A prospective study (SCOPE) comparing the cardiometabolic and respiratory effects of air pollution exposure on healthy and pre-diabetic individuals.

Air pollution is known to be a major risk factor for cardiopulmonary disease, but this is unclear for cardiometabolic disease (e.g. diabetes). This is of considerable public health importance, given the nationwide epidemic of diabetes, accompanied by severe air pollution, in China. The evidence so far remained inadequate to answer questions of whether individuals with cardiometabolic dysfunctions are susceptible to air pollution and whether air pollution exacerbates diabetes development via certain biological pathways. In this manuscript, we summarize the results and limitations of studies exploring these two topics and elaborate our design of a prospective panel study (SCOPE) as a solution. We assessed and compared the health effect of air pollution among pre-diabetic individuals and matched healthy controls through four repeated clinical visits over 1 year. Comprehensive evaluation was made to both health endpoints and exposure. The primary biomarkers were assessed to reveal the impact on multiple biological pathways, including glycolipid metabolism and insulin resistance, endothelial function, and inflammation. Detailed chemical and size fractional components of particulate matter were measured in this study, along with the application of personal monitors. The work should increase our understanding of how air pollution affects individuals with cardiometabolic dysfunction and the underlying mechanisms.

Urinary NGAL deficiency in recurrent urinary tract infections.

INTRODUCTION: Children with recurrent urinary tract infections (rUTI) often show no identifiable cause of their infections. Neutrophil gelatinase-associated lipocalin (NGAL) is known to be upregulated within the uroepithelium and kidney of patients with UTI and exhibits a localized bacteriostatic effect through iron chelation. We hypothesize that some patients with rUTI without an identifiable cause of their recurrent infections have locally deficient NGAL production. We therefore explored whether a lack of NGAL production may be a factor in the pathogenesis of rUTI. MATERIALS AND METHODS: Patients seen in the urology clinic for rUTI who were <21 years of age were enrolled. Patients were excluded if they had UTI at the time of enrollment, evidence of renal disease, decreased renal function, known anatomic abnormality of the genitourinary tract, or other reasons that predispose to UTI, such as neurogenic bladder, the need for intermittent catheterization, or unrepaired posterior urethral valves. Control patients were healthy children enrolled from the emergency department with no history of UTI or renal dysfunction, normal urinalysis at the time of enrollment, and presenting no diagnosis associated with increased NGAL levels, such as acute kidney injury or infection. NGAL was measured by immunoblot. RESULTS: Fifteen cases and controls were enrolled. Median urinary NGAL levels were significantly decreased in rUTI patients compared with controls [15 (14-29) ng/ml vs 30 (27-61) ng/ml; p = 0.002)] Although comparatively diminished, measurable NGAL levels were present in all patients with rUTI. CONCLUSIONS: Urinary NGAL is significantly decreased in patients with compared with patients without rUTI. These data suggest that some patients with rUTI may be predisposed to UTI because of a relative local deficiency in urinary NGAL production.

Metabolism of [D10]phenanthrene to tetraols in smokers for potential lung cancer susceptibility assessment: comparison of oral and inhalation routes of administration.

