Histamine H3 receptor antagonists - Roles in neurological and endocrine diseases and diabetes mellitus.

Human histamine H3 receptor (H3R) was initially described in the brain of rat in 1983 and cloned in 1999. It can be found in the human brain and functions as a regulator of histamine synthesis and release. H3 receptors are predominantly resident in the presynaptic region of neurons containing histamine, where they modulate the synthesis and release of histamine (autoreceptor) or other neurotransmitters such as dopamine, norepinephrine, gamma-aminobutyric acid (GABA), glutamate, acetylcholine and serotonin (all heteroreceptors). The human histamine H3 receptor has twenty isoforms of which eight are functional. H3 receptor expression is seen in the cerebral cortex, neurons of the basal ganglia and hippocampus, which are important for process of cognition, sleep and homoeostatic regulation. In addition, histamine H3R antagonists stimulate insulin release, through inducing the release of acetylcholine and cause significant reduction in total body weight and triglycerides in obese subjects by causing a feeling of satiety in the hypothalamus. The ability of histamine H3R antagonist to reduce diabetes-induced hyperglycaemia is comparable to that of metformin. It is reasonable therefore, to claim that H3 receptor antagonists may play an important role in the therapy of disorders of cognition, the ability to sleep, oxidative stress, inflammation and anomaly of glucose homoeostasis. A large number of H3R antagonists are being developed by pharmaceutical companies and university research centres. As examples of these new drugs, this review will discuss a number of drugs, including the first histamine H3R receptor antagonist produced.

Lipocalin-2: Structure, function, distribution and role in metabolic disorders.

Lipocalin-2 (LCN-2) is a novel, 198 amino acid adipocytokine also referred to as neutrophil gelatinase-associated lipocalin (NGAL). LCN-2 is a circulatory protein responsible for the transportation of small and hydrophobic molecules (steroid, free fatty acids, prostaglandins and hormones) to target organs after binding to megalin/glycoprotein and GP330 SLC22A17 or 24p3R LCN-2 receptors. LCN-2 has been used as a biomarker for acute and chronic renal injury. It is present in a large variety of cells including neutrophil, hepatocytes, lung, bone marrow, adipose tissue, macrophages, thymus, non-neoplastic breast duct, prostate, and renal cells. Different functions have been associated with LCN-2. These functions include antibacterial, anti-inflammatory, and protection against cell and tissue stress. Moreover, LCN-2 can increase the pool of matrix metalloproteinase 9 in human neutrophil granulocytes. Other reported functions of LCN-2 include its ability to destroy the extracellular matrix, which could enable cancer progression and spread of metastasis. Recent reports show that the tissue level of LCN-2 is increased in metabolic disorders such as obesity and type 2 diabetes, suggesting an association between LCN-2 and insulin sensitivity and glucose homeostasis. The precise role of LCN-2 in the modulation of insulin sensitivity, glucose and lipid metabolism is still unclear. This review explores the structure of LCN-2, tissue distribution, and its interaction with important metabolic pathways.

Occurrence of Hypothyroidism, Diabetes Mellitus, and Celiac Disease in Emirati Children with Down's Syndrome.

OBJECTIVES: Autoimmune diseases are known to occur in people with Down's syndrome (DS), especially celiac disease, type 1 diabetes mellitus (DM), and hypothyroidism. Since there are common genetic risk factors involved in the occurrence of these autoimmune disorders, the risks would differ in different populations. We sought to determine the prevalence of type 1 DM, celiac disease, and hypothyroidism in Emirati patients with DS in Abu Dhabi, UAE. METHODS: Ninety-two patients with DS were investigated for the presence of anti-thyroid antibodies, antithyroglobulin, and anti-thyroid peroxidase antibodies for hypothyroidism, anti-glutamic acid decarboxylase antibodies for type 1 DM, and anti-tissue transglutaminase immunoglobulin A antibodies for celiac disease. RESULTS: Karyotyping was performed on 89 patients. Eighty-seven had non-disjunction of chromosome 21 (97.8%), one was a mosaic, and one had translocation. Of the patients studied, 19.6% had hypothyroidism, 4.3% had type 1 DM, and 1.1% had celiac disease. Out of the 92 patients studied, 66 (71.7%) did not have any autoimmune disease, 25 (27.2%) had one autoimmune disease, and one (1.1%) had two autoimmune diseases. CONCLUSIONS: Celiac disease was the least prevalent autoimmune disease in patients with DS patients, while type 1 DM and hypothyroidism were both significantly associated with DS.

