Frequency and clinical correlates of bipolar features in acute coronary syndrome patients.

BACKGROUND: Depression and acute coronary syndrome (ACS) are both extremely prevalent diseases. Studies aimed at evaluating whether depression is an independent risk factor for cardiac events provided no definitive results. In most of these studies, depression has been broadly defined with no differentiation between unipolar (MDD) versus bipolar forms (BD). The aim of this study was to evaluate the frequency of DSM-IV BD (bipolar I and bipolar II subtypes, cyclothymia), as well as temperamental or isolated bipolar features in a sample of 171 patients hospitalized for ACS. We also explored whether these psychopathological conditions were associated with some clinical characteristics of ACS. METHODS: Patients with ACS admitted to three neighboring Cardiac Intensive Care Units (CICUs) in a 12-month continuative period of time were eligible for inclusion if they met the criteria for either acute myocardial infarct with or without ST-segment elevation or unstable angina, verified by standard ACS criteria. All patients underwent standardized cardiological and psychopathological evaluations. RESULTS: Of the 171 ACS patients enrolled, 37 patients (21.7%) were found to have a DSM-IV mood disorder. Of these, 20 (11.7%) had bipolar type I or type II or cyclothymia, while 17 (10%) were the cases of MDD. Rapid mood switches ranged from 11% of ACS patients with no mood disorders, to 47% of those with MDD to 55% of those with BD. Linear regression analysis showed that a diagnosis of BD (p=.023), but not that of MDD (p=.721), was associated with a significant younger age at the index episode of ACS. A history of previous coronary events was more frequent in ACS patients with BD than in those with MDD. CONCLUSIONS: Our data indicate that bipolar features and diagnosis are frequent in ACS patients. Bipolar disorder has a negative impact on cardiac symptomatology. Further research in this area is warranted.

Origin of anomalous magnetite properties in crystallographic matched heterostructures: Fe3O4(111)/MgAl2O4(111).

Magnetite films grown on crystallographically matched substrates such as MgAl2O4 are not expected to show anomalous properties such as negative magnetoresistance and high saturation fields. By atomic resolution imaging using scanning transmission electron microscopy we show direct evidence of anti-phase domain boundaries (APB) present in these heterostructures. Experimentally identified 1/4<101> shifts determine the atomic structure of the observed APBs. The dominant non-bulk superexchange interactions are between 180° octahedral-Fe/O/octahedral-Fe sites which provide strong antiferromagnetic coupling across the defect interface resulting in non-bulk magnetic and magnetotransport properties.

Role of translocator protein (18 kDa) in adult separation anxiety and attachment style in patients with depression.

BACKGROUND AND OBJECTIVES: A role for the protein that mediates the rate-limiting step of steroidogenesis, the 18 kDa Translocator Protein (TSPO), has been suggested in the pathophysiology of Adult Separation Anxiety Disorder (ASAD). It has been shown that ASAD patients have 1) low TSPO expression levels and 2) a high frequency of the allele that substitutes Ala with Thr at position 147 of TSPO. The Thr147 ASAD-associated allele has been recently related with a low pregnenolone production. The aim of the present work was to evaluate the relationship between TSPO expression levels and Ala147Thr single nucleotide polymorphism (SNP), which are the two TSPO biological parameters that we have previously examined separately. A further aim was to confirm the genetic association of Ala147Thr SNP with ASAD in an extended case-control sample and to investigate whether this SNP was related to an anxious attachment style that is thought to be connected to ASAD. METHODS: TSPO expression levels were compared among patients with ASAD (n=26), without ASAD (n=26) and control samples (n=10) stratified into the two genotype groups: those with the Ala147 genotype (named "normal pregnenolone production") and those with the Thr147 genotype (named "reduced pregnenolone production"). The case-control genetic study included patients with (n=87) or without (n=101) ASAD and 236 controls. In the patient group, the association between the Ala147Thr SNP and an anxious attachment style was analysed by stepwise logistic regression analysis. RESULTS: The genotype with the lowest TSPO expression levels was the "normal pregnenolone production" genotype in the ASAD group. The genetic Ala147Thr SNP confirmed an excess of the Thr147 allele in ASAD patients. Stepwise logistic regression analysis did not show an association with an anxious attachment style. CONCLUSIONS: ASAD individuals who expressed normal TSPO levels exhibited the "reduced pregnenolone production" genotype. In contrast, the ASAD individuals with the "normal pregnenolone production" genotype expressed low TSPO levels. It is possible that low TSPO expression levels could compromise normal pregnenolone production. Such evidence may have therapeutic implications because it has been documented that drugs targeting TSPO increased pregnenolone production and have anxiolytic effects.

