Diet quality and markers of endothelial function: the CARDIA study.

BACKGROUND AND AIM: Dietary patterns are associated cross-sectionally with cellular adhesion molecules (CAMs). We studied prospective associations of three dietary patterns with CAMs. METHODS AND RESULTS: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, diet was assessed at years 0 (1985-86) and 7 (1992-93) examinations. Four circulating CAMs (E-selectin, P-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), and vascular cellular adhesion molecule (VCAM)) were assayed at years 7 and 15 (2000-01). We created one index score "A Priori Diet Quality Score" and derived dietary patterns using principal components analysis (PCA). Multivariable linear regression models predicted year 15 CAMs from averaged (year 0/7) dietary patterns. The A Priori Diet Quality Score rated 46 food groups beneficial, neutral or adverse based on hypothesized health effects. We derived two PCA dietary patterns: "fruit and vegetables (FV)" (high intakes of fruit, vegetables, and whole grains) and "meat" (high intakes of red meat, refined grain, and butter). All dietary patterns were related to E-selectin and sICAM-1. P-selectin was not related to the FV dietary pattern. VCAM was only related to the A Priori Diet Quality Score. Strongest associations were for the meat dietary pattern with E-selectin (effect size 28% of an SD (+3.9/13.7 ng/mL)) and P-selectin (effect size 37% of an SD (+4.1/11.2 ng/mL)) and the A Priori Diet Quality Score with sICAM-1 (effect size 34% of an SD (-15.1/44.7 ng/mL)) and VCAM (effect size of 26% of an SD (-45.1/170.3 ng/mL)). CONCLUSION: This prospective analysis suggests that dietary patterns are associated with CAMs.

Longitudinal association between serum urate and subclinical atherosclerosis: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

OBJECTIVE: The aim of the present study was to determine whether serum urate (sUA) concentration is positively associated with subclinical atherosclerosis, independent of body mass index (BMI), amongst generally healthy adults. DESIGN AND SETTING: The CARDIA study followed 5115 Black and White individuals aged 18-30 years in 1985-1986 (year 0). Subclinical atherosclerosis comprised coronary artery calcified plaque (CAC; years 15, 20 and 25), and maximum common carotid intima-media thickness (IMT; year 20). sUA (years 0, 10, 15 and 20) was modelled as gender-specific quartiles that were pooled. Discrete-time hazard regressions and generalized linear regressions were used for analyses. RESULTS: Mean sUA concentration was lower in women than in men and increased with age. Adjusting for demographic and lifestyle factors, the highest versus lowest quartile of sUA at year 0 was associated with a 44% [95% confidence interval (CI) 20%, 73%] greater risk of CAC progression from years 15 to 25 (Ptrend  < 0.001), which was attenuated by adjustment for BMI at year 0 (Ptrend  = 0.45). A stronger association was found between sUA at year 15 and CAC progression at year 20 or 25 (hazard ratio 2.07, 95% CI 1.66, 2.58 for the highest versus lowest sUA quartile Ptrend  < 0.001), which was attenuated, but remained significant with additional adjustment for BMI at year 15 (Ptrend  = 0.01). A greater increment in sUA concentration from year 0 to year 15, independent of change in BMI, was related to a higher risk of CAC progression (Ptrend  < 0.001). Similar associations were found between sUA and IMT, but only in men. CONCLUSION: sUA may be an early biomarker for subclinical atherosclerosis in young adults; starting in early middle age, sUA predicts subclinical atherosclerosis independently of BMI.

Higher parity is associated with an increased risk of type-II diabetes in Chinese women: the Singapore Chinese Health Study.

