Systemic sclerosis medications and risk of scleroderma renal crisis.

BACKGROUND: Scleroderma Renal Crisis (SRC) is associated with significant morbidity and mortality. While prednisone is strongly associated with SRC, there are no previous large cohort studies that have evaluated ace inhibitor (ACEi) calcium channel blocker (CCB), angiotensin receptor blocker (ARB), endothelin receptor blocker (ERB), non-steroidal anti-inflammatory drug (NSAID), fluticasone, or mycophenolate mofetil (MMF) use in systemic sclerosis (SSc) and the risk of SRC. METHODS: In this retrospective cohort study of the entire military electronic medical record between 2005 and 2016, we compared the use of ACEi, ARB, CCB, NSAID, ERB, fluticasone, and MMF after SSc diagnosis for 31 cases who subsequently developed SRC to 322 SSc without SRC disease controls. RESULTS: ACEi was associated with an increased risk for SRC adjusted for age, race, and prednisone use [odds ratio (OR) 4.1, 95% confidence interval (CI) 1.6-10.2, P = 0.003]. On stratified analyses, ACEi was only associated with SRC in the presence [OR 5.3, 95% CI 1.1-29.2, p = 0.03], and not the absence of proteinuria. In addition, a doubling of ACEi dose [61% vs. 12%, p < 0.001) and achieving maximum ACEi dose [45% vs. 4%, p < 0.001] after SSc diagnosis was associated with future SRC. CCB, ARB, NSAIDs, ERB, fluticasone, and MMF use were not significantly associated with SRC. CONCLUSION: ACEi use at SSC diagnosis was associated with an increased risk for SRC. Results suggest that it may be a passive marker of known SRC risk factors, such as proteinuria, or evolving disease. SSC patients that require ACEi should be more closely monitored for SRC.

Population diversity: its extent and extinction.

Genetically distinct populations are an important component of biodiversity. This work estimates the number of populations per area of a sample of species from literature on population differentiation and the average range area of a species from a sample of distribution maps. This yields an estimate of about 220 populations per species, or 1.1 to 6.6 billion populations globally. Assuming that population extinction is a linear function of habitat loss, approximately 1800 populations per hour (16 million annually) are being destroyed in tropical forests alone.

Alkaloids from Prosopis juliflora leaves induce glial activation, cytotoxicity and stimulate NO production.

Prosopis juliflora is used for feeding cattle and humans. Intoxication with the plant has been reported, and is characterized by neuromuscular alterations and gliosis. Total alkaloidal extract (TAE) was obtained using acid/basic-modified extraction and was fractionated. TAE and seven alkaloidal fractions, at concentrations ranging 0.03-30 microg/ml, were tested for 24h on astrocyte primary cultures derived from the cortex of newborn Wistar rats. The MTT test and the measure of LDH activity on the culture medium, revealed that TAE and fractions F29/30, F31/33, F32 and F34/35 were cytotoxic to astrocytes. The EC(50) values for the most toxic compounds, TAE, F31/33 and F32 were 2.87 2.82 and 3.01 microg/ml, respectively. Morphological changes and glial cells activation were investigated through Rosenfeld's staining, by immunocytochemistry for the protein OX-42, specific of activated microglia, by immunocytochemistry and western immunoblot for GFAP, the marker of reactive and mature astrocytes, and by the production of nitric oxide (NO). We observed that astrocytes exposed to 3 microg/ml TAE, F29/30 or F31/33 developed compact cell body with many processes overexpressing GFAP. Treatment with 30 microg/ml TAE and fractions, induced cytotoxicity characterized by a strong cell body contraction, very thin and long processes and condensed chromatin. We also observed that when compared with the control (+/-1.34%), the proportion of OX-42 positive cells was increased in cultures treated with 30 microg/ml TAE or F29/30, F31/33, F32 and F34/35, with values raging from 7.27% to 28.74%. Moreover, incubation with 3 microg/ml F32, 30 microg/ml TAE, F29/30, F31/33 or F34/35 induced accumulation of nitrite in culture medium indicating induction of NO production. Taken together these results show that TAE and fractionated alkaloids from P. juliflora act directly on glial cells, inducing activation and/or cytotoxicity, stimulating NO production, and may have an impact on neuronal damages observed on intoxicated animals.

