Real-time organic aerosol chemical speciation in the indoor environment using extractive electrospray ionization mass spectrometry

Understanding the sources and composition of organic aerosol (OA) in indoor environments requires rapid measurements, since many emissions and processes have short timescales. However, real-time molecular-level OA measurements have not been reported indoors. Here, we present quantitative measurements, at a time resolution of five seconds, of molecular ions corresponding to diverse aerosol-phase species, by applying extractive electrospray ionization mass spectrometry (EESI-MS) to indoor air analysis for the first time, as part of the highly instrumented HOMEChem field study. We demonstrate how the complex spectra of EESI-MS are screened in order to extract chemical information and investigate the possibility of interference from gas-phase semivolatile species. During experiments that simulated the Thanksgiving US holiday meal preparation, EESI-MS quantified multiple species, including fatty acids, carbohydrates, siloxanes, and phthalates. Intercomparisons with Aerosol Mass Spectrometer (AMS) and Scanning Mobility Particle Sizer suggest that EESI-MS quantified a large fraction of OA. Comparisons with FIGAERO-CIMS shows similar signal levels and good correlation, with a range of 100 for the relative sensitivities. Comparisons with SV-TAG for phthalates and with SV-TAG and AMS for total siloxanes also show strong correlation. EESI-MS observations can be used with gas-phase measurements to identify co-emitted gas- and aerosol-phase species, and this is demonstrated using complementary gas-phase PTR-MS observations.     

Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.     

Neurochemical characterization of the alterations in the noradrenergic afferents to the cerebellum of adult rats exposed to X-irradiation at birth

A single dose of x-irradiation was applied on the cephalic end of newborn rats, and the alterations in the noradrenergic afferents to the cerebellum were studied 180 days later. A net increase in the noradrenaline content of cerebellum was found (122% of nonirradiated controls). The response of noradrenaline content to reserpine injection (0.9 mg/kg, i.p.) was similar in exposed and control rats. Likewise, the 3H release induced by Ro 4-1284 from cerebellar cortex slices labeled with [3H]noradrenaline was unmodified by x-rays, although a mild increase in the spontaneous efflux of 3H was found. The retention of 3H by the slices was reduced in exposed animals (58% of controls). Both the in vitro activity of tyrosine hydroxylase and the accumulation of L-3,4-dihydroxyphenylalanine (L-DOPA) were not significantly different between x-treated rats and controls. In contrast, monoamine oxidase activity was markedly reduced in x-irradiated cerebellum (38% of controls). The x-ray-induced decrease in cerebellar weight (-60%) resulted in marked increases in noradrenaline concentration (223%), tyrosine hydroxylase activity per milligram of protein (206%), and 3H retention (50%). The accumulation of L-DOPA per gram of tissue was also increased at every time considered. These data indicate that x-irradiation at birth produces a cerebellar loss not completely shared by the noradrenergic afferents, and a permanent imbalance between the noradrenergic afferent input and its target cells might eventually result.(ABSTRACT TRUNCATED AT 250 WORDS)     

The ultrasound appearances of neonatal renal vein thrombosis

Renal vein thrombosis (RVT) is the most frequently occurring vascular condition in the new-born kidney. The predisposing factors include dehydration, sepsis, birth asphyxia, maternal diabetes, polycythaemia and the presence of an indwelling umbilical venous catheter. (RVT) may present clinically with a flank mass, haematuria, hypertension or renal failure. Many imaging modalities have been employed, but ultrasound is the technique most commonly used in the evaluation of neonates with suspected RVT. Thrombosis commences in the small renal veins and subsequently propagates via larger interlobar veins to the main renal vein and inferior vena cava (IVC). The ultrasound appearances depend upon the stage at which the examination is performed and extent of the thrombus. Initially, the interlobular and interlobar thrombus appears as highly echogenic streaks. These streaks commence in a peripheral, focal segment of the involved kidney and only persist for a few days. In the first week the affected kidney swells and becomes echogenic with prominent echopoor medullary pyramids. Later, the swelling increases and the kidney becomes heterogenous with loss of corticomedullary differentiation. Grey scale ultrasound readily demonstrates thrombus within the renal vein and IVC. Adrenal haemorrhage is a recognized association and may be identified ultrasonically. Colour Doppler scanning provides additional information. In the early stages of RVT, colour Doppler may demonstrate absent intrarenal and renal venous flow. Ultimately, the kidney may recover, show focal scarring or become atrophic. Thus, ultrasound provides an accessible and reliable tool in the assessment of suspected neonatal RVT.     

