Lipid and protein metabolism in asthma. Effects of diet and corticosteroid therapy

BACKGROUND: Because little is known about the effects of asthma and asthma therapy on lipid and protein metabolism, we have investigated the characteristics of diet and plasma/serum levels of fat and protein in a group of asthma patients with various degrees of severity. METHODS: A case-control study was carried out on 118 asthma patients recruited from an outpatient clinic and 121 healthy subjects. Asthma severity was characterized in four groups according to clinical symptoms, lung-function tests, and therapy. Normal dietary intake was estimated from a food frequency questionnaire. Serum protein, albumin, and fatty acids were determined by standard methods. RESULTS: The dietary energy intake of the asthmatics was significantly lower than that of the controls. However, no differences in the body mass index were found between asthma patients and healthy subjects. There were no differences in serum/plasma levels in any of the measured biochemical parameters between healthy subjects and asthmatics. Plasma levels of protein and albumin were significantly lower in severely corticosteroid-dependent patients. There was a significant negative correlation between plasma protein (r=0.36, P<0.05) and plasma albumin levels (r=0.43, P<0.01) and the daily dose of oral corticosteroids. We did not find any differences in plasma levels of cholesterol, HDL-cholesterol, LDL-cholesterol, and fatty acids between cortico-dependent patients and those not receiving this therapy. No correlation was found between any biochemical parameters and the daily dose of inhaled corticosteroids. CONCLUSIONS: Our results suggest that asthma induces a decrease in energy intake that does not result in a decreased body weight. Inhaled corticosteroids do not exert any metabolic effect, whereas severe asthma with regular oral corticosteroid therapy is associated with reduced plasma protein and albumin levels.     

Improved antioxidant status among HIV-infected injecting drug users on potent antiretroviral therapy

Low serum antioxidant levels in HIV-infected people have been attributed to altered metabolism associated with excess oxidative stress. We conducted a study to examine serum antioxidant levels in 175 HIV-positive and 210 HIV-negative injecting drug users (IDUs) in Baltimore, Maryland. At the time of data collection, 30 of the HIV-positive IDUs were receiving antiretroviral therapies (ART) including a protease inhibitor (PI), 43 ART without a PI, 22 monotherapies, and 80 not on any ART. Serum antioxidants examined included retinol, alpha-tocopherol and gamma-tocopherol, alpha-carotene and beta-carotene, lycopene, lutein/zeaxanthin, and beta-cryptoxanthin. Mean serum levels of lycopene and lutein/zeaxanthin were significantly lower in HIV-positive IDUs than HIV-negative IDUs. Contrary to the findings in other studies, however, levels of the remaining antioxidants in HIV-positive study subjects were not lower than in HIV-negative study subjects. In fact, serum alpha-tocopherol levels were significantly higher in HIV-positive IDUs than HIV-negative IDUs (medians = 744 microg/dl and 718 microg/dl, respectively; p = .04). Among HIV-positive study subjects, there were significant differences in antioxidant levels by ART regimen. In multivariate models adjusting for injecting drug use, dietary intake, supplement intake, gender, and alcohol intake, significant overall differences by ART regimen were observed for alpha-tocopherol, beta-carotene, and beta-cryptoxanthin. Serum levels of these three antioxidants were significantly higher in the PI group than in the other three ART groups combined (p = .0008, 0.02, and 0.02, respectively). These data provide indirect evidence of the effectiveness of PIs in lowering oxidative stress levels in HIV-positive IDUs.     

Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer's disease

In order to assess peripheral levels and activities of a broad spectrum of non-enzymatic and enzymatic antioxidants in elderly subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD), plasma levels of water-soluble (Vitamin C and uric acid) and of lipophilic (Vitamin A, Vitamin E and carotenoids including lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene) antioxidant micronutrients as well as activities of plasma and red blood cell (RBC) superoxide dismutase (SOD) and of plasma glutathione peroxidase (GPx) were measured in 25 patients with MCI, 63 AD patients and 53 controls. Peripheral levels and activities of antioxidants were similarly lower in MCI and AD patients as compared to controls. As MCI may represent a prodromal stage of AD, and oxidative damage appears to occur as one of the earliest pathophysiological events in AD, an increased intake of antioxidants in patients with MCI could be helpful in lowering the risk of conversion to dementia.     

