Reversible reduction of oxygen to peroxide facilitated by molecular recognition

Generation of soluble sources of peroxide dianion (O(2)(2-)) is a challenge in dioxygen chemistry. The oxidizing nature of this anion renders its stabilization in organic media difficult. This Report describes the chemically reversible reduction of oxygen (O(2)) to cryptand-encapsulated O(2)(2-). The dianion is stabilized by strong hydrogen bonds to N-H groups from the hexacarboxamide cryptand. Analogous stabilization of peroxide by hydrogen bonding has been invoked recently in crystalline saccharide and protein systems. The present peroxide adducts are stable at room temperature in dimethyl sulfoxide (DMSO) and N,N'-dimethylformamide (DMF). These adducts can be obtained in gram quantities from the cryptand-driven disproportionation reaction of potassium superoxide (KO(2)) at room temperature.     

A Novel Approach to the Treatment and Prevention of Laminitis: Botulinum Toxin Type A for the Treatment of Laminitis

Laminitis is an inflammation of the lamina of hoofed animals. According to the United States Department of Agriculture (USDA), laminitis impacts approximately 2% of the horse population each year. Because of the severity of the inflammation and chronic pain, it is frequently necessary to euthanize these horses. Surviving horses may be left useless, with resultant economic and social impact on the industry. Current interventions for laminitis are based on supportive care and alteration of biomechanical forces on the digit. The transition from laminitis to laminar failure (founder) is believed to be caused by the “weight of the horse and the forces of locomotion driving the bone down into the hoof capsule.” We hypothesize that an important factor is the torsional forces placed on the distal phalanx (coffin bone) by the deep digital flexor muscle and tendon. The paralyzing effect of botulinum toxin will result in a decrease of these torsional forces and therefore will aid in the prevention or treatment of the sequelae of laminitis. Seven horses with varying degrees of laminitis were evaluated. Each underwent pretreatment and posttreatment radiographs as well as pretreatment and posttreatment Obel grading. Each horse received botulinum toxin type A injected into the belly of the deep digital flexor muscle. In all cases there was radiographic stabilization of pedal displacement from the dorsal hoof wall. Obel scores showed improvement of 1 to 2 grades during the time monitored.     

Effect of hypocalcaemia on blood flow distribution in sheep

Cardiac output, the proportion of blood passing through arteriovenous shunts and blood flow distribution to various organs were measured and compared in five normocalcaemic and five hypocalcaemic sheep using radioactive microspheres. Hypocalcaemia was induced by infusing sodium EDTA solution intravenously for two hours. There was evidence that microspheres were leached from liver, muscle, adrenal and thyroid tissues during the induction of hypocalcaemia. Hypocalcaemia reduced blood flow rates by more than 58 per cent in all tissues examined except kidney (48 per cent), heart (53 per cent), lung (10 per cent) and bladder (47 per cent) and reduced cardiac output from 3.70 +/- 0.19 (mean +/- SE) litres min-1 to 2.39 +/- 0.14 litres min-1. Approximately 2.2 per cent of cardiac output passed through arteriovenous shunts. This percentage was unaffected by hypocalcaemia.     

Metastatic immune infiltrates correlate with those of the primary tumour in canine osteosarcoma

Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumour to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We, therefore, collected 21 matched pairs of primary tumours and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T‐lymphocyte (CD3), FOXP3+ cell, B‐lymphocyte (Pax‐5), and CD204+ macrophage infiltration. We found that T‐lymphocytes and FOXP3+ infiltrates in primary tumours positively correlated with that of metastatic lesions (ρ = 0.512, P = 0.038 and ρ = 0.698, P = 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ = 0.404, P = 0.087). We also observed T‐ and B‐lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumour (P = 0.018, P = 0.018, P = 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumour and metastasis lesions were compared without pairing (P = 0.036). Together, these findings suggest that the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumour immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We, therefore, provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti‐tumour activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumours.     

COMPARISON OF UPPER GASTROINTESTINAL RADIOGRAPHIC FINDINGS TO HISTOPATHOLOGIC OBSERVATIONS: A RETROSPECTIVE STUDY OF 41 DOGS AND CATS WITH SUSPECTED SMALL BOWEL INFILTRATIVE DISEASE (1985 to 1990)

It was the intent of this study to define which, if any, radiographic observations corresponded with specific causes of diffuse infiltrative small bowel disease and if radiographic findings could differentiate inflammatory disease from neoplastic disease and either of them from normal. Bowel spasticity, luminal narrowing, and thumbprinting tend to indicate the presence of tumor more often than inflammatory disease. Increased bowel gas in cats and barium adhesion in dogs and cats suggest that a component of enteritis is present. Decreased bowel gas in dogs is more often associated with obstructive disease, but is not helpful in differentiating diffuse inflammatory disease from diffuse neoplastic disease. While several observations that can foster differentiation of neoplastic from inflammatory disease were found, this study also indicated that the UGI lacks a high degree of predictive value other than to indicate the presence of infiltrative small bowel disease.     