Anticonvulsant and reproductive toxicological studies of the imidazole-based histamine H3R antagonist 2-18 in mice.

The imidazole-based H3R antagonist 2-18 with high in vitro H3R antagonist affinity, excellent in vitro selectivity profile, and high in vivo H3R antagonist potency was tested for its anticonvulsant effect in maximal electroshock (MES)-induced convulsions in mice having valproic acid (VPA) as a reference antiepileptic drug (AED). Additionally, H3R antagonist 2-18 was evaluated for its reproductive toxicity in the same animal species. The results show that acute systemic administration (intraperitoneal; i.p.) of H3R antagonist 2-18 (7.5, 15, 30, and 60 mg/kg, i.p.) significantly and dose dependently protected male as well as female mice against MES-induced convulsion. The protective action observed for H3R antagonist 2-18 in both mice sexes was comparable to that of VPA and was reversed when mice were pretreated with the selective H3R agonist (R)-alpha-methylhistamine (RAMH, 10 mg/kg, i.p.). Moreover, the results show that acute systemic administration of single (7.5, 15, 30, or 60 mg/kg, i.p.) or multiple doses (15×3 mg/kg, i.p.) of H3R antagonist 2-18 on gestation day (GD) 8 or 13 did not affect the maternal body weight of mice when compared with the control group. Furthermore, no significant differences were observed in the average number of implantations and resorptions between the control and H3R antagonist 2-18-treated group at the early stages of gestation and the organogenesis period. However, oral treatment with H3R antagonist 2-18 (15 mg/kg) on GD 8 induced a reduced number of live embryos when compared with the i.p.-treated mice. In addition, no significant changes in the fetal body and placental weights were observed after injection of H3R antagonist 2-18 with all selected doses. However, three dose groups of i.p. and oral 15 mg/kg on GD 13 significantly affected the placental weight when compared with control group. Notably, the treatment of pregnant female with the H3R antagonist 2-18 did not produce significant malformation in the fetus in both groups. In conclusion, the novel H3R antagonist 2-18 proves to be a very safe compound and displays a low incidence of malformations, demonstrating that H3R antagonist 2-18 may have a potential future therapeutic value in epilepsy.

Genetic polymorphisms of cytochrome P450-1A2 (CYP1A2) among Emiratis.

Cytochrome P450 1A2 (CYP1A2) is one of the CYP450 mixed-function oxidase system that is of clinical importance due to the large number of drug interactions associated with its induction and inhibition. In addition, significant inter-individual differences in the elimination of drugs metabolized by CYP1A2 enzyme have been observed which are largely due to the highly polymorphic nature of CYP1A2 gene. However, there are limited studies on CYP1A2 phenotypes and CYP1A2 genotypes among Emiratis and thus this study was carried out to fill this gap. Five hundred and seventy six non-smoker Emirati subjects were asked to consume a soft drink containing caffeine (a non-toxic and reliable probe for predicting CYP1A2 phenotype) and then provide a buccal swab along with a spot urine sample. Taq-Man Real Time PCR was used to determine the CYP1A2 genotype of each individual. Phenotyping was carried out by analyzing the caffeine metabolites using High Performance Liquid Chromatography (HPLC) analysis. We found that 1.4%, 16.3% and 82.3% of the Emirati subjects were slow, intermediate and rapid CYP1A2 metabolizers, respectively. In addition, we found that 1.4% of the subjects were homozygote for derived alleles while 16.1% were heterozygote and 82.5% were homozygote for the ancestral allele. The genotype frequency of the ancestral allele, CYP1A2*1A/*1A, is the highest in this population, followed by CYP1A2 *1A/*1C and CYP1A2 *1A/*1K genotypes, with frequencies of 0.825, 0.102 and 0.058, respectively. The degree of phenotype/genotype concordance was equal to 81.6%. The CYP1A2*1C/*1C and CYP1A2*3/*3 genotypes showed significantly the lowest enzyme phenotypic activity. The frequency of slow activity CYP1A2 enzyme alleles is very low among Emiratis which correlates with the presence of low frequencies of derived alleles in CYP1A2 gene.

