ABSTRACT
BACKGROUND: The use of complementary and alternative medicine including herbal medicine (phytotherapy), vitamins, minerals and food supplements is frequent among people living with HIV/AIDS (PLWHAs) who take antiretroviral (ARV) drugs, but is often not known by their prescribing physicians. Some drug-supplement combinations may result in clinically meaningful interactions. AIMS: In this literature review, we aimed to investigate the evidence for complementary and alternative medicine interactions with ARVs. SOURCES: A bibliographic search of all in vitro, human studies and case reports of the PubMed database was performed to assess the risk of interactions between complementary and alternative self-medication products and ARVs. The 'HIV drug interaction' (https://www.hiv-druginteractions.org) and 'Natural medicines comprehensive database' (https://naturalmedicines.therapeuticresearch.com) interaction checkers were also analysed. CONTENT: St John's wort, some forms of garlic, grapefruit and red rice yeast are known to have significant interaction and thus should not be co-administered, or should be used with caution with certain ARV classes. Data on other plant-based supplements come from in vitro studies or very small size in vivo studies and are thus insufficient to conclude the real in vivo impact in case of concomitant administration with ARVs. Some polyvalent minerals such as calcium, magnesium, and iron salts can reduce the absorption of integrase inhibitors by chelation. Potential interactions with vitamin C and quercetin with some ARVs should be noted and efficacy and tolerance of the treatment should be monitored. IMPLICATIONS: This review shows the importance of screening all PLWHAs for complementary and alternative medicine use to prevent treatment failure or adverse effects related to an interaction with ARVs. Further human studies are warranted to describe the clinical significance of in vitro interactions between numerous complementary and alternative medicine and ARVs.
Subject(s)
Anti-HIV Agents/pharmacokinetics , Dietary Supplements , HIV Infections/drug therapy , Phytotherapy , Anti-HIV Agents/administration & dosage , Drug Interactions , Drug-Related Side Effects and Adverse Reactions , HumansABSTRACT
OBJECTIVE: The lack of patient adherence to medical treatment has become a major concern for healthcare professionals. The World Health Organization estimated patient adherence to treatment at 50% only. The inadequate use of antibiotics can cause bacterial resistance the progression of which reduces therapeutic alternatives. The objective of this pilot study was to assess the patient's adherence to anti-infective agents prescribed for acute infection, after returning home. METHOD: Thirty-seven patients hospitalized in the Infectious and Tropical Diseases unit were included. Their adherence to anti-infective drugs was assessed indirectly through data collected by calling the pharmacy and the patient in the week following discontinuation of anti-infective treatment. RESULTS: Sixteen patients were identified as non-adherent (43.2%). A single patient could have several behaviors: extension of treatment (50%), dose modification (6.3%), voluntary omission (12.5%), and involuntary (6.3%). One patient (6.3%) did not take his anti-infective treatment. There was no major cause of non-adherence; every patient had his own reasons. The comparison of several criteria between adherent and non-adherent patients did not reveal any predictive risk factors. CONCLUSION: Our study results revealed for the first time that 50% of patients were adherent to anti-infective agents, after returning home. They confirm the need to implement preventive actions such as a discharge pharmaceutical consultation.
