Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein

Leukotrienes are proinflammatory products of arachidonic acid oxidation by 5-lipoxygenase that have been shown to be involved in respiratory and cardiovascular diseases. The integral membrane protein FLAP is essential for leukotriene biosynthesis. We describe the x-ray crystal structures of human FLAP in complex with two leukotriene biosynthesis inhibitors at 4.0 and 4.2 angstrom resolution, respectively. The structures show that inhibitors bind in membrane-embedded pockets of FLAP, which suggests how these inhibitors prevent arachidonic acid from binding to FLAP and subsequently being transferred to 5-lipoxygenase, thereby preventing leukotriene biosynthesis. This structural information provides a platform for the development of therapeutics for respiratory and cardiovascular diseases.     

Impact of land-use type and harvesting on population structure of a non-timber forest product-providing tree in a semi-arid savanna, West Africa

Non-timber forest products (NTFPs) strongly contribute to livelihood security in the semi-arid tropics. Main factors determining the populations of NTFP-providing species are human activities. This study examined the impact of land-use, combined with rates and patterns of debarking and chopping on a NTFP-providing tree (Anogeissus leiocarpa) in Burkina Faso. We compared stands in a protected area (W National Park) with those of its surrounding communal area (fallows, croplands) in order to (i) obtain an indication on the status of the population, (ii) assess its harvesting tolerance, (iii) estimate the sustainability of present management, and (iv) derive which additional management strategies may foster its conservation. Our results reveal that the stands of A. leiocarpa are in healthy states in fallows and in the park. In croplands, the absence of saplings gives evidence of a declining population. Nearly all individuals of A. leiocarpa were harvested in croplands and fallows, while the number of harvested individuals in the park was negligible. Intensity of debarking and chopping was tree size-specific. The sprouting ability significantly increased with higher chopping intensity. We conclude that despite the land-use impact and the intense harvesting, stands of A. leiocarpa are still well preserved due to the species life history (fast growing and high sprouting) and due to indirect positive influences of human activities by providing better environmental conditions for its recruitment. Thus, the population of A. leiocarpa is not at risk to over-harvesting and land-use even though it is not protected.     

Preliminary investigation of concurrent administration of phenylbutazone and romifidine in healthy horses

ObjectiveTo characterize the cardiorespiratory and electrocardiographic effects of the combined administration of phenylbutazone and romifidine.Study designProspective four-period, four-treatment, blinded, randomized, crossover trial.AnimalsFive, healthy, mixed breed horses.MethodsPrior to treatment administration, a catheter was introduced into the intra-thoracic cranial vena cava via the jugular vein and a subcutaneously located carotid artery was catheterised. All treatments were administered intravenously (IV) and consisted of saline placebo (PLC), phenylbutazone (PBZ, 4.4 mg kg^?1) romifidine (ROM, 80 μg kg^?1) and a combination of phenylbutazone (4.4 mg kg^?1) and romifidine (80 μg kg^?1). There was at least a 1 week washout period between treatments. Heart rate (HR), respiratory rate (f_R), systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures and central venous pressure (CVP) were recorded for baseline (prior to drug administration) and at 5 minute intervals thereafter for 30 minutes. Electrocardiographic abnormalities were recorded. Data were analyzed by anova.ResultsFor the cardiovascular variables there were no statistically significant (p > 0.05) differences between horses treated with ROM and PBZ_ROM. Statistically significant (p < 0.05) differences only occurred between treatments with romifidine (ROM and PBZ_ROM) and without romifidine (PLC and PBZ). Within treatments, for ROM, changes over time were statistically significant (p < 0.05) for HR, SAP, DAP, MAP and CVP. For PBZ_ROM, changes over time were statistically significant (p < 0.05) for CVP. Sino-atrial and atrio-ventricular blocks occurred in horses treated with ROM and PBZ_ROM.Conclusions and clinical relevanceThe combined IV administration of phenylbutazone and romifidine had no statistically significant effect on cardiorespiratory variables. These limited data suggest no evidence why both agents should not be included in a preoperative medication protocol for healthy horses but do not exclude the possibility of interactions occurring in a larger population.     