Studies on N-Acetyltransferase (NAT2) Genotype Relationships in Emiratis: Confirmation of the Existence of Phenotype Variation among Slow Acetylators.

BACKGROUND AND PURPOSE: Individuals with slow N-acetylation phenotype often experience toxicity from drugs such as isoniazid, sulfonamides, procainamide, and hydralazine, whereas rapid acetylators may not respond to these medications. The highly polymorphic N-acetyltransferase 2 enzyme encoded by the NAT2 gene is one of the N-acetylators in humans with a clear impact on the metabolism of a significant number of important drugs. However, there are limited studies on N-acetylation phenotypes and NAT2 genotypes among Emiratis, and thus this study was carried out to fill this gap. METHODS: Five hundred seventy-six Emirati subjects were asked to consume a soft drink containing caffeine (a nontoxic and reliable probe for predicting the acetylation phenotype) and then provide a buccal swab along with a spot urine sample. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotype of each individual. Phenotyping was carried out by analyzing the caffeine metabolites using high-performance liquid chromatography (HPLC) analysis. RESULTS: We found that 78.5%, 19.1%, and 2.4% of the Emirati subjects were slow, intermediate, and rapid acetylators, respectively. In addition, we found that 77.4% of the subjects were homozygous or heterozygous for two nonreference alleles, whereas 18.4% and 4.2% were heterozygous or homozygous for the reference allele (NAT2*4), respectively. The most common genotypes found were NAT2*5B/*7B, NAT2*5B/*6A, NAT2*7B/*14B, and NAT2*4/*5B, with frequencies of 0.255, 0.135, 0.105, and 0.09, respectively. The degree of phenotype/genotype concordance was 96.2%. The NAT2*6A/*6A, NAT2*6A/*7B, NAT2*7B/*7B, and NAT2*5A/*5B genotypes were found to be associated with the lowest 5-acetylamino-6-formylamino-3-methyluracil/1-methylxanthine (AFMU/1X) ratios. CONCLUSIONS: There is a high percentage of slow acetylators among Emiratis, which correlates with the presence of nonreference alleles for the NAT2 gene. Individuals who carried NAT2*6A/*6A, NAT2*6A/*7B, NAT2*7B/*7B, or NAT2*5A/*5B genotypes might be at higher risk of toxicity with some drugs and some diseases compared to others, as these genotypes are associated with the slowest acetylation status.

National growth charts for United Arab Emirates children with Down syndrome from birth to 15 years of age.

BACKGROUND: Specific centile growth charts for children with Down syndrome (DS) have been produced in many countries and are known to differ from those of normal children. Since growth assessment depends on the growth pattern characteristic for these conditions, disorder-specific charts are desirable for various ethnic groups. AIMS: To provide cross-sectional weight, height, and head circumference (HC) references for healthy United Arab Emirates (UAE) children with DS. METHODS: A retrospective and cross-sectional growth study of Emirati children with DS, aged 0 to 18 years old, was conducted. Height, weight, and HC were measured in each child. Cole's LMS statistical method was applied to estimate age-specific percentiles, and measurements were compared to UAE reference values for normal children. RESULTS: Incidence of DS in the UAE population is 1 in 374 live births (267 in 10 000 live births). We analyzed 1263 growth examinations of 182 children with DS born between 1994 and 2012. The male-to-female ratio was 1.6:1. Height, weight, and HC centile charts were constructed for ages 0 to 13 years. The prevalence of overweight and obesity in DS children aged 10 to 13 years of age was 32% and 19%, respectively. The DS children were significantly shorter and heavier than normal children in the UAE. CONCLUSIONS: Weight, height, and HC growth charts were created for children with DS. These can be used as a reference standard for the UAE children with DS. Overweight and obesity are quite common in DS children ≥ 10 years of age, as DS children tend to be shorter and heavier than non-DS children.

