CQESTR-Simulated Response of Soil Organic Carbon to Management, Yield, and Climate Change in the Northern Great Plains Region.

Traditional dryland crop management includes fallow and intensive tillage, which have reduced soil organic carbon (SOC) over the past century, raising concerns regarding soil health and sustainability. The objectives of this study were: (i) to use CQESTR, a process-based C model, to simulate SOC dynamics from 2006 to 2011 and to predict relative SOC trends in cropping sequences that included barley ( L.), pea ( L.), and fallow under conventional tillage or no-till, and N fertilization rates through 2045; and (ii) to identify best dryland cropping systems to increase SOC and reduce CO emissions under projected climate change in eastern Montana. Cropping sequences were conventional-till barley-fallow (CTB-F), no-till barley-fallow (NTB-F), no-till continuous barley (NTCB), and no-till barley-pea (NTB-P), with 0 and 80 kg N ha applied to barley. Under current crop production, climatic conditions, and averaged N rates, SOC at the 0- to 10-cm depth was predicted to increase by 1.74, 1.79, 2.96, and 4.57 Mg C ha by 2045 for CTB-F, NTB-F, NTB-P, and NTCB, respectively. When projected climate change and the current positive US barley yield trend were accounted for in the simulations, SOC accretion was projected to increase by 0.69 to 0.92 Mg C ha and 0.41 to 0.47 Mg C ha, respectively. According to the model simulations, adoption of NT, elimination of fallow years, and N fertilizer management will likely have the greatest impact on SOC stocks in the top soil as of 2045 in the Northern Great Plains.

Simulated Soil Organic Carbon Changes in Maryland Are Affected by Tillage, Climate Change, and Crop Yield.

The impact of climate change on soil organic C (SOC) stocks in no-till (NT) and conventionally tilled (CT) agricultural systems is poorly understood. The objective of this study was to simulate the impact of projected climate change on SOC to 50-cm soil depth for grain cropping systems in the southern Mid-Atlantic region of the United States. We used SOC and other data from the long-term Farming Systems Project in Beltsville, MD, and CQESTR, a process-based soil C model, to predict the impact of cropping systems and climate (air temperature and precipitation) on SOC for a 40-yr period (2012-2052). Since future crop yields are uncertain, we simulated five scenarios with differing yield levels (crop yields from 1996-2014, and at 10 or 30% greater or lesser than these yields). Without change in climate or crop yields (baseline conditions) CQESTR predicted an increase in SOC of 0.014 and 0.021 Mg ha yr in CT and NT, respectively. Predicted climate change alone resulted in an SOC increase of only 0.002 Mg ha yr in NT and a decrease of 0.017 Mg ha yr in CT. Crop yield declines of 10 and 30% led to SOC decreases between 2 and 8% compared with 2012 levels. Increasing crop yield by 10 and 30% was sufficient to raise SOC 2 and 7%, respectively, above the climate-only scenario under both CT and NT between 2012 and 2052. Results indicate that under these simulated conditions, the negative impact of climate change on SOC levels could be mitigated by crop yield increases.

Simulated Soil Organic Carbon Response to Tillage, Yield, and Climate Change in the Southeastern Coastal Plains.

Intensive tillage, low-residue crops, and a warm, humid climate have contributed to soil organic carbon (SOC) loss in the southeastern Coastal Plains region. Conservation (CnT) tillage and winter cover cropping are current management practices to rebuild SOC; however, there is sparse long-term field data showing how these management practices perform under variable climate conditions. The objectives of this study were to use CQESTR, a process-based C model, to simulate SOC in the top 15 cm of a loamy sand soil (fine-loamy, kaolinitic, thermic Typic Kandiudult) under conventional (CvT) or CnT tillage to elucidate the impact of projected climate change and crop yields on SOC relative to management and recommend the best agriculture management to increase SOC. Conservation tillage was predicted to increase SOC by 0.10 to 0.64 Mg C ha for six of eight crop rotations compared with CvT by 2033. The addition of a winter crop [rye ( L.) or winter wheat ( L.)] to a corn ( L.)-cotton ( L.) or corn-soybean [ (L.) Merr.] rotation increased SOC by 1.47 to 2.55 Mg C ha. A continued increase in crop yields following historical trends could increase SOC by 0.28 Mg C ha, whereas climate change is unlikely to have a significant impact on SOC except in the corn-cotton or corn-soybean rotations where SOC decreased up to 0.15 Mg C ha by 2033. The adoption of CnT and cover crop management with high-residue-producing corn will likely increase SOC accretion in loamy sand soils. Simulation results indicate that soil C saturation may be reached in high-residue rotations, and increasing SOC deeper in the soil profile will be required for long-term SOC accretion beyond 2030.

