Decreased levels of metalloproteinase-9 and angiogenic factors in skin lesions of patients with psoriatic arthritis after therapy with anti-TNF-α

Background

Inflammation represents an early and key event in the development of both the cutaneous psoriasis and psoriatic arthritis. Compelling evidences indicate that the production of TNF-α plays a central role in psoriasis by sustaining the inflammatory process in the skin as well as in the joints. Among the multiple effects produced by TNF-α on keratinocytes, the induction of matrix metalloproteinase-9 (MMP-9), a collagenase implicated in joint inflammatory arthritis which acts as an angiogenesis promoting factor, might represent a key mechanism in the pathogenesis of the disease. Aims of the present study were to investigate a) the role of MMP-9 in the development of psoriasis by assessing the presence of MMP-9 in lesional skin and in sera of psoriatic patients; b) the association of MMP-9 with the activity of the disease; c) the relationship between MMP-9 and TNF-α production.

Methods

Eleven psoriatic patients, clinically presenting joint symptoms associated to the cutaneous disease, were included in a therapeutic protocol based on the administration of anti-TNF-α monoclonal antibody (Infliximab). Sera and skin biopsies were collected before treatment and after 6 weeks of therapy. Tissues were kept in short term cultures and production soluble mediators such as TNF-α, MMP-9, MMP-2, VEGF and E-Selectin, which include angiogenic molecules associated to the development of plaque psoriasis, were measured in the culture supernatants by immunoenzymatic assays (ng/ml or pg/ml per mg of tissue). MMP-9 concentrations were also measured in the sera. The cutaneous activity of disease was evaluated by the Psoriasis Area and Severity Index (PASI).

Results

Clinical and laboratory assessment indicated that all but one patients had a significant improvement of the PASI score after three months of therapy. The clinical amelioration was associated to a significant decrease of MMP-9 (P = 0.017), TNF-α (P = 0.005) and E-selectin (P = 0.018) levels, spontaneously released by lesional biopsies before and after therapy. In addition, significant correlations were found between the PASI measurements and TNF-α (r² = 0.33, P = 0.005), MMP-9 (r² = 0.25, P = 0.017), E-selectin (r² = 0.24, P = 0.018) production. MMP-9 levels were significantly correlated with those of TNF-α (r² = 0.30, P = 0.008). A significant decrease of MMP-9 in the sera, associated to the clinical improvement was also found.

Conclusion

Our findings show the existence of a direct relationship between MMP-9 and TNF-α production strongly suggesting that MMP-9 may play a key role in the skin inflammatory process in psoriasis.

     

How does protein supplementation affect the selectivity and performance of Charolais cows on extensively grazed pastures in late autumn?

Management of beef cows grazing extensively grazed semi-natural pastures in temperate regions in late autumn can require supplements to be offered. The effects of supplementation with soya bean meal on the diet selected by Charolais cows and on their subsequent performance were examined for an 8-week period in late autumn in 2 years. Three groups of eight cows were compared: non-supplemented dry cows (D), non-supplemented (L) and supplemented (LS) lactating cows. The amount of soya bean meal supplement offered per cow was 250 g d⁻¹ in year 1 and 800 g d⁻¹ in year 2. Dietary choices were measured by direct observations and herbage intake was estimated in year 2. Supplementation affected neither diet selection (L: 0·42 vs. LS: 0·43 for the proportion of bites on green patches in year 1; 0·24 vs. 0·22 in year 2) nor daily organic matter intake of herbage (L: 15·6 vs. LS: 15·9 kg d⁻¹), which may have resulted from an adequate crude protein concentration of herbage. The higher total dry matter intake by cows offered the supplement reduced losses in live weight (L: −1212 vs. LS: −828 g d⁻¹; P  < 0·01) rather than increased milk production (L: 5·1 vs. LS: 5·0 kg d⁻¹). This may be linked to the low milk yield potential of the Charolais cows. The use of lactating cows rather than dry cows for pasture management in late autumn would increase the utilization of herbage but a reduction in liveweight losses of cows by supplementation is unlikely to be economic.     

Higher crop performance of rice hybrids than of elite inbreds in the tropics: 2. Does sink regulation,rather than sink size,play a major role?

