Dissolved organic carbon diminishes manganese oxide-driven oxidation of chromium.

Oxidation of chromium (Cr)-bearing minerals by manganese (Mn) oxides is viewed as the dominant mechanism controlling geogenic production of Cr(VI) and its contamination of groundwater. This process may be modulated by other chemical constituents found in the natural environment, but such confounding factors have not been quantified. Here, we evaluated the mechanism of Cr(III) oxidation by mixed-valence Mn oxide in the presence of citric and gallic acids, two natural organic matter (NOM) constituents commonly found in the soil environment. Incubation experiments showed that each organic acid enhanced solubilization of Cr(III) and Mn over controls without organic addition but increasing organic acid concentration decreased production of Cr(VI), with approximately 8.5 times less Cr(VI) produced in the citric acid than gallic acid experiments. X-ray absorption spectroscopy showed that negligible Cr(VI) was present in solid-phase reaction products, regardless of treatment. Geochemical modeling revealed that in the citric acid experiments, unprotonated Cr(III)-citrate was the dominant organo-metallic complex in solution, while (CrOH)2+ distribution positively correlated with concentrations of Cr(VI) produced. Collectively, these results illustrate how NOM can modify expected chemical pathways driving Cr cycling, and such mechanistic information should be better integrated into models predicting Cr redox dynamics and availability in the environment.

Are the fabellae bisected by the femoral cortices in a true craniocaudal pelvic limb radiograph?

OBJECTIVES: To assess whether the bisection of the fabellae by their respective femoral cortices is a useful criterion for assessing positioning of craniocaudal pelvic limb radiographs, and whether this is consistent in limbs affected or unaffected by medial patella luxation. METHODS: Computed tomography multi-planar reconstructions were used to determine the relative positions of the fabellae with respect to the femoral cortices. RESULTS: Only 36% of fabellae overall were bisected by the femoral cortex. There was no significant difference between limbs affected or unaffected by medial patella luxation. CLINICAL SIGNIFICANCE: The accurate measurement of femoral varus angle is important in pre-surgical planning of distal femoral ostectomy. Radiography is normally used to obtain the femoral varus angle, and femoral rotational malpositioning will induce errors in the femoral varus angle measured. Bisection of the fabellae by the femoral cortices is commonly cited as a criterion by which to assess whether a radiographic projection is truly craniocaudal, yet this study has shown this not to be valid.

Avascular necrosis of the canine radial carpal bone: a condition analogous to Preiser's disease?

An eight-year-old male neutered Staffordshire bull terrier was presented for investigation of right forelimb lameness of 14 months' duration. Radiography showed mottled osteolysis of the right radial carpal bone. Histopathology of the bone demonstrated replacement of healthy bone with granulation tissue suggestive of ischaemic necrosis. Lameness resolved following pancarpal arthrodesis. In humans, Preiser's disease is a condition in which idiopathic ischaemic necrosis of the scaphoid bone, the equivalent of the canine radial carpal bone, occurs. This disease may be analogous to the presentation seen in this case. To the authors' knowledge, this is the first report of such a condition in a dog.

Electron hydration and ion-electron pairs in water clusters containing trivalent metal ions.

The hydrated electron is one of the most fundamental nucleophiles in aqueous solution, yet it is a transient species in liquid water, making it challenging to study. The solvation thermodynamics of the electron are important for determining the band structure and properties of water and aqueous solutions. However, a wide range of values for the electron solvation enthalpy (-1.0 to -1.8 eV) has been obtained from previous methods, primarily because of the large uncertainty as to the value for the absolute proton solvation enthalpy. In the gas phase, electron interactions with water can be investigated in stable water clusters that contain an excess electron, or an electron and a solvent-separated monovalent or divalent metal ion. Here, we report the generation of stable water clusters that contain an excess electron and a solvent-separated trivalent metal ion that are formed upon electron capture by hydrated trivalent lanthanide clusters. From the number of water molecules lost upon electron capture, adiabatic recombination energies are obtained for La(H(2)O)(n)(3+) (n = 42-160). The trend in recombination energies as a function of hydration extent is consistent with a structural transition from a surface-located excess electron at smaller sizes (n or= approximately 60). The recombination enthalpies for n > 60 are extrapolated as a function of the geometrical dependence on cluster size to infinite size to obtain the bulk hydration enthalpy of the electron (-1.3 eV). This extrapolation method has the advantages that it does not require estimates of the absolute proton or hydrogen hydration enthalpies.