Simulated Soil Organic Carbon Responses to Crop Rotation, Tillage, and Climate Change in North Dakota.

Understanding how agricultural management and climate change affect soil organic carbon (SOC) stocks is particularly important for dryland agriculture regions that have been losing SOC over time due to fallow and tillage practices, and it can lead to development of agricultural practice(s) that reduce the impact of climate change on crop production. The objectives of this study were: (i) to simulate SOC dynamics in the top 30 cm of soil during a 20-yr (1993-2012) field study using CQESTR, a process-based C model; (ii) to predict the impact of changes in management, crop production, and climate change from 2013 to 2032; and (iii) to identify the best dryland cropping systems to maintain or increase SOC stocks under projected climate change in central North Dakota. Intensifying crop rotations was predicted to have a greater impact on SOC stocks than tillage (minimum tillage [MT], no-till [NT]) during 2013 to 2032, as SOC was highly correlated to biomass input ( = 0.91, = 0.00053). Converting from a MT spring wheat (SW, L.)-fallow rotation to a NT continuous SW rotation increased annualized biomass additions by 2.77 Mg ha (82%) and SOC by 0.22 Mg C ha yr. Under the assumption that crop production will stay at the 1993 to 2012 average, climate change is predicted to have a minor impact on SOC (approximately -6.5%) relative to crop rotation management. The CQESTR model predicted that the addition of another SW or rye ( L.) crop would have a greater effect on SOC stocks (0- to 30-cm depth) than conversion from MT to NT or climate change from 2013 to 2032.

Possible new role for NF-kappaB in the resolution of inflammation.

Inflammation involves the sequential activation of signaling pathways leading to the production of both pro- and anti-inflammatory mediators. Although much attention has focused on pro-inflammatory pathways that initiate inflammation, relatively little is known about the mechanisms that switch off inflammation and resolve the inflammatory response. The transcription factor NF-kappaB is thought to have a central role in the induction of pro-inflammatory gene expression and has attracted interest as a new target for the treatment of inflammatory disease. We show here that NF-kappaB activation in leukocytes recruited during the onset of inflammation is associated with pro-inflammatory gene expression, whereas such activation during the resolution of inflammation is associated with the expression of anti-inflammatory genes and the induction of apoptosis. Inhibition of NF-kappaB during the resolution of inflammation protracts the inflammatory response and prevents apoptosis. This suggests that NF-kappaB has an anti-inflammatory role in vivo involving the regulation of inflammatory resolution.

Inducible cyclooxygenase may have anti-inflammatory properties.

Cyclooxygenase (COX) has two isoforms. Generally, COX 1 is constitutively expressed in most tissues, where it maintains physiological processes; inducible COX 2 is considered a pro-inflammatory enzyme and a chief target for the treatment of inflammatory diseases. Here we present evidence that COX 2 may have anti-inflammatory properties. In carrageenin-induced pleurisy in rats, the predominant cells at 2 hours are polymorphonuclear leucocytes, whereas mononuclear cells dominate from 24 hours until resolution at 48 hours. In this model, COX 2 protein expression peaked initially at 2 hours, associated with maximal prostaglandin E2 synthesis. However, at 48 hours there was a second increase in COX 2 expression, 350% greater than that at 2 hours. Paradoxically, this coincided with inflammatory resolution and was associated with minimal prostaglandin E2 synthesis. In contrast, levels of prostaglandin D2, and 15deoxy delta(12-14)prostaglandin J2 were high at 2 hours, decreased as inflammation increased, but were increased again at 48 hours. The selective COX 2 inhibitor NS-398 and the dual COX 1/COX 2 inhibitor indomethacin inhibited inflammation at 2 hours but significantly exacerbated inflammation at 48 hours. This exacerbation was associated with reduced exudate prostaglandin D2 and 15deoxy delta(12-14)prostaglandin J2 concentrations, and was reversed by replacement of these prostaglandins. Thus, COX 2 may be pro-inflammatory during the early phase of a carrageenin-induced pleurisy, dominated by polymorphonuclear leucocytes, but may aid resolution at the later, mononuclear cell-dominated phase by generating an alternative set of anti-inflammatory prostaglandins.