Comparison of bioaugmentation and biostimulation for the enhancement of dense nonaqueous phase liquid source zone bioremediation.

Two 11.7-m(3) experimental controlled release systems (ECRS), packed with sandy model aquifer material and amended with tetrachloroethene (PCE) dense nonaqueous phase liquid (DNAPL) source zone, were operated in parallel with identical flow regimes and electron donor amendments. Hydrogen Releasing Compound (Regenesis Bioremediation Products, Inc., San Clemente, California), and later dissolved lactate, served as electron donors to promote dechlorination. One ECRS was bioaugmented with an anaerobic dechlorinating consortium directly into the source zone, and the other served as a control (biostimulated only) to determine the benefits of bioaugmentation. The presence of halorespiring bacteria in the aquifer matrix before bioaugmentation, shown by nested polymerase chain reaction with phylogenetic primers, suggests that dechlorinating catabolic potential may be somewhat widespread. Results obtained corroborate that source zone reductive dechlorination of PCE is possible at near field scale and that a system bioaugmented with a competent halorespiring consortium can enhance DNAPL dissolution and dechlorination processes at significantly greater rates than in a system that is biostimulated only.

Occurrence of proteins immunoreactive with anti-coupling factor B in phosphorylating membrane preparations.

Coupling factor B has been isolated from beef heart mitochondria, apparently in multiple forms which differ in molecular weight and specific activity. Since it has no known intrinsic catalytic activity, detection and quantitation have been based upon the factor B-dependent stimulation of ATP-linked activities in factor B-deficient sub-mitochondrial particles. This communication reports the development of a reliable and more universally applicable enzyme-linked immunosorbent assay (ELISA) for detection and quantitation of factor B in soluble or membranous preparations. The assay requires nanoliter volumes of rabbit antiserum raised against purified factor B and will detect nanogram amounts of the coupling factor. Analysis of beef heart submitochondrial particles using a competitive binding ELISA indicated a factor B content of 0.27 nmol/mg protein, making factor B stoichiometric with F1 (0.3--0.6 nmol/mg). Furthermore, application of the factor B ELISA has indicated the presence of material cross-reacting with the beef heart factor B-antiserum in phosphorylating membranes from chloroplasts, Escherichia coli, Paracoccus denitrificans and the thermophilic bacterium, PS3. Negative results were obtained with mitochondria and microsomes from rat liver, purple membranes from Halobium halobacterium and sarcoplasmic reticulum from rabbit skeletal muscle.

Effect of prior exercise and insulin on potential thermogenic systems in rat skeletal muscle.

We previously reported that insulin stimulates oxygen consumption by the perfused rat hindquarter after high-intensity exercise. The purpose of the present study was to examine whether fructose 6-phosphate-fructose 1,6-bisphosphate cycling or an uncoupling of mitochondrial respiration contributes to this phenomenon. Hindquarter skeletal muscle was analyzed after perfusion in the absence or presence of insulin (150-200 microU/ml) for high-energy phosphate content, fructose 6-phosphate-fructose 1,6-bisphosphate cycling of glucose before incorporation into glycogen, and mitochondrial respiratory control. Muscle from exercised rats perfused with insulin did not display greater rates of glucose cycling or mitochondrial uncoupling; in fact, insulin decreased the rate of fructose 6-phosphate cycling and tended to increase respiratory control in skeletal muscle mitochondria. In addition, the concentrations of ATP and creatine phosphate and the calculated free ADP level in muscle of previously exercised rats perfused with insulin were similar to those of control rats. The results do not exclude the possibility that localized subcellular changes in ADP occurred, however. In conclusion, the results suggest that insulin-induced increases in other substrate cycles, ion transport systems, and/or as yet unidentified energy-requiring processes account for the 25-30% increase in hindquarter oxygen consumption after intense exercise.