Reduced platelet glutathione peroxidase activity and serum selenium concentration in atopic asthmatic patients

Background Asthmatic inflammation results in increased oxygen free radical generation and assessment of the activity of the selenitim (Se) dependent anti-oxidant enzyme, glutathione peroxidase (GSH-Px) in asthma may therefore be important. Objective To test the hypothesis that reduced GSH-Px activity and Se intake contribute to asthmatic infiammation, platelet and whole blood GSH-Px activities and serum and whole blood Se concentrations were measured and compared in atopic and non-atopic asthmatic patients and non-asthmatic control subjects. Methods GSH-Px activities of whole blood and isolated platelets were assessed in 41 asthmatic patients (33 atopic) and 41 age- and sex-matched non-asthmatic sttbjects (15 atopic) by spectrophotometric assay based oti the oxidation of NADPH. Se concentrations were determined by semi-automated fluorimetric assay. Results Mean (± sd) platelet GSH-Px activity was lower in asthmatic (89.5 ± 45.7 μmol NADPH oxidized min^?1 g^?1 of protein) than in non-asthmatic subjects (109,9 ± 41.9; P= 0.038) and in atopic (89.7 ± 45.1, n = 48) compared with non-atopie subiects (113.7 ± 40.9, n= 34: P= 0.016). Mean whole blood GSH-Px activity was also lower in atopic (12.2 ± 5.2 μmol NADPH oxidized min^?1 g^?1 of Hb) than in non-atopic subjects (14.5 ± 4.2; P= 0.038). In non-asthmatic subjects, the mean whole blood GSH-Px activity was lower in men (9.9 ± 3.5) than in women (14.5 ± 3.7; P = 0.0004) and was positively correlated with age (r= 0.51; P = 0.0006). Mean serum Se was lower in asthmatic (1.07 ± 0.12 μmol/L) than in non-asthmatic subjects (1.16 ± 0.31; P = 0.036), Using multiple linear regression, asthma was an independent predictor of decreased platelet GSH-Px after gender, age and serum Se were taken into account (P = 0.048) while atopy was a significant predictor of low whole blood GSH-Px independent of asthma, gender, age and whole blood Se (P = 0.033). Conclusions In addition to Se status, atopy, gender and uge all appear to influence GSH-Px activity, although the relative importance of these factors may difler in asthmatic and non-asthmatic populations. It seems likely that the reduced activity of this enzyme in platelets und hiood may reflect mechanisms associated with the pathogenesis and severity of asthma.     

Markers of platelet activation in plasma of patients suffering from persistent allergic rhinitis with or without asthma symptoms

BACKGROUND: Increased circulating levels of platelet release products are detected in various types of inflammation. It has been demonstrated that allergen challenge promotes platelet activation and leads to the release of chemokines such as platelet factor 4 (PF-4) and beta-thromboglobulin (beta-TG). OBJECTIVE: The aim of this study was to determine whether or not circulating platelets get into an activated state during allergic inflammatory reactions induced by long-term natural exposure to allergens. METHODS: Plasma levels of PF-4 and beta-TG (established markers of in vivo platelet activation) were determined by ELISA method in symptomatic patients with allergy to house dust mites, suffering from persistent allergic rhinitis (PAR) in the absence of asthma symptoms (12 men and 8 women; mean age 22 years) and from PAR with mild asthma (10 men and 6 women; mean age 23 years), as well as in healthy controls (10 men and 10 women; mean age 23 years). RESULTS: No significant differences were found between PAR patients with or without symptoms of asthma and healthy non-atopic subjects with respect to plasma levels of PF-4 and beta-TG as well as platelet count. CONCLUSIONS: It seems that patients undergoing continuous natural exposure to sensitizing allergens, with subsequent PAR alone or with concomitant mild asthma, have no altered platelet activity in vivo, as reflected by plasma levels of the chemokines. These findings, in conjunction with earlier data, indicate that differences may exist in platelet activity, including releasability of platelet products between patients with distinct clinical manifestation of atopy.     

