Rapha Myr®, a Blend of Sulforaphane and Myrosinase, Exerts Antitumor and Anoikis-Sensitizing Effects on Human Astrocytoma Cells Modulating Sirtuins and DNA Methylation.

Brain and other nervous system cancers are the 10th leading cause of death worldwide. Genome instability, cell cycle deregulation, epigenetic mechanisms, cytoarchitecture disassembly, redox homeostasis as well as apoptosis are involved in carcinogenesis. A diet rich in fruits and vegetables is inversely related with the risk of developing cancer. Several studies report that cruciferous vegetables exhibited antiproliferative effects due to the multi-pharmacological functions of their secondary metabolites such as isothiocyanate sulforaphane deriving from the enzymatic hydrolysis of glucosinolates. We treated human astrocytoma 1321N1 cells for 24 h with different concentrations (0.5, 1.25 and 2.5% v/v) of sulforaphane plus active myrosinase (Rapha Myr®) aqueous extract (10 mg/mL). Cell viability, DNA fragmentation, PARP-1 and γH2AX expression were examined to evaluate genotoxic effects of the treatment. Cell cycle progression, p53 and p21 expression, apoptosis, cytoskeleton morphology and cell migration were also investigated. In addition, global DNA methylation, DNMT1 mRNA levels and nuclear/mitochondrial sirtuins were studied as epigenetic biomarkers. Rapha Myr® exhibited low antioxidant capability and exerted antiproliferative and genotoxic effects on 1321N1 cells by blocking the cell cycle, disarranging cytoskeleton structure and focal adhesions, decreasing the integrin α5 expression, renewing anoikis and modulating some important epigenetic pathways independently of the cellular p53 status. In addition, Rapha Myr® suppresses the expression of the oncogenic p53 mutant protein. These findings promote Rapha Myr® as a promising chemotherapeutic agent for integrated cancer therapy of human astrocytoma.

Bronchodilator response as a marker of poor asthma control.

BACKGROUND: Asthma guidelines emphasise the importance of monitoring disease control in managing asthma. OBJECTIVE: The aim of this study was to evaluate the relationship between lung function, including bronchodilator response in terms of improving in FEV1 after administration of salbutamol, and asthma control. METHODS: 246 patients with known asthma and in regular chronic treatment according to international guidelines were consecutively enrolled in a 12 month-period. All patients were evaluated by asthma control test (ACT), spirometry and bronchodilator test with salbutamol 400 mcg. RESULTS: Mean ACT value was 18.8. Patients with significant bronchial reversibility had lower ACT mean values. This finding was confirmed in both patients with airway obstruction and in those with normal spirometry. There was a significant correlation between ACT values and bronchodilator response. CONCLUSIONS: The persistence of a significant degree of bronchodilator response despite regular treatment according to guidelines was a marker of worse asthma control. CLINICAL IMPLICATIONS: Bronchodilator response, correlating with worse asthma control even in patients with normal spirometry, should be test at every visit as it may add information on asthma control.

High prevalence of Anisakis simplex hypersensitivity and allergy in Sicily, Italy.

BACKGROUND: Anisakis simplex can elicit allergic reactions when ingested in raw or marinated fish. The prevalence of A simplex hypersensitivity and allergy in Sicily (Italy), an area where the consumption of raw or marinated fish is very common, has not been investigated thus far. OBJECTIVE: To investigate the prevalence of A simplex sensitization and its clinical relevance in a large group of unselected patients. METHODS: All consecutive patients referred to the authors' allergy clinic during a 22 month-period were included in the study, evaluated for sensitization to A simplex and other allergens depending on their clinical history, and investigated for allergic symptoms after the ingestion of raw or marinated fish. RESULTS: Of 3,419 patients screened, 527 (15.4%) were sensitized to A simplex and 29 of these (5.5% of sensitized patients) had a history of A simplex allergy. Approximately 30% of patients had mono-sensitization to A simplex. Co-sensitization to house dust mites or molds yielded an odds ratio of 1.98 or 3.18, respectively, for allergy to A simplex. CONCLUSION: A high prevalence of A simplex sensitization in a large proportion of patients with mono-sensitization was found, confirming that eating habits influence sensitization to this nematode. Allergic symptoms from A simplex ingestion in raw or marinated fish were quite frequent, with symptoms ranging from oral allergy syndrome to anaphylaxis. Patients sensitized to A simplex were more prone to have allergic symptoms when they had co-sensitization to house dust mites or molds, suggesting possible cross-reactive but clinically relevant allergens between these allergenic sources.