Frequency and clinical correlates of adult separation anxiety in a sample of 508 outpatients with mood and anxiety disorders.

OBJECTIVE: To evaluate the frequency and clinical correlates of adult separation anxiety disorder in a large cohort of patients with mood and anxiety disorders. METHOD: Overall, 508 outpatients with anxiety and mood disorders were assessed by the structured clinical interview for diagnostic and statistical manual (IV edition) axis I disorders for principal diagnosis and comorbidity and by other appropriate instruments for separation anxiety into adulthood or childhood. RESULTS: Overall, 105 subjects (20.7%) were assessed as having adult separation anxiety disorder without a history of childhood separation anxiety and 110 (21.7%) had adult separation anxiety disorder with a history of childhood separation anxiety. Adult separation anxiety was associated with severe role impairment in work and social relationships after controlling for potential confounding effect of anxiety comorbidity. CONCLUSION: Adult separation anxiety disorder is likely to be much more common in adults than previously recognized. Research is needed to better understand the relationships of this condition with other co-occurring affective disorders.

Induction of a putative monooxygenase of crabs (Carcinus spp.) by polycyclic aromatic hydrocarbons.

As part of a programme to develop biomarker assays for polycyclic aromatic hydrocarbons (PAHs) in marine invertebrates, two species of crabs, Carcinus maenas and Carcinus aestuarii were exposed to benzo(a)pyrene (B(a)P) or crude oil. Microsomes were prepared from the midgut gland (hepatopancreas), examined by gel electrophoresis and Western blotting and assayed for B(a)P monooxygenase activity. In early experiments there was evidence of protein degradation and results were inconsistent and inconclusive. However, when steps were taken to minimize this in subsequent experiments, including the inclusion of four protease inhibitors in the homogenization buffer, there was consistent evidence for an increase of proteins of estimated molecular weight 45-60 kDa, and particularly of a distinct band at c. 48 kDa, following exposure to PAH at levels down to 0.1 ppm in ambient water. In C. aestuarii the increase in this band was found to coincide with an 8-12-fold increaseof B(a)P monooxygenase activity in midgut gland microsomes. These results suggest that one or more forms of cytochrome P450 may be induced by PAHs in these species. However, Western blotting using antibodies raised to vertebrate P450s, and representing four different gene families, failed to recognize any proteins in either the PAH-treated samples or in the controls. The isolation and characterization of induced protein, and the production of antibodies may provide the basis for a biomarker assay to measure a response to environmental PAHs in crabs.

Interspecies variation of "B" esterases in birds: the influence of size and feeding habits.

Interspecies differences in "B" esterases were evaluated in seven species of wild birds in order to investigate their different susceptibilities to organophosphorus (OP) insecticides. The relationship between "B" esterases and body size and the influence of feeding habits in the evolution of esterase activities were explored. An in vitro inhibition test was carried out with paraoxon and azinphos methyl oxon in order to investigate the role of equilibrium binding parameters (acetylcholinesterase/ organophosphorus compounds affinity) in determining susceptibility of the different species to parathion and azinphos methyl. Esterase activities were different in all species. The smallest bird studied (the sparrow) had the highest brain acetylcholinesterase (AChE) and plasma carboxylesterase (CbE) activities. The largest bird (the cormorant) had the lowest level of both activities. For microsomal CbE, the coot had the highest activity. An inverse correlation was found between brain AChE and plasma CbE activity in relation to body size. Omnivorous species showed the highest brain AChE and plasma CbE activities which were low in species with a specialised diet. The in vitro inhibition test demonstrated the active involvement of equilibrium binding parameters in determining different susceptibilities to these contaminants in birds.