The scale of resource specialization and the distribution and abundance of lycaenid butterflies.

Numerous hypotheses have been proposed for the commonly observed, positive relationship between local abundance and geographic distribution in groups of closely related species. Here I consider how hostplant specialization and abundance affect the relative abundance and distribution of lycaenid butterflies (Lepidoptera: Lycaenidae). I first discuss three components of specialization: local specialization, turnover of specialization across a species' range, and the minimum number of resources (or habitats) required by a species. Within this framework, I then consider one dimension of a lycaenid species' niche, larval hostplant specialization. In a subalpine region of Colorado, I surveyed 11 lycaenid species and their hostplants at 17 sites. I compare this local information to continental hostplant use and large-scale distributions of the lycaenids and their hostplants. Local abundance of a lycaenid species is positively correlated with its local distribution (the number of sites occupied), but not with its regional or continental distribution. Neither local specialization (the number of hostplants used within one habitat) nor continental specialization (the number of hostplants used across many habitats) is correlated with local lycaenid abundance. Continental specialization is positively correlated with a species' continental distribution, however. Finally, while generalist butterflies tend to have more hostplant available to them, differences in resource availability do not explain the differences in butterfly abundance. Although local abundance is correlated only with local distribution, I suggest that abundance-distribution relationships might emerge at regional and continental scales if local abundance were averaged across many habitat types. Consideration of the scale of a species' resource specialization (within or among habitats) appears to be key to understanding the relationships between resource specialization, resource availability, and a species' abundance and distribution.

Studies on plant-mediated fate of the explosives RDX and HMX.

The fate of the explosives RDX and HMX on exposure to plants was investigated in 'natural' aquatic systems of Myriophyllum aquaticum for 16 days, and in axenic hairy root cultures of Catharanthus roseus for > or = 9 weeks. Exposure levels were: HMX, 5 mg/l; and RDX, approximately 8 mg/l. Exposure outcomes observed include: HMX, no transformation by aquatic plants, and minimal biological activity by axenic roots; and RDX, removal by both plant systems. In the case of RDX exposure to axenic roots, since 14C-RDX was included, removal was confirmed by the accumulation of 14C-label in the biomass. The intracellular 14C-label in these RDX studies was detected in two forms: intact RDX and bound unknown(s).

Remediation of dinitrotoluene contaminated soils from former ammunition plants: soil washing efficiency and effective process monitoring in bioslurry reactors.

A pilot-scale bioslurry system was used to test the treatment of soils highly contaminated with 2,4-dinitrotoluene (2,4-DNT) and 2,6-dinitrotoluene (2,6-DNT). The treatment scheme involved a soil-washing process followed by two sequential aerobic slurry reactors augmented with 2,4-DNT- and 2,6-DNT-mineralizing bacteria. Test soils were obtained from two former army ammunition plants, the Volunteer Army Ammunition Plant (VAAP, Chattanooga, TN) and the Badger Army Ammunition Plant (BAAP, Baraboo, WI). Soil washing was used to minimize operational problems in slurry reactors associated with large particulates. The Eimco slurry reactors were operated in a draw-and-fill mode for 3 months and were monitored for the biodegradation of 2,4-DNT and 2,6-DNT, nitrite production, NaOH consumption, and oxygen uptake rate. Results show that soil washing was very effective for the removal of sands and the recovery of soil fines containing 2,4-DNT and 2,6-DNT. Bioslurry reactors offered rapid and nearly complete degradation of both DNT isomers, but require real time monitoring to avoid long lag periods upon refeeding. Results found a significant discrepancy between the measured DNT concentrations and calculated DNT concentrations in the slurry reactors because of solids profiles in the slurry reactors and the presence of floating crystal of DNTs. Based on the actual amount of dinitrotoluene degradation, nitrite release, NaOH consumption, and oxygen uptake were close to the theoretical stoichiometric coefficients of complete DNT mineralization. Such stoichiometric relationships were not achieved if the calculation was based on the measured DNT concentrations due to the heterogeneity of DNT in the reactor. Results indicate that nitrite release, NaOH consumption, and oxygen uptake rates provide a fast assessment of 2,4-DNT degradation and microbial activity in a slurry reactor, but could not be extended to a second reactor in series where the degradation of a much lower concentration of 2,6-DNT degradation was achieved.

