Subject(s)
Anaphylaxis/diagnosis , Drug Hypersensitivity/diagnosis , Drug-Related Side Effects and Adverse Reactions/diagnosis , Hemostatics/therapeutic use , Tranexamic Acid/therapeutic use , Adolescent , Anaphylaxis/etiology , Bronchial Spasm , Female , Hemostatics/adverse effects , Humans , Immunization , Male , Middle Aged , Skin Tests , Tachycardia , Tranexamic Acid/adverse effectsABSTRACT
INTRODUCTION: This article is a review of literature data concerning the use of selective serotonin reuptake inhibitors (SSRIs) by depressed pregnant women. LITERATURE FINDINGS: The adverse effects for the foetus, the newborn and the child were evaluated. The prevalence of depression during pregnancy is of around 10 to 20% of the population of childbearing women. Depression is often misdiagnosed and underestimated in pregnant women. Starting a pharmacological treatment for depression in these women is not easy because data concerning the safety of antidepressants during pregnancy are still unclear. The non-treated pathology is associated with higher risk of maternal morbidity, including arterial hypertension, which could lead to preeclampsia or eclampsia, ideation and suicide attempts, and postpartum depression. Foetal development is also affected and adverse outcomes such as prematurity, low birth weight, irritability, and sleep disorders are frequent. Pharmacological therapy is necessary when non-pharmacological treatment is insufficient. Suicide attempts and relapse of depression have been described when depressive women stopped their pharmacological treatment during pregnancy. Pregnant women diagnosed with depression must be treated. Selective SSRIs are now largely used in this pathology and have replaced tricyclic antidepressants because of fewer side effects. In general, drugs have a low teratogenic potential, only 4 to 5% of malformations are iatrogenic. Teratogenic risk is high between conception until the end of the second month of gestation. Safety of SSRIs treatment during pregnancy and potential risk for the foetus and newborn were unquestioned before publication, in the late 2005, of some alarming data concerning a possible teratogenic effect. Studies showed an increased risk for all congenital malformations with SSRIs and particularly with paroxetin. A few studies after 2005 have also found an association between prenatal exposure to SSRIs (especially paroxetin) and congenital malformations. However, other studies failed to demonstrate this association and the risk for cardiovascular malformations also does not seem to be significantly increased. Numerous studies in pregnant women have shown that SSRI treatments are associated with a significant increase of spontaneous abortion, preterm birth, and low birth weight. Exposure to SSRIs in late pregnancy has been associated with a three-fold increased risk of neonatal behavioural syndrome, including signs of withdrawal or serotonin impregnation. Restlessness, poor tone, respiratory distress, hypoglycaemia were the most frequent signs. These symptoms occur during the first days of life and are usually brief and not serious. Recent studies have also documented an increased risk of persistent pulmonary hypertension and cases of cerebral haemorrhage have been described. Data concerning a possible effect on motor and cognitive development at school age in children prenatally exposed to SSRIs are limited. DISCUSSION: Although a number of studies revealed that SSRIs are not teratogenic, some of them showed congenital malformations associated with use of these antidepressants; in particular an increased risk of cardiac defects with paroxetin. In practice, the potential risk implies that the decision to treat a pregnant woman with SSRIs (notably paroxetin) should be taken carefully; this means double-checking the diagnosis, the potential benefits, adverse effects and possible alternatives. Neonatal toxicity seems to be relatively frequent when SSRIs are prescribed during late pregnancy. For all depressed pregnant women, the severity of the depression must be taken into consideration before introducing a pharmacological treatment. When depressive women are already treated, studies have shown that antidepressants must be maintained during pregnancy to prevent relapse and suicide attempts.