The relative frequency in which empiric dosages of radioiodine would potentially overtreat or undertreat patients who have metastatic well-differentiated thyroid cancer.

The dosage of (131)I for the treatment of metastatic well-differentiated thyroid cancer is typically selected empirically. Benua and Leeper implemented a method to estimate the maximum dosages of (131)I that could be administered to a patient so as not to exceed a maximum tolerated radiation absorbed dose (MTD), which was defined as 200 rads (cGy) to the blood. The objective of this study was to determine the frequency of (131)I treatments in which the patient (1) would have exceeded the MTD (i.e., overtreatment) or (2) would have been able to receive higher dosages of (131)I thereby delivering a potentially higher radiation absorbed dose to their metastases (i.e., undertreatment) had the patient been administered various assumed empiric dosages of (131)I. The dosimetrically-determined maximum tolerated radioactivities (MTA) to deliver 200 rads to the blood (MTD) were tabulated at our facility. Data were then grouped to determine the percentage of patients who would have received less than or more than the MTD for various assumed empiric dosages of (131)I. A total of 127 dosimetries were performed. For assumed empiric dosages of (131)I (100 mCi, 150 mCi, 200 mCi, 250 mCi, and 300 mCi), the percentage of treatments for which patients would have exceeded the MTD were less than 1%, 5%, 11%, 17%, and 22%, respectively, and could have received a higher dosage of (131)I were more than 99%, 95%, 89%, 83%, and 78%, respectively. A significant number of patients receiving various empiric dosages of (131)I may exceed 200 rads (cGy) to the blood (potential overtreating). Likewise, the majority of patients may be able to receive much higher dosages of (131)I relative to empiric dosages thereby delivering potentially higher radiation absorbed doses to the metastases without exceeding 200 rads (cGy) to the blood (potential undertreating).

Systemic efficacy of nodulisporamides against fleas on dogs.

Nodulisporic acid A (NSA) has been shown previously to be safe in dogs and to deliver >90% flea control for 4 days following a single oral administration. Three newly prepared nodulisporamide derivatives were subsequently identified from an artificial membrane flea feeding system as exhibiting potency substantially greater than NSA. To determine if they have superior in vivo activity, these 3 nodulisporamides, as well as NSA, were evaluated in dogs at 15 mg/kg/os. Parasite challenges were made by placing 100 live Ctenocephalides felis fleas onto the dorsum of dogs every 48 hr and examining efficacy at each of those intervals over a 22-day period. Results showed that NSA produced >90% efficacy at day 2 and 81% efficacy at day 4, and its residual flea killing fell to approximately 50% by day 6 posttreatment. All dogs treated with the 3 new experimental nodulisporamides were 100% protected from flea challenges to day 8 posttreatment, and 2 of the compounds continued to produce >90% residual activity to 2 wk posttreatment. Pharmacokinetic analysis showed that plasma profiles and half-lives of NSA and these 3 new compounds correlated closely with flea efficacy. These results demonstrate that specific substitutions to the pharmacophore of NSA can substantially increase the duration of activity against fleas.

Synthesis of nodulisporic acid 2' '-oxazoles and 2' '-thiazoles.

[reaction--see text] The semisynthetic conversion of nodulisporic acid A (1) into a set of three heterocyclic side chain derivatives provided compounds, highlighted by 6, with an improved spectrum of ectoparasiticidal activity and pharmacokinetic profile relative to the natural product.