OBJECTIVE: The association between parity and type-II diabetes has been studied primarily in Western populations, and the findings have been inconsistent. Here, we examine whether parity was positively associated with incident type-II diabetes in Singaporean Chinese women. DESIGN: Prospective cohort study. SETTING: Singapore. POPULATION: A total of 25,021 Singaporean Chinese women aged 45-74 years from the Singapore Chinese Health Study who were free of cancer, heart disease, stroke, and diabetes at baseline (1993-1998). METHODS: Women were followed through 2004 for incident diabetes. Hazard ratios for type-II diabetes were computed across parity (of live births) categories and adjusted for baseline age, interview year, dialect, education, smoking, dietary pattern, physical activity, age at menarche, oral contraceptive use, menopausal status, hormone therapy use, and body mass index (BMI). MAIN OUTCOME MEASURE: Self-reported diabetes, as diagnosed by a doctor. RESULTS: Over an average of 5.7 person-years of follow-up, 1294 women were diagnosed with diabetes. Before and after multivariable adjustment there was a positive graded association between parity and type-II diabetes risk (P < 0.001). In the fully adjusted model, which included adult BMI, the risk of type-II diabetes increased by 31% (from -2 to 76%), 62% (from 22 to 116%), and 74% (from 29 to 133%) for women with one or two, three or four, and five or more live births, respectively, compared with women with no live births. Moreover, in a supplementary multivariate analysis in non-diabetic women we found a positive monotonic association between parity and glycated haemoglobin (HbA1c) (P = 0.01). CONCLUSIONS: Increased parity may be a risk factor for type-II diabetes in Chinese women. More research is needed on lifestyle and physiologic factors that may explain this association.

Association between genetic variants in adhesion molecules and outcomes after hematopoietic cell transplants.

Allogeneic hematopoietic cell transplant (HCT) is associated with a high morbidity and mortality. Adhesion molecules play an important role in endothelial activation and initiation of inflammatory response. We hypothesized that single nucleotide polymorphisms (SNPs) in the endothelial molecules may contribute to heterogeneity in HCT outcomes. We evaluated the association of 4 SNPs in ICAM1 (rs5498), PECAM1 (rs668 and rs1131012) and SELL (rs2229569) genes with acute and chronic graft-versus-host disease (GvHD) and those experiencing transplant-related mortality (TRM) within 1 year among 425 allogeneic HCT recipient-donor pairs. Using a Fine and Gray proportional hazards model to evaluate the association between genetic variants and clinical outcomes, after adjustment for recipient age, race, diagnosis, disease status, gender mismatch, cytomegalovirus serostatus, gender, donor type, conditioning regimen and year of transplant, only rs5498 in the ICAM1 gene among both recipients and donors was associated with a decreased risk of TRM (P ≤ 0.02). None of the SNPs were associated with acute or chronic GvHD risk. These findings suggest that genetic variants in the vascular adhesion molecules may be used to identify patients at high risk for TRM.

Contemporary nuclear medicine imaging of neuroendocrine tumours.

Neuroendocrine tumours (NETs) are rare, heterogeneous, and often hormonally active neoplasms. Nuclear medicine (NM) imaging using single photon- and positron-emitting radiopharmaceuticals allows sensitive and highly specific molecular imaging of NETs, complementary to anatomy-based techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI). Somatostatin-receptor scintigraphy is a whole-body imaging technique widely used for diagnosis, staging and restaging of NETs. The increasing availability of hybrid single-photon emission CT (SPECT)/CT cameras now offers superior accuracy for localization and functional characterization of NETs compared to traditional planar and SPECT imaging. The potential role of positron-emission tomography (PET) tracers in the functional imaging of NETs is also being increasingly recognized. In addition to 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG), newer positron-emitting radiopharmaceuticals such as (18)F-dihydroxyphenylalanine (DOPA) and (68)Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) peptides, show promise for the future. This article will summarize the role of current and emerging radiopharmaceuticals in NM imaging of this rare but important group of tumours.

Scintigraphic localization of adrenal tumors.

Scintigraphy has historically added much to the evaluation of adrenal dysfunction and tumor localization. The early development of radiopharmaceuticals for adrenocortical imaging provided vital clinical information well before the widespread availability of computed tomography (CT), but beginning in the early 1980's nuclear imaging became supplanted in large part by high resolution CT and more recently by magnetic resonance imaging. The parallel emergence of radiopharmaceuticals for adrenomedullary imaging also provided important functional insight in evaluating these neoplasms, but despite the clinical value of such nuclear probes they too, were relegated to a less prominent role in tumor characterization because of advances in anatomic imaging. However, with the recent introduction of dual-modality imaging platforms that directly combine CT with scintigraphy, either as single photon emission tomography (SPECT)/CT or positron emission tomography (PET)/CT, nuclear medicine studies once again play an integral role in adrenal tumor evaluation.

Incidentally discovered adrenal masses.