UAE population reference standard charts for body mass index and skinfold thickness, at ages 0-18 years.

AIMS: To determine a range of anthropometric measurements including skinfold thickness measurements in four different areas of the body, to construct population growth charts for body mass index (BMI), skinfolds, and to compare these with growth charts from other countries. One aim was also to validate body fat charts derived from skinfold thickness. METHODS: A national cross-sectional growth survey of children, 0-18 years old, was conducted using multistage stratified random sampling. The sample size included at least 200 children in each age-sex group. Height, weight, biceps skinfold, triceps skinfold, subscapular skinfold, suprailiac skinfold, and mid-upper-arm circumference were measured in each child. We describe correlation, standard deviation scores relative to the other standards, and calculation of body density in the United Arab Emirates population. We determined whether any of the above is a good indicator of fatness in children. RESULTS: BMI, upper-arm circumference, sum of four skinfolds, and percentage body fat charts were constructed using the LMS method of smoothing. BMI was very significantly correlated with sum of skinfold thicknesses, and mid-upper-arm circumference. Prevalence of obesity and overweight in ages 13-17 years was respectively 9.94% and 15.16% in females and 6.08% and 14.16% in males. Derived body fat charts were found not to be accurate. CONCLUSION: A national BMI, upper-arm circumference, and sum of four skinfolds chart has been constructed that can be used as a reference standard for the United Arab Emirates. Sum of four skinfold thickness charts can be used as crude determinants of adiposity in children, but derived body fat charts were shown to be inaccurate.

Identification of new alleles and the determination of alleles and genotypes frequencies at the CYP2D6 gene in Emiratis.

CYP2D6 belongs to the cytochrome P450 superfamily of enzymes and plays an important role in the metabolism of 20-25% of clinically used drugs including antidepressants. It displays inter-individual and inter-ethnic variability in activity ranging from complete absence to excessive activity which causes adverse drug reactions and toxicity or therapy failure even at normal drug doses. This variability is due to genetic polymorphisms which form poor, intermediate, extensive or ultrarapid metaboliser phenotypes. This study aimed to determine CYP2D6 alleles and their frequencies in the United Arab Emirates (UAE) local population. CYP2D6 alleles and genotypes were determined by direct DNA sequencing in 151 Emiratis with the majority being psychiatric patients on antidepressants. Several new alleles have been identified and in total we identified seventeen alleles and 49 genotypes. CYP2D6*1 (wild type) and CYP2D6*2 alleles (extensive metaboliser phenotype) were found with frequencies of 39.1% and 12.2%, respectively. CYP2D6*41 (intermediate metaboliser) occurred in 15.2%. Homozygous CYP2D6*4 allele (poor metaboliser) was found with a frequency of 2% while homozygous and heterozygous CYP2D6*4 occurred with a frequency of 9%. CYP2D6*2xn, caused by gene duplication (ultrarapid metaboliser) had a frequency of 4.3%. CYP2D6 gene duplication/multiduplication occurred in 16% but only 11.2% who carried more than 2 active functional alleles were considered ultrarapid metabolisers. CYP2D6 gene deletion in one copy occurred in 7.5% of the study group. In conclusion, CYP2D6 gene locus is heterogeneous in the UAE national population and no significant differences have been identified between the psychiatric patients and controls.

Toxicokinetics of aflatoxin in pregnant mice.

Our objective was to study the toxicokinetics of aflatoxin (AF) in pregnant mice. Aflatoxin B1 (AFB1) was administered intraperitoneally (IP) to groups of pregnant mice in single doses of 20 mg/kg on gestation day (GD) 13 and orally at the same gestational age. Controls received (IP and oral) a proportionate volume of solvent only. Maternal blood was collected at 15, 30, 45, 60, 90, 120, and 150 minutes posttreatment. Their AFB1 contents were determined. Aflatoxin B1 concentrations following maternal exposure to AFB1 were highly correlated with time after exposure. The serum concentrations were predictable and the highest serum levels were seen immediately at 15 minutes in mice given AFs IP and at 30 minutes in those given it orally. The absorption was 5.0 microg/min and elimination was 3.0 microg/min. The toxicokinetics of AFB1 have been delineated. Aflatoxins are easily and rapidly absorbed both from the gastrointestinal tract (GI) tract and through the peritoneum.

