How can nanoparticle-based technologies revolutionize the topical therapy in psoriasis?

Psoriasis is one of the most common dermatoses with a heterogeneous pathogenesis which can be successfully exploited therapeutically as it is increasingly well understood. Topical therapy is the gold standard for psoriasis patients with mild disease courses and for complementary and maintenance treatment in moderate and severe forms. However, while new systemic therapies are rapidly implemented in the daily routine as our pathomechanistic understanding of psoriasis evolves, the development of topical psoriasis therapies stagnates. Modern topical treatments though would require not only new active substances but also improved galenics. Due to their unique ability to directly exert biological functions, but also to deliver drugs in optimal concentrations, enabling increased therapeutic efficacy, reduced adverse effects and improved patient compliance, nanoparticles may represent ideal drug carriers for local therapeutics in psoriasis. In recent years, a series of reports added important insights into the biology of skin-nanoparticles interactions and on how they impact the epidermal and dermal inflammatory compartments in vitro and in psoriasis plaques. Furthermore, by targeting anti-inflammatory substances to specific skin compartments, nanotechnological advances offer the exciting opportunity to fine-tune skin inflammation at molecular and cellular levels, paving the road to a high-precision, skin-directed topical therapy in psoriasis. However, nanoparticle-based therapies have not yet found their way into clinical routine in dermatology. We here resume the current advances in the research of nanoparticles and skin inflammation in general and psoriasis in particular and discuss how this promising technology should develop in order to fulfil the requirements of an optimal skin therapy.

Optimization and validation of the liquid chromatography coupled to tandem mass spectrometry method for assessing octreotide release from microspheres during inflammation in rabbit models.

To study the effect of acute-phase reaction (APR) of inflammation on the release of octreotide acetate microsphere (Sandostatin®, SLAR) at a clinical dose, a more sensitive liquid chromatography coupled to tandem mass spectrometry analysis method needs to be developed because of the low plasma concentrations of octreotide. Solid-phase microextraction with an Oasis® HLB µElution plate was adopted for sample preparation. Extraction recovery ranged from 65.7 % to 73.2 %, and the matrix effect was negligible. High sensitivity and an intense chromatographic peak were acquired by optimizing the chromatography and mass spectrometry conditions. The lower limit of quantitation (LLOQ) was 0.01 ng/mL based on 100 µL of plasma, and linearity ranged from 0.01 to 5.0 ng/mL. The coefficients of variations for intraday and interday precision were less than 4.4 %, and the relative error of accuracy was within 5.7 %. The validated method was successfully applied to pharmacokinetics studies of SLAR in a seven-day inflammation model of rabbits, indicating that the APR did not affected the release and pharmacokinetics of the octreotide microspheres.

Anti-Inflammatory Activity of Exopolysaccharides from Phormidium sp. ETS05, the Most Abundant Cyanobacterium of the Therapeutic Euganean Thermal Muds, Using the Zebrafish Model.

The Euganean Thermal District (Italy) represents the oldest and largest thermal center in Europe, and its therapeutic mud is considered a unique product whose beneficial effects have been documented since Ancient Roman times. Mud properties depend on the heat and electrolytes of the thermal water, as well as on the bioactive molecules produced by its biotic component, mainly represented by cyanobacteria. The investigation of the healing effects of compounds produced by the Euganean cyanobacteria represents an important goal for scientific validation of Euganean mud therapies and for the discovering of new health beneficial biomolecules. In this work, we evaluated the therapeutic potential of exopolysaccharides (EPS) produced by Phormidium sp. ETS05, the most abundant cyanobacterium of the Euganean mud. Specifically, Phormidium EPS resulted in exerting anti-inflammatory and pro-resolution activities in chemical and injury-induced zebrafish inflammation models as demonstrated using specific transgenic zebrafish lines and morphometric and expression analyses. Moreover, in vivo and in vitro tests showed no toxicity at all for the EPS concentrations tested. The results suggest that these EPS, with their combined anti-inflammatory and pro-resolution activities, could be one of the most important therapeutic molecules present in the Euganean mud and confirm the potential of these treatments for chronic inflammatory disease recovery.