Degradation of polycyclic aromatic hydrocarbons (PAHs) by indigenous mixed and pure cultures isolated from coastal sediments.

The goal of this paper was to quantify and characterize microorganisms (bacteria) in sediment samples contaminated with polycyclic aromatic hydrocarbons (PAHs: fluorene and naphthalene). The isolated organisms were evaluated for their ability to degrade PAHs compounds. The results indicated that the total number of recovered heterotrophic colony forming units was higher than zone forming units produced by the PAHs compounds. There was a relationship between the biomass of the bacteria recovered from the sediment and the degradation of the compounds. This indicated the utilization of the compounds by the bacteria as a carbon source. Two bacterial species were isolated from the contaminated sediments and identified as Pseudomonas sp. and Ochrobactrum sp.

Bone conduction errors at high frequencies: implications for clinical and medico-legal practice.

The magnitude and origin of audiometric air-bone gaps in the range 3 kHz to 8 kHz was investigated in 20 normal subjects. The average gap ranged from a minimum of about 3 dB at 3 kHz to a maximum of about 19 dB at 6 kHz. Approximately 5 dB of the gap at high frequencies is caused by excess air-radiated sound from the bone vibrator. A larger error appears to result from discrepancies between the air and bone conduction standards to which audiometers are calibrated. These errors may influence diagnosis and we recommend that bone conduction tests at frequencies greater than 4 kHz are avoided. These findings have implications for medico-legal work where small air-bone gaps have diagnostic significance.

Microbial fuel cell technology for measurement of microbial respiration of lactate as an example of bioremediation amendment.

Microbial fuel cell (MFC) based sensing was explored to provide for the development of an in situ bioremediation monitoring approach for substrate concentrations and microbial respiration rates. MFC systems were examined in column systems where Shewanella oneidensis MR1 used an external electron acceptor (an electrode) to metabolize lactate (a bioremediation additive) to acetate. Column systems were operated with varying influent lactate concentrations (0-41 mM) and monitored for current generation (0.01-0.39 mA). Biological current generation paralleled bulk phase lactate concentration both in the influent and in the bulk phase at the anode; current values were correlated to lactate concentration at the anode (R(2) = 0.9), The electrical signal provided real-time information for electron donor availability and biological activity. These results have practical implications for efficient and inexpensive real-time monitoring of in situ bioremediation processes where information on substrate concentrations is often difficult to obtain and where information on the rate and nature of metabolic processes is needed.

Microbial fuel cell biosensor for in situ assessment of microbial activity.

Microbial fuel cell (MFC)-based sensing was explored to provide useful information for the development of an approach to in situ monitoring of substrate concentration and microbial respiration rate. The ability of a MFC to provide meaningful information about in situ microbial respiration and analyte concentration was examined in column systems, where Geobacter sulfurreducens used an external electron acceptor (an electrode) to metabolize acetate. Column systems inoculated with G. sulfurreducens were operated with influent media at varying concentrations of acetate and monitored for current generation. Current generation was mirrored by bulk phase acetate concentration, and a correlation (R(2)=0.92) was developed between current values (0-0.30 mA) and acetate concentrations (0-2.3 mM). The MFC-system was also exposed to shock loading (pulses of oxygen), after which electricity production resumed immediately after media flow recommenced, underlining the resilience of the system and allowing for additional sensing capacity. Thus, the electrical signal produced by the MFC-system provided real-time data for electron donor availability and biological activity. These results have practical implications for development of a biosensor for inexpensive real-time monitoring of in situ bioremediation processes, where MFC technology provides information on the rate and nature of biodegradation processes.