Soothing methods used to calm a baby in an Arab country.

UNLABELLED: This study was undertaken to determine how mothers soothed their crying infants. A total of 1137 mothers of different cultural backgrounds were approached, 998 agreed to participate in the study, but only 716 completed the questionnaire through a telephone interview. Analysis was restricted to 702 mothers from the UAE nationality, other Arabs, other Muslims, Indians and Philippinos. The questionnaire contained 23 questions on different soothing methods. The most common soothing method was breast-feeding (99.1%), followed by holding and carrying the infant (96.9%), letting infant suck on his thumb or finger (87.3%), herbal tea (65%), night bottle (42.1%) and swaddling infant (19.5%). Over 90% of mothers of all nationalities, preferred not to use pacifiers. Soothing herbs were often used, with the commonest being anise (165 mothers used anise). Fennel tea was also used by a substantial number of mothers (75), with gripe water (64), cumin (33), chamomile (32), mint (22) and fenugreek (16) making up most of the rest. CONCLUSION: Mothers' ethnicity and nationality strongly impacted on the soothing methods used, with Arabs more often using herbal tea, prone positioning and swaddling to calm infants and illustrate the importance of culture in the upbringing of children from a very early age.

R58fs mutation in the HGD gene in a family with alkaptonuria in the UAE.

This study was conducted to determine the prevalence of alkaptonuria in the UAE population and to identify the genotype of affected individuals. In a 3 stage sampling technique 2981 pupils from Government schools in Al Ain and private schools in Dubai were selected to take part in the study, of whom 2857 provided urine samples. Urine collected was analysed for homogentisic acid by gas chromatography-mass spectrometry. Genomic DNA was isolated from the white blood cells of all family members of the affected case following standard established protocols. Specific PRC primers were designed to amplify all 14 exons of the HGD gene with the flanking intronic sequences including the splice site sequences. 2857 children returned a viable urine sample, of which one was highly positive for homogentisic acid. All 12 members of this girl's family were studied and one, a 22 year old brother, was found to excrete HGA. Another, a sister who had not provided a urine sample, was discovered by genetic testing. There were no complaints of joint pain or other symptoms in any member of this family. Parents were first cousins. We found a single nucleotide deletion c.342delA, located in exon 3, which resulted in a frameshift at amino acid position 58 (p.Arg58fs or p.R58fs). Alkaptonuria may be more common than it is thought to be with an allele prevalence estimated at 0.0107 (95% CI 0.000392-0.03473). The R58fs mutation is old, perhaps having occurred several thousand years ago, and has spread over a large geographical area.

National growth charts for the United Arab Emirates.

BACKGROUND: Information on the health and growth status of the population is essential for planning and administering health promotion programs. METHODS: This is a cross-sectional study of the anthropometric measurements of United Arab Emirates (UAE) children aged 0-18 years, by a multistage stratified random sampling technique based on age and sex. Healthy, full-term children of UAE nationality who did not have any diseases that could affect their growth pattern were included in the study. Children were selected using multistage sampling, using sampling proportional to size methods in 9 geographical areas. Growth charts for various anthropometric measures were created using Cole's LMS statistical package. This package estimates age-specific percentiles with the use of smoothing splines after transformation to normality. RESULTS: A total of 21,068 children (12,159 females) between the ages of 0 and 18 years were studied. In the present study, we included 8-15% of the population aged 0-18 years. The growth chart for 0-36 months is very similar to the NCHS growth reference chart in terms of both weight for age and length and height for age. The mean (+SD) length/height in children was 49.9 +/- 3.2 cm at birth, 75.9 +/- 5.7 cm at 12 months, 86.4 +/- 4.5 cm at 24 months, 95.1 +/- 5.9 cm at 36 months, and 111.1 +/- 6.4 cm at 60 months. The height of UAE children in the first 3 years of life, especially at the ages of 2 and 3 years, mirrored those achieved by Brazilian children in the WHO study. CONCLUSION: The results of the present study are useful for growth assessment of UAE children.