An investigation of Leishmania spp. in Didelphis spp. from urban and peri-urban areas in Bauru (São Paulo, Brazil)

Blood and bone marrow samples were taken from 112 Didelphis spp., collected between March 2005 and February 2006, from urban and peri-urban areas of Bauru, São Paulo State, Brazil, to evaluate the hypothesis that these animals might constitute a reservoir of Leishmania spp. Anti-Leishmania ssp. antibodies were screened in the serum samples using an enzyme-linked immuno-sorbent assay (ELISA) and the polymerase chain reaction (PCR). PCR was performed on fragments of DNA samples from Leishmania spp. using primers 13A and 13B, and showed a positive outcome in 91.6% of the 112 samples tested. Of the 107 samples analyzed by ELISA, 71% were positive. Evidence of epidemiological risk factors such as a circulating parasite and freely moving vectors suggests that Didelphis spp. may participate in the transmission cycle of Leishmania spp. in Bauru.     

The pelagic habitat analysis module for ecosystem‐based fisheries science and management

We have developed a set of tools that operate within an aquatic geographic information system to improve the accessibility, and usability of remote‐sensed satellite and computer‐modeled oceanographic data for marine science and ecosystem‐based management. The tools form the Pelagic Habitat Analysis Module (PHAM), which can be applied as a modeling platform, an investigative aid in scientific research, or utilized as a decision support system for marine ecological management. Applications include fisheries, marine biology, physical and biological oceanography, and marine spatial management. The GIS provides a home for diverse data types and automated tools for downloading remote sensed and global circulation model data. Within the GIS environment, PHAM provides a framework for seamless interactive four‐dimensional visualization, for matching between disparate data types, for flexible statistic or mechanistic model development, and for dynamic application of user developed models for habitat, density, and probability predictions. Here we describe PHAM in the context of ecosystem‐based fisheries management, and present results from case study projects which guided development. In the first, an analysis of the purse seine fishery for tropical tuna in the eastern Pacific Ocean revealed oceanographic drivers of the catch distribution and the influence of climate‐driven circulation patterns on the location of fishing grounds. To support management of the Common Thresher Shark (Alopias vulpinus) in the California Current Ecosystem, a simple empirical habitat utilization model was developed and used to dynamically predict the seasonal range expansion of common thresher shark based on oceanographic conditions.     

AGE AND DIET EFFECTS ON RELATIVE RENAL ECHOGENICITY IN GERIATRIC BITCHES

Under controlled, but varied dietary conditions 35 geriatric, uninephrectomized, spayed Beagle bitches (dogs) observed for 4 years, renal cortical and renal medullary echogenicity was measured relative to hepatic and splenic echogenicity. Regardless of the diet fed, 60-75% of these aged dogs had renal cortical echogenicity less than that of either the liver or spleen across time; 25-35% of these dogs had renal cortical echogenicity equal to that of the liver, but less than that of the spleen across time. Less than 3% of these dogs had renal cortical echogenicity greater than that of the liver, but less than that of the spleen. Only 1 (one) of these dogs had renal cortical echogenicity equal to that of the spleen and that occurred at only one of the 14 chronologic assessments. Therefore, in either mature or aged dogs imaged with 4.0 to 5.0 MHz equipment, the renal cortical echogenicity should be considered normal if it is less than or equal to that of the liver and less than that of the spleen. In 29 dogs imaged with the 4.0/5.0 MHz equipment and 6 dogs imaged with 7.5 MHz equipment, there was no significant diet or individual dog effect. The 7.5 MHz (6 dog) group had significantly higher average cortical echogenicity scores than the 4.0/5.0 MHz (29 dog) group. However, the occurrence of renal cortical echogenicity greater than liver echogenicity was seen in only 5 of 83 samples (approximately 6.0%) made on 6 dogs imaged with 7.5 MHz equipment and only 1 of 375 samples (approximately 0.27%) made on 29 dogs with 4.0/5.0 MHz equipment. With the exception of one occurrence, all dogs had renal medullary echogenicity less than that of the liver or spleen regardless of imaging equipment frequency. The renal medulla was always hypoechoic compared to the cortex.     