Polycyclic aromatic hydrocarbons (PAHs) are believed to be among the causative agents for lung cancer in smokers. PAHs require metabolic activation for carcinogenicity. One pathway produces diol epoxides that react with DNA, causing mutations. Because diol epoxides are converted to tetraols, quantitation of tetraols can potentially be used to identify smokers who may be at higher risk for lung cancer. Our approach uses [D(10)]phenanthrene, a labeled version of phenanthrene, a noncarcinogenic PAH structurally analogous to carcinogenic PAH. Although smokers are exposed to PAH by inhalation, oral dosing would be more practical for phenotyping studies. Therefore, we investigated [D(10)]phenanthrene metabolism in smokers after administration by inhalation in cigarette smoke or orally. Sixteen smokers received 10 µg of [D(10)]phenanthrene in a cigarette or orally. Plasma and urine samples were analyzed for [D(10)]r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene ([D(10)]PheT), the major end product of the diol epoxide pathway, by gas chromatography-negative ion chemical ionization-tandem mass spectrometry. The ratios of [D(10)]PheT (oral dosing/inhalation) in 15 smokers were 1.03 ± 0.32 and 1.02 ± 0.35, based on plasma area under the concentration-time curve (0-∞) and total 48-h urinary excretion, respectively. Overall, there was no significant difference in the extent of [D(10)]PheT formation after the two different routes of exposure in smokers. A large interindividual variation in [D(10)]PheT formation was observed. These results demonstrate that the level of [D(10)]PheT in urine after oral dosing of [D(10)]phenanthrene can be used to assess individual capacity of PAH metabolism by the diol epoxide pathway.

Very low-grade albuminuria reflects susceptibility to chronic kidney disease in combination with cardiovascular risk factors.

Low-grade albuminuria has been proposed as a cardiovascular risk factor that is below the conventional cut-off point for microalbuminuria, which has been previously identified as a marker for cardiovascular disease and chronic kidney disease (CKD). Metabolic syndrome has also been shown to be related with microalbuminuria and CKD. We assessed the relationship among low-grade albuminuria, CKD and metabolic syndrome among 5998 non-diabetic subjects. The subjects were divided into six groups: subjects with urine albumin-to-creatinine ratio (UACR) <30 mg g(-1) were divided into five groups in accordance with their UACR values, and subjects with 30

[Detection of urate tubulointerstitial nephritis: contribution of diagnostic questionnaire]. / Raspoznovanie uratnogo tubulointerstitsial'nogo nefrita s ispol'zovaniem diagnosticheskoi ankety.

AIM: To develop a diagnostic questionnaire to identify individuals with uric acid hyperproduction and risk of urate tubulointerstitial nephritis (UTIN). MATERIALS AND METHODS: Clinical symptoms of 650 patients with verified hyperuricemia or hyperuricosemia have been summarized to design a special questionnaire which will be able to identify subjects to whom test for uricemia and uricosuria may be recommended to prevent onset and/or progression of UTIN. RESULTS: The questionnaire has been compiled which has rather high sensitivity and specificity in identification of persons with hyperuricemia and/or hyperuricosuria at risk to develop UTIN. CONCLUSION: The designed questionnaire allows to select subjects with existing UTIN or at UTIN risk both in population and individual studies.

Ambulatory blood pressure nondipping status in salt-sensitive and salt-resistant black adolescents.

This study examined the relationship between salt sensitivity and ambulatory blood pressure in 53 healthy black adolescents. Salt sensitivity was defined as an increase in mean blood pressure greater than or exceeding 5 mm Hg from a 5-day low-salt diet (50 mmol/24 h) to a 10-day high-salt diet (150 mmol/24 h NaCl supplement). Sixteen subjects were salt sensitive and 37 subjects were salt resistant (showed < 5 mm Hg increase in mean blood pressure). Subjects were classified as dippers (> or =10% decrease in blood pressure from awake to asleep) based on their 24-h ambulatory blood pressure values. Nondippers showed higher systolic, diastolic, and mean asleep blood pressures than dippers (P < .05 for all). Salt-sensitive subjects showed greater daytime diastolic and mean blood pressures than salt-resistant subjects (P < .05 for both). A significantly greater percentage of nondippers were salt sensitive, compared with salt resistant for diastolic blood pressure (P < .001) and mean blood pressure (P < .05). For both of these blood pressure measures, 50% of the salt-sensitive subjects had a nondipping status, compared with only 5.4% of the salt-resistant subjects for diastolic blood pressure, and 18.9% of the salt-resistant subjects for mean blood pressure. These results are the first to indicate that salt sensitivity is associated with nondipper blood pressure status in a black normotensive adolescent population.