C60 in water: nanocrystal formation and microbial response.

Upon contact with water, under a variety of conditions, C60 spontaneously forms a stable aggregate with nanoscale dimensions (d = 25-500 nm), termed here "nano-C60". The color, hydrophobicity, and reactivity of individual C60 are substantially altered in this aggregate form. Herein, we provide conclusive lines of evidence demonstrating that in solution these aggregates are crystalline in order and remain as underivatized C60 throughout the formation/stabilization process that can later be chemically reversed. Particle size can be affected by formation parameters such as rates and the pH of the water addition. Once formed, nano-C60 remains stable in solution at or below ionic strengths of 0.05 I for months. In addition to demonstrating aggregate formation and stability over a wide range of conditions, results suggest that prokaryotic exposure to nano-C60 at relatively low concentrations is inhibitory, indicated by lack of growth (> or = 0.4 ppm) and decreased aerobic respiration rates (4 ppm). This work demonstrates the fact that the environmental fate, distribution, and biological risk associated with this important class of engineered nanomaterials will require a model that addresses not only the properties of bulk C60 but also that of the aggregate form generated in aqueous media.

Erythrocyte micronuclei in winter flounder (Pseudopleuronectes americanus): results of field surveys during 1980-1988 from Virginia to Nova Scotia and in Long Island Sound.

Erythrocyte micronuclei (MN) frequencies of 280 winter flounder (Pseudopleuronectes americanus) from Chesapeake Bay to the southern Scotian Shelf including Long Island Sound were measured. The MN data were combined with data previously reported for 224 flounder and the combined data sets were analyzed. Incidences of MN were elevated sixfold in flounder from the New York Bight Apex as compared to frequencies for fish from the inshore Gulf of Maine and Block Island Sound, and twice those found in Georges Bank and Long Island Sound flounder. Inshore New Jersey fish had higher MN frequencies than those from inshore Gulf Of Maine and Block Island Sound. The occurrence of MN in flounder from inshore Virginia was higher than in flounder from inshore Gulf of Maine and Block Island Sound. The large subset of stations from Long Island Sound indicated higher frequencies of MN in flounder from Hempstead and Shoreham as compared to most other sites in the Sound. There was no significant difference in the frequency of MN between males and females, but males had significantly more MN than sexually immature flounder. Flounder over the entire sampling area had increased levels of MN during the fall months of the year. This is probably influenced by the maternal cycle of gonadal maturation.

Inhibition of coupling factor B activity by cadmium ion, arsenite-2,3-dimercaptopropanol, and phenylarsine oxide, and preferential reactivation by dithiols.

Coupling factor B activity was measured by the stimulation of the ATP-driven NAD+ reduction by succinate or the 32Pi-ATP exchange activity of Factor B-depleted submitochondrial particles. Half-maximal coupling activity was inhibited by 30 microM cadmium, 5 microM phenylarsine oxide, or 0.3 mM arsenite-2,3-dimercaptopropanol. The inhibition was relieved by slight excess of dithiol but not by a 10-fold molar excess of 2-mercaptoethanol. Inhibition of coupling activity by phenylarsine oxide or cadmium was not due to interference in binding of Factor B to depleted particles. Isolated Factor B binds phenylarsine oxide resulting in loss of ability to stimulate depleted submitochondrial particles. The inhibition was largely overcome by dithiol but not by monothiols. The residual coupling activity of depleted submitochondrial particles was highly resistant to cadmium or arsenical. Moreover, binding of arsenical to the depleted particles per se, did not result in inhibition of Factor B-stimulated activity. Furthermore, the addition of phenylarsine oxide to H+-ATPase resulted in loss of Pi-ATP exchange and stimulation of oligomycin-sensitive ATPase activities. Both effects were further potentiated by 2-mercaptoethanol and reversed by dithiols. These effects parallel uncoupling of oxidative phosphorylation in mitochondria by these inhibitors and point to Factor B as the probable component sensitive to these inhibitors.

