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.

     

Polymorphism of the PE domain of PE/PE_PGRS sequences in clinical isolates of Mycobacterium bovis in Mexico

Polymorphism of the PE domain of PE/PE_PGRS sequences was studied in Mycobacterium bovis isolates from different Mexican states. Samples were analyzed by spolygotyping and RFLP using IS6110 and a 235-bp fragment of the PE domain of PE/PE_PGRS as probes. With the PE probe, three different genotypes were observed, one being predominant in all states. These results confirm the high conservation of the PE domain and suggests a potential role for PE sequence as a stable genetic marker for bovine tuberculosis.     

Wnt gradient formation requires retromer function in Wnt-producing cells

Wnt proteins function as morphogens that can form long-range concentration gradients to pattern developing tissues. Here, we show that the retromer, a multiprotein complex involved in intracellular protein trafficking, is required for long-range signaling of the Caenorhabditis elegans Wnt ortholog EGL-20. The retromer functions in EGL-20-producing cells to allow the formation of an EGL-20 gradient along the anteroposterior axis. This function is evolutionarily conserved, because Wnt target gene expression is also impaired in the absence of the retromer complex in vertebrates. These results demonstrate that the ability of Wnt to regulate long-range patterning events is dependent on a critical and conserved function of the retromer complex within Wnt-producing cells.     

Antioxidant composition in cherry and high-pigment tomato cultivars

Fourteen cultivars of cherry tomatoes and four cultivars of high-pigment tomato hybrids were cultivated in southern Italy, and the red-ripe fruits were analyzed for their content in different classes of antioxidants and for their antioxidant activity. Among the different cultivars, significant differences were found between lycopene, beta-carotene, alpha-tocopherol, vitamin C (ascorbic acid and dehydroascorbic acid), and total phenolic and flavonoid contents. LS203 and Corbus appear to be the cultivars with the highest content of lipophilic and hydrophilic antioxidants among cherry tomatoes, respectively. All cultivars of high-pigment tomato hybrids showed an expected exceptionally high lycopene content. Among them, the highest content of lipophilic and hydrophilic antioxidants was found in cv. HLY 13. Hydrophilic and lipophilic antioxidant activities were both significantly influenced by genotype. Such results highlight an existing unexploited variability in tomato germplasm and stress the need to evaluate the biodiversity and to support conventional breeding programs to improve tomato nutritional value.     

Chemometrical characterization of four italian rice varieties based on genetic and chemical analyses

This paper describes a method for achieving qualitative identification of four rice varieties from two different Italian regions. To estimate the presence of genetic diversity among the four rice varieties, we used polymerase chain reaction-randomly amplified polymorphic DNA (PCR-RAPD) markers, and to elucidate whether a relationship exists between the ground and the specific characteristics of the product, we studied proximate composition, fatty acid composition, mineral content, and total antioxidant capacity. Using principal component analysis on genomic and compositional data, we were able to classify rice samples according to their variety and their district of production. This work also examined the discrimination ability of different parameters. It was found that genomic data give the best discrimination based on varieties, indicating that RAPD assays could be useful in discriminating among closely related species, while compositional analyses do not depend on the genetic characters only but are related to the production area.     

欧洲控制PMWS的多种管理策略

自从断奶仔猪多系统衰竭综合征（PMWS）在欧洲发现后,人们应用不同的策略试图对该病进行防制,虽然取得了不同程度的成功,但还没有任何一种单一的方法能够完全控制这种疾病。     

Wide Range Applications of Spirulina: From Earth to Space Missions

Spirulina is the most studied cyanobacterium species for both pharmacological applications and the food industry. The aim of the present review is to summarize the potential benefits of the use of Spirulina for improving healthcare both in space and on Earth. Regarding the first field of application, Spirulina could represent a new technology for the sustainment of long-duration manned missions to planets beyond the Lower Earth Orbit (e.g., Mars); furthermore, it could help astronauts stay healthy while exposed to a variety of stress factors that can have negative consequences even after years. As far as the second field of application, Spirulina could have an active role in various aspects of medicine, such as metabolism, oncology, ophthalmology, central and peripheral nervous systems, and nephrology. The recent findings of the capacity of Spirulina to improve stem cells mobility and to increase immune response have opened new intriguing scenarios in oncological and infectious diseases, respectively.     

Aroma volatility from aqueous sucrose solutions at low and subzero temperatures

The gas-liquid partition coefficients of ethyl acetate and ethyl hexanoate have been measured in water and aqueous sucrose solutions from 25 to -10 degrees C by dynamic headspace. Experiments were carried out on sucrose solutions at temperatures where no ice formation was possible. Results showed that when sucrose concentration increased, aroma volatility increased except for ethyl hexanoate and in the highest sucrose concentration solution (57.5%). A quasi-linear temperature decrease on aroma volatility was observed in sucrose solutions from 25 to around 4 and 0 degrees C. Then, from 0 to -10 degrees C, aroma volatility did not decrease: ethyl acetate volatility remained constant but that of ethyl hexanoate increased. Enthalpy of vaporization and activity coefficients of the aroma compounds were calculated.     

Above-ground biomass dynamics after reduced-impact logging in the Eastern Amazon

Changes in above-ground biomass (AGB) of 17 1 ha logged plots of terra firme rain forest in the eastern Amazon (Brazil, Paragominas) were monitored for four years (2004–2008) after reduced-impact logging. Over the same time period, we also monitored two 0.5 ha plots in adjacent unlogged forest. While AGB in the control plots changed little over the observation period (increased on average 1.4 Mg ha⁻¹), logging resulted in immediate reductions in ABG that averaged 94.5 Mg ha⁻¹ (±42.0), which represented 23% of the 410 Mg ha⁻¹ (±64.9) present just prior to harvesting. Felled trees (dbh > 55 cm) accounted for 73% (±15) of these immediate losses but only 18.9 Mg ha⁻¹ (±8.1) of biomass was removed in the extracted logs. During the first year after logging, the annual AGB balance (annual AGB gain by recruitment and growth − annual AGB loss by mortality) remained negative (−31.1 Mg ha⁻¹ year⁻¹; ±16.7), mainly due to continued high mortality rates of damaged trees. During the following three years (2005–2008), average net AGB accumulation in the logged plots was 2.6 Mg ha⁻¹ year⁻¹ (±4.6). Post-logging biomass recovery was mostly through growth (4.3 ± 1.5 Mg ha⁻¹ year⁻¹ for 2004–2005 and 6.8 ± 0.9 Mg ha⁻¹ year⁻¹ for 2005–2008), particularly of large trees. In contrast, tree recruitment contributed little to the observed increases in AGB (1.1 ± 0.6 Mg ha⁻¹ year⁻¹ for 2004–2005 and 3.1 ± 1.3 Mg ha⁻¹ year⁻¹ for 2005–2008). Plots with the lowest residual basal area after logging generally continued to lose more large trees (dbh ≥70 cm), and consequently showed the greatest AGB losses and the slowest overall AGB gains. If 100% AGB recovery is desired and the 30-year minimum cutting cycle defined by Brazilian law is adhered to, current logging intensities (6 trees ha⁻¹) need to be reduced by 40–50%. Such a reduction in logging intensity will reduce financial incomes to loggers, but might be compensated for by the payment of environmental services through the proposed REDD (reduced emissions from deforestation and forest degradation) mechanism of the United Nations Framework Convention on Climate Change.