Subject(s)
Anti-Infective Agents/therapeutic use , Medication Adherence , Adult , Aged , Ambulatory Care , Bacterial Infections/drug therapy , Female , Humans , Male , Medication Adherence/psychology , Middle Aged , Prospective Studies , Self AdministrationABSTRACT
Previous work has suggested that activation of mGlu5 receptor augments NMDA receptor function and thereby may constitute a rational approach addressing glutamate hypofunction in schizophrenia and a target for novel antipsychotic drug development. Here, we report the in vitro activity, in vivo efficacy and safety profile of 5PAM523 (4-Fluorophenyl){(2R,5S)-5-[5-(5-fluoropyridin-2-yl)-1,2,4-oxadiazol-3-yl]-2-methylpiperidin-1-yl}methanone), a structurally novel positive allosteric modulator selective of mGlu5. In cells expressing human mGlu5 receptor, 5PAM523 potentiated threshold responses to glutamate in fluorometric calcium assays, but does not have any intrinsic agonist activity. 5PAM523 acts as an allosteric modulator as suggested by the binding studies showing that 5PAM523 did not displace the binding of the orthosteric ligand quisqualic acid, but did partially compete with the negative allosteric modulator, MPyEP. In vivo, 5PAM523 reversed amphetamine-induced locomotor activity in rats. Therefore, both the in vitro and in vivo data demonstrate that 5PAM523 acts as a selective mGlu5 PAM and exhibits anti-psychotic like activity. To study the potential for adverse effects and particularly neurotoxicity, brain histopathological exams were performed in rats treated for 4 days with 5PAM523 or vehicle. The brain exam revealed moderate to severe neuronal necrosis in the rats treated with the doses of 30 and 50 mg/kg, particularly in the auditory cortex and hippocampus. To investigate whether this neurotoxicity is mechanism specific to 5PAM523, similar safety studies were carried out with three other structurally distinct selective mGlu5 PAMs. Results revealed a comparable pattern of neuronal cell death. Finally, 5PAM523 was tested in mGlu5 knock-out (KO) and wild type (WT) mice. mGlu5 WT mice treated with 5PAM523 for 4 days at 100 mg/kg presented significant neuronal death in the auditory cortex and hippocampus. Conversely, mGlu5 KO mice did not show any neuronal loss by histopathology, suggesting that enhancement of mGlu5 function is responsible for the toxicity of 5PAM523. This study reveals for the first time that augmentation of mGlu5 function with selective allosteric modulators results in neurotoxicity.
Subject(s)
Antipsychotic Agents/toxicity , Benzamides/toxicity , Brain/drug effects , Cell Death/drug effects , Excitatory Amino Acid Agents/toxicity , Oxadiazoles/toxicity , Receptor, Metabotropic Glutamate 5/metabolism , Allosteric Regulation , Animals , Antipsychotic Agents/chemistry , Antipsychotic Agents/pharmacokinetics , Benzamides/chemistry , Benzamides/pharmacokinetics , Brain/pathology , Brain/physiopathology , CHO Cells , Cell Death/physiology , Cells, Cultured , Cricetulus , Excitatory Amino Acid Agents/chemistry , Excitatory Amino Acid Agents/pharmacokinetics , Female , Humans , Male , Mice, 129 Strain , Mice, Knockout , Necrosis/pathology , Necrosis/physiopathology , Neurons/drug effects , Neurons/pathology , Neurons/physiology , Neurotoxicity Syndromes/pathology , Neurotoxicity Syndromes/physiopathology , Oxadiazoles/chemistry , Oxadiazoles/pharmacokinetics , Rats, Sprague-Dawley , Rats, Wistar , Receptor, Metabotropic Glutamate 5/geneticsABSTRACT
Immunochemical stool blood tests have a significantly higher sensitivity for the detection of advanced neoplasia and colorectal cancer. Based on national and international studies it has been required to include them into the national cancer screening programme in Germany also. The sensitivity (detection limit) can be set by the manufacturer in order to achieve an optimal and balanced result between sensitivity and specificity. The present study was conducted with 639 patients who have undergone both the screening colonoscopy, as well as the immunochemical stool blood test. The test "immoCARE-C" provided by the company CARE diagnostica Laborreagenzien GmbH was used in the study. The test has been evaluated with seven levels of detection limits between 500 âng/mL and 25 âng/mL. The best sensitivity for detection of advanced lesions was demonstrated by a cut-off of 50 ng/mL and 25 âng/mL. The specificity did not fall below 90 â%. These positive results lead to considerations to organise a primary access to such tests in the prevention of colorectal cancer as a kind of filter before offering the screening colonoscopy.