The inhibition of colon-26 adenocarcinoma development and angiogenesis by topical diclofenac in 2.5% hyaluronan.

Topical diclofenac in 2.5% hyaluronan inhibits basal cell carcinoma, actinic keratosis, and murine colon-26 growth in vivo. colon-26 tumor growth was preceded by angiogenesis and reduced apoptotic and mitotic indices. Diclofenac reduced proliferation and viability in vitro, and stimulated apoptosis. Hyaluronan inhibited proliferation and viability at 1 mg/ml but was inactive below this level. Topical application of diclofenac inhibited tumor prostaglandin synthesis and retarded angiogenesis and tumor growth (ratio of treatment:control, 0.174). The mitotic index remained unaltered in vivo, whereas the apoptotic index and necrosis were increased. Topical vehicle exhibited slight antitumor and antiangiogenesis activity. The substantial quantities of diclofenac delivered locally in hyaluronan may exhibit antitumor activity in similar fashion to those seen in vitro and explain its clinical efficacy.

New insights into the role of COX 2 in inflammation.

Cyclo-oxygenase (COX) is responsible for the synthesis of bioactive prostanoids, the inhibition of which serves as the basis for the mode of action of clinically used nonsteroidal anti-inflammatory drugs. While there were suggestions as early as the 1970s that an inducible isoform of COX exists, it was only in the early 1990s that COX 2 was identified, cloned and sequenced. Not surprisingly, this new isoform was expressed at sites of inflammation and reported to contribute to the inflammatory response. Recently, however, evidence is emerging to suggest that COX 2 also has anti-inflammatory properties. In this review, the two faces of COX 2 are examined, with emphasis on its role in regulating inflammatory resolution, including possible mechanisms of action

Cyclooxygenase enzymes as targets for therapeutic intervention in inflammation.

The synthesis of bioactive prostanoids is controlled, in part, by the action of the cyclooxygenase (COX; prostaglandin H synthase; prostaglandin endoperoxidase) family of enzymes. Inhibition of these enzymes underlies the therapeutic action of the nonsteroidal antiinflammatory drugs (NSAIDs) and also leads to the adverse side effects, such as gastrointestinal ulceration, associated with these drugs. Interest in the therapeutic targeting of this system as a means of controlling inflammation was further expanded by the demonstration in the early 1990s of the existence of a second, inducible, isoform of COX, COX-2. Originally, it was believed that this isoform was expressed at sites of inflammation but not in noninflamed tissue, where a constitutively expressed isoform, COX-1, was thought to be responsible for the physiological production of eicosanoid mediators. This presented the opportunity to develop novel "super aspirins," which could selectively inhibit the inducible isoform, exert potently antiinflammatory effects and, importantly, be largely devoid of the deleterious side effects of conventional NSAIDs. However, it is now being increasingly accepted that COX-2 is also expressed in chronic inflammatory diseases and is seen during the resolution of inflammatory reactions and in areas undergoing wound healing. Inhibition of this isoform in these situations has revealed potential, previously hidden, pitfalls associated with COX-2 inhibition. This article examines the roles of the COX enzymes in inflammation, with emphasis on the emerging role of COX-2 during inflammatory resolution, as well as discussion of some future directions for antiinflammatory therapy that this research has suggested.

Potential adverse effects of cyclooxygenase-2 inhibition: evidence from animal models of inflammation.

