The human herpesvirus 8 chemokine receptor vGPCR triggers autonomous proliferation of endothelial cells

We have used a novel conditional transgenic system to study the mechanisms of angioproliferation induced by viral G protein–coupled receptor (vGPCR), the constitutively active chemokine receptor encoded by human herpesvirus 8 (HHV8, also known as Kaposi sarcoma herpesvirus). Using this system, we were able to control temporal expression of vGPCR and to monitor its expression in situ via the use of the surrogate marker LacZ. Upon treatment with doxycycline (DOX), cells expressing vGPCR and LacZ (vGPCR/LacZ(+) cells) progressively accumulated in areas where angioproliferation was observed. Sorted vGPCR/LacZ(+) cells from angiogenic lesions expressed markers characteristic of endothelial progenitor cells, produced angiogenic factors, and proliferated in vitro. Prolonged treatment of transgenic mice with DOX led to development of tumors in the skin of ears, tail, nose, and paws. vGPCR/LacZ(+) cells were frequent in early lesions but scarce within these tumors. Finally, transfer of vGPCR/LacZ(+) cells into Rag1(–/–) mice treated with DOX led to angioproliferation and, with time, to development of tumors containing both vGPCR/LacZ(+) and vGPCR/LacZ(–) cells. Taken together, these results indicate that vGPCR triggers angioproliferation directly and suggest a novel role for this molecule in the pathogenesis of Kaposi sarcoma

Transient receptor potential ankyrin 1 channel expression on peripheral blood leukocytes from rheumatoid arthritic patients and correlation with pain and disability

Patients with rheumatoid arthritis (RA) suffer from pain and joint disability. The transient receptor potential ankyrin 1 (TRPA1) channel expressed on sensory neurones and non-neuronal cells mediates pain transduction and inflammation and it has been implicated in RA. However, there is little information on the contribution of TRPA1 for human disease. Here, we investigated the expression of TRPA1 on peripheral blood leukocytes and the circulating levels of its endogenous activators 4-hydroxynonenal (4-HNE) and hydrogen peroxide (H(2)O(2)) in RA patients treated or not with the anti-rheumatic leflunomide (LFN) or the anti-TNFα adalimumab (ADA). We also assessed whether TRPA1 expression correlates with joint pain and disability, in addition to the immune changes in RA. TRPA1 expression on peripheral blood leukocytes correlated with pain severity and disability. TRPA1 levels on these cells were associated with the numbers of polymorphonuclear and the activation of CD14(+) cells. No correlations were found between the lymphocyte population and TRPA1 expression, pain or disability. Patients recently diagnosed with RA expressed increased levels of TRPA1 on their leukocytes whilst treatment with either LFN or ADA down-regulated this receptor probably by reducing the numbers of polymorphonuclears and the activation of CD14(+) cells. We suggest that the activation levels of CD14(+) cells, the numbers of PMNs in the peripheral blood and the expression of TRPA1 on peripheral blood leukocytes correlate with RA progression, affecting joint pain sensitivity and loss of function

Use of Some Asteraceae Plants for the Treatment of Wounds: From Ethnopharmacological Studies to Scientific Evidences

Severe wounds result in large lesions and/or loss of function of the affected areas. The treatment of wounds has challenged health professionals due to its complexity, especially in patients with chronic diseases (such as diabetes), and the presence of pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. Taking this into consideration, the development of new therapies for wound healing requires immediate attention. Ethnopharmacological studies performed in different countries have shown the use of several plants from the Asteraceae family as wound-healing agents. Evidences gained from the traditional medicine have opened new ways for the development of novel and more efficient therapies based on the pharmacological properties of these plants. In this article, we discuss the literature data on the use of Asteraceae plants for the treatment of wounds, based on the ethnopharmacological relevance of each plant. Special attention was given to studies showing the mechanisms of action of Asteraceae-derived compounds and clinical trials. Ageratina pichinchensis (Kunth) R.M. King and H. Rob. and Calendula officinalis L. preparations/compounds were found to show good efficacy when assessed in clinical trials of complicated wounds, including venous leg ulcers and foot ulcers of diabetic patients. The compounds silibinin [from Silybum marianum (L.) Gaertn.] and jaceosidin (from Artemisia princeps Pamp.) were identified as promising compounds for the treatment of wounds. Overall, we suggest that Asteraceae plants represent important sources of compounds that may act as new and efficient healing products

Monitoring of Peripheral Blood Leukocytes and Plasma Samples: A Pilot Study to Examine Treatment Response to Leflunomide in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a painful inflammatory disease of the joints which affects a considerable proportion of the world population, mostly women. If not adequately treated, RA patients can become permanently disabled. Importantly, not all the patients respond to the available anti-rheumatic therapies, which also present diverse side effects. In this context, monitoring of treatment response is pivotal to avoid unnecessary side effects and costs towards an ineffective therapy. Herein, we performed a pilot study to investigate the potential use of flow cytometry and attenuated total reflection–Fourier transform infrared (ATR-FTIR) spectroscopy as measures to identify responders and non-responders to leflunomide, a disease-modifying drug used in the treatment of RA patients. The evaluation of peripheral blood CD62L+ polymorphonuclear cell numbers and ATR-FTIR vibrational modes in plasma were able to discriminate responders to leflunomide (LFN) three-months after therapy has started. Overall, the results indicate that both flow cytometry and ATR-FTIR can potentially be employed as additional measures to monitor early treatment response to LFN in RA patients