progressively worsened and ascites occurred 5 years after the patient stopped vitamin A intake. Initially, serum retinyl palmitate concentration was increased whereas serum retinol concentration was normal. There was no hepatic fibrosis on light microscopic examination of liver biopsy specimens. Five years after the patient stopped excessive vitamin A intake, serum retinol and retinol-binding protein concentrations were below the normal range even though there was an increased hepatic retinyl ester content. This was attributed to the late development of peri-sinusoidal fibrosis. This case mainly shows the importance of retinyl ester level determination: serum retinyl palmitate should be measured immediately after intoxication and hepatic retinyl esters should be measured initially and particularly later. Indeed, later serum and hepatic retinol levels in chronic hyper-vitaminosis A may be normal and lead to under-estimation of liver vitamin A overload.

Dietary essential fatty acid deficiency differentially affects tissues of rats.

Quantitative variations of polyunsaturated fatty acids (PUFA) were studied in various tissues: red blood cells (RBC), hepatic microsomes, kidney, skeletal muscle and heart of young rats fed either a control diet (n = 7) or an essential fatty acid (EFA)-deficient diet (n = 7). After 4 wk, the EFA-[deficient rats had significantly lower proportions of (n-6) and (n-3) fatty acids in RBC, hepatic microsomes and kidney than the control group. Paradoxically, normal proportions of arachidonic acid [20:4(n-6)] and 5,8,11,14,17-eicosapentaenoic acid [20:5(n-3)] were retained in heart and skeletal muscle despite generally lower proportions of the precursors, 18:2(n-6) and 18:3(n-3). Moreover, absolute levels of 20:4(n-6) and 20:5(n-3) in skeletal muscle of the EFA deficient group were significantly higher than in controls and 22:5(n-3) and 22:6(n-3) levels were comparable. This suggests that fatty acid proportions alone, without any consideration of long-chain polyunsaturated fatty acid quantities, may not reflect the (n-6) and (n-3) PUFA status of individual tissues. This study indicates that diet-[induced changes in the PUFA composition of RBC, which are often used in clinical investigations, do not fully reflect the changes in the fatty acid composition of organs, and that individual tissues respond differently to EFA deficiency. The conservation of proportional and absolute levels of 20:5(n-3) and 20:4(n-6), and the decrease in the more unsaturated homologues in the heart, suggest that this organ may avidly retain 20:5(n-3) and 20:4(n-6) in order to maintain eicosanoid production.

Decreases in retinol and retinol-binding protein during total parenteral nutrition in rats are not due to a vitamin A deficiency.

Perfusion feeding in rats induced a decrease in circulating retinol despite an adequate supply of vitamin A. We studied the effect of total parenteral nutrition (TPN) on the retinol specific carrier in rat, analyzing holo-RBP (bound to retinol) and apo-RBP (without retinol) in serum and in liver. Vitamin A-sufficient (A+) and -deficient (A-) rats were characterized in terms of vitamin A and RBP status and then perfused (TPN-A+ and TPN-A-) or orally pair-fed (O-A+ and O-A-) with vitamin A. In A+ rats, a decrease in serum retinol (2.6-fold) and an increase in apo-RBP was concomitant with a massive accumulation of RBP in the liver. In TPN-A rats, both circulating RBP and liver total RBP were decreased. In TPN-A+ rats, there was a decrease in circulating retinol (2.4-fold) in parallel to a decrease of serum and liver RBP protein and mRNA. We provide evidence that infused retinyl palmitate was not responsible for serum retinol and RBP decrease and that retinol depletion was not due to vitamin A deficiency. Whatever the vitamin A status, TPN may induce in rats a down-regulation of hepatic RBP synthesis, which may, at least partially, explain the alteration of retinol and RBP in serum.

Plasma and hepatic antioxidant control and vitamin A nutritional status.