Aggregate community properties and the strength of species' interactions.

Although humanity depends on the continued, aggregate functioning of natural ecosystems, few studies have explored the impact of community structure on the stability of aggregate community properties. Here we derive the stability of the aggregate property of community biomass as a function of species' competition coefficients for a two-species model. The model predicts that the stability of community biomass is relatively independent of the magnitude of the interaction strengths. Instead, the degree of asymmetry of the interactions appears to be key to community stability.

Biologically-enhanced removal of PCE from NAPL source zones.

The influence of dechlorinating microorganisms on PCE and its reduction products in a residual nonaqueous phase liquid (NAPL) source zone was investigated. Experiments were conducted in upflow columns containing glass beads (diameters 500-750 microns) contaminated with a residual NAPL consisting of tridecane and labeled 14C-PCE. Three columns were inoculated with a mixed PCE-dechlorinating culture, that was fed electron donor (pyruvate) at concentrations of 25, 100, and 250 mM. Pyruvate was fermented in all columns with essentially no methanogenic activity. Comparisons between actively dechlorinating columns and abiotic-PCE columns demonstrated that dechlorination resulted in an increase in total PCE removal, up to a factor of 16 over dissolution. PCE was sequentially reduced to trichloroethene, cis-dichloroethene, and vinyl chloride without ethene formation over the experimental period in the two columns operated at the lower electron donor levels. Total chlorinated ethenes removal for the columns that retained dechlorinating populations was enhanced from 5.0 to 6.5 times over the removal that would have resulted from dissolution alone. The system fed the highest pyruvate levels, interestingly, lost dechlorinating activity early in the experiment.

On the role of factor B and oligomycin on generation and discharge of the proton gradient.

Bovine mitochondrial coupling factor B (FB) stimulates oxidative phosphorylation as well as other energy-linked reactions which are supported by ATP hydrolysis. Extraction of FB from submitochondrial particles results in a decrease in ATP-dependent proton translocation (delta pH) and binding of the voltage-sensitive dye, oxonol VI. Reconstitution of deficient particles with FB restores ATP-dependent proton translocation and oxonol binding but has little effect on oxonol binding supported by respiratory substrates.l In contrast, low levels of oligomycin stimulate oxonol binding supported by either ATP or NADH. In the case of oligomycin, the stimulatory effect is associated with a decrease in the rate of discharge of the proton gradient, but the depletion of FB or its restoration has no detectable effect on the discharge rate. The data indicate that the primary effect of FB is upon the rate of H+ translocation coupled to ATP hydrolysis, while that of low oligomycin is on the H+ permeability of the membrane.

Activation of potassium-dependent H+ efflux from mitochondria by cadmium and phenylarsine oxide.

Addition of Cd2+ or phenylarsine oxide (PhAsO) to respiring rat liver mitochondria results first in acidification of the medium (H+ efflux) followed by disappearance of H+ (discharge of the pH gradient or uncoupling). The first phase of H+ efflux is dependent upon the presence of K+ in the medium, and is not seen in the presence of valinomycin, which is consistent with the conclusion that H+ efflux is linked to membrane potential-dependent uptake of K+. These effects are abolished by low levels of 2,3-dimercaptopropanol but potentiated by excess of 2-mercaptoethanol, showing involvement of a dithiol type of group in the response. Mersalyl produces only the H+ efflux, and subsequent addition of Cd2+ of PhAsO produces collapse of the delta pH.