Cyanobacteria Secondary Metabolites as Biotechnological Ingredients in Natural Anti-Aging Cosmetics: Potential to Overcome Hyperpigmentation,Loss of Skin Density and UV Radiation-Deleterious Effects

The loss of density and elasticity, the appearance of wrinkles and hyperpigmentation are among the first noticeable signs of skin aging. Beyond UV radiation and oxidative stress, matrix metalloproteinases (MMPs) assume a preponderant role in the process, since their deregulation results in the degradation of most extracellular matrix components. In this survey, four cyanobacteria strains were explored for their capacity to produce secondary metabolites with biotechnological potential for use in anti-aging formulations. Leptolyngbya boryana LEGE 15486 and Cephalothrix lacustris LEGE 15493 from freshwater ecosystems, and Leptolyngbya cf. ectocarpi LEGE 11479 and Nodosilinea nodulosa LEGE 06104 from marine habitats were sequentially extracted with acetone and water, and extracts were analyzed for their toxicity in cell lines with key roles in the skin context (HaCAT, 3T3L1, and hCMEC). The non-toxic extracts were chemically characterized in terms of proteins, carotenoids, phenols, and chlorophyll a, and their anti-aging potential was explored through their ability to scavenge the physiological free radical superoxide anion radical (O₂^•−), to reduce the activity of the MMPs elastase and hyaluronidase, to inhibit tyrosinase and thus avoid melanin production, and to block UV-B radiation (sun protection factor, SPF). Leptolyngbya species stood out for anti-aging purposes: L. boryana LEGE 15486 presented a remarkable SPF of 19 (at 200 µg/mL), being among the best species regarding O₂^•− scavenging, (IC₅₀ = 99.50 µg/mL) and also being able to inhibit tyrosinase (IC₂₅ = 784 µg/mL), proving to be promising against UV-induced skin-aging; L. ectocarpi LEGE 11479 was more efficient in inhibiting MMPs (hyaluronidase, IC₅₀ = 863 µg/mL; elastase, IC₅₀ = 391 µg/mL), thus being the choice to retard dermal density loss. Principal component analysis (PCA) of the data allowed the grouping of extracts into three groups, according to their chemical composition; the correlation of carotenoids and chlorophyll a with MMPs activity (p < 0.01), O₂^•− scavenging with phenolic compounds (p < 0.01), and phycocyanin and allophycocyanin with SPF, pointing to these compounds in particular as responsible for UV-B blockage. This original survey explores, for the first time, the biotechnological potential of these cyanobacteria strains in the field of skin aging, demonstrating the promising, innovative, and multifactorial nature of these microorganisms.     

Comparison of pharmacokinetics of danofloxacin and enrofloxacin in calves challenged with Mannheimia haemolytica

OBJECTIVE: To compare concentrations of danofloxacin, enrofloxacin, and ciprofloxacin in plasma and respiratory tissues of calves treated after challenge with Mannheimia haemolytica. ANIMALS: 75 calves. PROCEDURE: 24 hours after challenge with M. haemolytica, 72 calves with clinical signs of respiratory tract disease were randomly assigned to 1 of 12 equal treatment groups.Three nonchallenged, nontreated calves formed a control group. Challenged calves were treated with danofloxacin (6 and 8 mg/kg, SC) and enrofloxacin (8 mg/kg, SC) once. At 1, 2, 6, and 12 hours after treatment, 6 calves from each treatment group were euthanatized. Antimicrobial drug concentrations were assayed in various specimens. Peak plasma concentration (Cmax)-to-minimum inhibitory concentration (MIC; Cmax-to-MIC) ratios and the area under the concentration versus time curve over a 12-hour period-to-MIC ratios (AUC(12h)-to-MIC) were calculat-ed. RESULTS: Danofloxacin and enrofloxacin had MICs of 0.03 microg/mL for the M. haemolytica challenge isolate. Danofloxacin administered at doses of 6 and 8 mg/kg resulted in numerically higher geometric mean concentrations of danofloxacin in plasma and all respiratory tissues than geometric mean concentrations of enrofloxacin after treatment with enrofloxacin. Geometric mean concentrations of enrofloxacin were numerically higher than geometric mean concentrations of ciprofloxacin metabolite in plasma and almost all respiratory tissues. Danofloxacin and enrofloxacin achieved Cmax-to-MIC ratios >10 and AUC(12h)-to-MIC ratios >125 hours. CONCLUSIONS AND CLINICAL RELEVANCE: When used to treat pneumonic pasteurellosis in calves, danofloxacin and enrofloxacin can be expected to deliver concentration-dependent bactericidal activity against M. haemolytica, the bacteria most commonly associated with bovine respiratory tract disease.