Cyclooxygenase (COX; prostaglandin H synthase, prostaglandin endoperoxidase) is the key enzyme in the synthesis of the prostaglandin and thromboxane families of eicosanoid mediators, and is the target for the nonsteroidal anti-inflammatory drugs (NSAIDs). The identification of an inducible COX isoform, COX-2, and the demonstration of its specific expression at sites of inflammation suggested that it may provide a useful therapeutic target for novel anti-inflammatory drugs. Inhibition of an enzyme that is not expressed in most healthy tissues would potentially avoid most of the adverse effects associated with NSAIDs, which target a constitutively expressed isoform, COX-1. The development of novel 'super aspirins' with high selectivity towards the inhibition of COX-2 showed that this hypothesis was well-founded and that high levels of these drugs could be tolerated without these serious adverse effects. The first two of these new generation NSAIDs, celecoxib and rofecoxib, are now in clinical use. More recently, however, concern has been expressed that COX-2 inhibition may in fact have a number of potential, previously hidden, pitfalls. These have arisen from the demonstration that COX-2 induction is not exclusively associated with the onset of an inflammatory reaction, with expression limited to inflammatory sites. In fact, COX-2 is expressed more chronically, and is also seen during the resolution of inflammation and in areas of wound-healing. The application of COX-2-selective inhibitors during these periods has been shown to be deleterious in that resolution of inflammation is delayed, gastric ulcer healing is delayed and, in some patients, ulcers have been shown to progress further to perforation. The suggestion has now been made that, in these situations, COX-2 may help resolve the pathology, perhaps by generating alternative series of prostaglandins such as the cyclopentenone prostaglandins. The finding that these prostaglandins can affect proteins by direct chemical modifications as well as having their own receptor families has rekindled debate on the deleterious and beneficial effects of prostanoids, and the implications of inhibiting the production of these mediators, in the body. Therefore, in this review we discuss the role of COX-2 in inflammation and the potential adverse effects of its inhibition.

Mechanisms of the anti-inflammatory activity of low-dose radiation therapy.

PURPOSE: To investigate the hypothesis that modulation of the function of activated macrophages is one of the mechanisms of the clinically observed anti-inflammatory and analgesic efficacy of low-dose radiotherapy in the treatment of a variety of painful joint diseases with total doses between 1 and 6 Gy. MATERIALS AND METHODS: Metabolic activity, cell proliferation, reproductive integrity, nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by unstimulated or [LPS/gamma-IFN-stimulated macrophages in vitro was investigated at different times after radiation doses ranging from 0.3 Gy to 10 Gy. In vivo, chronic granulomatous air pouches were induced in mice and either sham treated or irradiated with 2 Gy on day 2 or day 6, or with five daily doses of 0.5 Gy. On day 7, the iNOS expression was assessed by Western blot and localized by immuno-histochemistry in cryostat sections. RESULTS: In stimulated macrophages, metabolic activity, proliferation and reproductive integrity were not affected by radiation doses up to 10 Gy since they are apparently irreversible post-mitotic cells. However, a dose-dependent modulation of the NO pathway was observed with significant inhibition by the low radiation doses used in anti-inflammatory radiotherapy but with super-stimulation by the high radiation doses used in cancer therapy. CONCLUSIONS: The empirically based anti-inflammatory radiotherapy of benign diseases appears to act through specific modulation of different pathways of inflammatory reactions such as the nitric oxide pathway in stimulated macrophages.

The chemotactic properties of cartilage glycosaminoglycans for polymorphonuclear neutrophils.

Cartilage breakdown products have been tested for their effects on the locomotion of rat polymorphonuclear neutrophils in vitro. Chondroitin sulphate, keratan sulphate and hyaluronic acid were used in checkerboard migration assays to differentiate chemotaxis from chemokinesis. All test substances showed both chemokinetic and chemotactic activities. The same substances were then injected intradermally to determine their effects on vascular permeability and leukocyte accumulation in vivo. There was no significant effect on vascular permeability 30 minutes after injection as measured by a dye-leakage method. Histological examination of skin sections taken 6 hours after injection showed modest accumulations of polymorphonuclear neutrophils. It is suggested that cartilage breakdown products may account for the persistence of polymorphonuclear neutrophils in some chronic inflammatory joint diseases.

The effects of heparin and cortisone on an experimental model of pannus.