Twenty-seven rats were divided into three groups and fed on diets containing 0.3, 6 or 60 RE (retinol equivalent) retinyl palmitate/g food. After 7 weeks, hepatic vitamin A uptake was found to be more efficient in vitamin A-deficient rats than in rats given adequate vitamin A. We showed that during the metabolic adaptation of the animals to the level of vitamin A in the diet, extensive modifications occur in the antioxidant defences of the organism. In parallel with the increase in the level of vitamin A, the decrease in the level of alpha-tocopherol in the plasma can bring about a greater susceptibility of the lipoproteins to oxidative stress. Similarly, the decrease in the hepatic alpha-tocopherol level and in glutathione peroxidase activity leads to the weakening of the liver's antioxidant defences.

Micronutrient levels in HIV-1-infected children.

OBJECTIVE: Micronutrients (zinc, copper, selenium, vitamin A, E, and carotenoids) are essential for the integrity of host defences. This study was designed to determine the prevalence of abnormalities of the micronutrient levels in HIV-1-seropositive children. DESIGN: Prospective study. SETTING: The study was performed on HIV-1-infected children at the Paediatric Haematology and Oncology Unit of Toulouse Hospital, France. PATIENTS: Twenty-one children, suffering from HIV-1 infection and 21 control subjects of similar age (2-9 years) were included in the study. In the HIV-1-infected children, two subgroups were considered according to stage (non-AIDS or AIDS), based on the Centers for Disease Control and Prevention 1987 criteria. RESULTS: The first statistically significant deficiencies occurred at non-AIDS stage and were confirmed at AIDS stage: P < 0.05 for lycopene, retinol, tocopherol and P < 0.001 for transthyretin and serum albumin. Levels of copper (40%) and long-chain polyunsaturated fatty acids (21%) were higher in the non-AIDS group than the controls. CONCLUSION: Biological impairing of the micronutrient levels was observed in the non-AIDS stage without clinical sign. This information is useful in delineating eventual and well considered nutritional intervention strategies that may improve the clinical status of HIV-1-infected children and perhaps alter the course of their disease.

alpha-Tocopherol and trolox block the early intracellular events (TBARS and calcium rises) elicited by oxidized low density lipoproteins in cultured endothelial cells.

Low-density lipoproteins (LDLs), treated by UV-C radiations under conditions permitting mildly oxidized LDL (6 +/- 2 nmol TBARS/mg apoB, without major structural or functional alteration of apoB), have been used for studying their cytotoxicity to cultured bovine aortic endothelial cells and the cytoprotective effect of various analogs of alpha-tocopherol. Toxic doses of oxidized LDL evoked intracellular events, such as cellular thiobarbituric acid reactive substances (TBARS) and a sustained peak of [Ca2+]i (cytosolic calcium). The sustained [Ca2+]i peak seems to be directly involved in the genesis of cell injury leading to cell death in contrast to cellular TBARS, which seems to be either an earlier step of signal transduction or a side effect, as shown by inhibiting the [Ca2+]i rise by ethylene glycol-O,O'-bis(amino ethyl)-N1N1N'1N'-tetraacetic acid (EGTA) added just before the time of the [Ca2+]i peak. When alpha-tocopherol or trolox (a short-chain, water-soluble analog of alpha-tocopherol) were added to the culture medium simultaneously with oxidized LDL, they were able to increase the resistance of endothelial cells against the cytotoxic effect of oxidized LDL, whereas alpha-tocopheryl acetate and alpha-tocopheryl succinate were almost completely ineffective because of the liberation of only very low levels of alpha-tocopherol. Trolox exhibited a more potent cytoprotective effect than alpha-tocopherol (IC50: 1 +/- 0.2 and 8 +/- 2 mumol/l for trolox and alpha-tocopherol, respectively). As shown by preincubating cells with effective concentrations of alpha-tocopherol or trolox, the cytoprotective effect was completely independent of any inhibition of LDL oxidation and was remanent for 2 d with alpha-tocopherol or for 3-4 d with trolox. Cytoprotective concentrations of trolox and alpha-tocopherol did not inhibit LDL uptake but acted at the cellular level by blocking the formation of cellular TBARS and the sustained [Ca2+]i peak as well. The potential relevance of these data in relation to the prevention of atherosclerosis is discussed.

A randomised controlled trial to test equivalence between retinyl palmitate and beta carotene for vitamin A deficiency.