A quick and efficient screen for resistance to iron toxicity in lowland rice

Iron (Fe) toxicity is a major stress to rice in many lowland environments worldwide. Due to excessive uptake of Fe²⁺ by the roots and its acropetal translocation into the leaves, toxic oxygen radicals may form and damage cell structural components, thus impairing physiological processes. The typical visual symptom is the “bronzing” of the rice leaves, leading to substantial yield losses, particularly when toxicity occurs during early vegetative growth stages. The problem is best addressed through genotype improvement, i.e., tolerant cultivars. However, the time of occurrence and the severity of symptoms and yield responses vary widely among soil types, years, seasons, and genotypes. Cultivars resistant in one system may fail when transferred to another. Better targeting of varietal improvement requires selection tools improving our understanding of the resistance mechanisms and strategies of rice in the presence of excess iron. A phytotron study was conducted to develop a screen for seedling resistance to Fe toxicity based on individual plants subjected to varying levels of Fe (0–3000 mg L^–1 Fe supplied as Fe(II)SO₄), stress duration (1–5 d of exposure), vapor‐pressure deficit (VPD; 1.1 and 1.8 kPa), and seedling age (14 and 28 d). Genotypes were evaluated based on leaf‐bronzing score and tissue Fe concentrations. A clear segregation of the genotypic tolerance spectrum was obtained when scoring 28 d old seedlings after 3 d of exposure to 2000 mg L^–1 Fe in a high‐VPD environment. In most cases, leaf‐bronzing scores were highly correlated with tissue Fe concentration (visual differentiation in includer and excluder types). The combination of these two parameters also identified genotypes tolerating high levels of Fe in the tissue while showing only few leaf symptoms (tolerant includers). The screen allows selecting genotypes with low leaf‐bronzing score as resistant to Fe toxicity, and additional analyses of the tissue Fe concentration of those can identify the general adaptation strategy to be utilized in breeding programs.     

Effect of transpiration on iron uptake and translocation in lowland rice

We evaluated six lowland rice (Oryza sativa L.) genotypes with contrasting responses to increasing Fe²⁺ concentrations under conditions of both low (0.3 kPa) and high (2.4 kPa) vapor pressure deficit. Dry atmospheric conditions generally enhanced transpiration with concomitant increases in Fe uptake and leaf bronzing. Some resistant genotypes were able to limit the water loss by transpiration under higher Fe concentrations thus attenuating negative effects associated with increased Fe²⁺ translocation at high vapor pressure deficit.     

Thiamin deficiency in cats and dogs associated with feeding meat preserved with sulphur dioxide

Thiamin deficiency was diagnosed in cats and dogs being fed fresh minced meat, which contained sulphur dioxide as a preservative and less than 0.5 mg/kg thiamin. Thiamin in the meat and in added dietary ingredients, including a supplementary vitamin mixture, was destroyed by the sulphur dioxide.     

Effects of physiologic and pharmacologic agents on serum prolactin concentrations in the nonpregnant mare

Four studies were conducted to evaluate the effects of several physiologic and pharmacologic agents on serum prolactin concentrations in the nonpregnant mare. An increase in prolactin measured in response to administration of thyrotropin-releasing hormone (TRH; 50 micrograms, iv) was found not to vary (P = .20) in mares in estrus compared with mares in diestrus (5 to 10 d post-ovulation). Administration in the dopamine receptor blocker, metoclopramide (25 or 100 mg, im), rapidly increased serum prolactin, and the response was dependent on dose administered (total prolactin measured for 420 min was 3,362.7 +/- 182.1 ng for 25 mg, and 4,485.7 +/- 212.6 ng for 100 mg administered im; P less than .05), but not on route of injection (3,026.3 +/- 492.3 ng prolactin with 25 mg, iv; P less than .05). Similarly, sulpiride, a D-2 dopamine receptor blocker, induced an increase in serum prolactin, which appeared to be maximal at a dose of 25 mg (6,556.3 +/- 636.9 ng prolactin/420 min compared with 6,594.5 +/- 169.3 ng prolactin/420 min with 100 mg sulpiride; P less than .10). Finally, bromocriptine, a dopamine agonist, decreased serum prolactin compared with vehicle-injected controls, but the inhibitory effect was found only when basal levels of serum prolactin were highest (in May). These data suggest that mechanisms controlling prolactin secretion in the mare are similar to those described in other mammalian species, and that the seasonal decline in serum prolactin is not the result of increased sensitivity to the proposed prolactin-inhibiting factor, dopamine.