Subject(s)
Biomarkers, Tumor/blood , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Feces/chemistry , Mass Screening/statistics & numerical data , Occult Blood , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/epidemiology , Female , Humans , Male , Middle Aged , Prevalence , Reproducibility of Results , Risk Assessment , Sensitivity and SpecificityABSTRACT
BACKGROUND/OBJECTIVES: Lower-income subgroups consume fewer servings of fruit and vegetables (FVs) compared with their more advantaged counterparts. To overcome financial barriers, FV voucher delivery has been proposed. SUBJECTS/METHODS: In a 12-month trial, 302 low-income adults 18-60 years old (defined by evaluation of deprivation and inequalities in health examination centers, a specific deprivation score) were randomized into two groups: dietary advice alone ('advice'), or dietary advice plus FV vouchers ('FV vouchers') (10-40 euros/month) exchangeable for fresh fruits and vegetables. Self-reported data were collected on FV consumption and socioeconomic status at baseline, 3, 9 and 12 months. Anthropometric and blood pressure measurements were conducted at these periods, as well as blood samples obtained for determination of vitamins. Descriptive analyses, multiple linear regression and logistic regression were performed to evaluate the impact of FV. RESULTS: Between baseline and 3-month follow-up, mean FV consumption increased significantly in both the 'advice' (0.62±1.29 times/day, P=0.0004) and 'FV vouchers' groups (0.74±1.90, P=0.002), with no difference between groups. Subjects in the FV vouchers group had significantly decreased risk of low FV consumption (<1 time/day) compared with those in the advice group (P=0.008). No change was noted in vitamin levels (vitamin C and ß-carotene). The high number of lost-to-follow-up cases did not permit analysis at 9 or 12 months. CONCLUSION: In the low-income population, FV voucher delivery decreased the proportion of low FV consumers at 3 months. Longer-term studies are needed to assess their impact on nutritional status.
Subject(s)
Diet/economics , Food Services , Health Education , Income , Poverty , Social Class , Social Welfare , Adolescent , Adult , Counseling , Diet/standards , Female , Food Supply , Fruit , Humans , Linear Models , Logistic Models , Male , Middle Aged , Nutritional Status , Self Report , Vegetables , Young AdultABSTRACT
AIM: The authors wanted to identify the factors associated with prescription or non-prescription of antibiotics by general practitioners (GPs), for three frequent infectious diseases: tonsillitis, acute bronchitis (AB) and exacerbations of chronic bronchitis (ECB). PATIENTS AND METHODS: A cross-sectional study included 574 patients followed by 58 randomly selected GPs in Eastern France. Data on physicians, patients (clinical, social and environmental) and antibiotic treatment (type, motivations) was collected during the consultation via a standardized questionnaire. RESULTS: Official recommendations for tonsillitis, AB and ECB were known by GPs in 100, 96 and 91% of the cases, respectively. An antibiotic was administered in 61% of tonsillitis cases, 64% of AB and 84% of ECB. The correlation between prescribing or not antibiotics and official recommendations was variable (tonsillitis: 81.3%, ECB 89.6%, AB: 36.5%). Clinical criteria were the main factors influencing antibiotic prescription. A rapid antigen detection test for streptococcus A was performed in 65% of tonsillitis cases (positive in 55%) increased conformity with recommendations to 93.7%. A second consultation, poor tolerance and patient demand were also significantly associated with a higher rate of antibiotic prescription. CONCLUSIONS: Recommendations were known, but semiologic definitions and nosologic limits varied from one physician to another. Recommendations must be based on routine medical practice surveys to include factors influencing prescription, even if non significant. Paraclinical tests help in therapeutic decision making and in the non-prescription of antibiotics but such tests need to be more commonly used.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Nonprescription Drugs/therapeutic use , Physicians, Family , Prescription Drugs/therapeutic use , Adolescent , Adult , Bacterial Infections/drug therapy , Child , Child, Preschool , Cross-Sectional Studies , Drug Tolerance , France , Humans , Patient Selection , Urban Population , Young AdultABSTRACT
Carotenoids are colored molecules that are widespread in the plant kingdom, but animals cannot synthesize them. Carotenes are long, apolar molecules which require fully functioning digestive processes to be absorbed properly. Hence they could be interesting markers of intestinal absorption and digestion. Indeed, only few tests are available to assess these processes and only the D-xylose tolerance test is routinely used. However D-xylose is a sugar that tests only the absorption of water-soluble compounds and it only tests duodenal absorption. In this study, we have evaluated carotenoids as markers of digestion and absorption. We compared fasting plasma carotenoids concentrations in 21 control subjects, 20 patients with Crohn's disease, and 18 patients with pancreatic cancer. Crohn's disease alters intestinal absorption while pancreatic cancer decreases pancreatic enzyme secretion thus impairing digestion. Results show that all carotenoids are significantly lower in Crohn's and cancer patients as compared to control subjects and the multifactorial analysis shows that this decrease is mostly independent of dietary intake. Interestingly, maldigestion as seen in pancreatic cancer more strongly influences plasma lutein and lycopene concentrations while malabsorption in Crohn's disease acts on other carotenoids. Thus carotenoids could be interesting alternatives for testing and following patients that are suspected of having malabsorption or maldigestion syndromes.