Elevation of plasma transforming growth factor beta1 levels in stable nonatopic asthma.

BACKGROUND: Increased transforming growth factor beta1 (TGF-beta1) levels have been reported in bronchoalveolar lavage fluid and bronchial biopsy specimens from asthmatic patients. However, systemic TGF-beta1 levels have not been reported in asthma. OBJECTIVE: To evaluate the levels of plasma TGF-beta1 in asthmatic patients and matched, healthy controls to determine the associations with atopic status, disease severity, and duration. METHODS: Asthmatic patients and healthy controls were recruited prospectively from a university hospital outpatient department between January 2001 and May 2002. Plasma TGF-beta1 and serum IgE levels were estimated using established methods. Patients were classified as atopic or nonatopic based on the presence or absence of serum specific IgE directed to common allergens. RESULTS: Of the 56 patients recruited for the study, 32 were atopic and 24 nonatopic. The median value of plasma TGF-beta1 was significantly higher in nonatopic asthmatic patients (2.5 ng/mL) compared with controls (1.5 ng/mL, P = .002) and atopic asthmatic patients (1.4 ng/mL, P = .008). The median absolute neutrophil count in the nonatopic asthmatic patients (4.0 x 10(9)/L) was significantly higher compared with atopic asthmatic patients (3.0 x 10(9)/L) and healthy controls (3.5 x 10(9)/L) (P = .01 and P = .04). There was no significant correlation between the duration or severity of asthma and plasma TGF-beta1 levels. The distribution of moderate-persistent asthma cases was similar in atopic and nonatopic groups. CONCLUSION: Compared with atopic asthmatic patients and healthy controls, patients with nonatopic asthma have elevated plasma TGF-beta1 levels and leukocytosis. These data suggest that nonatopic asthmatic patients exhibit an altered inflammatory response, perhaps to a respiratory infection.     

Leukotriene EM4 plasma levels in adult asthmatic patients with variable disease severity

Chavis C, van Vyve T, Chanez P, Farce M, Bousquet J, Michel FB, Godard P. Leukotriene E4 plasma levels in adult asthmatic patients with variable disease severity.
Cysteinyl leukotrienes 'C-LTs' are local inflammatory mediators involved in bronchial asthma. Seventeen asthmatic patients 'FEV₁ ranging from 41 to 99.8% of predicted values' and 11 healthy subjects were studied. The clinical severity of asthma was assessed by the Aas score. Plasma C-LTs were measured by enzyme immunoassay 'EIA' after sample purification by solid-phase extraction 'SPE', to investigate whether differences may exist between asthmatic and control subjects and whether leukotriene E₄'LTE₄' levels were related to the severity of disease. LT measurements showed that 87.6±1.2% was recovered as LTE₄ and 9.4±1.3% as LTC4. In asthmatic subjects, LTE₄ plasma levels were found to be significantly higher than those in the control group '1.073±0.133 and 0.53±0.19 ng/ml of plasma, respectively; P < 0.002'. Moreover, there was a significant correlation between LTE₄ plasma levels and the Aas clinical score ' P < 0.005'. These data suggest that plasma LTE₄ levels might be used to assess the severity of asthma.     

Oxidative stress and genetic and epidemiologic determinants of oxidant injury in childhood asthma