The effects of heparin and cortisone were investigated in a model of experimental pannus-mediated cartilage degradation. Rat femoral head cartilages were implanted bilaterally (sc.) into female mice either non-wrapped or wrapped in cotton. Animals were treated with tap water (p.o.), heparin 1000 Units (p.o.), cortisone 2 mg/kg (s.c) and heparin-cortisone combined. After 14 days, the implants were removed and analysed for exudate volume, granulation-tissue dry weight and cartilage glycosamino-glycan (GAG) content. In the heparin-treated animals there was a significant (p less than 0.001) increase in the granulation-tissue dry weight, whilst combined treatment significantly (p less than 0.001) reduced both exudate volume and cartilage degradation. It is possible that the effects on angiogenesis may indicate novel treatment for the growth of pannus and cartilage breakdown.

A cytochemical study of the adjuvant inflamed air pouch in the rat.

The oxidative biochemistry of the adjuvant-inflamed rat air pouch has been studied using the techniques of quantitative cytochemistry. Highly significant increases in the maximal activities of glucose-6-phosphate dehydrogenase, lactate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase were observed. These changes are similar to those that have been reported by others in both human rheumatoid synovial tissue and the synovial tissue of rabbits with allergic arthritis. It is suggested that modulation of these changes by putative therapeutic agents may form the basis for a readily quantifiable drug screening programme.

The protective effects of cell-free fluid exudate on cartilage degradation in vitro.

In a short-term culture system, polymorphonuclear neutrophils (PMNs) were shown to cause significant loss of glycosaminoglycan (GAG) from cartilage. In addition, a lysate of these cells, and in particular cells stimulated with a phorbol ester, greatly enhanced this loss of GAG. This loss could be partially or completely inhibited by the addition of cell-free fluid exudate to the system. In other long-term culture experiments, IL-1a was shown to enhance fibroblast-induced GAG loss from cartilage. In this system too the breakdown was inhibited by cell-free fluid exudate. Initial characterization of the protective agent or agents shows them to be heat-stable at 56 degrees C and to be non-dialysable. It is proposed that in the chronic inflammatory joint disease, rheumatoid arthritis, the fluid phase of an inflammatory response may have a protective effect against the underlying pathological processes.

Myofibroblasts in cotton-induced granulation tissue and the bovine adrenal capsule: morphological aspects.

Ultrastructural studies of one week old cotton-induced granulation tissue revealed the presence of polymorphonuclear neutrophils (PMN), macrophages and mast cells, whilst the granulation tissue from two week old cotton implants contained fibroblasts, myofibroblasts and abundant collagen fibres. Similarly, the bovine adrenal capsule contained both fibroblasts and myofibroblasts. It is proposed that the bovine adrenal capsule and two week cotton-induced granulation tissue could be utilized as in-vitro models to study the mechanism(s) involved in myofibroblast contraction.

[Comparison of the pharmacologic effect of diacerein and a selective COX-2 inhibitor in the mouse induced-granuloma model]. / Etude pharmacologique comparant l'effet de la diacerhéine et d'un inhibiteur COX-2 sélectif dans le modèle du granulome induit chez la souris.

UNLABELLED: ANIMAL MODEL OF DEGENERATIVE JOIN DISEASE: A mouse model of joint disease with an induced granuloma has demonstrated that diacerein inhibits loss of hydroxyproline and proteoglycans in joint cartilage, an effect not observed with conventional nonsteroidal antiinflammatory drugs (NSAID) or with a specific inhibitor of cyclooxygenase-2 (COX-2). Specific COX-2 inhibitors could thus be beneficially combined with disease modifying osteoarthritis drugs DMOD such as diacerein. ANTIINFLAMMATORY EFFECTS OF COX-2: During the process of inflammation, COX-2 activity appears to occur at two specific time points, with a peak at 2 hours, associated with maximal activity of PGE(2) synthase (proinflammatory prostaglandin) and a second peak after 48 hours, associated with increased levels of PGD(2) and cyclopentenones (anti-inflammatory prostaglandins). THERAPEUTIC IMPLICATIONS: Treatment with NSAID or selective anti-COX-2 agents appears to have a beneficial effect during acute phases of inflammation but their use in long-term regimens appears to have less favorable effects. Use of long-action symptomatic treatments without any apparent effect on COX-2, for example diacerein, could protect against the potentially deleterious effects of COX-2 inhibition.