Subject(s)
Carotenoids/blood , Crohn Disease/blood , Ileitis/blood , Pancreatic Neoplasms/blood , Adult , Aged , Biomarkers/blood , Diet , Digestion , Female , Humans , Intestinal Absorption , Male , Middle Aged , Sex Characteristics , Surveys and QuestionnairesABSTRACT
OBJECTIVES: The data was collected during the inclusion step of the SUpplémentation en VItamines et Minéraux AntioXydants (SU.VI.MAX) study. This article deals with the study's first stage before any supplementation. The collected data shows factors influencing blood vitamin concentrations and may reflect the vitamin status of volunteers. MATERIAL AND METHODS: A total of 12,741 volunteers were enrolled in the SU.VI.MAX study 7,713 women 35-60 years of age and 5,028 men 50-60 years of age. The serum concentrations of retinol, alpha-tocopherol, and beta-carotene were measured by HPLC, and vitamin C concentration was measured by spectrofluorimetry using a Technicon continuous flow analysis apparatus. The volunteers recorded their 24 h diet by means of a specific terminal that was connected to the main central computer of the SU.VI.MAX study. Volunteers recorded the food they consumed daily and estimated its quantity by comparing pictures of dishes. RESULTS: Retinol concentration was significantly higher in older volunteers, and was higher in male than in female volunteers. Smoking had no effect on serum retinol, but the latter was higher in the autumn than in the winter. Serum retinol concentrations were higher in the Southwest region and lower in the Ile-de-France and East-Centre regions. Serum alpha-tocopherol was slightly higher in older volunteers and also higher in male volunteers. Serum alpha-tocopherol was significantly lower in smokers, and former smokers showed intermediate levels. Like retinol, serum alpha-tocopherol was higher in the autumn, and higher in the Southwest as compared to the East-Centre Serum beta-carotene was slightly higher in younger volunteers, and concentrations were higher in female than in male volunteers. Tobacco smoking decreased serum beta-carotene, which was higher in the autumn, and higher in the East, West, and North regions. Serum vitamin C was higher in female volunteers, and was not age related. Serum vitamin C was lower in smokers, was season-dependant, but contrary to fat-soluble vitamins, concentrations were higher in the winter and spring. Serum vitamin C was higher in the Southeast and East-Centre, but lower in the North region. CONCLUSION: These results suggest that serum retinol concentrations depend on gender, age, seasons, and location of residence. Similarly, serum alpha-tocopherol concentrations were slightly influenced by age, but more by tobacco smoking, seasons, dietary intake, and location of residence. Serum concentrations of beta-carotene depend on gender, age, smoking status, dietary intake, and location of residence. Serum vitamin C concentrations depend on gender, age, smoking status, seasons, dietary intake, and location of residence. Contrary to beta-carotene, retinol concentrations were higher in male than in female volunteers. Such a reversed relation suggests a higher beta-carotene-retinol conversion in male volunteers.