Subject(s)
Abnormalities, Drug-Induced/etiology , Antidepressive Agents, Second-Generation/adverse effects , Antidepressive Agents, Second-Generation/therapeutic use , Depressive Disorder/drug therapy , Pregnancy Complications/drug therapy , Selective Serotonin Reuptake Inhibitors/adverse effects , Selective Serotonin Reuptake Inhibitors/therapeutic use , Abnormalities, Drug-Induced/prevention & control , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Female , Gestational Age , Humans , Infant, Newborn , Paroxetine/adverse effects , Paroxetine/therapeutic use , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/psychology , Prenatal Exposure Delayed Effects/diagnosis , Prenatal Exposure Delayed Effects/etiology , Risk , Secondary PreventionABSTRACT
Our previous work on rat hippocampus showed that a loss of docosahexaenoic acid (DHA) occurs in the fatty acid composition of phosphatidylethanolamine (PE), plasmenylethanolamine (PmE) and phosphatidylserine (PS) with increasing age. The present study investigated whether a DHA-enriched phospholipid dietary supplement could restore DHA levels and cholinergic activity. Male rats were fed a balanced diet containing both linoleic and alpha-linolenic acids until the age of 2, 18 and 21 months. From 18 to 21 months, one subgroup received a diet supplemented with DHA-enriched phospholipids from egg yolk (E-PL), and another a diet with DHA-enriched phospholipids from pig brain (B-PL). Compared to the control diet, the E-PL diet restored the proportion of polyunsaturated fatty acids (PUFAs: 22:6n-3 and 20:4n-6) in PE and PmE, while enhancing spontaneous and evoked-acetylcholine (Ach) release. The B-PL diet had no effect on PUFAs, but increased basal extracellular levels of Ach in 21-month-old rats as compared to the age-matched control. Our results show that supplementation with DHA-enriched egg PL can enhance Ach release and correct PUFA composition.
Subject(s)
Aging/metabolism , Docosahexaenoic Acids/pharmacology , Hippocampus/metabolism , Acetylcholine/metabolism , Animal Feed , Animals , Diet , Egg Yolk , Fatty Acids, Unsaturated/metabolism , Hippocampus/drug effects , Male , Microdialysis , Phosphatidylethanolamines/metabolism , Phosphatidylserines/metabolism , Phospholipids/pharmacology , Plasmalogens/metabolism , Potassium/metabolism , Rats , Rats, WistarABSTRACT
Plasmalogens are often considered as antioxidant molecules that protect cells from oxidative stress. Their vinyl ether bond could indeed be among the first targets for newly formed radicals. However, the long chain aldehydes released from plasmalogens were seldom studied and possible injurious or harmless effects were poorly examined. Thus, the sensitivity of the vinyl ether bond of plasmalogens was investigated in a cerebral cortex homogenate under UV irradiation- or Fe2+/ascorbate-induced peroxidation. Kinetics of aldehyde production was followed by gas chromatography/mass spectrometry. This confirmed that plasmalogens were highly sensitive to oxidative stress (70% cleavage after 90 min UV irradiation and 30% after 30 min of Fe2+/ascorbate). The aldehydes corresponding to sn-1 position 16:0, 18:0, or 18:1 were poorly detected. Conversely, oxidation of plasmalogens yielded preferentially 15:0, 17:0, and 17:1 aldehydes under UV and the alpha-hydroxyaldehydes 16:0-OH and 18:0-OH following a Fe2+/ascorbate oxidation. Kinetics showed that free aldehydes and above all free alpha-hydroxyaldehydes disappeared from the medium as soon as produced. Consequently, the behavior of these released aldehydes in the tissues has to be investigated in order to ascertain the protective effect of plasmalogens against oxidation.