BACKGROUND: The factors contributing to the oxidant/antioxidant imbalance in asthma are incompletely understood. OBJECTIVE: To determine the factors associated with oxidative stress including asthma severity and the genotype of the antioxidant enzymes. METHODS: A total of 196 children with mild asthma, 116 children with moderate-severe asthma, and 2 healthy control groups (187 and 68 children) were included in the study. Plasma levels of malondialdehyde were measured as the indicator of oxidative stress, and reduced glutathione levels as the indicator of antioxidant defense. Children were genotyped for null variants of glutathione S transferase (GST) T1 and GSTM1, and ile105val variant of GSTP1. Risk factors were analyzed with multivariate logistic regression. RESULTS: Systemic levels of malondialdehyde increased and reduced glutathione levels decreased significantly from healthy controls to patients with mild asthma and then to patients with moderate-severe asthma (P < .001 for each). Multivariate logistic regression identified asthma and asthma severity as independent factors associated with oxidative stress (odds ratio between 17 and 56; P < .001). Children with asthma with GSTP1 val/val genotype had higher malondialdehyde and lower glutathione levels compared with other genotypes (P = .023 and P = .014, respectively). GSTP1 val/val genotype was independently associated with asthma severity (odds ratio, 4.210; 95% CI, 1.581-11.214; P = .004). CONCLUSION: Our study indicates the presence of a strong oxidative stress in children with asthma that increases with the severity of the disease. In this population, val/val genotype at GSTP1 ile105val locus may be an important factor in determining the degree of oxidant injury. CLINICAL IMPLICATIONS: Children with asthma with val/val genotype at GSTP1 ile105val locus may be good candidates for supplemental antioxidant therapy.     

Antioxidants and allergic disease: a case of too little or too much?

Speculation persists as to the possible role, if any, of dietary antioxidants in allergic disease. While it has been hypothesized that the recent increase in allergic disease is a consequence of declining dietary antioxidant intake, an alternative hypothesis proposes that the increase in allergic disease is due to increasing antioxidant intake. Dietary trends are conflicting; the intake of some antioxidants has declined, for others intakes are likely to have increased. Animal model studies demonstrate that antioxidant supplementation at the time of primary and subsequent allergen exposure attenuates allergic inflammatory responses. The data from human studies are less clear. Observational epidemiological studies of humans are beset by several methodological limitations associated with the assessment of diet and predominantly focus on asthma. Most observational studies report potentially beneficial associations between dietary antioxidants and allergic outcomes, but a small minority report potentially adverse associations. Human intervention studies suggest that single antioxidant supplements confer minimal, if any clinical benefit in adults with asthma, however, there is still scope for studies in children, atopic dermatitis, allergic rhinitis (AR) and of antioxidant combinations. More recently, it has been suggested that dietary antioxidants in the developmental context of fetal and infant development influence the development childhood asthma and atopic sensitization possibly by affecting the first interactions between the neonatal immune system and allergens. While a small number of birth cohort studies have reported potentially beneficial associations between maternal intake of some antioxidants during pregnancy and childhood asthma, there is very limited data suggesting associations between maternal antioxidant intake and childhood atopic dermatitis and AR. The available epidemiological, animal, molecular and immunological data suggest that there are associations between antioxidants and asthma and to a much lesser extent, atopic dermatitis and AR. However, the exact nature of the relationships and the potential for therapeutic intervention remain unclear. Cite this as: K. Allan, F. J. Kelly and G. Devereux, Clinical & Experimental Allergy, 2010 (40) 370–380.     

Increased total serum IgE levels in patients with asthma and promoter polymorphisms at CTLA4 and FCER1B.

BACKGROUND: Increasing evidence indicates that total serum IgE levels are largely determined by genetic factors, and we recently established that the -109C/T promoter polymorphism at FCER1B is a genetic factor that affects total serum IgE levels. The gene encoding cytotoxic T lymphocyte antigen 4 (CTLA4) is another candidate factor in high IgE responsiveness, because B7-CD28/CTLA4 interaction can promote the differentiation and development of the T(H)2 lymphocyte subset. OBJECTIVE: We intended to determine whether CTLA4 is associated with increased levels of total serum IgE or with the development of asthma or atopy. METHODS: We performed a case-control study involving 339 patients with asthma and 305 healthy control subjects, of whom 226 of the patients with asthma and 219 of the healthy control subjects had previously been genotyped for the -109C/T promoter polymorphism at FCER1B. In the current study, we genotyped 2 polymorphisms in the CTLA4 gene, one involving the promoter (-318C/T) and the other involving exon 1 (+49A/G), in addition to the FCER1B promoter polymorphism. RESULTS: Patients with asthma who were homozygous for the -318C allele at the CTLA4 promoter region had higher levels of total serum IgE than patients with asthma carrying the -318T allele (P =.00470). The analysis of -318C/T (at CTLA4) and -109C/T (at FCER1B) promoter polymorphisms showed a significant correlation between the combined genotypes and increased levels of total IgE in patients with asthma (P =.000014). In contrast, no correlation between total serum IgE levels and -318C/T or +49A/G genotypes was detected in 305 healthy control subjects. There was no evidence indicating an association between a putative allele for asthma or atopy and alleles at any of the CTLA4 polymorphic loci. CONCLUSION: Our findings suggest that promoter polymorphisms of both CTLA4 and FCER1B are genetic factors that influence total serum IgE levels in patients with asthma. This supports the theory that variance in total serum IgE levels in patients with asthma is determined by mutations in multiple genes, each of which has a relatively small effect on the phenotype.     