Subject(s)
Antioxidants/metabolism , Ascorbic Acid/blood , Diet , Vitamin A/blood , alpha-Tocopherol/blood , beta Carotene/blood , Adult , Age Factors , Analysis of Variance , Antioxidants/administration & dosage , Ascorbic Acid/administration & dosage , Chromatography, High Pressure Liquid/methods , Demography , Diet Records , Female , France , Humans , Male , Middle Aged , Nutritional Status , Seasons , Sex Factors , Smoking , Vitamin A/administration & dosage , alpha-Tocopherol/administration & dosage , beta Carotene/administration & dosageABSTRACT
OBJECTIVE: To assess relationships between energy, nutrient and food intakes, alcohol consumption, smoking status and body mass index (BMI), and serum concentrations of beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc. METHODS: Data on health status, alcohol consumption, smoking habits, anthropometric data and biochemical measurements were obtained in 1821 women aged 35-60 y and 1307 men aged 45-60 y, participant to the SU.VI.MAX Study. Data on dietary intake were available on a subsample who reported six 24-h dietary records during the first 18 months of the study. RESULTS: Women had higher baseline serum beta-carotene and vitamin C concentrations and lower concentration for serum vitamin E, zinc and selenium than men. In women, younger age was associated with lowered mean concentration of serum beta-carotene, vitamin E and selenium. In men, only differences were observed for serum zinc, which was lower in older men. Current smokers of both sexes had significantly lower concentrations of serum beta-carotene, vitamin C and selenium, and, only in women, of vitamin E, than nonsmokers. Alcohol consumers had lower concentrations of serum beta-carotene and higher selenium concentrations. Serum beta-carotene and vitamin C concentrations were lower in obese subjects. There were positive associations of dietary beta-carotene, vitamin C and E with their serum concentrations. Age, nutrient and alcohol intakes, serum cholesterol, BMI and smoking status explained 15.2% of the variance of serum beta-carotene in men and 13.9% in women, and 10.8 and 10.0% for serum vitamin C, and 26.3 and 28.6% for serum vitamin E, respectively. CONCLUSION: Serum antioxidant nutrient concentrations are primarily influenced by sex, age, obesity, tobacco smoking, alcohol consumption and especially dietary intake of those antioxidant nutrients.
Subject(s)
Antioxidants/metabolism , Diet , Obesity/blood , Trace Elements/blood , Adult , Age Factors , Alcohol Drinking/blood , Antioxidants/administration & dosage , Antioxidants/analysis , Ascorbic Acid/administration & dosage , Ascorbic Acid/blood , Blood Chemical Analysis , Energy Intake , Female , France , Humans , Male , Middle Aged , Selenium/administration & dosage , Selenium/blood , Sex Factors , Smoking/blood , Trace Elements/administration & dosage , Trace Elements/analysis , Vitamin E/administration & dosage , Vitamin E/blood , Zinc/administration & dosage , Zinc/blood , beta Carotene/administration & dosage , beta Carotene/bloodABSTRACT
Our knowledge about intestinal absorption and cleavage of carotenoids has rapidly grown during the last years. New facts about carotenoid absorption have emerged while some controversies about cleavage are close to end. The knowledge of the absorption and conversion processes is indispensable to understand and interpret the perturbations that can occur in the metabolism of carotenoids and vitamin A. Recently, it has been shown that the absorption of certain carotenoids is not passive - as believed for a long time - but is a facilitated process that requires, at least for lutein, the class B-type 1 scavenger receptor (SR-B1). Various epidemiological and clinical studies have shown wide variations in carotenoid absorption from one subject to another, such differences are now explained by the structure of the concerned carotenoid, by the nature of the food that is absorbed with the carotenoid, by diverse exogenous factors like the intake of medicines or interfering components, by diet factors, by genetic factors, and by the nutritional status of the subject. Recently, the precise mechanism of beta-carotene cleavage by betabeta-carotene 15,15' monooxygenase (EC 1.14.99.36) - formerly called beta-carotene 15,15' dioxygenase (ex EC 1.13.11.21) - has been discovered, and a second enzyme which cleaves asymmetrically the beta-carotene molecule has been found. beta-carotene 15,15' monooxygenase only acts on the 15,15' bond, thus forming two molecules of retinal from one molecule of beta-carotene by central cleavage. Even though the betabeta-carotene 15,15' monooxygenase is much more active on the beta-carotene molecule, a study has shown that it can act on all carotenoids. Searchers now agree that other enzymes that can catalyse an eccentric cleavage of carotenoids probably exist, but under physiological conditions the betabeta-carotene 15,15' monooxygenase is by far the most active, and it is mainly effective in the small bowel mucosa and in the liver. However the conversion of provitamin A carotenoids into vitamin A is only partial, and requires a satisfactory protein status.