Child care practice in the United Arab Emirates: the ESACCIPS study.

AIMS: This study was undertaken to monitor infant care practice associated with SIDS and establish the incidence of SIDS in the UAE. METHODS: A total of 996 families were recruited for the study. One questionnaire was completed during the first 7 days after delivery, and was used to collect information about the socio-demographic features, mother's medical history, delivery status and infant's medical history, and another questionnaire was completed after 12 weeks through telephone interviews of the mothers. 716 completed both questionnaires. Registers at the two hospitals, and at the Preventive Medicine Department were studied and all infant deaths in a 5-year period were recorded. RESULTS: In all 18.9% of infants were placed in the prone position. Mothers preferred supine position (49.3%) to other positions when putting their babies to bed. Ninety eight percent preferred that their infant slept in the same room as the parents. On the whole, 40% occasionally shared their beds with their infants. Swaddling the babies was quite common (83.2%) and 91.9% of their mothers were also swaddled when they were babies. More than 80% of all infants used bedding duvets for their infants both in the summer and in the winter. SIDS mortality rate was 0.66 per thousand live births and contributed 7.25% to the infant mortality rate. CONCLUSION: These data provide useful baseline information on child care practice and should be of immense benefit to the understanding of the risks and causal mechanisms of SIDS and to the UAE health authorities should they wish to develop strategies to reduce the risk of SIDS.

Trace element composition of plasma and breast milk of well-nourished women.

A wide variation in the composition of breast milk has been reported from various countries. This study was undertaken to determine the trace element content of breast milk and plasma in lactating women. Mothers of children 4 weeks to 80 weeks in age, were studied. Blood and breast milk from the mothers were analysed for trace element content. Prepared samples were analysed using ICP-MS. 209 women agreed to take part in the study, 68 of whom were from the UAE and 124 were other nationalities (17 did not fill the this part of the questionnaire). Ninety-seven infants were male. The concentration of different trace elements in blood and breast milk were little different between women from the UAE and those from outside the UAE. Molybenum, chromium and arsenic significantly increased with increasing age of the infant, while manganese, copper and zinc significantly decreased with increasing age of the infant. The trace element concentrations of breast milk and maternal blood were comparable to published values. Normal values for plasma and breast milk trace metal concentrations have been obtained for UAE women.

Intrauterine growth restriction and skeletal variations in mouse fetuses induced by vigabatrin administered at preimplantation stages of development.

Epileptic women do not withdraw antiepileptic drug (AED) therapy during pregnancy, therefore, exposure to AED during preimplantation stages might result in considerable embryonic concentrations endangering development. Neither clinical nor experimental research has addressed this important issue adequately. Vigabatrin (VGB), a second generation AED, is both effective and well tolerated as an add-on therapy in epilepsy with partial seizures. However, there is little data on the possible reproductive toxicity of this widely used drug. The objective of the present study was to evaluate the effects of VGB on pregnancy and pregnancy outcome in an experimental model. VGB was administered in single doses of 450 mg/kg intraperitoneally (i.p.) to groups of mice on one of gestation days (GD) 1, 3, or 5. The treated animals consumed moderately reduced amounts of food and water on the day of treatment, so the controls were saline-injected and food and water-restricted to match the amounts consumed by the experimental animals. All animals were killed on GD 18. VGB treatment did not interfere with implantation, nor did it cause significant embryo resorption. However, it caused significant reduction in fetal bodyweight and increased frequency of growth restricted fetuses which weighed two standard deviations (SD) less than the mean of the controls. The VGB group fetuses also had retarded development of the skeletal system in terms of delay in maturity of the suproccipital bone development, cervical and coccygeal vertebral hypoplasia, and poor ossification of the bones of the fore and hind paws. Another major finding was the increased incidence of minor malformations, such as the presence of cervical ribs and sternal anomalies. The results of this study show that VGB administered at preimplantation stages of development causes intrauterine growth restriction (IUGR) and augments minor malformation rates in mice. Future studies must address the mechanisms of VGB-induced IUGR and minor malformations.