Multiresponse biomarker evaluation of interactions between methylmercury and Arochlor 1260 in quail.

The single and combined effects of methylmercury and Arochlor 1260 were investigated in experimental quail treated chronically with the two compounds at low and high doses. A series of metabolic and biochemical biomarkers were evaluated together with mercury and PCB accumulation to pinpoint the effects of treatment with one or both chemicals. Methylmercury alone was associated with a decrease in serum cholesterol. Less PCBs were accumulated in tissues when Arochlor 1260 was combined with methylmercury than when the former was administered alone. Liver monooxygenase (MFO) activity was depressed 50% more in the presence of methylmercury than with Arochlor 1260 alone. Single or combined treatment with high doses of the two compounds resulted in similar degrees of DNA damage. This approach was found to provide a good picture of the interaction between environmental contaminants.

Interspecies differences in mixed function oxidase activity in birds: Relationship between feeding habits, detoxication activities and organochlorine accumulation.

The relationship between feeding habits and interspecies differences in the detoxication ability of the mixed function oxidase (MFO) system was investigated in birds. The role of MFO (particularly aldrin epoxidase activity) in the detoxication/bioaccumulation of organochlorines was also investigated. Euriphagic (yellow-legged herring gull (Larus cachinnans), black-headed gull (Larus ridibundus), jackdaw (Corvus monedula), magpie (Pica pica) and stenophagic (cormorant (Phalacrocorax carbo), coot (Fulica atra) and sparrow (Passer italiae)) species were collected in northern and central Italy. The following liver microsomal monooxygenase activities were measured: aldrin epoxidase, ethoxyresorufin dealkylation (EROD), benzyloxyresorufin dealkylation (BROD) and pentoxyresorufin dealkylation (PROD). NADPH-and NADH-cytochrome c reductase (NAD(P)H-CYT-CRED) and NADH-ferricyanide reductase (NADH-FERRIRED) activities were also measured in the liver microsomal fraction. Glutathione concentration (GSH) was measured in the liver cytosolic fraction. As a marker of liver damage gamma-glutamyl transpeptidase (GGTP) activity was assayed in the serum. The residues of organochlorines (HCB, pp'DDTs and PCBs) were determined in muscle samples. Omnivorous species, particularly the yellow-legged herring gull, had the highest aldrin epoxidase activities. In the yellow-legged herring gull the activity was approximately twice as high as in the jackdaw (p < 0.05), black-headed gull (p < 0.05) and coot (p < 0.05). Values five times lower were detected in the specialist fish-eater, the cormorant (p < 0.001). The lowest values of aldrin epoxidase activity were detected in the sparrow. Feeding habits were found to be related to evolutionary interspecies differences in MFO activity. A significant statistical correlation (r = 0.656) was found between the 'omnivore index' and MFO detoxication activity expressed as aldrin epoxidation. Organochlorines, and particularly PCBs, were higher in cormorants and yellow-legged herring gulls from a polluted lagoon than in the other species analysed (black-headed gull p < 0.01; sparrow p < 0.001; jackdaw p < 0.01; coot p < 0.001). Levels of pp'DDE were much higher in the cormorant and sparrow than in the other birds. Knowledge of the different species-specific detoxication abilities was found to be a useful tool for the identification of species potentially at risk in environments with high pollution by chlorinated hydrocarbons, or in general contaminants metabolized by the MFO system.