Subject(s)
Carotenoids/metabolism , Intestinal Absorption , Vitamin A/metabolism , Animals , Biological Availability , Carotenoids/blood , Cats , Child , Dietary Fiber , Humans , Infant, Newborn , Intestinal Mucosa/enzymology , Intestine, Small/enzymology , Liver/enzymology , Lycopene , Mixed Function Oxygenases/metabolism , Nutritional Status , Pharmacokinetics , Rats , Time Factors , Vitamin A Deficiency/metabolism , Xanthophylls/metabolismABSTRACT
Hedgehog interacting protein (Hip) is considered as a membrane protein implicated in sequestering the hedgehog (hh) morphogens during embryonic development. Here, we demonstrate that Hip transcription also occurs in cells scattered in discrete brain areas of adult rodents and we identify the presence of membrane-associated and soluble forms of Hip in the mature brain. Moreover, we show that soluble forms of Hip, present in the conditioned medium of HEK293 cells overexpressing Hip, inhibit Sonic hedgehog (Shh)-induced differentiation of C3H10T1/2 cells, a well-characterised response associated with Shh signalling. After transfection in HEK293 cells, Hip partitions with the raft component ganglioside GM1 during density gradient centrifugation. Analysis of tagged Hip constructs reveals that the putative transmembrane domain of Hip is not cleaved suggesting that other mechanisms are implicated in the release of its soluble forms. Taken together, these data are consistent with the involvement of both membrane-associated and soluble Hip in the regulation of Shh signalling in adult neural tissues.
Subject(s)
Brain/metabolism , Carrier Proteins/chemistry , Carrier Proteins/metabolism , Cell Membrane/metabolism , G(M1) Ganglioside/metabolism , Membrane Glycoproteins/chemistry , Membrane Glycoproteins/metabolism , Neurons/metabolism , Animals , Brain/ultrastructure , Brain Chemistry , CHO Cells , Carrier Proteins/genetics , Cell Differentiation/drug effects , Cell Differentiation/genetics , Cell Membrane/chemistry , Cricetinae , Culture Media, Conditioned/pharmacology , Hedgehog Proteins , Humans , Male , Membrane Glycoproteins/genetics , Membrane Microdomains/chemistry , Mice , Neurons/ultrastructure , Protein Structure, Tertiary/physiology , RNA, Messenger/biosynthesis , Rats , Solubility , Subcellular Fractions/chemistry , Trans-Activators/antagonists & inhibitors , Trans-Activators/metabolismABSTRACT
This study was undertaken with the aim to develop an optimised protocol for the evaluation of DNA damage in frozen whole blood. This was achieved by use of the single-cell gel electrophoresis (SCGE) or comet assay in its alkaline version. After collection of blood, the total blood sample was mixed with dimethyl sulfoxide (DMSO), a cryoprotectant commonly used for prevention of freezing-induced damage to living cells, and then stored at -80 degrees C. We observed no statistically significant differences in the level of DNA damage between fresh blood samples and frozen blood samples, as assessed by the comet assay. Considering the absence of effects of the freezing step, a frozen blood sample was included as a control sample in subsequent experiments. Thus the protocol was applied to blood samples of twenty healthy subjects including smokers and non-smokers. The comparative analysis indicated that the level of DNA damage was 56% higher in smokers than in non-smokers (P = 0.01). Altogether, this study strongly suggests that frozen whole blood could be utilised in association with the comet assay in human epidemiological bio-monitoring for the assessment of genetic damage in populations at risk.
Subject(s)
Blood , Comet Assay , DNA Damage , Smoking/blood , Case-Control Studies , Freezing , HumansABSTRACT
OBJECTIVE: To investigate the possible beneficial effects of a micronutrient supplementation to apparently healthy pregnant women on maternal biological status and new born anthropometric characteristics. SETTING: Departments of Obstetric of the University Hospital of Grenoble (France) and Lyon (France), Laboratoire of Biology of Oxidative Stress, UFR de Pharmacie. Grenoble (France). STUDY DESIGN: Double-blind, randomized placebo-controlled intervention trial. SUBJECTS: A total of 100 apparently healthy pregnant women were recruited at 14+/-2 weeks of gestation to delivery. At the end, they were 65 women to follow out the study. INTERVENTIONS: Daily consumption over gestation of a micronutrients supplement or placebo. MAIN OUTCOME MEASURES: Plasma micronutrient levels and oxidative stress parameters were measured in mothers at 14 and 38 weeks of gestation. New born's anthropometric characteristics were measured at delivery. RESULTS: In the supplemented group, folic acid, vitamin C, E, B2, B6 and beta-carotene levels were higher than in the placebo group. Oxidative stress parameters were not different between the groups. Birth weights were increased by 10% and the number of low newborn weights (<2700 g) decreased significantly when the mother received the supplementation. Maternal plasma Zn levels were positively correlated to the newborn heights. CONCLUSION: A regular intake of a micronutrient supplement at nutritional dose may be sufficient to improve micronutrient status of apparently healthy pregnant women and could prevent low birth weight of newborn.