Micronutrient (Zn, Cu, Fe)-gene interactions in ageing and inflammatory age-related diseases: implications for treatments

In ageing, alterations in inflammatory/immune response and antioxidant capacity lead to increased susceptibility to diseases and loss of mobility and agility. Various essential micronutrients in the diet are involved in age-altered biological functions. Micronutrients (zinc, copper, iron) play a pivotal role either in maintaining and reinforcing the immune and antioxidant performances or in affecting the complex network of genes (nutrigenomic approach) involved in encoding proteins for a correct inflammatory/immune response. By the other side, the genetic inter-individual variability may affect the absorption and uptake of the micronutrients (nutrigenetic approach) with subsequent altered effects on inflammatory/immune response and antioxidant activity. Therefore, the individual micronutrient-gene interactions are fundamental to achieve healthy ageing. In this review, we report and discuss the role of micronutrients (Zn, Cu, Fe)-gene interactions in relation to the inflammatory status and the possibility of a supplement in the event of a micronutrient deficiency or chelation in presence of micronutrient overload in relation to specific polymorphisms of inflammatory proteins or proteins related of the delivery of the micronutriemts to various organs and tissues. In this last context, we report the protein-metal speciation analysis in order to have, coupled with micronutrient-gene interactions, a more complete picture of the individual need in micronutrient supplementation or chelation to achieve healthy ageing and longevity.     

Immune response to influenza vaccine in healthy elderly: lack of association with plasma beta-carotene, retinol, alpha-tocopherol, or zinc

Immunity and nutritional status are compromised with age, yet the relationship between them is unclear. Immune responses and plasma micronutrient levels of 61 healthy elderly (mean 81 years) and 27 young (mean 27 years) were assessed before and after immunization with trivalent influenza vaccine (FLU). FLU-induced proliferation and IFN-gamma levels of elderly were lower than young before and after immunization. Proliferation and IFN-gamma levels increased after immunization of young, but not elderly. FLU-induced IL-6 and IL-10 levels did not change after immunization of either group. While antibody titers to all three FLU components increased after vaccination of young and elderly, post-vaccination titers of elderly were lower than young. Although plasma retinol and zinc levels of young and elderly were similar before and after vaccination, elderly had higher plasma beta-carotene and alpha-tocopherol levels at both assessments that increased after vaccination. Importantly, plasma micronutrient levels were comparable for elderly with or without intact (titers >/=40 and fourfold rise post-vaccination) antibody responses after vaccination. These results suggest that differences in these plasma micronutrients (1) are not required to observe decreased FLU responses of healthy elderly compared to young and (2) are not associated with differences in antibody responses among healthy elderly.     