Coronary bypass in vascular patients: a relatively high-risk procedure

A premise of cardiac risk stratification is that the added risk of coronary artery bypass grafting (CABG) is offset by the improved safety of subsequent vascular reconstruction (VR). We questioned if elective CABG is patients with severe peripheral vascular disease (PVD) is a relatively high-risk procedure. A cohort study of 680 elective CABG patients from January 1993 to December 1994 was performed using three mutually exclusive outcomes of complication-free survival, morbidity, and mortality. Patient characteristic, operative, and outcome data were prospectively collected. Retrospective review determined that 58 patients had either a standard indication for or a history of VR. Overall CABG mortality was 2.5%, with statistically similar but relatively higher rates for PVD as compared to non-PVD patients. In contrast, major morbidity occurred at rates 3.6-fold higher in PVD patients (39.7%) than in disease-free patients (16.7%) after adjustment for the effects of patient and operative variables (odds ratio [OR] 3.67, 95% confidence interval [CI] 1.93-6.99). CABG morbidity in the PVD patient was most likely in those patients with aortoiliac (OR 9.51, CI 3.20-28.27) and aortic aneurysmal (OR 5.24, CI 1.28-21.41) disease types. CABG in PVD patients is associated with significant major morbidity. Such morbidity may preclude or alter the timing of subsequent VR.     

Chronic fluoride exposure does not cause detrimental, extraskeletal effects in nutritionally deficient rats

On the basis of observations that endemic fluorosis occurs more often in malnourished populations, a series of studies tested the hypothesis that deficient dietary intake of calcium, protein or energy affects fluoride metabolism so that the margin of safe fluoride exposure may be reduced. The objective of the investigation was to determine whether changes in fluoride metabolism in nutritionally deficient rats resulted in manifestation of any extraskeletal toxic fluoride effects not observed in healthy animals. This investigation included two studies, one that monitored the effect of calcium deficiency on the effects of chronic fluoride exposure, and a second study that observed fluoride effects in rats that were deficient either in protein or in energy and total nutrient intake. Control and experimental rats received drinking water containing 0, 0.26 (5), 0.79 (15) or 2.63 (50) mmol fluoride/L (mg/L) for 16 or 48 wk. Control rats were fed optimal diets and experimental rats were fed diets deficient in calcium (Study 1) or protein (Study 2). An additional group of experimental rats (Study 2) was provided with a restricted amount of diet; thus these rats were deficient in energy and total nutrient intake. The intake, excretion and retention of fluoride were monitored; after the rats were killed, tissue fluoride levels and biochemical markers of tissue function were analyzed. Bone marrow cells were harvested from some of the rats, after 48 wk of treatment, for determining the frequency of sister chromatid exchange, a marker of genetic damage. Although there were significant differences among fluoride treatment groups in fluoride excretion and retention that resulted in significantly greater fluoride levels in tissues of the experimental rats, we were unable to detect any harmful, extraskeletal biochemical, physiologic or genetic effects of fluoride in the nutritionally deficient rats.     

trans-2-phenylcyclopropylamine is a substrate for and inactivator of horseradish peroxidase

Horseradish peroxidase (HRP) is well known for mediating the electron-transfer oxidation of electron-rich aromatic 'donors' such as phenols and anilines, but has not been described to oxidize aliphatic amines. We here confirm the inability of HRP to oxidize typical aliphatic amines, even those which would exist significantly as free bases at the operative pH. In contrast, trans-2-phenylcyclopropylamine (2-PCPA) is both a substrate (turnover product is cinnamaldehyde) and a time-dependent inactivator of HRP. These activities of 2-PCPA are consistent with either a concerted or rapid sequential one-electron-oxidation/ring-opening to give an intermediate capable of covalent binding to the enzyme. 2-PCPA is the first known example of a simple aliphatic amine which serves as a substrate for HRP under turnover conditions.