Subject(s)
Birth Weight/drug effects , Dietary Supplements , Infant, Newborn/growth & development , Micronutrients/administration & dosage , Nutritional Status , Adult , Anthropometry , Double-Blind Method , Female , Health Status , Humans , Infant, Low Birth Weight , Micronutrients/blood , Oxidative Stress/drug effects , Placebos , Pregnancy , Pregnancy Complications/prevention & control , Pregnancy Outcome , Zinc/administration & dosage , Zinc/bloodSubject(s)
Aging/drug effects , Vitamins/therapeutic use , Age Factors , Aged , Aged, 80 and over , Animals , Antioxidants/therapeutic use , Ascorbic Acid/administration & dosage , Ascorbic Acid/analysis , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , Bone Diseases/drug therapy , Eye Diseases/drug therapy , Female , Flavonoids/therapeutic use , Humans , Male , Middle Aged , Retinoids/pharmacology , Retinoids/therapeutic use , Risk Factors , Sex Factors , Skin/chemistry , Skin/drug effects , Skin Aging/drug effects , Vitamin A/pharmacology , Vitamin A/therapeutic use , Vitamin D/administration & dosage , Vitamin D/pharmacology , Vitamin D/therapeutic use , Vitamin E/therapeutic use , Vitamin K/therapeutic use , Vitamins/administration & dosage , Vitamins/pharmacologySubject(s)
Biotechnology , Plants , Vitamins , Animals , Ascorbic Acid/metabolism , Biological Availability , Biotin/biosynthesis , Biotin/metabolism , Carotenoids , Cell Line , Female , Humans , Male , Plants/chemistry , Plants/enzymology , Plants/genetics , Plants/metabolism , Plants, Edible/chemistry , Plants, Edible/metabolism , Pregnancy , Nicotiana/cytology , Nicotiana/metabolism , Vitamin B Complex/metabolism , Vitamin E/metabolism , Vitamins/metabolismSubject(s)
Avitaminosis , Nutrition Disorders , Adolescent , Adult , Anorexia Nervosa/complications , Avitaminosis/complications , Avitaminosis/epidemiology , Avitaminosis/etiology , Avitaminosis/prevention & control , Child , Child, Preschool , Cohort Studies , Cystic Fibrosis/complications , Developing Countries , Female , Humans , Male , Niacin/deficiency , Nutrition Disorders/complications , Nutrition Disorders/prevention & control , Oxidative Stress , Pregnancy , Risk Factors , Thiamine Deficiency/diagnosis , Vitamin B 12 Deficiency/diagnosis , Vitamin D Deficiency/diagnosis , Vitamins/administration & dosage , Vitamins/therapeutic useABSTRACT
The "SUpplementation en VItamines et Minéraux AntioXidants" (SU.VI.MAX) study is a randomized double-blind, placebo controlled, primary-prevention trial designed to test the efficacy of a daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 microg; and zinc, 20 mg) at nutritional doses (one to three times the daily recommended dietary allowances), in reducing the frequency of cancers and cardiovascular diseases. The study involves 12,735 eligible subjects (women aged 35-60 years, men aged 45-60 years) included in 1994 in France. They will be followed up for 8 years. The targeted population is the general population. The aim of this specific analysis is to assess the effect of 2 years of supplementation on biochemical indicators of vitamin and trace element on a subsample of 1000 subjects. The mean (+/- standard deviation) concentrations of plasma beta-carotene, alpha-tocopherol, vitamin C, selenium and zinc among participants who were randomly assigned to receive a daily supplementation with beta-carotene, vitamin E, vitamin C, selenium and zinc for 2 years were significantly higher than those who were assigned to receive placebo. Specifically, the mean concentrations among men in the intervention group were 0.86 +/- 0.70 micromol/L for beta-carotene, 35.3 +/- 9.3 micromol/L for alpha-tocopherol, 11.5 +/- 4.7 microg/ mL for vitamin C, 1.65 +/- 0.33 micromol/L for selenium, and 16.2 +/- 3.9 micromol/L for zinc. The mean concentrations among women in the intervention were 1.25 +/- 0.90 micromol/L for beta-carotene, 34.9 +/- 8.4 micromol/L for alpha-tocopherol, 12.6 +/- 4.0 microg/mL for vitamin C, 1.68 +/- 0.37 micromol/L for selenium, and 15.3 +/- 3.9 micromol/L for zinc. The values observed for beta-carotene and vitamin E in the supplementation group after 2 years of intervention are those that have been associated with the lowest risk of cancer in observational studies. They are definitely lower than concentrations reported in intervention studies showing an apparent negative effect of high levels of beta-carotene supplementation on the lung cancer incidence rate in high-risk subjects (initial level multiplied by 12-18). Data from the follow-up will ascertain if any plausible reduction in the incidence rate of cancers may be associated with such amounts of antioxidant agents.
