Correlations between the level of bacterial resistance and the rate of clinical efficiency in the therapy of community-acquired respiratory tract infections

The aim of the study is to evaluate the efficiency of the first-line antibiotic treatment of the community-acquired respiratory tract infections in a population of young adults from an urban setting and to establish the pattern of antibiotic resistance of the germs involved. The bacteria most frequently identified have been: S. pneumoniae, H. influenzae, M. catarrhalis, atypical agents also being suspected. Antibiotic treatment has been chosen accordingly to the recent guidelines, total clinical remission rate being of 91.08%, despite the increasing resistance for the commonly used antibiotics; a close monitoring of the phenomenon is mandatory.     

Vasoactive intestinal peptide generates human tolerogenic dendritic cells that induce CD4 and CD8 regulatory T cells

Induction of antigen-specific tolerance is critical for autoimmunity prevention and immune tolerance maintenance. In addition to their classical role as sentinels of the immune response, dendritic cells (DCs) play important roles in maintaining peripheral tolerance through the induction/activation of regulatory T (T(reg)) cells. The possibility of generating tolerogenic DCs opens new therapeutic perspectives in autoimmune/inflammatory diseases. Characterizing endogenous factors that contribute to the development of tolerogenic DCs is highly relevant. We here report that the immunosuppressive neuropeptide vasoactive intestinal peptide (VIP) induces the generation of human tolerogenic DCs with the capacity to generate CD4 and CD8 T(reg) cells from their respective naive subsets. The presence of VIP during the early stages of DC differentiation from blood monocytes generates a population of IL-10-producing DCs unable to fully mature after the effects of inflammatory stimuli. CD4 T(reg) cells generated with VIP-differentiated DCs resemble the previously described Tr1 cells in terms of phenotype and cytokine profile. CD8 T(reg) cells generated with tolerogenic VIP DCs have increased numbers of IL-10-producing CD8(+)CD28(-)-CTLA4(+) T cells. CD4 and CD8 T(reg) cells primarily suppress antigen-specific T(H)1-mediated responses. Therefore, the possibility of generating or expanding ex vivo tolerogenic DC(VIPs) opens new therapeutic perspectives for treating autoimmune diseases and graft-versus-host disease after allogeneic transplantation in humans.     

Modulation of doxorubicin-induced oxidative stress by a grape (Vitis vinifera L.) seed extract in normal and tumor cells

The major limitation of Doxorubicin (Dox) clinical use is the development of chronic and acute toxic side effects induced through the generation of reactive oxygen species. The present work was designated to investigate in vitro effects of a red grape-seed hydroethanolic extract Burgund Mare (BM), in associated administration with Dox (30 min before drug administration) in normal (Hfl-1) and tumor cell lines (HepG2 and Mls). The BM concentrations administered were below the level of the extract cytotoxiciy threshold (40 μg gallic acid [GA] Eq/mL; 37.5, 25.0, and 12.5 μg GA Eq/mL). The antioxidant capacity of the BM extract was assessed by measuring the acute toxicity at 24 h, lipid peroxides (LP), and protein oxidation. In normal cells, the product statistically decreased cytotoxicity and markedly inhibited LP and protein carbonyl (PC) formation, in a dose-dependent relationship. On contrary, in tumor cells, such treatment resulted in a reversed effect, cell death, malondialdehyde, and PC contents increasing with BM dose enhancement. BM extract treatment prior to subsequent administration of Dox afforded a differential protection against Dox-negative toxic side effects in normal cells without weakening (even enhancing) Dox's antitumor activity.     

Multicenter,Double-Blind,Randomized, Placebo-Controlled,Parallel-Group Study of the Efficacy,Safety, and Tolerability of THC:CBD Extract and THC Extract in Patients with Intractable Cancer-Related Pain

This study compared the efficacy of a tetrahydrocannabinol:cannabidiol (THC:CBD) extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract, with placebo, in relieving pain in patients with advanced cancer. In total, 177 patients with cancer pain, who experienced inadequate analgesia despite chronic opioid dosing, entered a two-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. Patients were randomized to THC:CBD extract (n = 60), THC extract (n = 58), or placebo (n = 59). The primary analysis of change from baseline in mean pain Numerical Rating Scale (NRS) score was statistically significantly in favor of THC:CBD compared with placebo (improvement of ?1.37 vs. ?0.69), whereas the THC group showed a nonsignificant change (?1.01 vs. ?0.69). Twice as many patients taking THC:CBD showed a reduction of more than 30% from baseline pain NRS score when compared with placebo (23 [43%] vs. 12 [21%]). The associated odds ratio was statistically significant, whereas the number of THC group responders was similar to placebo (12 [23%] vs. 12 [21%]) and did not reach statistical significance. There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups. No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment. However, the results from the European Organisation for Research and Treatment of Cancer Quality of Life Cancer Questionnaire showed a worsening in nausea and vomiting with THC:CBD compared with placebo (P = 0.02), whereas THC had no difference (P = 1.0). Most drug-related adverse events were mild/moderate in severity. This study shows that THC:CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids.     

Epidermal growth factor receptor (EGFR) expression in periocular and extraocular sebaceous carcinoma

Sebaceous carcinoma has a predominant periocular origin but can also be extraocular. These two groups have distinct clinical courses. Insight into the molecular determinants of tumorigenesis and metastasis is limited. There is no effective treatment for metastatic sebaceous carcinoma. Epidermal growth factor receptor (EGFR) is implicated in tumorigenesis and can be a therapeutic target in certain settings. We evaluated EGFR levels by immunohistochemistry (IHC), comparing its expression between periocular and extraocular tumors and assessed EGFR mutation status. IHC was performed in 36 cases: 19 periocular and 17 extraocular (10 associated with Muir‐Torre syndrome—MTS). EGFR IHC was scored for percentage of positive cells (< 5%, 5–25%, 26–50%, > 50%) and intensity (+1 = low , +2 = moderate , +3 = high ). Extraocular carcinomas showed markedly increased levels of EGFR when compared to periocular carcinoma cases, both in terms of distribution (88% were > 25% of tumor cells vs. 16%) and intensity (77% were 2+ or 3+ vs. 21%) (p < 0.001). Among extraocular cases, there was significantly lower EGFR expression in MTS‐related cases (p < 0.05). No EGFR mutations were identified. Our results underscore the divergent mechanisms underlying the tumorigenesis of periocular and extraocular sebaceous carcinoma and suggest an association between aggressive behavior and increased EGFR expression in extraocular sebaceous carcinoma. Ivan D, Prieto VG, Esmaeli B, Wistuba II, Tang X, Lazar AJF. Epidermal growth factor receptor (EGFR) expression in periocular and extraocular sebaceous carcinomas.