Independently, endocrinology, radiology, and nuclear medicine can not optimally differentiate the etiology of the incidental adrenal mass. Rather, the insight necessary for this task must be contributed by all three disciplines. Incidentally discovered adrenal masses are being detected at an increasing rate. This trend is expected to continue based on the incidence of adrenal masses in autopsy series and the increasing use of high resolution abdominal imaging techniques. CT and MRI are able to definitely characterize only a minority of these lesions (simple cyst, myelolipoma, obvious local malignant invasion). Biochemical screening for hormone excess is essential regardless of a nonsuggestive complete history and physical examination. An argument may be made for not further pursuing nonhypersecreting lesions with the typical features of a benign adenoma on CT scan and an attenuation value of 0 HU or less. Adrenocortical scintigraphy is recommended in all patients with normal biochemical screening tests, especially those with CT attenuation values greater than 0 HU. In this setting, we believe that the functional and anatomical information provided by NP-59 and [75Se]selenomethylnorcholesterol scintigraphy allows one to noninvasively, accurately, and less expensively (Table 9) categorize adrenal masses as benign nonhypersecretory adenomas (the vast majority) vs. a possibly malignant lesion (the minority). In the presence of normal biochemistry, a concordant NP-59 imaging pattern is diagnostic of a nonhypersecretory benign adrenal adenoma and requires no immediate therapeutic intervention. Conversely, patients with discordant patterns of NP-59 scintigraphy have lesions that carry a significant risk for malignancy, and the pursuit of a tissue diagnosis is indicated, usually by means of FNA. Normal adrenocortical tissue on cytological studies in this setting may represent inadvertent sampling of adjacent normal adrenocortical tissues or the presence of a well differentiated adrenocortical carcinoma. In patients with lesions larger than 2 cm in whom NP-59 scintigraphy is nonlateralizing, the possibility of a periadrenal or pseudoadrenal mass is likely and should prompt review, or perhaps even repeat, of high resolution adrenal imaging (occasionally angiography may be helpful). In lesions shown to be 2 cm or less in size with a nonlateralizing NP-59-scan, there is a possibility of a periadrenal or pseudoadrenal mass; however, once this is excluded it must be recognized that benign and malignant lesions, because of the limitations of scintigraphy, cannot always be clearly distinguished by this method when masses are small.(ABSTRACT TRUNCATED AT 400 WORDS)

The scintigraphic imaging of endocrine organs.

The nuclear medicine approach to the portrayal of endocrine organs is unique; the scintigraphic images provide not only anatomic and localization information, but in many instances allow a quantitative assessment of organ function. The ability to image endocrine glands is based upon the design of radionuclides and radiopharmaceuticals with characteristics to take advantage of many unique and specific biochemical and advantage of many unique and specific biochemical and metabolic functions of these tissues. The recent introduction of new radiopharmaceutical and tracers has provided the consulting endocrinologist with imaging procedures that allow localization and functional characterization not available by other single, noninvasive diagnostic modalities. This review will serve as an update of the available techniques to image and quantitate the function of the endocrine glands using the nuclear medicine approach.

Association between asthma and serum adiponectin concentration in women.

BACKGROUND: The association of murine asthma with adiposity may be mediated by adiponectin, an anti-inflammatory adipokine with reduced serum concentrations in obese subjects. A study was undertaken to examine whether the serum adiponectin concentration is associated with human asthma and whether it explains the association between adiposity and asthma, particularly in women and in premenopausal women. METHODS: A cross-sectional analysis was performed of 2890 eligible subjects at year 15 of the Coronary Artery Risk Development in Young Adults (CARDIA) cohort and its YALTA ancillary study who had either current asthma or never asthma at that evaluation. Obesity was defined as body mass index (BMI) >or=30 kg/m(2). Multivariable logistic regression analysis was performed with current asthma status as the dependent variable. RESULTS: Women, but not men, with current asthma had a lower mean unadjusted serum adiponectin concentration than those with never asthma (p<0.001; p for sex interaction <0.001). Similarly, current asthma was related to obesity only in women (OR 3.31, 95% CI 2.00 to 5.46, p for sex interaction = 0.004); this association was little affected by adjusting for serum adiponectin. The prevalence of current asthma in premenopausal women was reduced in the highest compared with the lowest tertile of serum adiponectin concentration (OR 0.46, 95% CI 0.26 to 0.84, p = 0.03), after adjusting for BMI. However, the interaction between serum adiponectin concentration and BMI category on current asthma status was not significant in premenopausal women or women overall. CONCLUSIONS: A high serum adiponectin concentration may protect against current asthma in premenopausal women but does not explain the association between asthma and adiposity.