Subject(s)
Aldehydes/metabolism , Cerebral Cortex/metabolism , Fatty Acids/metabolism , Oxidative Stress/physiology , Plasmalogens/metabolism , Animals , Gas Chromatography-Mass Spectrometry/methods , Hydroxyl Radical/metabolism , In Vitro Techniques , Kinetics , Male , Oxidation-Reduction , Rats , Rats, Wistar , Singlet Oxygen/metabolismABSTRACT
Astrocytes are known to play a key role in buffering extracellular pH variations and, in addition, they are particularly resistant to oxidative stress and subsequent lipid peroxidation. This great resistance may be ascribed to the presence of high concentrations of certain antioxidants, but another explanation may be the presence of a high quantity of plasmalogens, which are a special group of glycerophospholipids characterized by a vinyl ether bond instead of an ester bond in the sn-1 position of the glycerol backbone. Plasmalogens are sensitive to free radical attack and acidity, and numerous works have supported the hypothesis that they may be antioxidant molecules that protect cells from oxidative stress. The aim of this work was to investigate, on astrocytes in lactic acid-induced oxidative stress (pH 5.5), the behavior of phospholipids and, in particular, plasmalogens. Two main techniques, based on the susceptibility of the vinyl ether bond to hydrolysis, were employed in this study to measure plasmalogen levels. In both cases, the sn-1 vinyl ether linkage was cleaved using mercuric chloride, producing a lysophospholipid that was assessed by phosphorus measurement or using HCl treatment, producing a long-chain fatty aldehyde assayed by gas chromatography/mass spectrometry. On astrocytes in culture, only plasmenylethanolamine (PlmEtn) was evidenced, representing 40% of glycerophosphoethanolamine lipids. When astrocytes were incubated with lactic acid, no modification in the amount of PlmEtn was seen. Furthermore, free aldehydes and aldehydes corresponding to the quantity of intact plasmalogens were similar to those observed on controls. In addition, the constancy of two lipid peroxidation markers, thiobarbituric acid reactive substances and polyunsaturated fatty acids, was clear evidence of the resistance of these cells in lactic acid conditions. In conclusion, our results fail to demonstrate a major role of plasmalogens in the resistance of astrocytes in lactic acid-induced oxidative stress.
Subject(s)
Acidosis, Lactic/metabolism , Antioxidants/metabolism , Astrocytes/metabolism , Oxidative Stress/physiology , Plasmalogens/physiology , Acidosis, Lactic/chemically induced , Animals , Animals, Newborn , Astrocytes/drug effects , Cells, Cultured , Cerebral Cortex/cytology , Fatty Acids/analysis , Gas Chromatography-Mass Spectrometry , Lactic Acid/pharmacology , Lipid Peroxidation/drug effects , Oxidative Stress/drug effects , Plasmalogens/analysis , Plasmalogens/classification , Rats , Rats, Sprague-Dawley , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
The cleavage of the specific vinyl ether linkage at the sn-1 position of plasmalogens leads to the formation of two products: the 1-lyso-2-acyl glycerophospholipid and a long-chain fatty aldehyde. Plasmalogens are measured by quantifying one of these two products. In this paper, we describe a rapid and sensitive procedure for measuring plasmalogens via quantification of long-chain fatty aldehydes. After lipid extraction, the sn-1 vinyl ether bond of plasmalogens is cleaved by acidic hydrolysis. The produced aldehydes are then derivatized with (pentafluorobenzyl)hydroxylamine hydrochloride and analyzed by gas chromatography/mass spectrometry in selected-ion mode. Plasmalogens are then indirectly quantified by subtracting the free aldehydes obtained without prior HCl treatment from the total aldehydes obtained after acidic hydrolysis. This method is applied to three rat brain areas selected for this study. Two of these are affected in neurodegenerative diseases (cerebral cortex and hippocampus) and one is rich in white matter (cerebellum). In comparison to other procedures, the advantages of this method are not only its usefulness in plasmalogen quantification but also the identification of aldehydic breakdown products.
Subject(s)
Aldehydes/analysis , Gas Chromatography-Mass Spectrometry/methods , Plasmalogens/analysis , Animals , Brain/metabolism , Humans , Male , Plasmalogens/metabolism , Rats , Rats, WistarABSTRACT
The use of benzodiazepines is not negligible in pregnant woman and self-medication is considerable. To investigate the effects on the fetus of benzodiazepines used during pregnancy, we reviewed animal and clinical studies completed with observations of CRPV (Centres Régionaux de Pharmacovigilance). Pooled results indicate that the risk of malformations associated with first-trimester exposure to benzodiazepines remains small. However, in a fetus exposed essentially to long-acting benzodiazepines on a long-term basis, neonatal hypotonicity, failure to feed and/or withdrawal syndrom could be observed.