Effect of maternal administration of vigabatrin during late gestation on fetoplacental amino acid profile in the mouse.

The objectives were to determine if vigabatrin in late gestation affects fetal growth and causes alterations in amino acid concentrations in the mouse. A single dose of 450 mg/kg VGB in saline or a proportionate volume of saline was administered intraperitoneally (IP) to Theiler outbred (TO) mice on gestation day 15 and maternal plasma, placentae and fetuses were collected at different time intervals after treatment. VGB attained peak concentration in the maternal plasma and the fetus at 2 h after treatment and in the placenta at 4 h. At 12 h significantly lower concentrations of several amino acid including methionine were found in the placentae and fetuses in the treated group. After 24 h, no difference was seen in the plasma amino acid concentrations but in the placentae and fetuses a significant decrease occurred in some amino acids in the treated group. At 48 and 72 h, a generalized increase in most amino acid levels occurred in the fetus and placenta but not in maternal plasma of the treated group although the fetal and placental weights were significantly reduced. VGB during late gestation causes fetal growth retardation accompanied by an initial disruption of amino acid supply followed by an increase in amino acid concentrations for the next 2 days. This increase did not help restore growth suggesting that early fetal period is particularly vulnerable to VGB-induced intrauterine growth retardation in the mouse.

Beta-thalassemia major and its effect on amino acid metabolism and growth in patients in the United Arab Emirates.

BACKGROUND: There may be a marked reduction in essential amino acids in the serum of children with thalassemia major and this is related to decreased growth in affected children. METHODS: One hundred patients with beta-thalassemia and 50 control children selected from among those who had presented with minor disorders unrelated to hematological disease were recruited. Urine and heparinized blood were collected from fasting thalassemic patients. After deproteinization and dilution, amino acid concentrations were measured using ion-exchange chromatography. RESULTS: Isoleucine (p<0.0001), phenylalanine (p<0.05), tyrosine (p<0.0001), taurine (p<0.0001) and glutamine (p<0.01) were significantly decreased in the plasma of thalassemic patients compared to the control group. Whereas glutamate (p<0.0001), serine (p<0.05) and proline (p<0.05) were significantly higher in thalassemic patients, threonine, glycine, alanine, valine, methionine, leucine, ornithine, lysine, histidine and arginine values were not different. The essential amino acids taurine (p<0.0001), methionine (p<0.01), valine (p<0.01), phenylalanine (p<0.01) and leucine (p<0.05) were significantly decreased in urine of thalassemic patients vs. controls, but threonine and ornithine were not different. The mean urinary excretion rate of beta-aminoisobutyric acid was not different (69+/-96 in thalassemics vs. 41+/-52 in controls). However, most plasma and urinary essential amino acids were found to be lower in thalassemics. Thalassemic patients were also found to be significantly growth impaired for age, both in height and weight compared to controls. CONCLUSION: Lower plasma values of essential amino acids and a decrease in urinary amino acids occur in thalassemic patients. Growth impairment both in height and weight also occurs in thalassemic patients compared to a control population.

Morbidity in neonates of mothers who have ingested aflatoxins.

This study was undertaken to assess whether aflatoxin M(1) concentrations in newborn infants correlated with those of their mothers and to determine whether the presence of aflatoxin M(1) in cord blood was associated with an increase in morbidity in the newborn. There was a strong correlation (r =0.797, p <0.0001) between mothers' and cord blood levels of aflatoxin. There was also a strong negative correlation between aflatoxin levels and birthweight (r =-0.565, p <0.001) but there was no association between aflatoxin M(1) concentration in maternal or cord blood and rates of jaundice or infection.

Aflatoxin M1 in breast-milk of UAE women.

A study was undertaken to determine whether breast-milk of mothers from the United Arab Emirates (UAE) contained aflatoxins. One hundred and forty lactating mothers, 55 who had delivered premature infants (<2500 g,