Scintigraphic imaging of adrenal disease.

The nuclear medicine approach to adrenal imaging spans six decades with radiopharmaceuticals designed to take advantage of the unique characteristics of the functional divisions of the gland, substrate accumulation, hormone biosynthesis, receptor-ligand interactions and pharmacologic manipulation of mechanisms of central control. The recent introduction of hybrid imaging techniques that combine high resolution anatomy with the functional maps derived from the scintigraphic images is yet another step in the evolution of integrated imaging techniques that can be used to diagnostic advantage in the evaluation of disease of the adrenal gland.

Occlusion in implant dentistry. A review of the literature of prosthetic determinants and current concepts.

Today the clinician is faced with widely varying concepts regarding the number, location, distribution and inclination of implants required to support the functional and parafunctional demands of occlusal loading. Primary clinical dilemmas of planning for maximal or minimal numbers of implants, their axial inclination, lengths and required volume and quality of supporting bone remain largely unanswered by adequate clinical outcome research. Planning and executing optimal occlusion schemes is an integral part of implant supported restorations. In its wider sense this includes considerations of multiple inter-relating factors of ensuring adequate bone support, implant location number, length, distribution and inclination, splinting, vertical dimension aesthetics, static and dynamic occlusal schemes and more. Current concepts and research on occlusal loading and overloading are reviewed together with clinical outcome and biomechanical studies and their clinical relevance discussed. A comparison between teeth and implants regarding their proprioceptive properties and mechanisms of supporting functional and parafunctional loading is made and clinical applications made regarding current concepts in restoring the partially edentulous dentition. The relevance of occlusal traumatism and fatigue microdamage alone or in combination with periodontal or peri-implant inflammation is reviewed and applied to clinical considerations regarding splinting of adjacent implants and teeth, posterior support and eccentric guidance schemes. Occlusal restoration of the natural dentition has classically been divided into considerations of planning for sufficient posterior support, occlusal vertical dimension and eccentric guidance to provide comfort and aesthetics. Mutual protection and anterior disclusion have come to be considered as acceptable therapeutic modalities. These concepts have been transferred to the restoration of implant-supported restoration largely by default. However, in light of differences in the supporting mechanisms of implants and teeth many questions remain unanswered regarding the suitability of these modalities for implant supported restorations. These will be discussed and an attempt made to provide some current clinical axioms based where possible on the best available evidence.

Central serotonergic stimulation of aldosterone secretion.

Serotonin stimulates aldosterone secretion both in vitro and in vivo, and serotonin antagonism decreases plasma aldosterone levels in patients with idiopathic aldosteronism. This study was designed to assess the effects of the serotonin precursor, 5-hydroxytryptophan (5HTP), upon aldosterone secretion in man, and to determine whether stimulatory effects of 5HTP are mediated through the central nervous system. Oral 5HTP, administered as a single 200-mg dose, increased plasma aldosterone levels from 4.7 +/- 0.6 to 13.3 +/- 2.8 ng/dl in dexamethasone-pretreated, normal volunteers. Peripheral inhibition of decarboxylation of 5HTP, achieved by pretreatment with carboxydopa, 25 mg three times daily for 3 d, significantly increased the stimulatory effects of 5HTP on aldosterone levels (P less than 0.001). No change in aldosterone levels occurred in subjects who received placebo after pretreatment with dexamethasone and carboxydopa. Increased aldosterone was not accompanied by increases in plasma levels of renin activity, potassium, or ACTH. Plasma levels of 5HTP were markedly increased by carboxydopa pretreatment, but peak plasma levels of serotonin were not significantly altered. Four patients with idiopathic aldosteronism all had an increase in plasma aldosterone levels after 5HTP administration, whereas the response in four patients with aldosterone-producing adenoma was variable. Incubation of isolated human and rat adrenal glomerulosa cells with serotonin resulted in increased aldosterone secretion by both sets of cells, whereas 5HTP was ineffective in stimulating aldosterone secretion in vitro. We conclude that central serotonergic pathways are involved in the stimulation of aldosterone induced by administration of 5HTP. This mechanism may be an important etiologic factor in the hypersecretion of aldosterone that occurs in patients with idiopathic aldosteronism.