Inflammation related responses of intestinal cells to plum and cabbage digesta with differential carotenoid and polyphenol profiles following simulated gastrointestinal digestion.

SCOPE: Plums/cabbages represent fruits/vegetables rich in carotenoids and polyphenols, and have been associated with anti-inflammatory properties. METHODS AND RESULTS: We tested four plum (Italian Plum, Plum 620, Ersinger, and Cherry Plum) and cabbage varieties (Duchy, Kalorama, Kale, Scots Kale) with contrasting carotenoid/polyphenol content for their capability to alter inflammation/oxidative stress following simulated gastrointestinal digestion. Digesta were exposed to Caco-2(TC-7) and to a triple-culture(Caco-2/HT-29-MTX (90:10 v/v) including THP-1 like macrophages), stimulated to induce inflammation (10 µg/mL LPS, 100 ng/mL TNF-α, 25 ng/mL IL-1-ß for 24 h, the last 18 h with digesta). Endpoints investigated included IL-6, IL-8, PGE-2, NO (all ELISA), NF-κB, MAPK, IL-6, IL-8, iNOS, Nrf2, COX-2 (real-time-PCR) and Nrf2 (immunostaining). IL-6 secretion was reduced in THP-1 cells by Scots Kale and Kalorama (up to 22%, p<0.05), and IL-8 secretion in the coculture (up to 35% in plums, p<0.05). This was accompanied by decreased NF-kB expressions in THP-1 cells (up to 30%, p<0.05). Nrf2 translocation to the nucleus was partly reduced by plums and cabbages (up to 40% (p<0.05). CONCLUSIONS: Some varieties, especially in the triple-culture, reduced inflammation, though this was unrelated to concentrations of carotenoids/polyphenols. The potential of phytochemical-rich fruits and vegetables to ameliorate gastrointestinal inflammation should be further investigated.

Neurodevelopmental Animal Models Reveal the Convergent Role of Neurotransmitter Systems, Inflammation, and Oxidative Stress as Biomarkers of Schizophrenia: Implications for Novel Drug Development.

Schizophrenia is a life altering disease with a complex etiology and pathophysiology, and although antipsychotics are valuable in treating the disorder, certain symptoms and/or sufferers remain resistant to treatment. Our poor understanding of the underlying neuropathological mechanisms of schizophrenia hinders the discovery and development of improved pharmacological treatment, so that filling these gaps is of utmost importance for an improved outcome. A vast amount of clinical data has strongly implicated the role of inflammation and oxidative insults in the pathophysiology of schizophrenia. Preclinical studies using animal models are fundamental in our understanding of disease development and pathology as well as the discovery and development of novel treatment options. In particular, social isolation rearing (SIR) and pre- or postnatal inflammation (PPNI) have shown great promise in mimicking the biobehavioral manifestations of schizophrenia. Furthermore, the "dual-hit" hypothesis of schizophrenia states that a first adverse event such as genetic predisposition or a prenatal insult renders an individual susceptible to develop the disease, while a second insult (e.g., postnatal inflammation, environmental adversity, or drug abuse) may be necessary to precipitate the full-blown syndrome. Animal models that emphasize the "dual-hit" hypothesis therefore provide valuable insight into understanding disease progression. In this Review, we will discuss SIR, PPNI, as well as possible "dual-hit" animal models within the context of the redox-immune-inflammatory hypothesis of schizophrenia, correlating such changes with the recognized monoamine and behavioral alterations of schizophrenia. Finally, based on these models, we will review new therapeutic options, especially those targeting immune-inflammatory and redox pathways.

Strategy for prevention of cancers of the esophagus.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the animal reflux-inflammation models for Barrett's esophagus and esophageal adenocarcinoma; genomic/epigenomic analyses; eflornithine-based combinations; the molecular derangements that promote neoplastic transformation; the role of COX-2 inhibitors, proton pump inhibitors, and phase II trials in Barrett's adenocarcinoma; statins in chemoprevention and treatment of esophageal cancer; and biomarkers as potential targets in Barrett's adenocarcinoma.