Systemic activity of the avermectins against the cat flea (Siphonaptera: Pulicidae).

Ivermectin has potent systemic activity against numerous species of nematodes and arthropods, but there are some important species in these two groups, such as the cat flea, Ctenocephalides felis (Bouché), that appear to be refractory to it. In an effort to determine if the lack of systemic activity against C. felis is specific to ivermectin, or if it is a class-wide phenomenon, 20 avermectin derivatives were tested in an artificial membrane flea feeding system at concentrations of 20, 10, and 1 microg/ml. Results showed that ivermectin had LC90 and LC50 values against fleas of 19.1 and 9.9 microg/ml, respectively. Only four of the other 19 compounds evaluated possessed both LC90 and LC50 values more potent than ivermectin and even then the advantage was modest. Among those four compounds was a two-fold increase in potency relative to ivermectin when the LC90 values were considered (range, 9.2-10.3 microg/ml) and a two- to eight-fold increase when the LC50 values were examined (range, 1.23-5.26 microg/ml). Neither the possession nor the number of oleandrosyl sugars on the macrocyclic backbone were relevant for additional flea activity because among these four compounds were two disaccharides, a monosaccharide and an aglycone. Also, bond disposition between C-22 and 23 did not contribute to increase in activity because these molecules comprise members with either single or double bonds. One of these avermectin analogs was scaled-up and tested subcutaneously in a dog at >100 times the commercial ivermectin dosage and zero efficacy was observed against the flea. We conclude that even the best in vitro avermectin does not have the in vivo potential to become a commercial oral or subcutaneous flea treatment for companion animals.

Systemic efficacy of nodulisporic acid against fleas on dogs.

Nodulisporic acid A (NSA) is a novel natural product from a new structural class that was shown previously to have insecticidal activity against blowfly larvae. To determine if there was useful systemic efficacy against fleas (Ctenocephalides felis). NSA was evaluated in an artificial membrane flea feeding device and in dogs. In the artificial membrane flea feeding device, adult C. felis were allowed to feed on bovine blood containing various concentrations of NSA through a Parafilm membrane. NSA killed the fleas with a 50% lethal concentration of 0.68 microg/ml and was approximately 10-fold more potent than the systemic insecticide ivermectin. In the initial probe dog test, a single beagle was challenged with 100 C. felis before oral dosing with 15 mg/kg of NSA. Flea counts conducted at 72 hr postdosing showed an 88% reduction relative to control. Re-challenge of the same dog at 5 days postdosing showed 50% reduction of fleas at day 7, demonstrating some residual flea activity. In a confirmatory study, 8 dogs were challenged with 100 fleas just before oral dosing with 15 mg/kg of NSA (4 dogs) or vehicle (4 dogs). There was 99% reduction of fleas at 48 hr postdosing in the NSA-treated dogs relative to control. Additional challenges with 100 fleas were performed on these 8 dogs at 48-hr intervals to determine the duration of efficacy, and there was 97, 51, and 0% reduction of fleas relative to control on days 4, 6, and 8, respectively. No adverse effects were observed in the dogs in these studies. These data show that NSA has potent oral activity in the dog for the control of fleas, while lacking overt mammalian toxicity.

Chemical modification of nodulisporic acid A: preliminary structure-activity relationships.

Medicinal chemistry efforts were initiated to identify the key constituents of the nodulisporic acid A (1) pharmacophore that are integral to its potent insecticidal activity. New semisynthetic derivatives delineated 1 into 'permissive' and 'nonpermissive' regions and led to the discovery of new nodulisporamides with significantly improved flea efficacy.

Development of an assay for the screening of compounds against larvae of the cat flea (Siphonaptera: Pulicidae).