OBJECTIVES: To determine whether beta carotene is therapeutically equivalent to retinyl palmitate in the formulation currently recommended by the World Health Organisation. DESIGN: Randomised blind equivalence trial. SETTING: Rural area in Senegal. SUBJECTS: Children aged 2-15 years suffering from vitamin A deficiency as defined by abnormal results on eye cytology were randomly allocated treatment with retinyl palmitate (n = 256) and beta carotene (n = 254). MAIN OUTCOME MEASURE: Reversion to normal results on eye cytology as defined by the reappearance of goblet cells and normalisation of the epithelial cells. RESULTS: Seven weeks after the supplement was given the percentages were 51.2% (124/242) children taking retinyl palmitate and 50.0% (123/246) of those taking beta carotene, who had reverted to normal eye cytology, a difference of 1.2% (95% confidence interval 6.2% to 8.6%) [corrected]. According to an equivalence testing procedure, the two treatments were statistically equivalent; the null hypothesis of non-equivalence was rejected (one tailed p value = 0.03). CONCLUSIONS: beta Carotene supplementation seems to be a promising candidate for the alleviation of vitamin A deficiency. It could be given either as high dose capsule or through increased dietary intake. The challenge now is to improve dietary intake of vitamin A in programmes that are effective and sustainable at the community level.

Assessment of vitamin A deficiency in a rural area in Mali. Estimation of sample size for the impression cytology test.

The prevalence of vitamin A deficiency among two to ten years old children in a rural area of Mali was assessed by ophthalmic examination, determination of plasma retinol levels and impression cytology with transfer tests. A Public Health problem of vitamin A deficiency was identified in this rural area by: the prevalence of nightblindness significantly (p < 0.001) above the cut-off (1%) defined by the World Health Organization (WHO); the prevalence of corneal scarring significantly (p < 0.001) above the WHO's cut-off (0.05%); the percentage of subjects with plasma retinol levels below 0.35 mumol/l (10 micrograms/dl) significantly (p < 0.001) higher than the WHO's threshold (5%); and 52.8 +/- 8.2% children with "Abnormal" impression cytology as determined by the impression cytology test (IC). This preliminary survey confirmed widespread vitamin A deficiency in Mali. The minimum sample size required for a study using the impression cytology test to determinate a Public Health problem in a population was calculated for different situations. Ophthalmic examination indicated a very high rate of active trachoma (29.6 +/- 7.0%), and a relationship between active trachoma and impression cytology results was identified.

Increased concentrations of endogenous 13-cis- and all-trans-retinoic acids in diffuse idiopathic skeletal hyperostosis, as demonstrated by HPLC.

Endogenous 13-cis- and all-trans-retinoic acids have been quantitated in human serum using a solvent extraction procedure followed by isocratic reversed phase high performance liquid chromatography and UV detection. In healthy adults, after an overnight fasting period, the concentrations of 13-cis- and all-trans-retinoic acids yielded 5.3 +/- 2.43 nmol/l and 11.8 +/- 3.3 nmol/l, respectively (mean +/- SD). The method has been successfully applied to the analysis of both isomers in serum from patients with idiopathic skeletal hyperostosis in whom, the 13-cis- as well as all-trans-retinoic acid levels were raised as compared to the control group.

Retinol storage in the rat liver after daily intramuscular administration of physiological doses of a vitamin A oil emulsion.

We have recently shown the kinetic behavior of liver retinyl esters in rats with adequate vitamin A levels receiving oral vitamin supplementation. In the present work we have studied the effects of intramuscular administration of a vitamin A preparation on the metabolism of vitamin A in the rat. Retinol administered intramuscularly to rats in the form of an emulsion brought about a significant increase in the serum and liver concentration of vitamin A; this increase was slightly less than in orally treated rats. In each group, retinyl palmitate constituted 80-85% of the total retinyl esters, followed by stearate (9-13%), laurate, palmitoleate, myristate, linoleate and pentadecanoate making up 3-10%. The subcellular localization of all retinyl esters is similar and dependent on age but not on the route of administration. These results indicate that although the best hepatic storage is achieved with an orally administered vitamin A emulsion, the intramuscular administration of a physiological dose might provide an effective supplementation method if oral vitamin A is contraindicated.