Antioxidant intake is associated with semen quality in healthy men

BACKGROUND: We seek to determine whether dietary and supplement intake of specific micronutrients (zinc and folate) and antioxidants (vitamins C, E and beta-carotene) is associated with semen quality. METHODS: Ninety-seven healthy, non-smoking men provided semen and were interviewed. Average daily nutrient intake from food and supplements was derived from a self-administered food frequency questionnaire. Intake levels were summarized as low, moderate and high. Semen volume, sperm concentration, total sperm count, motility, progressive motility and total progressively motile sperm count (TPMS) were measured. RESULTS: After controlling for covariates, a high intake of antioxidants was associated with better semen quality but, in almost all cases, there was no clear dose relationship in that moderate intake groups had the poorest semen quality. For example, positive associations were observed between vitamin C intake and sperm number as reflected in the higher mean count (P=0.04), concentration (P=0.05) and TPMS (P = 0.09); between vitamin E intake and progressive motility (P = 0.04) and TPMS (P = 0.05); and between beta-carotene intake and sperm concentration (P = 0.06) and progressive motility (P = 0.06). Folate and zinc intake were not associated with improved semen quality. CONCLUSIONS: In a convenience sample of healthy non-smoking men from a non-clinical setting, higher antioxidant intake was associated with higher sperm numbers and motility.     

Significance and confounders of peripheral DJ-1 and alpha-synuclein in Parkinson's disease

DJ-1 and α-synuclein are leading biomarkers for Parkinson's disease diagnosis and/or monitoring disease progression. A few recent investigations have determined DJ-1 and α-synuclein levels in plasma or serum, a more convenient sample source than cerebrospinal fluid; but the results were variable or even contradictory. Besides limitations in detection technology and limited number of cases in some studies, inadequate control of several important confounders likely has contributed to these inconsistent results. In this study, the relative contribution of each blood component to blood DJ-1 and α-synuclein was evaluated, followed by quantification of plasma levels of both markers in a larger cohort of patients/subjects (∼300 cases) whose cerebrospinal fluid DJ-1 and α-synuclein levels have been determined recently. The results demonstrated that the DJ-1 and α-synuclein in blood resided predominantly in red blood cells (>95%), followed by platelets (1–4%), white blood cells and plasma (≤1%), indicating that variations in hemolysis and/or platelet contamination could have a significant effect on plasma/serum DJ-1 and α-synuclein levels. Nonetheless, after adjusting for the age, although there was a trend of decrease in DJ-1 and α-synuclein in patients with Parkinson's or Alzheimer's disease compared with healthy controls, no statistical difference was observed in this cohort between any groups, even when the extent of hemolysis and platelet contamination were controlled for. Additionally, no correlation between DJ-1 or α-synuclein and Parkinson's disease severity was identified. In conclusion, unlike in cerebrospinal fluid, total DJ-1 or α-synuclein in plasma alone is not useful as biomarkers for Parkinson's disease diagnosis or progression/severity.     

Activin A is an acute allergen-responsive cytokine and provides a link to TGF-beta-mediated airway remodeling in asthma

BACKGROUND: Allergic asthma typically shows activated, allergen-specific CD4(+) T cells in the early phase and airway remodeling in the late phase of the disease. Although TGF-beta plays a crucial role in airway remodeling, it is only marginally induced in CD4(+) T cells in the early allergen-dependent activation of the immune system. OBJECTIVE: To elucidate the transition between early- and late-phase events, we investigated the role of activin A, a close family member of TGF-beta. METHODS: Activin A and TGF-beta(1) levels were measured systemically in the serum and in CD4(+) T cells of asthmatic patients, as well as locally in the lung. RESULTS: Activin A serum levels were increased in patients with severe asthma compared with levels in patients with moderate asthma and healthy control subjects, whereas all patients showed significantly increased TGF-beta(1) serum levels independent of disease severity. In T cells only patients with moderate asthma showed increased activin A mRNA expression, whereas TGF-beta(1) expression was equal to that seen in healthy subjects. Accordingly, ovalbumin sensitization in a mouse model of allergic asthma could induce activin A mRNA expression, but not TGF-beta(1) expression, in the lung. Immunohistochemistry of mice and human specimens revealed an abundant expression of activin A by infiltrating lymphocytes and structural cells of the lung. Although TGF-beta(1) more potently enhanced proliferation and Smad 2/3-dependent reporter genes in fibroblasts, activin A was capable of inducing TGF-beta(1) and vice versa. CONCLUSION: Activin A provides a link between acute allergen-specific T-cell responses and chronic TGF-beta(1)-mediated airway remodeling in asthma.     