Larvae of the cat flea, Ctenocephalides felis (Bouché), are the target of numerous growth regulators. This study explores the development of an assay that tests the susceptibility of cat flea larvae to a wide range of compounds. Different rearing media and containment units were tested that would facilitate optimization. Larvae of various ages were compared, and 7-d-old larvae were found to be optimal because they were the most uniform in size and age and exhibited a need to feed. The assay could be used to distinguish insecticides from growth inhibitors. The insecticides chlorpyrifos and carbaryl caused 100% larval mortality in 24 h at 10 ppm, and cythioate and fipronil killed the larvae at concentrations of > or = 100 ppm within 24 h. The insect growth regulators methoprene and pyriproxifen caused molt delay at concentrations of 100 ppm and bioallethrin delayed molt at 1,000 ppm. This assay can be used to identify compounds that are specific to cat flea larvae that may be useful in the control of cat flea infestations.

Reproductive strategies of the cat flea (Siphonaptera:Pulicidae): parthenogenesis and autogeny?

The objective of this study was to determine if there is evidence of parthenogenesis or autogenous reproduction in the cat flea, Ctenocephalides felis (Bouché). To examine parthenogenesis, 400 newly eclosed virgin female fleas were collected from a laboratory colony and 100 were placed into each of 4 feeding cages and fed bovine blood through a Parafilm membrane. Three of the feeding cages were monitored for egg production for 7 d and each group of 100 virgin female fleas produced an average 1,119 eggs per cage, but none was viable. Fifty male fleas were added to those 3 feeding cages on day 7, and within 24 h the female fleas began ovipositing fertile eggs and nearly quadrupled their egg output. The other cage in which no males were introduced served as a control and did not produce a single viable egg in the 14-d experimental period. A similar experiment examined the continuance of virgin females to lay nonviable eggs and it was found that they continued to lay nonviable eggs for at least 58 d. Egg production was also studied in unfed fleas and it was found that unfed fleas did not produce eggs. These results suggest that neither parthenogenetic reproduction nor autogeny are exhibited by the cat flea.

Regulation of N-formyl-methionyl-leucyl-phenylalanine receptor recycling by surface membrane neutral endopeptidase-mediated degradation of ligand.

Neutrophil responses to alpha-N-formyl-L-Met-L-Leu-L-Phe (fMLF) are modulated by inhibitors of surface membrane neutral endopeptidase (NEP), such as phosphoramidon (PPAD). Because receptor recycling is presumably required for a sustained cellular response, the effect of PPAD on receptor reexpression was examined. After down-regulation of surface fMLF receptors by fMLF, PPAD blocked the normal reexpression of surface receptors in a manner that was related to the time of prior exposure to fMLF. Internalized fML[3H]F was hydrolyzed by NEP at a rate comparable to the rate of receptor reexpression at the cell surface, suggesting that ligand hydrolysis is rate limiting. To test this hypothesis, cells were incubated with fluorescein-labeled formyl-Met-Leu-Phe-Nle-Tyr-Lys at 15 degrees C. After binding was complete, but before internalization of receptor-ligand complexes, high-affinity antifluorescein antibody F(ab')2 fragments were added and the cells incubated at 37 degrees C for 60 min in the presence of PPAD. Under these conditions, the inhibitory effects of PPAD were largely reversed and nonimmune F(ab')2 fragments were without effect.

A cluster of tuberculosis among crack house contacts in San Mateo County, California.

In March 1992, a cluster of 89 persons with tuberculosis infection was identified in San Mateo County, California. Thirteen persons (15%), including 11 children, were diagnosed with active pulmonary tuberculosis. All contacts were African Americans who resided in or visited one of two houses used for crack cocaine smoking or dealing. The patient with the index case, a male infected with human immunodeficiency virus, contributed to the transmission of tuberculosis as a transient resident of several dwellings. Public health authorities applied unique intervention methods to control the outbreak, including the use of a mobile health van. Further innovative strategies will be necessary to meet the challenge of this reemerging disease.