The lizard Gallotia galloti as a bioindicator of organophosphorus contamination in the Canary Islands.

The aim of this study is to propose a bioindicator organism, the lizard Gallotia galloti, and a nondestructive biomarker assay, utilising serum butyrylcholinesterase, for the assessment of the toxicological impact of organophosphorus (OP) insecticides in the Canary Islands. Laboratory and field studies were performed using the OP insecticide Trichlorphon. In the laboratory study, experimental groups of Gallotia galloti were treated with 5, 50 and 100 mg/kg of Trichlorphon, respectively, and after 24 h the following enzyme activities were assayed: brain acetylcholinesterase (AChE), serum butyrylcholinesterase (BChE), microsomal carboxylesterase (CbE) and microsomal 7-ethoxyresorufin dealkylation (EROD). BChE activity was monitored in two groups of lizards treated with 50 and 100 mg/kg of Trichlorphon, respectively, for a period of 21 and 31 days after treatment. In the field study, BChE activity was detected in Gallotia galloti specimens, 24 and 48 h after treatment of an experimental area with 10 kg/ha of Dipterex sp80 (80% Trichlorphon). Three conclusions can be drawn. (1) Gallotia galloti has the features of an ideal bioindicator: high sensitivity to OPs and extremely slow recovery of serum BChE with respect to other vertebrate species; this property extends the temporal application of this biomarker in field studies. (2) A high correlation was found between the destructive biomarker brain AChE and the nondestructive biomarker serum BChE, 24 h after treatment. (3) The results of the field study show the relative 'non-toxicity' of Trichlorphon for nontarget organisms, such as lizards, at the average concentrations used in agriculture.

Serum esterase inhibition in birds: a nondestructive biomarker to assess organophosphorus and carbamate contamination.

With the aim of proposing a nondestructive biomarker for monitoring the toxicological risk to birds of exposure to the organophosphorus insecticide azamethiphos and the carbamate insecticide methomyl, laboratory studies were performed on serum "B" esterases in Japanese quail (Coturnix coturnix japonica). The birds received two single dose treatments of each compound (azamethiphos and methomyl), i.e., 50 mg/kg and 250 mg/kg respectively. In the first treatment, serum butyrylcholinesterase (BChE) and carboxylesterase (CbE) were drastically inhibited in the azamethiphos-treated group, 24 h after the dose. No inhibition was detected for BChE and CbE activities in the methomyl-treated group, 24 h after the dose. In the second treatment, the birds died or were sacrificed 3 h after the dose. Serum BChE and brain acetylcholinesterase (AChE) were strongly inhibited after treatment with both insecticides. Serum CbE, hepatic microsomal CbE and 7-ethoxyresorufin dealkylation activities were also inhibited. A statistically significant correlation between serum BChE and brain AChE was found at lethal and sublethal doses of these xenobiotics. The experimental results indicate that the nondestructive biomarker BChE can give an early qualitative and semi-quantitative warning of the toxic effects of organophosphate and carbamate insecticides in birds.

Influence of cadmium on polychlorobiphenyl uptake, MFO activity, and serum lipid levels in Japanese quail.

The effect of cadmium on the metabolism of polychlorobiphenyls (PCBs) (Aroclor 1260) was investigated in quails fed diets containing 100 ppm Cd, 100 ppm PCBs (Aroclor 1260) and 100 ppm Cd + 100 ppm PCBs for a period of 45 days. The presence of Cd in the diet did not interfere with MFO activity (EROD and ALDE) and cytochrome P-450 enzymes. Quails fed simultaneously with Cd and PCBs, accumulated PCBs in muscle five times greater than quails fed PCBs only. Quails fed with Cd-containing diet showed a slight increase of cholesterol and triglycerides. These data suggest that a combined chronic exposure to Cd and PCBs could modify PCBs metabolism. The interaction seems due not to inhibition of drug-metabolizing enzymes but to the increase of circulating lipids that favor the accumulation of lipophilic compounds.