Subject(s)
Abnormalities, Drug-Induced/etiology , Benzodiazepines/adverse effects , Pregnancy Complications/drug therapy , Abnormalities, Drug-Induced/epidemiology , Adult , Animals , Anti-Anxiety Agents/adverse effects , Anti-Anxiety Agents/classification , Anti-Anxiety Agents/pharmacokinetics , Anti-Anxiety Agents/toxicity , Anticonvulsants/adverse effects , Anticonvulsants/classification , Anticonvulsants/pharmacokinetics , Anticonvulsants/toxicity , Benzodiazepines/classification , Benzodiazepines/pharmacokinetics , Benzodiazepines/toxicity , Cleft Lip/chemically induced , Cleft Palate/chemically induced , Clinical Trials as Topic , Contraindications , Cricetinae , Drug Evaluation, Preclinical , Female , France/epidemiology , Hernia, Inguinal/etiology , Humans , Infant, Newborn , Maternal-Fetal Exchange , Mice , Pregnancy , Prospective Studies , Rabbits , Rats , Registries , Self Medication , Substance Withdrawal Syndrome/etiologyABSTRACT
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.
Subject(s)
Brain Chemistry , Cerebellum/anatomy & histology , Corpus Striatum/anatomy & histology , Dietary Fats, Unsaturated/metabolism , Ethanolamines/metabolism , Fatty Acids, Omega-3/metabolism , Fatty Acids/metabolism , Frontal Lobe/anatomy & histology , Phosphatidylethanolamines/metabolism , Plasmalogens/metabolism , Animals , Body Weight , Cerebellum/chemistry , Cerebellum/metabolism , Corpus Striatum/chemistry , Corpus Striatum/metabolism , Fats, Unsaturated/chemistry , Fatty Acids/chemistry , Fatty Acids, Omega-3/administration & dosage , Female , Frontal Lobe/chemistry , Frontal Lobe/metabolism , Male , Organ Size , Phosphatidylethanolamines/chemistry , Phospholipids/chemistry , Phospholipids/metabolism , Plasmalogens/chemistry , Rats , Rats, WistarABSTRACT
The purpose of this study was to compare the nephrotoxicity of gentamicin and vancomycin alone and in combination. Thirty-two male Sprague-Dawley rats were randomized into 4 groups of 8 animals. Each group received 200mg/kg gentamicin (G) i.m., or 300 mg/kg vancomycin (V) i.v., or an association of 200 mg/kg gentamicin + 300 mg/kg vancomycin (i.m. and i.v., respectively), or 0.9% NaCl solution i.m. and i.v. (controls). To determine AAP, GGT, and NAG enzyme excretions, urine samples were taken over 24-h periods before and after the start of the experiment. A single renal cortical sample was obtained at necropsy for quantitation of antibiotic levels. No significant modifications of urinary excretions of creatinine and enzymuria were noted during the 24-h period before each drug administration or in controls. AAP, GGT, and NAG excretions were significantly increased after G and G + V injections (p < 0.001), whereas only AAP and GGT were statistically higher in rats receiving V (p < 0.05). NAG elimination (mean +/- SD) was higher in G + V (16.0 +/- 0.2 IU/mmol creatinine/24 h; p < 0.001) than g (8.8 +/- 0.6) or V (1.7 +/- 0.2). Surprisingly, mean vancomycin cortical levels decreased in the combination (827 +/- 131 vs. 1964 +/- 23 micrograms/g for V alone; p < 0.001), whereas gentamicin concentration was unchanged (826 +/- 66 vs. 839 +/- 28 micrograms/g for G alone). Determination of enzymuria allowed the nephrotoxicity of the antibiotics to be graded in the following order: vancomycin + gentamicin > gentamicin > vancomycin.
Subject(s)
Anti-Bacterial Agents/toxicity , Enzymes/urine , Gentamicins/toxicity , Kidney Cortex/drug effects , Vancomycin/toxicity , Acetylglucosaminidase/urine , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , CD13 Antigens/urine , Creatinine/urine , Drug Combinations , Gentamicins/administration & dosage , Gentamicins/pharmacokinetics , Immunoassay , Infusions, Intravenous , Kidney Cortex/enzymology , Male , Random Allocation , Rats , Rats, Sprague-Dawley , Vancomycin/administration & dosage , Vancomycin/pharmacokinetics , gamma-Glutamyltransferase/urineABSTRACT
5-fluoro-uracil (5-FU) cardiotoxicity has been often reported during chemotherapy. We collect four atypical cases of cardiac side effects in patients treated by 5-FU for head and neck tumors. We review the literature about the subject, and we propose criteria to detect patients with a high risk level, and to prevent this adverse effect incidence.