99mTc-sestamibi radio-guided surgery of loco-regional 131Iodine-negative recurrent thyroid cancer.

AIM: We report here our experience in a larger series of differentiated thyroid cancer (DTC) patients who had been treated by (99m)Tc-sestamibi radio-guided surgery (RGS) for (131)Iodine ((131)I)-negative loco-regional recurrent disease. METHODS: Fifty-eight patients with loco-regional (131)I-negative recurrent disease from DTC were studied with (99m)Tc-sestamibi directed RGS using a hand-held 11-mm gamma probe as an intra-operative detector. Patients were selected for RGS on the basis of (a) progressive increase of serum thyroglobulin (Tg) levels after first treatment during follow-up, (b) negative high dose (100 mCi, 3.7 GBq) (131)I whole-body scan, and (c) positive pre-operative (99m)Tc-sestamibi scintigraphy for the presence of loco-regional recurrent disease. There were 41 papillary (1 "tall" cell variant), 13 follicular and 4 Hürthle cells tumours. In 14 patients thyroid cancer recurred in the thyroid bed while cervical lymph node metastases were found in 37 patients, and 7 patients had recurrent disease both in the thyroid bed and in cervical lymph nodes. RESULTS: At bilateral neck exploration, 147 metastatic foci ranging from 4 mm to 51 mm in largest diameter (mean tumour diameter=17.3+/-9.5mm) were removed. Eighty-five of them (58%) had been pre-operatively identified at (99m)Tc-sestamibi scintigraphy. After RGS, serum Tg levels normalised in 43 of 58 patients (serum Tg<2 ng/ml--they were considered disease-free), serum Tg remained slightly increased in 12 patients without evidence of metastatic disease at scintigraphic and radiologic imaging (serum Tg<10 ng/mg--they were considered living with microscopic disease), while serum Tg significantly increased up to values>900 ng/ml in 3 patients who developed lung metastases. The mean lesion to background (99m)Tc-sestamibi uptake ratios decreased in all 58 patients (p<0.0001). Post-surgical follow-up ranged 6-72 months (mean+/-SD=29.6+/-13.5 months). The operating surgeon assessed RGS as very useful in 14 patients in whom metastatic foci were embedded in fibrotic tissues or located behind blood vessels, useful in 22 patients, moderately useful 17 patients and not useful in 5 patients. CONCLUSION: Our data suggest that a (99m)Tc-sestamibi intra-operative gamma probe can be used to identify and guide resection of recurrent loco-regional tumour in DTC patients with (131)I-negative loco-regional metastatic foci.

Iodine-131 radio-guided surgery in differentiated thyroid cancer: outcome on 31 patients and review of the literature.

In the present study we investigated the role of radio-guided surgery with Iodine-131 (I-131) in a group of 31 patients with differentiated thyroid cancer (DTC) and loco-regional recurrent disease. The principal inclusion criterion for I-131 radio-guided surgery in our protocol was the presence of an I-131 positive loco-regional disease relapse after previous total thyroidectomy and at least 2 ineffective conventional I-131 treatments. The protocol we used consisted of the following steps. Day 0: all patients were hospitalized and received a therapeutic 3.7 GBq (100 mCi) dose of I-131 after thyroid hormone therapy withdrawal in condition of overt hypothyroidism (serum TSH levels>30 microUI/ml). Day 3: a whole body scan following the therapeutic I-131 dose (TxWBS) administration was acquired. Day 5: neck surgery was performed through a wide bilateral neck exploration using a 15-mm collimated gamma probe, measuring the absolute intra-operative counts and calculating the lesion to background (L/B) ratio. Day 7: post-surgery TxWBS was performed using the remaining radioactivity to evaluate the completeness of tumoral lesions extirpation. The final histologic examination showed the presence of 184 metastatic foci; among them, 98 (53.2%) were evident by both TxWBS and gamma probe evaluation, 76 (41.3%) were demonstrated only by gamma probe, and 10 (5.4%) were negative by both TxWBS and gamma probe evaluation. During follow-up (8 months to 4.9 years, mean 2.8 years), DxWBS, serum Tg levels off l-T4, and US showed absence of loco-regional disease in 25 patients (80.6%) while 6 patients had persistent disease. In conclusion, this protocol allowed us to identify neoplastic foci with high sensitivity and specificity, enabling us to remove loco-regional I-131 disease recurrences resistant to previous conventional I-131 therapies. Furthermore, the gamma probe allowed detection of some additional tumoral foci in sclerotic areas or located behind vascular structures that were not visualized at the pre-surgery TxWBS evaluation.