Platelet serotonin and serum lipids in psychotic mania

BACKGROUND: The role of serotonergic system and lipid status in the etiology of mania and its subtypes is not clear. The aims of the study were to determine platelet serotonin (5-HT) concentration, platelet monoamine oxidase (MAO) activity, and serum total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) and triglycerides (TG) in patients with psychotic and nonpsychotic subtypes of mania and in healthy control subjects. METHODS: The serum lipids, platelet 5-HT and MAO were determined in 40 (17 psychotic, 23 nonpsychotic) drug free male inpatients with type I bipolar affective disorder, current episode mania (DSM-IV criteria), and in 32 healthy male subjects. RESULTS: Platelet 5-HT levels in manic patients were similar to the values in healthy controls. Serum cholesterol and LDL values were significantly lower in manic patients than in healthy controls. Patients with psychotic features had increased platelet 5-HT concentrations and decreased levels of cholesterol and LDL as compared to the nonpsychotic manic patients and healthy controls. There was no significant difference in age, body mass index, platelet MAO activity, serum levels of TG and HDL between psychotic and nonpsychotic manic patients and healthy subjects. LIMITATION: Data on physical activity, dietary habits and alcohol consumption before hospitalization were not collected. CONCLUSION: The results of the present study suggest that biological differences between subtypes of mania might depend upon the presence of the psychotic symptoms. Our data confirm our previous results showing the increased platelet 5-HT concentration in psychotic disorders across the different diagnoses.     

A controlled study of 9alpha,11beta-PGF2 (a prostaglandin D2 metabolite) in plasma and urine of patients with bronchial asthma and healthy controls after aspirin challenge

BACKGROUND: Prostaglandin D(2) (PGD(2)) is the predominant cyclooxygenase product of mast cells, the number of which is increased in bronchial asthma. Release of PGD(2) might reflect mast cell activation and disordered function of the asthmatic lung. OBJECTIVE: We sought to determine blood and urinary levels of 9alpha,11beta-PGF(2), a major stable PGD(2) metabolite in 2 well-defined phenotypes of asthma, aspirin-induced asthma (AIA) and aspirin-tolerant asthma (ATA), and in healthy control subjects and to study the effects of aspirin on PGD(2) release. METHODS: Using gas chromatography/mass spectrometry, we determined plasma and urinary concentrations of 9alpha,11beta-PGF(2) at baseline in 131 stable asthmatic patients, 65 of whom had AIA and 66 of whom had ATA. Fifty healthy nonatopic subjects served as the control group. The measurements were also performed after an aspirin challenge in 26 of 65 patients with AIA and in 24 of 50 control subjects. RESULTS: At baseline, patients with AIA had significantly higher plasma levels of 9alpha,11beta-PGF(2) than either patients with ATA or healthy subjects. A similar significant elevation of serum tryptase was observed in patients with AIA compared with patients with ATA and control subjects. Mean urinary 9alpha,11beta-PGF(2) values did not differ among the 3 groups. In patients with AIA, as opposed to healthy subjects, aspirin challenge invariably precipitated a clinical reaction, accompanied in most patients by a further rise in plasma levels of PGD(2) metabolite and tryptase. CONCLUSIONS: In stable AIA, though not in ATA, there is a steady release of PGD(2) into the blood, accompanied by the release of tryptase. Aspirin enhances this reaction in most patients. Release of bronchoconstrictive PGD(2) might contribute to the severe clinical course of AIA.     