Fatty acid composition and kinetic behaviour of liver retinyl esters in vitamin A sufficient and deficient rats.

Weanling rats were fed vitamin A deficient diets (-A) or diets supplemented with vitamin A (+A) (4.4 mg retinol equivalents/kg diet) for a period of 7 or 6 wk, respectively. In liver tissues of these two groups of animals both the subcellular localization as well as the fatty acid composition of the retinyl esters was studied. During vitamin A supplementation or deprivation, the kinetics of the different ester forms were investigated. Results indicate that the subcellular localization of all retinyl esters is similar and dependent on age. Two pools exist, ie one consisting of the nuclear/cell debris and mitochondrial-lysosomal fractions and the other containing the microsomal and cytosol fractions. HPLC analysis showed retinyl palmitate as the predominating (80%) form of the various retinyl esters. By supplementation clearly two kinetic behaviours can be demonstrated: one being a relatively stable storage of the palmitate and stearate, increasing with time and the second one being a more labile pattern for the ester forms with other saturated and unsaturated fatty acids. By vitamin A depletion all retinyl esters are affected indicating that the ester forms other than palmitate and stearate are also storage forms of vitamin A.

Effects of retinoic acid on hepatic cytochrome P-450 dependent enzymes in rats under different vitamin A status.

The temporal effects of retinoic acid supplementation on hepatic cytochrome P-450-dependent enzymes were studied on the rat. Four groups of male weanling rats were fed semi synthetic diets: two groups containing 0 or 4.4 mg retinol equivalents per kg diet as retinyl palmitate (A- RA- and A+ RA- groups) and two similar groups supplemented with all trans retinoic acid (12 mg/kg diet) (A- RA+ and A+ RA+ groups). After five or ten weeks of feeding, the rats were killed, liver microsomes were prepared and assayed for aniline hydroxylase, aminopyrine N demethylase activities and cytochrome P-450 levels. Whereas no change was observed between the four groups after 5 weeks, the following modifications appeared after 10 weeks: Vitamin A deficiency decreased hepatic drug metabolism by phase I enzymes (hydroxylase and N demethylase) but only when liver storage pool was not detectable. Vitamin A concentration as low as 4 micrograms/g is sufficient to avoid any perturbation of these enzymes. Parallel to a sparing effect on liver reserves of vitamin A, retinoic acid maintained a normal activity of enzymes of xenobiotic metabolism. However, retinoic acid treatment produced an alteration of phase I enzymes in vitamin A supplemented group (A+ RA+). As this was accompanied by a doubling of vitamin A liver reserves, compared to A+ RA- group, it is suggested that this might result from a liver vitamin A overloading, leading to membrane damage perturbing microsomal enzymes. These results indicate the need for a more careful use of retinoids as a therapeutic agent.

[Screening of essential fatty acid deficiency in children. Respective value of the assay of fatty acids in total lipids and lipid fractions of the serum]. / Dépistage d'une carence en acides gras essentiels chez l'enfant. Intérêt respectif du dosage des acides gras dans les lipides totaux et les fractions lipidiques du sérum.

This study was carried out in metabolically stable infants aged from one to six months receiving artificial food. The lipid serum fraction presenting changes characteristic of essential fatty acid (EFA) deficiency was determined. A preliminary study (n = 13 samples) showed that analysis of total fatty acids (TFA) and of phospholipids (PL) was more discriminatory than analysis of free fatty acids (FFA), triglycerides (TG) or esterified cholesterol (EC). Comparison of TFA and PL (n = 25 samples) confirmed literature data; in particular, C18: 2 n-6 and C20: 4 n-6 decreased whereas C20: 3 n-9 increased. These changes were clearer and significantly greater (p less than 0.001) for C20: 3 n-9 and C20: 4 n-6 of the PL, but were also very significant for the TFA compared to healthy controls. The C20: n-9/C20: n-6 ratio was identical for all fractions. TFA analysis by gas-liquid chromatography is faster and less costly than analysis of lipid fractions and provides sufficient data for screening of EFA deficiency.