The role of sentinel lymph node biopsy in patients with differentiated thyroid carcinoma.

AIM: To evaluate the "state of art" of clinical role of sentinel lymph node (SLN) biopsy procedure in patients affected by differentiated thyroid carcinoma. METHODS: All papers cited on PubMed/MEDLINE until June 2005, published in English, and referred to the key words "sentinel lymph node biopsy" AND "thyroid carcinoma" OR "thyroid cancer" were reviewed for the purpose of the present study. RESULTS: The first method used for SLN biopsy in thyroid carcinoma patients was the vital blue dye technique. This technique had some disadvantages as: (a) risk of disruption of the lymphatic channels deriving from the thyroid cancer; (b) difficulty in disclosing SLN lying outside the central compartment; (c) parathyroid glands can take up blue dye and, thus, can be misinterpreted as lymph nodes. Some of the above cited disadvantages were overcome by using the lymphoscintigraphy and intraoperative gamma probe technique. A combination of the blue dye and gamma probe technique has also been proposed with synergic results. CONCLUSION: The reported advantages of the SLN biopsy in small differentiated thyroid carcinoma patients can be resumed as follows: (a) better selection of patients who would benefit from compartment oriented nodal dissection; (b) more accurate lymph node staging; (c) better selection of patients who can require (131)I treatment after surgery (SLN positive for metastasis); (d) better identification of SLN located out of the central compartment.

18F-FDG PET/CT fusion imaging in paediatric solid extracranial tumours.

This paper aims at discussing the utility of 18F-FDG PET/CT in the evaluation of paediatric solid extracranial tumours. Following a brief discussion of the basic principles and methodology of PET/CT system, it reviews the main characteristics of the tumours that can be visualised with 18F-FDG PET and presents examples of cases where the combined use of 18F-FDG PET/CT fusion imaging helped in the management of patients. It will also discuss the physiologic biodistribution of 18F-FDG, outlining the normal variants in the paediatric patients that may lead to misinterpretation.

Tacrolimus-associated hypomagnesemia in renal transplant recipients.

BACKGROUND: Since hypomagnesemia occurs frequently in tacrolimus treated patients, we studied the correlation between renal magnesium wasting and tacrolimus blood levels in renal transplant patients. METHODS: Serum magnesium, fractional excretion of magnesium (FEMg), and 24-hour urinary excretion of magnesium were measured in 41 transplant patients and 10 healthy volunteers for correlation with tacrolimus level. RESULTS: Of tacrolimus-treated patients, 43% displayed hypomagnesemia. FEMg (7.42+/-3.59% versus 1.88+/-0.43%) and 24-hour urinary excretion (112.36+/-51.43 mg/dL versus 6.7+/-2.79 mg/dL) were significantly higher among tacrolimus-treated patients than controls. Magnesium replacement did not influence FEMg or 24-hour urinary magnesium excretion. Tacrolimus level was the best predictor of 24-hour urinary magnesium excretion and FEMg. Serum magnesium levels correlated inversely with tacrolimus concentrations and creatinine clearance. CONCLUSION: Hypomagnesemia in renal transplant recipients results from renal magnesium wasting. Tacrolimus levels and renal function impact on the excess renal magnesium excretion. Studies of longer duration are warranted to assess the long-term effects of this early posttransplant hypomagnesemia.

Accelerated platelet activation in Asian Indians with diabetes and coronary artery disease--The Chennai Urban Population Study (CUPS-13).