Increased oxidative stress and altered levels of antioxidants in asthma

BACKGROUND: Reactive oxygen species might play an important role in the modulation of airway inflammation. There is evidence of an oxidant-antioxidant imbalance in asthma. Although several oxidants and antioxidants are likely to be involved, alterations in only limited parameters have been studied in isolation. OBJECTIVE: We investigated changes in a wide range of oxidants and antioxidants to create a comprehensive picture of oxidant-antioxidant imbalance. METHODS: In the peripheral blood of 38 patients with bronchial asthma and 23 control subjects, oxidative stress was measured in terms of superoxide anion generation by leukocytes, lipid peroxidation products, total nitrates and nitrites, total protein carbonyls, and total protein sulfhydrils in plasma. Antioxidant status was evaluated by measuring red blood cell superoxide dismutase and catalase activity, total blood glutathione, and glutathione peroxidase activity in red blood cells and leukocytes and total antioxidant capacity in plasma. RESULTS: Asthmatic patients showed increased superoxide generation from leukocytes, increased total nitrites and nitrates, increased protein carbonyls, and increased lipid peroxidation products and decreased protein sulfhydrils in plasma, indicating increased oxidative stress. They also showed increased superoxide dismutase activity in red blood cells and increased total blood glutathione and decreased glutathione peroxidase activity in red blood cells and leukocytes. Red blood cell catalase activity and the total antioxidant capacity of plasma were not altered. CONCLUSION: There are alterations in a wide array of oxidants and antioxidants, with balance shifting toward increased oxidative stress in asthma. Therapeutic augmentation of the antioxidant defenses might be beneficial.     

Elevated serum melatonin is associated with the nocturnal worsening of asthma

BACKGROUND: Increased airway inflammation at night contributes to the nocturnal worsening of asthma. In vitro studies have shown exogenous melatonin to be pro-inflammatory in asthma, but it is unknown whether endogenous melatonin levels are a controller of airway inflammation in nocturnal asthma. OBJECTIVE: Our aim was to determine 24-hour patterns of serum melatonin and their relationship to overnight decline in physiology in subjects with nocturnal asthma, non-nocturnal asthma, and in healthy controls. METHODS: Observational study of pulmonary physiology and melatonin levels in patients with nocturnal asthma (n = 7), non-nocturnal asthma (n = 13), and healthy controls (n = 11). Subjects maintained a constant sleep-wake regimen for 7 days. On day 8, serum melatonin was measured every 2 hours by radioimmunoassay and analyzed by cosinor modeling. The correlation between serum melatonin levels and overnight change in spirometry was evaluated by Spearman's rank correlation analysis. RESULTS: In subjects with nocturnal asthma, peak melatonin levels were significantly elevated compared with healthy controls (67.6 +/- 5.0 pg/mL versus 53.5 +/- 4.0 pg/mL, P =.03). Melatonin acrophase was delayed in nocturnal asthma (02:54 versus 01:58 in healthy controls, P =.003, and 02:15 in non-nocturnal asthma, P =.01). In subjects with nocturnal asthma, increasing melatonin levels were significantly and inversely correlated with overnight change in FEV(1) (r = -.79, P =.04), a relationship that was not observed in non-nocturnal asthma or healthy controls. CONCLUSIONS: Nocturnal asthma is associated with elevation and phase delay of peak serum melatonin levels. Elevated melatonin levels might contribute to the pathogenesis of nocturnal asthma.     

Uteroglobulin-related protein 1 and severity of respiratory syncytial virus infection in children admitted to hospital

There are several reports suggesting that genetic factors contribute to the severity of infection with the respiratory syncytial virus (RSV). Infants hospitalized with lower respiratory tract infection (LRTI) due to RSV are at a significantly increased risk for both recurrent wheezing and childhood asthma. Uteroglobin-related protein 1 (UGRP1) is a secretory protein expressed in the airways, and speculated to have anti-inflammatory activity. The presence of the -112G/A polymorphism in the UGRP1 promoter was found to have a significant correlation with asthma phenotype. Also plasma UGRP1 levels were shown to be associated both with this polymorphism and the severity of asthma. The study population consisted of 62 previously healthy infants, ≤12 months of age, who were hospitalized with RSV LRTI, and a control group of 99 healthy adults. Genotyping was performed by restriction fragment length polymorphism. UGRP1 serum levels were determined using ELISA. There were no significant differences in the overall distribution of UGRP1 -112G/A polymorphism genotypes or alleles between the hospitalized infants and healthy adults. A comparison of serum UGRP1 concentration measured at the time of admission and discharge between patients with and without the -112A allele revealed that there was no relation between the presence of the -112A allele and serum UGRP1 in hospitalized infants with RSV infection. Furthermore, there was no relationship between severity of RSV infection and genotype or serum UGRP1 concentration. These results suggest that UGRP1 does not have a major role in the development of severe RSV infection.