Subject(s)
Antioxidants/administration & dosage , Biomarkers/blood , Trace Elements/administration & dosage , Trace Elements/blood , Vitamins/administration & dosage , Vitamins/blood , Adult , Ascorbic Acid/blood , Dietary Supplements , Double-Blind Method , Female , Humans , Male , Middle Aged , Selenium/blood , Zinc/blood , alpha-Tocopherol/blood , beta Carotene/bloodABSTRACT
Sonic hedgehog (SHH) is considered to play an important role in tissue induction and patterning during development, particularly in determining neuronal cell fate in the ventral neural tube and in the embryonic forebrain. SHH precursor is autoproteolytically cleaved to an aminoterminal fragment (SHHN) which retains all known SHH biological activities. Here, we demonstrate the expression of a 22-kDa SHHN immunoreactive peptide in developing and adult hamster brain regions using a rabbit antiserum directed against a mouse SHHN fragment. Interestingly, SHHN was developmentally regulated with the highest expression observed in the adult brain, was resistant to Triton X-100 solubilization at 4 degrees C and partitioned with the raft component ganglioside GM1 during density gradient centrifugation. In rat brain, Shh transcripts were identified by double in situ hybridization in GABAergic neurons located in various basal forebrain nuclei including globus pallidus, ventral pallidum, medial septum-diagonal band complex, magnocellular preoptic nucleus and in cerebellar Purkinje cells as well as in motoneurons of several cranial nerve nuclei and of the spinal cord. We show that radiolabelled SHHN peptides are synthesized in the adult hamster retina and are transported axonally along the optic nerve to the superior colliculus in vivo. Our data indicate that SHHN is associated with cholesterol rich raft-like microdomains and anterogradely transported in the adult brain, and suggest that the roles of this extracellular protein are more diverse than originally thought.
Subject(s)
Axonal Transport/physiology , Brain/metabolism , Trans-Activators/genetics , Trans-Activators/metabolism , Age Factors , Animals , Antibodies , Brain/cytology , Brain/growth & development , Cell Membrane/chemistry , Cholesterol/metabolism , Cricetinae , Detergents , G(M1) Ganglioside/analysis , Gene Expression/physiology , Hedgehog Proteins , Mesocricetus , Neurons/chemistry , Neurons/metabolism , RNA, Messenger/analysis , Retina/cytology , Spinal Cord/cytology , Spinal Cord/growth & development , Spinal Cord/metabolism , Trans-Activators/immunologyABSTRACT
Selenium is an essential trace element which is part of the active site of seleno-dependent glutathione peroxidase and type 1 deiodinase. Therefore, it plays a key role in thyroid hormone metabolism. The present work was undertaken in order to evaluate selenium status in two Ivory Coast populations: the first with high (Glanlé) and the second with low (Abidjan) prevalence of iodine deficiency. Selenium, glutathione peroxidase, glutathione reductase, glutathione and diglutathione were determined in blood and/or urine. In plasma and erythrocytes, selenium and glutathione peroxidase were dramatically low in Glanlé. Compared to Abidjan, selenium, glutathione peroxidase, vitamin E and riboflavin status were decreased whereas diglutathione was increased in Glanlé. The results clearly demonstrate a selenium deficiency and suggest an oxidant stress in Glanlé. Causes and consequences of this selenium deficiency and oxidant stress remain to be determined.