AIM: To assess platelet activation in south Indian type 2 diabetic subjects with and without CAD. METHODS: Four groups of subjects were studied; Group 1 comprised of non-diabetic subjects without coronary artery disease (CAD) (n = 30). Type 2 diabetic subjects without CAD formed Group 2 (n = 30); Group 3 comprised of type 2 diabetic subjects with CAD (n = 30) and Group 4 consisted of non- diabetic subjects with CAD (n=14). CAD was diagnosed based on coronary angiographic evidence of severe double or triple vessel disease. Platelet activation was tested after an overnight fast in blood obtained from a bleeding wound at 1 minute post-incision (wound-induced activation) as well as venous blood stimulated in vitro with collagen, using whole blood flow cytometry. In subjects with CAD, aspirin was withdrawn for 7 days and nitrates for 24 hours. RESULTS: Collagen induced GP IIb/IIIa binding was significantly higher among diabetic subjects with (28.10 +/-19.89; p<0.05) and without CAD (21.02+/-19.62; p<0.05) and non-diabetic subjects with CAD (23.89+/-15.65; p<0.05) compared to non-diabetic subjects without CAD (11.69+/-13.69). Regression analysis showed collagen induced GP IIb/IIIa binding to be significantly associated with CAD [odds ratio (OR): 1.029, p = 0.025] and diabetes (OR: 1.037, p = 0.007). CONCLUSION: Increased platelet activation is seen in urban south Indians with diabetes and CAD.

Oxidative stress, anti-oxidants and the cross-sectional and longitudinal association with depressive symptoms: results from the CARDIA study.

Depression may be accompanied by increased oxidative stress and decreased circulating anti-oxidants. This study examines the association between depressive symptoms, F2-isoprostanes and carotenoids in a US community sample. The study includes 3009 participants (mean age 40.3, 54.2% female) from CARDIA (Coronary Artery Risk Development in Young Adults). Cross-sectional analyses were performed on data from the year 15 examination (2000-2001) including subjects whose depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) and had measurements of plasma F2-isoprostanes (gas chromatography/mass spectrometry) or serum carotenoids (high-performance liquid chromatography). Carotenoids zeaxanthin/lutein, ß-cryptoxanthin, lycopene, α-carotene, ß-carotene were standardized and summed. Longitudinal analyses were conducted using the data from other examinations at 5-year intervals. Cross-lagged analyses investigated whether CES-D predicted F2-isoprostanes or carotenoids at the following exam, and vice versa. Regression analyses were controlled for sociodemographics, health and lifestyle factors. F2-isoprostanes were higher in subjects with depressive symptoms (CES-D ⩾ 16) after adjustment for sociodemographics (55.7 vs 52.0 pg ml(-1); Cohen's d = 0.14, P < 0.001). There was no difference in F2-isoprostanes after further adjustment for health and lifestyle factors. Carotenoids were lower in those with CES-D scores ⩾ 16, even after adjustment for health and lifestyle factors (standardized sum 238.7 vs 244.0, Cohen's d = -0.16, P < 0.001). Longitudinal analyses confirmed that depression predicts subsequent F2-isoprostane and carotenoid levels. Neither F2-isoprostanes nor carotenoids predicted subsequent depression. In conclusion, depressive symptoms were cross-sectionally and longitudinally associated with increased F2-isoprostanes and decreased carotenoids. The association with F2-isoprostanes can largely be explained by lifestyle factors, but lower carotenoids were independently associated with depressive symptoms.

Interactions between apolipoprotein E gene and dietary alpha-tocopherol influence cerebral oxidative damage in aged mice.

Cerebral oxidative damage is a feature of aging and is increased in a number of neurodegenerative diseases. We pursued the gene-environment interaction of lack of apolipoprotein E (apoE) and modulation of dietary alpha-tocopherol on cerebral oxidative damage in aged male and female mice by quantifying the major isomers of cerebral isoprostanes, derived from arachidonic acid (AA) oxidation, and neuroprostanes, derived from docosahexaenoic acid (DHA) oxidation. Mice fed alpha-tocopherol-deficient, normal, or -supplemented diet had undetectable, 4486 +/- 215, or 6406 +/- 254 ng of alpha-tocopherol per gram of brain tissue (p < 0.0001), respectively. Two factors, male gender and lack of apoE, combined to increase cerebral AA oxidation by 28%, whereas three factors, male gender, lack of apoE, and deficiency in alpha-tocopherol, combined to increase cerebral DHA oxidation by 81%. alpha-Tocopherol supplementation decreased cerebral isoprostanes but not neuroprostanes and enhanced DHA, but not AA, endoperoxide reduction in vivo and in vitro. These results demonstrated that the interaction of gender, inherited susceptibilities, and dietary alpha-tocopherol contributed differently to oxidative damage to cerebral AA and DHA in aged mice.