Obesity and diabetes genes are associated with being born small for gestational age: Results from the Auckland Birthweight Collaborative study

Background: Individuals born small for gestational age (SGA) are at increased risk of rapid postnatal weight gain, later obesity and diseases in adulthood such as type 2 diabetes, hypertension and cardiovascular diseases. Environmental risk factors for SGA are well established and include smoking, low pregnancy weight, maternal short stature, maternal diet, ethnic origin of mother and hypertension. However, in a large proportion of SGA, no underlying cause is evident, and these individuals may have a larger genetic contribution. Methods: In this study we tested the association between SGA and polymorphisms in genes that have previously been associated with obesity and/or diabetes. We undertook analysis of 54 single nucleotide polymorphisms (SNPs) in 546 samples from the Auckland Birthweight Collaborative (ABC) study. 227 children were born small for gestational age (SGA) and 319 were appropriate for gestational age (AGA). Results and Conclusion: The results demonstrated that genetic variation in KCNJ11, BDNF, PFKP, PTER and SEC16B were associated with SGA and support the concept that genetic factors associated with obesity and/or type 2 diabetes are more prevalent in those born SGA compared to those born AGA. We have previously determined that environmental factors are associated with differences in birthweight in the ABC study and now we have demonstrated a significant genetic contribution, suggesting that the interaction between genetics and the environment are important

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Amino acid neurotransmitter levels in the cerebral cortex of mice receiving imipenem/cilastatin - Lack of excitotoxicity in the central nervous system

Imipenem, a very potent carbapenem derivative beta-lactam antibiotic, has recently found a major place in the treatment of antibiotic-resistant nosocomial infections. However, a convulsive side effect is seen in 0.2-3 percent of patients. Although it is suggested that this effect is due to the inhibition of gamma-aminobutyric acid (GABA) mediated inhibitory transmission, no study has been reported so far showing its effect on the cerebral cortex free inhibitory and excitatory amino acid levels. Twenty-one male TO albino mice were divided into three equal groups and given therapeutic (40 mg/kg/day) or excessive (500 mg/kg/day) doses of imipenem/cilastatine (I/C) or saline solution intraperitoneally for 7 days. All animals in the excessive dose group showed seizure-like activity with ataxia and loss of gait. However, no differences in aspartate, glumatate, glycine or GABA levels were seen o gas chromatographic evaluation of the cerebral cortexes of all three groups of animals, which were dispatched on the 7th day. Therefore it is suggested that imipenem exerts its convulsive effect without causing any change in neurotransmitter levels of barin, possibly by effecting the neuronal receptors directly

Meconium enhances platelet-activating factor and tumor necrosis factor production by rat alveolar macrophages

PubMed ID: 15301793Meconium aspiration syndrome (MAS) frequently results in inactivation of surfactant, persistent pulmonary hypertension (PPHN) and respiratory failure among newborn infants. Inflammation and inflammatory mediators play an important role in MAS. Since alveolar macrophages are thought to be very important cells in the pathogenesis of various inflammatory diseases, we evaluated whether meconium could stimulate rat alveolar macrophages to generate platelet-activating factor (PAF) and tumor necrosis factor (TNF)-alpha in vitro. We also examined the response to A23187 (calcium ionophore), 1-0-Hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (synthetic PAF) and dexamethasone on meconium-induced release of PAF and TNF-alpha. PAF and TNF-alpha concentrations from supernatant fluid were measured after high-performance liquid chromatography purification by specific radioimmunoassay, and TNF-alpha concentrations were determined by using an enzyme-linked immunosorbent assay. Our results showed that alveolar macrophages exposed to meconium could enhance PAF and TNF-alpha production in a dose (0.1, 1, 5 and 10%, P<0.01)-dependent way. In the presence of A23187, the capability of meconium to stimulate PAF production was further enhanced in the supernatant fluids. Furthermore, treatment with synthetic PAF significantly increased the generation of TNF-alpha in response to meconium. On the other hand, dexamethasone effectively inhibited both PAF and TNF-alpha production stimulated by 5% meconium (P<0.01, P<0.01; respectively). We suggest that alveolar macrophages and PAF, TNF-alpha play an important role in the pathogenesis of lung injury and severe complications in MAS. Furthermore, the protective effect of glucocorticoids in MAS could be due, at least in part, to a suppression of PAF and TNF-alpha generation. © 2004 Elsevier Ltd. All rights reserved

Serum malondialdehyde levels in preterm and fullterm infants undergoing phototherapy

WOS: 000074040600029PubMed ID: 964175

Toxoplasmosis in last four years in Agean region, Turkey.

PubMed ID: 9257982Anti-Toxoplasma antibodies were determined with IFA and ELISA tests in 9410 patients who were different age groups, attended Department of Parasitology between 1991-1995. Anti-Toxoplasma IgG antibodies were found positive in 4651 (49.4%) of these patients. 2287 (21.4%) patients were pregnant women and the positivity was 55% of them. According to history of these patients, seropositivity was found 50% in women having spontaneous abortion, 52% in women having stillbirth, in 55% women having abnormal fetal births. These patients and their culinary habits, the presence of cats and relationship with other clinical symptoms were also evaluated

Free carnitine concentrations in cord blood in preterm and full-term infants with intrauterine growth retardation

WOS: 000167635800027PubMed ID: 1120801