Higher harvest index, widely reported as a main trait supporting major improvements in rice yield potential, also supports the higher performance of hybrids over inbreds. Although higher sink size is generally claimed for being the driver of higher grain filling in hybrid rice, it is relevant to question whether efficient sink regulation, that is timing and magnitude of the successive sink activities over crop growth from early stage, plays a role in supporting higher harvest index and is a key feature ensuring higher performance of hybrid rice. The partitioning coefficient (PC), as the increase in dry matter of one single organ over that of shoot, was calculated over short and successive periods to quantify the dynamics of dry matter partitioning. Four hybrid and four inbred genotypes of similar crop duration were grown under the same cropping management on the IRRI farm during a wet and a dry seasons. While PC to blade and sheath was similar for both plant types in both seasons at the early stage, PC to culm of hybrids was higher than that of inbreds, and PC to blade was lower, in the late vegetative and early reproductive phases. During the late reproductive phase, PC to panicle of hybrids was higher than that of inbreds, and PC to culm was lower whereas culm elongation was similar for both plant types. During grain filling, PC to culm was significantly more negative with hybrids which indicated stronger remobilization with hybrids. Specific culm length before anthesis, as low as 40 cm g⁻¹, accounted for storage ability, and at maturity, as high as 130 cm g⁻¹, for remobilization ability. Sink strength index, as a better indicator of dry matter partitioning efficiency than harvest index, and unfilled grain size, as an indicator of assimilate wastage, were suggested as key indices to account for the better sink regulation in hybrid rice and to improve screening protocols for increasing yield potential and tolerance to lodging.     

How Long can Rogued Potato Plants Left in the Field Be a Source of <Emphasis Type="Italic">Potato Virus Y</Emphasis> for Aphids?

Removal of diseased plants (roguing) is commonly practiced in seed potato production. Diseased plants left to desiccate in fields could possibly serve as sources of Potato virus Y (PVY). PVY acquisition by three aphid species (Myzus persicae, Rhopalosiphum padi, Aphis fabae) was evaluated with leaflets from rogued plants for seven days. Results showed greater PVY acquisition rates in non-colonizing aphids species compared to colonizing ones. The proportion of aphids leaving leaflets increased with time (i.e. days after plants were uprooted) and some aphids were carrying PVY in their stylets on each of the seven days of the experiment, suggesting that aphids were able to probe and acquire PVY even when plants wilted. These results confirmed that diseased plants left in fields can serve as a source of PVY for aphids even after they wilted and emphasises that proper actions must be taken to efficiently remove diseased plants from fields.     

Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial,Antidiabetic, Antifungal,Anti-Inflammatory,Antiprotozoal, Antituberculosis,and Antiviral Activities; Affecting the Immune and Nervous Systems,and other Miscellaneous Mechanisms of Action ?

The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories.     

Indirect changes associated with a selection program for increased seed-yield in wild species of Lesquerella (Brassicaceae): Are we developing a phenotype opposite to the expected ideotype?

Seed-yield stability, frequently associated with drought-tolerance strategies, is one of the main breeding objectives for the development of crops for semi-arid mediterranean-type environments. Since breeding of new industrial crops targeted for arid lands is not appreciably different from that of traditional crops, higher yield is achieved by increased harvest-index, at the cost of losing traits associated with drought-tolerance and reduced seed-yield stability. Using Lesquerella as a model we compared selected and unselected accessions of annual (L. gracilis and L. angustifolia) and perennial (L. pinetorum and L. mendocina) genotypes grown in field experiments in Patagonia, Argentina. Our objective was to assess the effects of breeding for increased seed-yield on traits related to the main characteristics that define the most common ideotype for mediterranean-type environments: early vigor, conservative growth strategy post-anthesis and reserves storage. Our specific question was: Have any of the attributes associated with seed-yield stability been indirectly selected during the domestication process? Our results show that these characteristics were reduced or lost, in selected lines compared to their wild relatives. Early vigor was lower in selected accessions and was associated mainly with reduced relative growth rate and CO₂ assimilation. During the reproductive period the growth strategy was changed by selection towards a non-conservative and more acquisitive resource use strategy. Traits associated with this strategy were linked to higher water use efficiency and growth capacity (higher CO₂ assimilation rate, specific leaf area, and leaf allocation), but also with loss of structural adaptation to low resource environments (i.e. low specific leaf area), an increase in nutrient and water demands, and reduced nutrient use efficiency. Carbohydrates accumulation pre-anthesis was lower in selected accessions of all four species, and also, just in perennials we found lower reserves storage post-anthesis. These changes in the pattern of carbohydrates accumulation could be associated to lower seed-yield stability due to the loss of buffer capacity linked with the use of pre-anthesis reserves for seed filling. On the other hand, in perennial species lower reserves storage after seed harvest could reduce plant longevity and survival. We conclude that indirect changes occurred during the preliminary domestication of both annual and perennial species of Lesquerella used in our experiment. These changes were against those required if these species were to be developed as crops for semi-arid, mediterranean environments and should result in low seed-yield stability.